Post-Approval Studies (PAS) Database

The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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Long-Term Study

General
Study Status	Terminated
Application Number / Requirement Number	H120003 / PAS001
Date Original Protocol Accepted	04/07/2015
Date Current Protocol Accepted	04/07/2015
Study Name	Long-Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to demonstrate the XVIVO Perfusion System (XPS) with STEEN Solution can be safely used for the flushing and temporary continuous normothermic machine perfusion of initially unacceptable excised donor lungs during which time the function of the lungs can be reassessed for transplantation. The study is a prospective, multicenter, controlled clinical trial.
Study Population	A total of 252 patients will include 220 from the premarket cohort and 32 newly enrolled patients. The treatment arm will consist of 126 who receive EVLP treated lungs that were initially unacceptable and the comparator arm will consist of 126 patients who are transplanted with standard lungs that are preserved with the cold storage method.
Sample Size	A total of 252 patients (126 per arm) will be included in the PAS.
Key Study Endpoints	The primary endpoint is 3 year survival rate. The secondary endpoints are quality of life, episodes of rejection per United Network for Organ Sharing (UNOS) registry, and Forced Expiratory Volume in 1 second (FEV1) at 1, 2, 3 years. Safety endpoint is the post transplant events captured in the UNOS Registry at 2, 3 years.
Follow-up Visits and Length of Follow-up	3 years (2nd and 3rd year with the UNOS Registry) Subjects will be followed for 3 years post transplant, with data collected at the 1, 2, and 3 year time points.
General
Study Status	Ongoing
Application Number / Requirement Number	P030053 / PAS008
Date Original Protocol Accepted	10/01/2014
Date Current Protocol Accepted	03/08/2022
Study Name	MemoryGel and Shape Glow Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The MemoryGel and Shape Glow Study was designed as part of the re-design of the LARGE PAS. This is a smaller cohort study (10 years follow-up) designed to address safety outcomes (i.e., including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problems, effects on mammography, effects on patient satisfaction with breasts and psychosocial wellbeing, and silicone subject compliance with magnetic resonance imaging (MRI) recommendations. This restructured PAS, once completed as designed, would satisfy the post-approval requirements for both the MemoryGel® (P030053) and Memory Shape (P060028) silicone breast implants. In addition, information gained from the NBIR will help strengthen the general understanding of implantation rates and certain risks associated with breast implants.
Study Population	Women who receive Mentor’s MemoryGel and MemoryShape breast implants for the purpose of primary or revisional breast augmentation and primary or revisional breast construction. Additionally, women who undergo aesthetic surgery (for example liposuction, rhinoplasty, brow lift, autoplasty, rhytidectomy, mentoplasty/genioplasty, otoplasty, or blepharoplasty) will be enrolled as concurrent controls.
Sample Size	The study will enroll 2,518 women who receive Memory Gel and MemoryShape Breast Implants for augmentation, reconstruction, augmentation revision, or reconstruction revision. The study will also enroll 300 women undergoing aesthetic surgery who will serve as concurrent control group. The study was designed to have 80% power to be able to detect as statistically significant a relative risk of 2.0 for adverse events that occur, without implants with a frequency of 5.0 per 10,000 person-years, based on a one-sided test conducted at level of significance of 0.05. Based on these specifications, it was determined that approximately 20,328 person-year, a total of at least 2,518 breast implants patients would be required. Patient are to be followed for 10 years. For purposes of sample size calculationns, assuming a follow-up rate of 65% at 10 years and a linear loss to follow-up, there would be an average of 8, 075 person-years per patient. Thus, in order to obtain the 20,328 person-years, a total of 2,518 breast implants patients would be required.
Key Study Endpoints	Safety Endpoints to be evaluated are as follows: Local complications, connective tissue diseases, rheumatologic and neurologic signs and symptoms, cancer, suicide, and lactation complications and magnetic resonance imaging (MRI) compliance and results. Effectiveness BREAST-Q will be assessed in a subset of breast implant patients, approximately 500 patients, by responses to questions addressing their perceived quality-of-life and satisfaction with their breast implants.
Follow-up Visits and Length of Follow-up	Patients will be followed for 10 years. MemoryGel and Memory Shape Breast Implant patients will be evaluated by the investigator at baseline and years 1, 5, and 10, and will complete questionnaires at baseline and annually for 10 years. A concurrent control group of women undergoing other aesthetic surgery (patients are referred to as Control participants) will complete questionnaires at baseline and annually for 10 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	3,611 total subjects
Actual Number of Sites Enrolled	62
Patient Follow-up Rate	The 2 year follow-up rates are: 82.6% - MemoryGel cohort 90.6% - MemoryShape Prospective cohort 83.3% - MemoryShape Retrospective cohort 76.7% - Control cohort
General
Study Status	Delayed
Application Number / Requirement Number	H190005 / PAS001
Date Original Protocol Accepted	01/13/2020
Date Current Protocol Accepted	06/10/2025
Study Name	The Tether Vertebral Tethering System PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective is to assess the ongoing safety and probable benefit of The Tether in a registry population.The study design is a single-arm, prospective, multicenter cohort, registry study.
Study Population	The study population is comprised of skeletally immature patients that require surgical treatment to obtain and maintain correction of progressive idiopathic scoliosis who receive the device in the post market environment. There is no comparator group.
Sample Size	At least 193 patients will be enrolled.
Key Study Endpoints	The primary probable benefit endpoint is the percentage of patients with maintenance of the major Cobb angle less than or equal to 40 degrees at 60 months post-surgery. The primary safety endpoints are serious adverse events (SAEs), and device- or procedure-related AEs.
Follow-up Visits and Length of Follow-up	Patients will be followed through 60-months from the time of each patient's index surgery.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Across 9 sites, 185 patients were actively enrolled. There will be a maximum N of 184 across the entire cohort, as one patient has yet to have their first erect visit, and are excluded from this report at this time. Due to an updated protocol amendment regarding inclusion and exclusion criteria, patients not originally enrolled in the PAS cohort have been retrospectively added to the cohort following institutional guidelines and IRB permissions. The changed criteria were the removal of surgeon and site caps on enrollment, the removal of the requirement for a preoperative PFT, and the allowance of telemedicine visits, which allowed sites with out of town patients to add to their cohort.
Actual Number of Sites Enrolled	9 active sites
Patient Follow-up Rate	Two patients at the MSH site were excluded from the study due to the discontinuation of the MSH site. The sponsor noted data quality issues such as late data and missed protocol visits.
General
Study Status	Completed
Application Number / Requirement Number	P180050 / PAS001
Date Original Protocol Accepted	08/16/2019
Date Current Protocol Accepted	01/20/2023
Study Name	Extended Phase BeAT-HF PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is continued follow up of the IDE cohort with additional enrollments post-approval to determine if the device can reduce cardiovascular mortality and heart failure hospitalizations.
Study Population	For patients who remain symptomatic despite treatment with guideline-directed medical therapy, are NYHA Class III or Class II (who had a recent history of Class III), have a left ventricular ejection fraction less than or equal to 35%, a NT-proBNP < 1600 pg/ml and excluding patients indicated for Cardiac Resynchronization Therapy (CRT) according to AHA/ACC/ESC guidelines
Sample Size	480 subjects
Key Study Endpoints	Rate of events (cardiovascular death and/or heart failure hostpitalization) is lower in treatment arm than control arm.
Follow-up Visits and Length of Follow-up	Follow-up continues to post-approval study completion.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1091 enrolled/ 467 randomized and 218 implanted
Actual Number of Sites Enrolled	92 sites enrolled, 73 sites enrolled subjects
Patient Follow-up Rate	2 weeks, 1, 1.5, 2, 3, 6, 9, 12, 24 months Note: 6MHW and NT-proBNP were collected until 12 months
Final Safety Findings	The safety results were evaluated at 6 months of follow-up with 264 randomized subjects. The results were reviewed in P180050. 125 subjects with the implant were included in the safety evaluation. There were 121 subjects who were MANCE-Free, which lead to a MANCE-Free Rate of 96.8%.
Final Effect Findings	At the 6 month follow-up, 3 outcomes (6MHW, QoL, and NT-proBNP) were evaluated between the device and medical management arm. All 3 outcomes showed an improvement. There was no statistically significant difference in performance between the device arm and control arm for mortality and morbidity (heart failure hospitalizations) over the duration of the study. Therefore, the primary endpoint was not met. The secondary analysis evaluated the symptomatic improvement: 6MHW and NT-proBNP at 12 months and MLWHF (QoL) and NYHA Class at 12 and 24 months. There was improvement seen for the 6MHW (12 month), QoL and NYHA Class (24 months). At 12 months, the medical management arm showed a larger improvement for the NT-proBNP. The Win Ratio was evaluated. The heart transplant/LVAD and MLWHF at 12 months showed a beneficial trend.
Study Strengths & Weaknesses	The study showed that the device provided symptomatic improvement at 6 months. There was symptomatic improvement found at 12 months; however, the improvement was not found in the NT-proBNP. Additionally, 6MHW test and NT-proBNP were not collected at 24 month follow up so it is unclear what the results would be for these metrics at 24 month follow up. Additionally, the primary endpoint was not met. The sponsor states that the NT-proBNP results need caution when interpreting because large number of subjects began ARNI during follow up, particularly in the control arm at 12 months.
Recommendations for Labeling Changes	Labeling changes were made to incorporate the PAS results in P180050/S009
General
Study Status	Completed
Application Number / Requirement Number	P000008 S017/ PAS001
Date Original Protocol Accepted	02/16/2011
Date Current Protocol Accepted	08/15/2011
Study Name	LBMI-002
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multiple-center, non-randomized, cohort study
Study Population	Patients enrolled in the study LBMI-001: Obesity (BMI ¡Ý 30 kg/m2 and < 35 kg/m2 with or without comorbid conditions and BMI ¡Ý 35 kg/m2 and < 40 kg/m2 without any severe comorbid conditions) at time of LBMI-001 enrollment
Sample Size	Up to 149 patients
Key Study Endpoints	Effectiveness: The percent of subjects treated with the LAP-BAND® who achieve successful weight loss, at 5 years post- implantation, will be statistically non-inferior to 60%, where successful weight loss is defined as at least 30% Excess Weight Loss (EWL). Safety: The primary measure is the percentage of those subjects who are explanted within 5 years postimplantation. Additionally safety measurements will include the incidence of adverse events, by severity and relation to device, observed over the study assessment period.
Follow-up Visits and Length of Follow-up	5 years post implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	149 subjects
Actual Number of Sites Enrolled	7 sites
Patient Follow-up Rate	72.5% (108/149)
Final Safety Findings	The 5-year explant rate (including explants with replacement) was 14.8%. Therefore, the primary safety endpoint that the 5-year explant rate is significantly lower than 32.5% has been met.
Final Effect Findings	76.9% of subjects attained successful weight loss (defined as greater than or equal to 30% excess weight loss) at 5 years. Therefore, the main effectiveness endpoint that 5-year successful weight loss will be noted in at least 60% of patients has been met.
Study Strengths & Weaknesses	Strengths of this study include a multi-center, prospective design of adequate sample size for long-term (5-year) evaluation of the primary safety and effectiveness endpoints. The main limitation is the limited generalizability of results, since this post-approval study is an extended follow-up of the premarket cohort. Given that this study is likely comprised of the best responders from the pivotal trial, the main study findings may be an over-estimate of the true device performance in the lower BMI indication.
Recommendations for Labeling Changes	Labeling changes are recommended based on the long-term safety and effectiveness results of the post-approval study.
General
Study Status	Terminated
Application Number / Requirement Number	P000008 S017/ PAS002
Date Original Protocol Accepted	02/16/2011
Date Current Protocol Accepted	03/03/2016
Study Name	Apollo-001
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	NOTE: The PAS requirement for the lower BMI patients is being closed prior to its completion because in clinical practice LAP-BAND is not widely used for the lower BMI patients. Continuing enrollment would not have added value. In addition, the label already reflects long-term performance for the higher BMI patients. Therefore, no labeling update is needed at this time. New enrollment study designed to evaluate the safety and effectiveness of Lap-Band. Prospective single-arm cohort.
Study Population	Patients with BMI >=30 kg/m2 and <40 kg/m2 and 1 or more obesity- related comorbidities. There is no control group in this study.
Sample Size	325 subjects will be enrolled across 20 U.S. sites. Assuming 20% attrition, a sample size of 260 subjects at 5 years provides 84% power to test the hypothesis that the reduction in diabetes prevalence at 5 years will be at least 5%. This will be tested using a 1-sided exact binomial test with a 5% significance level. Up to 65 subjects can be enrolled per site.
Key Study Endpoints	Primary safety endpoint: 5-year explant rate; Secondary effectiveness endpoints: 5-year responder rate (where response is defined as achieving >= 7% TBL), diabetes prevalence at 5 years, and change in obesity-related comorbidities at 5 years compared to baseline
Follow-up Visits and Length of Follow-up	10 Years - In-office visits before and after surgery, at 1, 2, 3, and 6 months, and 1, 3, 5, 7, and 10 years after surgery. Patients will complete a questionnaire at 2, 4, 6, 8, and 9 years after surgery.
Interim or Final Data Summary
Actual Number of Patients Enrolled	175 patients received device implant, 32 with low BMI of 30.00- 34.99
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	92.2% at 1 year (based on the number of subjects (77) eligible for the 1-year visit)
Final Safety Findings	The 1-year rates for device explant, band slippage, and erosion are same at 3.1% for low BMI patients of 30.00-34.99. The 1-year rate is 0% for device explant, 1.4% for slippage, and 0% for erosion in patient with BMI of 34.00-39.99 The long-term safety information is available from the 5-year HERO-002 study.
Final Effect Findings	Final effectiveness findings (key endpoints): The 1-year responder rate is 73.7% for low BMI patients (30.00-34.99), and 86.2% for patients with BMI of 34.00-39.99. The long-term effectiveness information is available from the 5-year the HERO-002 study.
Study Strengths & Weaknesses	Strength: Long-term data available through 5-years of follow-up from the 5-year the HERO-002 study. Weaknesses: Slow study enrollment was observed for lower BMI patients, since in clinical practice the device is not widely used for lower BMI patients. Therefore, the study was closed prior to its completion, since enrolling more patients would not have added value.
Recommendations for Labeling Changes	The label already reflects long-term performance; therefore, no additional labeling update is needed at this time.
General
Study Status	Completed
Application Number / Requirement Number	P080025 / PAS001
Date Original Protocol Accepted	03/14/2011
Date Current Protocol Accepted	03/14/2011
Study Name	FI-PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multicenter study
Study Population	Study subjects are individuals enrolled in IDE study with a history of chronic fecal incontinence who failed or were not candidates for more conservative treatments. Subjects serve as self controls.
Sample Size	285 subjects, 12 sites
Follow-up Visits and Length of Follow-up	5 years post implant Yearly up until at least 5 years post implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	120
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	60% (72/120)(Rate included 14 subjects who were lost due to death of Principal Investigator and 5 died of causes unrelated to the device or therapy)
Final Safety Findings	There were no specific study safety endpoints in this post approval study. Safety was monitored in a purely descriptive fashion. There were 21 serious device/therapy related adverse events and 351 non-serious device or therapy related adverse events, many of which required surgical intervention. Over the course of the study that there were 10 device revisions among 10 subjects, 40 device replacements among 29 subjects and 22 device explants among 22 subjects. The overall device revision and replacement rate was 24.4%, and the overall device explantation rate was 19%. The all cause surgical intervention rate for the 120 enrolled subjects was 35.6% for the first 5 years
Final Effect Findings	Primary Endpoint: Incontinent Episoides ( ¡Ý50% improvement from baseline): Proportion of Successes: 69% (95%CI- 60%-77%), based on last observation carried forward imputation method for missing subjects
Study Strengths & Weaknesses	Strength: Prospective hypothesis driven study, high level of quality control, multiple effectiveness outcomes evaluated including patient centered disease specific QoL questionnaires. Weakness: High loss to follow-up, no study safety hypothesis.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P000039 / PAS001
Date Original Protocol Accepted	12/05/2001
Date Current Protocol Accepted	08/16/2007
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, non-randomized, multi-site clinical study design. The purpose of this study is to prospectively evaluate the incidence of hemodynamic compromise and to obtain long-term survival data on patients implanted with the AMPLATZER Septal Occluder.
Study Population	Study Population: Patients implanted with the AMPLATZER Septal Occluder device. Indication: The AMPLATZER Septal Occluder device is also indicated in patients who have undergone a fenestrated Fontan procedure and who now require closure of the fenestration.
Sample Size	256 patients, 33 sites
Key Study Endpoints	The objective of the study was to assess the safety and effectiveness of the Amplatzer Septal Occluder device. The safety endpoints includes: 1) The incidence of System-Related Adverse Events by patient. System-Related and 2) Adverse Events are defined in the Definitions Section. The effectiveness endpoing include the percentage of patients for whom Closure Success was achieved.
Follow-up Visits and Length of Follow-up	Patients enrolled in the study will be evaluated pre-procedure, at implant post device deployment, pre-discharge, and at one month, one year, and two years post-implant. Patient data will be obtained at the time of visit and/or if appropriate through a telephone interview. A follow-up visit at the site is required for the pre-procedure, at implant post device deployment, pre-discharge and one month visits.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,000 subjects
Actual Number of Sites Enrolled	50 sites
Patient Follow-up Rate	At two years the follow-up rate was 93.1% (931/1000).
Final Safety Findings	Primary Endpoint: Hemodynamic compromise related to the device at two years: 0.65% (6/928, upper bound of exact 95% CI: 1.40%). This rate is below the performance goal was 1.65%. Rate of hemodynamic compromise related to the device: 35 per 10,000 subject-years. Co-Primary Safety Endpoint: Device- or delivery system-related adverse events at two years: 6.56% (61/930, 95% CI: 5.05% - 8.35%) Three subjects developed cardiac erosions during the two years of the study (0.3% (3/1000) or 15 per 10,000 subject-years). Secondary Endpoint #1: Hemodynamic compromise event rates by size (appropriate or under/oversized) at 2 years: -Appropriate: 0.19% (1/518) -Under/oversized: 1.4% (5/356) Secondary Endpoint #2: Hemodynamic compromise by high/low implanting physicians: -High implanting: 0.33% (1/307) -Low implanting: 0.69% (4/583)
Final Effect Findings	Co-Primary Effectiveness Endpoint Closure success at two years: 97.87% (966/987, 95% CI: 96.8% - 98.7%)
Study Strengths & Weaknesses	This study met its performance goal and had a large sample size. The study also had a low rate of attrition, thus minimizing selection bias. However, this study was not designed adequately to detect rare adverse events, such as cardiac erosion. Postmarket surveillance under Section 522 of the Federal Food, Drug and Cosmetic Act is being conducted to address safety concern related to erosion events (PS130046).
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term (2 years) postmarket performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P950015 / PAS001
Date Original Protocol Accepted	08/20/1998
Date Current Protocol Accepted
Study Name	Heart Laser CO2
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a two-armed prospective cohort, multi-stite registry study. The registry was randomly divided between those who received TMR at the time of enrollment and those whose TMR was delayed for 30 days.
Study Population	The study population was patients for whom the Chilli device is indicated, who had failed or were intolerant to drug therapy. The device is approved for the treatment of refractory class 3-4 angina secondary to objectively demonstrated coronary artery atherosclerosis not amenable to standard therapies such as CABG or PTCA.
Sample Size	600 patients. 39 sites. Patients to be randomly divided between those who received TMR at the time of enrollment and those who were delayed 30 days prior to treatment.
Key Study Endpoints	The primary endpoint was 30-day and one-year mortality. The secondary endpoint was adverse events.
Follow-up Visits and Length of Follow-up	The primary endpoints were evaluated at 30 days and one year.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	516 patients
Actual Number of Sites Enrolled	39 sites
Patient Follow-up Rate	92%
Final Safety Findings	There was a high one month mortality rate were compared to the pre-market study.
Study Strengths & Weaknesses	Weaknesses: The data that was internally inconsistent and there was no comparison of the primary endpoint with a meaningful control group.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P930039 S151/ PAS001
Study Name	MR conditional Tachy Therapys Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	N980003 / PAS001
Date Original Protocol Accepted	11/26/2003
Date Current Protocol Accepted
Study Name	Encore Keramos PDP Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Interim or Final Data Summary
Actual Number of Patients Enrolled	873 subjects with 975 implants
Actual Number of Sites Enrolled	There were 3 clinical sites in the study.
Patient Follow-up Rate	For implants, 79% for at least one follow-up visit For subjects, 85.7% with at least one follow-up
Final Effect Findings	Keramos Control Are You Satisfied with How Your Implant Is Functioning? Yes (n) No (n) Yes (n) No (n) Year 13 59 6 56 1 Year 14 60 5 52 1 Year 15 18 1 19 2
Study Strengths & Weaknesses	A strength of the study is its substantial sample size, with 873 study subjects and 975 total hip implants. A weakness of the study is the absence of clinical and radiographic examination in the final 5 years of follow-up.
Recommendations for Labeling Changes	The longer term revision rates were comparable between the Keramos and Control implants. There were a total of 64 revisions reported in the postcard follow-up with an average of 9.8 years after implantation. The proportion of intact implants in the Keramos subject at the end of the 2013 postcard follow-up was 92.3% vs. 89.8% in the Control subjects. In the time-to-event analysis, the survival curves for freedom from revision for the Study implants and the Control implants were completely overlapping. The unadjusted hazard ratio for revision comparing the Study implants to the Control implants was 0.99. After adjusting for age, gender, BMI and primary diagnosis, the hazard ratio was 0.88 favoring the Study implants (not statistically significant). There was also no subgroup difference in revision rates. Significant predictors for revisions include BMI (the higher the BMI, the higher the risk of revision) and primary diagnosis at baseline (OA diagnosis was associated with a lower risk of revision compared to other diagnosis).
General
Study Status	Completed
Application Number / Requirement Number	P040037 S050/ PAS001
Date Original Protocol Accepted	10/18/2013
Date Current Protocol Accepted	10/18/2013
Study Name	Extended F/u 25cm Viabahn Endoprosthesis
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Actual Number of Patients Enrolled	71 (58 subjects available at 1 year).
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	at 3 years (51 eligible subjects) – 90.2% (46/51)
Final Safety Findings	Total number of device- or procedure-related adverse reported = 62 Most common organ class was general disorders and administration site conditions- 46 events Proportion of subjects with device- or procedure-related adverse events, overall - 50.7% (36/71) Total number of device- or procedure-related serious adverse events reported = 40 Most common organ class was general disorders and administration site conditions- 31 events Proportion of subjects with device- or procedure-related serious adverse events, overall – 35.2% (25/71)
Final Effect Findings	Primary Endpoint The primary patency rate at 36 months by Kaplan Meier (KM) estimate was 40.6% Secondary Endpoints (by Kaplan Meier Analysis) Primary Assisted Patency rate at 24 and 36 months was 65.3% and 53.0% respectively Secondary patency rate at 24 and 36 months was 96.9% at each timepoint Freedom from target lesion revascularizations at 24 and 36 months was 65.1% and 55.5% respectively Freedom from the composite of death, target vessel revascularization and amputation at 24 and 36 months was 56.5% and 44.5% respectively The clinical Success rate at 24 and 36 months was 76.7% and 58.5% respectively. There were no reports of device fracture on X-ray
Study Strengths & Weaknesses	The study achieved an adequate follow-up rate of 90.2% at 3 years. Weaknesses This was a single arm study without a comparator. Thus, the study result was not evaluated by a formal statistical test.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Terminated
Application Number / Requirement Number	P010039 / PAS001
Date Original Protocol Accepted	04/03/2003
Date Current Protocol Accepted	09/27/2005
Study Name	Sonocur
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The sponsor originally agreed to perform a multi-center, non-randomized cohort study to examine device performance that called for a patient population of 223. The primary objective of the post-approval study is to assess the neurological status of the treated upper extremity secondary to extracorporeal shock wave therapy treatment using the Siemens SONOCUR Basic system.There are no formal study hypotheses. FDA approved a modified post-approval study protocol in October 2005 that reduced the sample size from 223 to 125 subjects.
Study Population	The deive is indicated as an alternative for the treatment of chronic lateral epicondylitis (commonly referred to as tennis elbow) for patients with symptoms of chronic lateral epicondylitis for 6 months or more and a history of unsuccessful conservative treatments. The study population consisted of subjects with chronic tennis elbow. Patients who present for routine clinical therapy for chronic lateral epicondylitis are eligible to participate. Patients who present with abnormal (diminished or absent) sensory function and abnormal (nonfunction) motor function in the hand (treatment side) at the baseline visit were not be included in the study.
Sample Size	223 subjects; however FDA approved a protocol modification to reduce sample size to 125 subjects
Key Study Endpoints	Subject evaluation at the 12 week visit will include an assessment of motor function, sensory test, pain intensity using the Thomsen provocation test, adverse event evaluation and a limited physical examination. The primary efficacy endpoint was at least a 50% reduction from baseline to week 12 post-treatment in the pain VAS during resisted wrist extension. The secondary efficacy endpoint was an improvement from baseline to Week 12 post-treatment in the patient's mean UEFS.
Follow-up Visits and Length of Follow-up	12 weeks after the last extracorporeal shock
Interim or Final Data Summary
Interim Results	Study Terminated. See Final Study Results
Actual Number of Patients Enrolled	2 subjects
Actual Number of Sites Enrolled	At the time study was terminated the 2 enrolled subjects had not completed the 12-week follow-up
Patient Follow-up Rate	0
Final Safety Findings	No data available
Study Strengths & Weaknesses	The study was only able to enroll 2 subjects.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P010031 S232/ PAS001
Date Original Protocol Accepted	04/04/2012
Date Current Protocol Accepted	06/29/2012
Study Name	REVERSE NCDR ICD Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study
Study Population	Patients meeting the expanded CRT-D indication criteria are eligible to participate the analysis cohort.
Sample Size	At least 1500 patients from US implanted with a Medtronic CRT-D device who meet the expanded indication criteria will be included in the analyses. A minimum of 500 patients with QRS duration will be included in the primary objective analysis.
Key Study Endpoints	5-year survival probability for patients implanted with a Medtronic CRT-D who meet the expanded indication criteria within percent precision.
Follow-up Visits and Length of Follow-up	5-years post-implant. Reconciliation of mortality for patients identified through the NCDR® ICD Registry¿ will be completed monthly through 5-years post-implant.
Interim or Final Data Summary
Actual Number of Patients Enrolled	4639 patients
Actual Number of Sites Enrolled	N/A: Patients are identified through the American College of Cardiology’s National Cardiovascular Data Registry for implantable cardioverter defibrillators (ACC-NCDR ICD registry). Mortality through five years will be tracked for this cohort using the National Death Index.
Patient Follow-up Rate	5 years post-implant
Final Safety Findings	Of the 4639 ICD Registry patients meeting expanded indication, a total of 799 deaths were identified. Of these deaths, 216 (27%) were female and 266 (33%) had narrow QRS (130 – 150 ms). Based on this data, the sponsor reported a survival probability at 5 years of 77.2% (95% CI: 75.4% - 78.8%) as well as a significant difference in survival probability between male and female. Among female subjects 216 subjects died compared with 583 deaths for male subjects (hazard ratio: 0.73, 95% CI: 0.62-0.85, p < 0.0001). No significant difference in survival probability between the narrow QRS group and the group with wider QRS was also reported by the sponsor. Among narrow QRS subjects 266 subjects died compared with 533 deaths for the subjects with wider QRS (hazard ratio: 1.10, 95% CI: 0.95-1.28, p = 0.19).
Final Effect Findings	Please see "safety" findings.
Study Strengths & Weaknesses	The sponsor has collected sufficient data to address the primary objective of the study which was to estimate the 5-year survival probability for patients implanted with a Medtronic CRT-D meeting the expanded indication criteria within 3% precision. The Agency recommends that the sponsor update the labeling to incorporate the study findings.
Recommendations for Labeling Changes	FDA recommends that the sponsor update the labeling for these devices to reflect the long-term data from the Post Approval Study.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P000008 / PAS001
Date Original Protocol Accepted	06/05/2001
Date Current Protocol Accepted	06/05/2001
Study Name	Lap-Band Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort, which involved continued follow-up of subjects from the premarket studies, from several different sites. Both prospective and retrospective collection of data was allowed and encouraged.
Study Population	Study Population: Patients included in the pre-market study. Indication: The LAGB is intended for use in weight reduction for morbidly obese adult patients with a Body Mass Index (BMI) of at least 40 kg/m2, a BMI of at least 35 kg/m2 with at least one co-morbid condition, or those who are 100 lbs. or more above their ideal body weight and who have failed at more conservative weight reducing alternatives.
Sample Size	300 patients, 15 sites
Key Study Endpoints	Safety endpoints included percent of excess weight loss, adverse events, and explantation of the device.
Follow-up Visits and Length of Follow-up	Patients who had completed three years of follow-up in the premarket studies were to be followed for an additional two years.
General
Study Status	Completed
Application Number / Requirement Number	P000006 / PAS001
Date Original Protocol Accepted	07/14/2000
Date Current Protocol Accepted
Study Name	Coloplast PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study was a multi-center cohort study whose patients were part of the premarket study.
Study Population	The study population is as per device indication. The device is indicated for male patients suffering from erectile dysfunction (impotence) who are considered to be candidates for implantation of a penile prosthesis.
Sample Size	326 subjects
Key Study Endpoints	The primary safety endpoint was the assessment of the rate of revision surgeries at 18 months post-implantation. The primary assessment of efficacy of the penile prosthesis was the determination that the device supplied sufficient penile rigidity to obtain an erection adequate to permit vaginal penetration. In addition, axial penile rigidity was measured in accordance with the Penile Rigidity Measurement Protocol.
Follow-up Visits and Length of Follow-up	Study subjects underwent clinical visits at 2, 3 and 5 postoperative years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	172 subjects
Actual Number of Sites Enrolled	Not Mentioned
Patient Follow-up Rate	73.80%
Final Safety Findings	A total of 93.2% of the implanted patients had adequate rigidity for intercourse. A total of 34 patients experienced a revision during the study period. Of these 34 revision cases, 17 were device explantations, 5 were device repair surgeries, and 12 were other surgeries, such as circumcision, that did not require explantation of the device. Using a Kaplan-Meier Survival Analysis, the probability of patients being free of revision at 18 months was 88.5%. The sponsor contended that these rates of revision and explantation were consistent with those in the published literature.
Study Strengths & Weaknesses	The follow-up rate is less than 80%. Losses to follow-up can introduce bais and limit the validity of study results.
Recommendations for Labeling Changes	Modify label to reflect the findings of the study
General
Study Status	Completed
Application Number / Requirement Number	P030006 / PAS001
Date Original Protocol Accepted	02/19/2004
Date Current Protocol Accepted	03/11/2005
Study Name	Prolieve PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an open label non-randomized prospective study . The primary objective of the study is to provide descriptive data on the long-term safety and effectiveness of Prolieve for Benign Prostate Hyperplasia . A secondary objective is to assess safety and effectiveness of re-treatment and to assess the proportion of patients electing re-treatment with Prolieve compared to alternative therapy (other localized therapy, surgery or drug therapy).
Study Population	Study population is as per device indication. Adult men men with prostate volume of 20 to 80 grams and in whom drug therapy (Proscar) is typically indicated.
Sample Size	The protocol proposes to enroll 250 new subjects in up to 30 study sites in the United States. The protocol states this will ensure at least 100 subjects will be followed for 5 years. In addition to newly enrolled subjects, the sponsor planned to encourage Pivotal Study participants and Continued Access Study participants to transfer to the postmarket study for the completion of 5 years of follow-up
Key Study Endpoints	Efficacy is evaluated using the following: Time to re-treatment, American Urological Association (AUA) Symptom Index, (Classifies the severity of subject symptoms related to urinary difficulties based on seven questions that form a total score. The score can range from 0-35). Pain/Discomfort, Sexual Function, Impact of Lower Urinary Tract Symptoms (LUTS) on quality of life (QOL), (Six questions related to urinary problems and how they interfere with daily living. The score ranges from 5-24), Quality of Life Questionnaire, (Six questions related to the subjects feelings about his urinary condition, perception of urinary difficulties, sexual function, activities of daily living, general well-being and social activities. The seven-point scale ranges from delighted to terrible and scores can range from 6-42), Brief Symptom Inventory (BSI), (Seven questions related to the interference of the subject s urinary problems with common activities, scores range from 7-35), BPH Impact Index (BII), (Four questions related to concern about urinary problems and the amount of physical discomfort experienced. Scores can range from 4-17. Safety is measured by: Use of pain medication pre-treatment and during treatment, Pain associated with treatment, Local and systemic symptoms during Prolieve treatment Catheterizations associated with treatment, PSA levels, Adverse events, Anticipated adverse events (associated with treatment or BPH), Hospitalizations , and MDR reportable events.
Follow-up Visits and Length of Follow-up	Study participants are to be evaluated at two weeks, three months and annually thereafter for a period of 5 years after treatment with Prolieve.
Interim or Final Data Summary
Actual Number of Patients Enrolled	225 subjects were enrolled.
Actual Number of Sites Enrolled	24 siteswere enrolled.
Patient Follow-up Rate	102/219 (46.6%) at five year follow-up.
Final Safety Findings	There were nine serious device/treatment-relatedadverse events that required hospitalization. The most common device/treatment-related AEswere micturition urgency (13.3 events per 100 person-years), dysuria (10.5), haematuria (7.8), urinary retention (7.2), bladder spasm (6.1), pollakiuria (5.7), urethral hemorrhage (5.2), and urine flow decrease (3.1).
Final Effect Findings	The retreatment rate was 51.1% (95% CI: 43.2, 59.0) at five years. Subjects showed a general improvement in symptoms; AUA (American Urological Association Symptom Index) total scores, peak flow rate, and quality of life scores all improved from baseline to five years. A smaller percentage of patients reported pain or discomfort in urethra at five years (10/98, 10.2%) than at baseline (55/220, 25.0%).
Study Strengths & Weaknesses	Strengths: Prospective design with five-year follow-up. Weaknesses: The follow-up rate was moderately low (46.6%). However, the study met the assumptions of the protocol to obtain five year follow-up data for at least 100 subjects. Additional sensitivity analyses did not show significant differences between subjects who completed follow-up and those who did not.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the results of the five year follow-up post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study design, results, and study strengths and limitations.
General
Study Status	Terminated
Application Number / Requirement Number	P030030 / PAS001
Date Original Protocol Accepted	12/16/2004
Date Current Protocol Accepted	12/16/2004
Study Name	Tegress PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	1. The Two-year Enhanced Surveillance Program (ESP) is actively soliciting adverse event information related to the use of Tegress Urethral Implant. The Program consists of two parts: (A) Two-part information card and (B) Quarterly contact with US physicians to obtain adverse event information. 2. The Five-year Registry's objectives are to evaluate long-term safety and effectiveness and to assess the incidence of material exposure and other adverse events. At time of this report, Bard has qualified 4 sites and planned to begin patient enrollment in the fall 2006. The anticipated enrollment table is listed in Appendix 2. An updated enrollment table would be required for the next postmarket report. These two studies were terminated.
Study Population	Study population as per device indication. This device is indicated for transurethral injection in the treatment of adult women diagnosed with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD).
Sample Size	N/A
Key Study Endpoints	Adverse events
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	PMA was withdrawn, see Final Safety findings
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	(1) For the Active surveillance System: the latest period for which FDA has data - The return rate was 53% (3203 returned/ 6071 unit sales). (2) For the Registry: protocol was approved by the FDA on 5/23/06. PMA withdrawn April 6, 2007; No PAS report for the Registry was received.
Final Safety Findings	Safety issues identified in the last Report received for the Active Surveillance System: The adverse events observed (such as erosion, necrosis, and rupture of the urethral wall) were not observed in the PMA trial. The exact mechanism of injury for the various cases was unclear. Some plausible explanations were proposed by the FDA, such as cytotoxicity from the solvent used with the implant material; tissue necrosis from a combination of causes such as blood loss, pressure, and cytotoxicity; and rupture as a mechanical event as the elastic limit is exceeded when the implant material expands. The sponsor conducted biocompatibility testing by repeating cytotoxicity, chemical evaluation and implant studies and the projected completion dates were 9/15/06 and 5/31/07. As per CTS, the PMA was withdrawn April 6, 2007
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	None, PMA withdrawn
General
Study Status	Completed
Application Number / Requirement Number	P970003 S050/ PAS001
Date Original Protocol Accepted	07/15/2005
Date Current Protocol Accepted	06/04/2015
Study Name	Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a 5-year, prospective, observational, multi-center patient outcome registry to follow the clinical course and outcome of patients with treatment-resistant depression (TRD) who are currently in a major depressive episode (MDE) treated with and without VNS Therapy. The study is a new enrollment study.
Study Population	The registry will enroll a minimum of 500 Treatment-Resistant Depression (TRD) patients treated with adjunctive VNS Therapy and a minimum of 300 TRD patients who are not treated with VNS Therapy.
Sample Size	500 TRD patients treated with adjunctive VNS Therapy and a minimum of 300 TRD patients who are not treated with VNS Therapy.
Key Study Endpoints	Primary Endpoint Response based on MADRS Assessment: Defined as ¡Ý 50% improvement from baseline in Montgomery Asberg Depression Rating Scale (MADRS) score at visit month assessment post-baseline across the 60 months of follow-up. Secondary Endpoints Secondary endpoints are separated into two groups: Group 1 includes clinically important prospectively defined endpoints that if found statistically significant (P < 0.05) will be submitted for consideration for label claim. Group 2 will include other supportive secondary endpoints. Group 1: Secondary Endpoints for Label Claim: (a) Response based on Clinical Global Impression (CGI): The Clinical Global Impressions is a clinicianrated scale used to assess the level of severity and improvement in depressive symptoms over time. For the analysis, a response is defined as achievement of CGI rating ¡°1¡± or ¡°2¡± (¡°Very much improved¡± or ¡°Much improved¡±) at visit month assessment post-baseline. (b) Duration (or maintenance) of response based on MADRS: Defined as the difference between the first recorded date post-baseline that response is achieved (MADRS ¡Ý 50%) and the first date at which maintenance of the MADRS reduction decreases to 40% or less. Sackeim et al. (2007) suggested using a criterion of maintenance of response at follow-up visit months assessments post-response to 40% in order to avoid characterizing a minor decrease (e.g., from 51% to 49%) as a loss of benefit. Only a subpopulation that achieved response will be included in the summary. (c) Remission based on MADRS: Defined as MADRS total score ¡Ü9 at visit month assessment postbaseline. (d) Duration of remission based on MADRS: Defined as the recorded post-baseline date of first recurrence/relapse (¡Ý 20 MADRS score) minus the recorded date of first achieved remission (MADRS score ¡Ü 9). Only a subpopulation that achieved remission will be included in the summary. Group 2: Supportive Exploratory Secondary Endpoints: (a) Response based on Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) (b) Remission based on SLICE-C Psychiatric Status Rating and QIDS-SR. (c) Recurrence/Relapse (d) Suicidality (e) Predictors of suicide attempts and suicidal ideation (f) Quality of Life, Health Outcomes and Depression Symptomatology (g) Safety Endpoints: (i) Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER); and (ii) MDR reportable events on VNS treated patients.
Follow-up Visits and Length of Follow-up	All of the patients are planned to be followed for 60 months after enrollment. Visits include a screening and a baseline visit, and follow up visits at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after baseline.
Interim or Final Data Summary
Actual Number of Patients Enrolled	795
Actual Number of Sites Enrolled	61
Patient Follow-up Rate	40-50%
Final Safety Findings	The percentage of patients experiencing a score of 5 or 6 (least favorable) on the frequency, intensity and burden subscales of the FIBSER, respectively, are similar in all groups and decrease over time for all groups. Increased scores on items from MADRS, QIDS-SR and the Assessment of Suicidality may indicate risk for suicide. In looking at each of these items, suicide risks decreased over time in all treatment groups, but greater for patients treated with VNS Therapy with statistically significant separation for VNS Therapy over TAU treated patients across all three assessments at multiple time points. A total of 308 MDR events for 166 patients were reported regarding VNS Therapy patients enrolled the study. None of the events reported would be classified as unanticipated adverse device effects. Patients in the VNS Therapy group experienced a greater than 50% reduction in all-Cause Mortality and completed suicides as compared with patients in the TAU group. Eight patients in the TAU group and 7 patients in the VNS Therapy group died during the trial. Of these, 4 (57%) deaths were considered suicides, 2 in the TAU group and 2 in the VNS group.
Final Effect Findings	A higher response rate based on MADRS was observed in the VNS treated group vs. TAU treated group (38.1% for the VNS D-23+D-21 group vs. 17.0% for the TAU; P<0.001). Also, a better response rate was seen in the VNS D-23 only group as compared to the TAU group (37.4% vs. 17.2%, respectively, P<0.001). The overall trend regarding response, remission and recurrence are consistent across efficacy instruments and shows superiority of VNS Therapy treated group over the TAU group. Patients in the VNS Therapy group experienced statistically significant benefits compared to patients in the TAU group for 13 out of 15 clinical outcomes measured and 2 of the 4 quality of life or health outcomes measured. Sensitivity analyses conducted to assess the impact of missing data did not change the general study conclusions.
Study Strengths & Weaknesses	Study Strengths: First study to evaluate safety and effectiveness of adjunctive VNS Therapy in patients with treatment resistant depression Prospective cohort study design is considered a design that can provide strong evidence in an observational study Large sample size with long-term follow-up Study Weaknesses: Substantial losses to follow-up (40-50%), which differed among the dosing and non-dosing groups Potential for residual confounding despite use of propensity scoring adjustment
Recommendations for Labeling Changes	labeling changes are recommended
General
Study Status	Completed
Application Number / Requirement Number	P020014 / PAS001
Date Original Protocol Accepted	11/04/2002
Date Current Protocol Accepted	11/04/2002
Study Name	Newly Trained Physicians
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was designed to document the bilateral placement rate at first attempt for newly trained physicians in the U.S. These data were used to evaluate the training procedures and to update labeling.
Study Population	Study population as per device indication . This device is indicated for permanent birth control (female sterilization) by bilateral occlusion of the fallopian tubes in adult women seeking permanent birth control.
Sample Size	The study was originally designed to enroll 800 women from 40 physicians in the commercial setting.
Key Study Endpoints	Data collected included: (1) successful bilateral placement rate at first attempt, and (2) identification of factors predictive of failure to achieve bilateral placement at first attempt.
Follow-up Visits and Length of Follow-up	No patient follow-up was conducted as part of this study, with the exception of the follow-up data of the HSGs performed to evaluate the reasons for placement failure in women who desired a second attempt of device placement.
Interim or Final Data Summary
Actual Number of Patients Enrolled	After reviewing the final report, the Agency considered the conditions of approval for this study to be satisfied, with 514 women enrolled.
Actual Number of Sites Enrolled	39
Patient Follow-up Rate	N/A
Final Safety Findings	Safety: There were 38 malfunctions in 27 cases, in 9 the distal tip was bent, the sponsor does not consider these are malfunctions. There were no reports of adverse events related to bent tips. There were 29 device malfunctions that included detachment problems, deployment issues, thumbwheel retraction difficulty, inner sleeve detachment and failure of delivery catheter to retract. Placement rate: There were 13 adverse events that included perforation, pelvic pain, bleeding, light headed, increased blood pressure and temporary decreased pulse. There were 476 women in whom bilateral placement was possible. After excluding all confounding, bilateral placement was achieved in 458 women for 96.2% (458/476) success rate. Bilateral failure happened in 10 women for 2.1% failure rate (10/476). After original approval of Essure system a new coil catheter was approved. The sponsor did a comparison of success rate by design. After excluding all confounding there were 184 procedures with the original model (gamma) and 297 procedures with the new model (coil catheter design). The new model performed better than the old, with a 96.0% success rate for the new coil catheter and 94.0% for the gamma model. Additionally, bilateral failure was less frequent with the new model (1.3% vs. 3.3%). The gamma model was discontinued in September 2003.
Study Strengths & Weaknesses	Study provided precise estimate of bilateral placement at first attempt among newly trained physicians. Although the sponsor did not enroll the required number of women as per protocol, they were able to demonstrate with Bayesian statistics, that the observed rate was not diffderent from the rate observed in experienced physcians.
Recommendations for Labeling Changes	Update label to include results from the PAS(bilaeral placement rate from newly trained physicians). Labeling should include the information on the number of patients excluded and why these patients were excluded from the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P040043 / PAS001
Date Original Protocol Accepted	03/23/2005
Date Current Protocol Accepted	08/31/2005
Study Name	Cohort Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, non-randomized, prospective observational study, designed to compare device users with historical controls.
Study Population	The study population will include subjects enrolled into the TAG pre-market studies (TAG 97-01, TAG 99-01, TAG 03-03, and TAG 04-02) and subjects enrolled into this study (TAG 05-02). In addition, the physician training program assessment portion of the study will enroll subjects diagnosed with aneurysm of the DTA who meet all inclusion/exclusion criteria. Patients previously treated with the commercially approved TAG device by a physician who has completed the GORE TAG Physician Training program may be retrospectively screened for enrollment into this study.
Sample Size	450 TAG subjects and 94 surgical control subjects, 35 sites
Key Study Endpoints	The primary objective of this study is to evaluate the long-term performance of the TAG device. The endpoints include: 1) 5-year aneurysm-related mortality rate, 2) Stroke, 3) Paraplegia and 4) Reintervention.
Follow-up Visits and Length of Follow-up	Follow-up visits will be accomplished at discharge, 30 days post-implant, and annually thereafter, for a total of five years.
Interim or Final Data Summary
Interim Results	Since the 4-year interim report, there have been no new cases of aneurysm-related mortality or no new endoleaks identified. Based on the data that was submitted, there are no trends that appear to be cause for concern.
Actual Number of Patients Enrolled	449 overall (150 training study + 299 IDE participants)
Actual Number of Sites Enrolled	25 (in training study)
Patient Follow-up Rate	78%
Final Safety Findings	Reintervention: Twenty�]nine (29) (6% of total) required 31 secondary interventions with additional endoprosthesis implants. Three (3) of these resulted in surgical conversions. 30�]Day Events: �]Major adverse event rate (requiring therapy and short hospitalization (24�]48 hours), major therapy, unplanned increase in level of care, prolonged hospitalization, permanent adverse sequelae, or death.) = 22% �]Stroke= 3% �]Paraplegia= 3%
Final Effect Findings	5�]year aneurysm�]related mortality rate = 94.7% 1 ruptured aneurysm (0.2%) 1 case of device migration (0.2%)
Study Strengths & Weaknesses	Strengths: Prospective cohort study; success criteria for primary endpoint met by large margin; concurrent control group. Weakness: Overall 5�]year attrition rate of 78%
Recommendations for Labeling Changes	Yes: Recommend update to reflect results of PAS
General
Study Status	Completed
Application Number / Requirement Number	H060002 / PAS001
Date Original Protocol Accepted	10/24/2008
Date Current Protocol Accepted	12/16/2014
Study Name	IBV Valve
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective observational study to collect safety information about the IBV Valve System for the treatment of prolonged air leak. Eligible subjects will be enrolled into the study on the day of valve treatment. The subjects will be monitored after treatment until discharge from the hospital (a minimum of 1 night stay after the procedure). After discharge, the subjects will be seen by the investigator for assessment of air leak status as clinically indicated. Valves will be removed after the air leak is resolved. If the air leak is not resolved, the valves will be removed no longer than 6 weeks after device placement and other options can be considered.
Study Population	Patients with prolonged air leaks of the lung, or significant air leaks that are likely to become prolonged air leaks following lobectomy, segmentectomy, or lung volume reduction surgery (LVRS).
Sample Size	32 patients will be enrolled at up to 15 clinical sites.
Key Study Endpoints	The safety endpoints include the total number, rate, type, timing, duration, severity and relationship to device or procedure of adverse events. Probable benefit data includes: 1) A positive response in air leak resolution; 2) Number of days after valve placement.
Follow-up Visits and Length of Follow-up	The duration of follow-up is a maximum of 6 weeks.
Interim or Final Data Summary
Actual Number of Patients Enrolled	39
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	100% (32/32 as per protocol)
Final Safety Findings	No unanticipated adverse device effects (UADE) have been reported for the Spiration PAS. SAE: There have been a total of two reported adverse events in two of the 32 subjects treated. One was serious and one was moderate. Both AEs are summarized below: Systolic arrest experienced prior to valve placement (day 0): reported as a serious adverse event (SAE), but deemed “Not related” to the device or the procedure. Notes provided on the CRF indicate that the event was due to acidosis from hypercapnia and resolved the same day. Atelectasis and thick mucus secretions in the left main stem bronchus experienced on day five. One of the four placed valves was removed to treat and meds were given; the event resolved in one day. The investigator deemed this event moderate and “Possibly” related to the device.
Final Effect Findings	Of the 32 subjects who received valves for treatment of air leak, 30 (94%) showed a positive response to valve placement. Two subjects (6%) showed no improvement in air leak. Of the 30 responders, eleven (11), or 36.7%, were noted as completely resolved. Nineteen (19), or 63.3%, of the subjects were classified as improvement in the air leak. There were no significant differences in the results between the single use catheter and reloadable catheter groups.
Study Strengths & Weaknesses	Strength: 100% follow-up Weaknesses: Limited number of female patients (10), small sample size (32), and no concomitant control group was included. If a new enrollment Post-Approval Study is required, FDA recommends considering exploring the possibility of using external registry on post-surgical prolonged air leaks data; for example, registries already established created and maintained by a professional organization, academia, and/or government, available inside or outside US, as potential platforms of existing infrastructure to conduct the PAS study.
Recommendations for Labeling Changes	The PAS study design, methods and results must be included in the labeling. Additionally, it should be indicated the reason why seven (7) valves could not being implanted.
General
Study Status	Terminated
Application Number / Requirement Number	H030003 / PAS001
Date Original Protocol Accepted	02/25/2004
Date Current Protocol Accepted	10/01/2010
Study Name	HeartAssist 5 Pediatric VAD
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective non-randomized single-armed registry study of pediatric patients implanted with the DeBakey VAD Child device.
Study Population	Pediatric patients (5-16 years old, with body surface areas >= 0.7m2 and <= 1.5m2). Indication: For patients who are in New York Heart Association Class IV end-stage heart failure, refractory to medical therapy and who are listed as candidates for cardiac transplant.
Sample Size	50 patients, the number of sites were not specified
Key Study Endpoints	Data collected for the registry will be taken from measurements routinely assessed in children with life threatening congestive heart failure. Baseline parameters to be assessed will include demographics, medical history (e.g. ventilator, dialysis, ionotropic, or antiplatelet support, echocardiographic and catheterization assessments, etc). At the time of implant, pump parameters, adverse events, etc will be documented. During support (i.e. post DeBakey VAD Child implantation), data will be collected at week 1 and months 1, 3 and 6. Parameters that will be assessed include pump operation, quality of life (PedsQL), neurological exam, echocardiography, hemodynamics (on POD 3 and on day of catheter removal). Data will also be collected at the time of explant and death (pump parameters and cause of death).
Follow-up Visits and Length of Follow-up	After device implantation, patient functional assessment (quality of life, neurological and cardiac) and device performance will be assessed 1, 3 and 6 months post implant and at anytime after a neurological event.
General
Study Status	Terminated
Application Number / Requirement Number	P030042 / PAS001
Date Original Protocol Accepted	11/03/2009
Date Current Protocol Accepted	07/16/2010
Study Name	ConservePlus Longer-Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multi-center, prospective, historically controlled
Study Population	Patients who were previously enrolled in the CONSERVE Plus Total Resurfacing Hip System IDE
Sample Size	353 patients
Key Study Endpoints	The primary endpoint is clinical success at 120 months post-operative for each patient.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical and radiographic evaluation post-operatively at years 5,8, & 10. Patients will also have serum levels of cobalt and chromium ions and renal function data collected postoperatively at years 5, 8, & 10. Length of follow-up : Until each patient has reached 10 years, which will be in 2016.
General
Study Status	Terminated
Application Number / Requirement Number	P030042 / PAS002
Date Original Protocol Accepted	11/03/2009
Date Current Protocol Accepted	06/21/2010
Study Name	ConservePlus New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm,Multi-center cohort
Study Population	Paitents who have unilateral joint disease
Sample Size	183 patients
Key Study Endpoints	Patients will undergo clinical and radiographic evaluation pre-operatively and post operated at 0-60 days, 12 and 24 months.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical and radiographic evaluation pre-operatively and post operated at 0-60 days, 12 and 24 months. Length of follow up: 10 years
General
Study Status	Completed
Application Number / Requirement Number	P950024 S002/ PAS001
Date Original Protocol Accepted	09/16/1999
Date Current Protocol Accepted
Study Name	Bipolar Model 4968
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 5-year, multi-center, single arm, prospective and retrospective cohort study. All subjects in the study receive the device.
Study Population	Study Population: Patients implanted with the device. Indication: The Medtronic Model 4968 CapSure Epi Steroid-Eluting Bipolar Epicardial Pacing Lead is an epicardial lead designed for pacing and sensing of either the atrium or ventricle.
Sample Size	100 subjects at multiple sites.
Key Study Endpoints	Endpoints include freedom from lead-related complications and post-market performance of the lead.
Follow-up Visits and Length of Follow-up	There is no specified timeframe for follow-up visits; they occur according to the routine care plan set by each site for all cardiac surgical subjects.
Interim or Final Data Summary
Interim Results	There have been 36 deaths in 370 subjects; 32 lead-related complications and 70 lead-related observations reported.
Actual Number of Patients Enrolled	370
Actual Number of Sites Enrolled	85
Patient Follow-up Rate	69.7%
Final Safety Findings	n/a
Final Effect Findings	The performance for the overall 5-year survival probability of the Model 4968 lead was 92.3%. The 5- year survival probability was 89.3% for patients 12 years old or younger, 93.9% for patients 13 ¿ 19 years of age and 98.9% for patients 20 years of age or older.
Study Strengths & Weaknesses	Strength: prospective, multi-center, long-term follow-up period (5 years). Weakness: Small sample size (101 subjects in 5-year follow up), slow enrollment, extended duration of study, retrospective enrollment, high participation at 2 centers, high complications at 1 center, deviations, missing data, and use of a non-pediatric patient population.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P010047 / PAS001
Date Original Protocol Accepted	01/14/2010
Date Current Protocol Accepted	03/16/2015
Study Name	Long Term Safety
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, controlled observational study with a ProGel PALS group and a comparison group of standard-of-care, multi-center cohort study.
Study Population	Newly enrolled consecutive patients post-approval study population
Sample Size	400 evaluable subjects (267 ProGEL Sealant + 133 Control) at up to 30 U.S. sites.
Key Study Endpoints	Primary Endpoints: The study will include evaluation of twelve safety endpoints (i.e. specified AE). These include: 1. Pneumothorax 2. Air leak, persistent 3. Air leak, late onset 4. Residual pleural space 5. Acute respiratory distress syndrome (ARDS) 6. Post-surgical renal abnormalities 7. Myocardial infarction 8. Atrial arrhythmia requiring treatment 9. Ventricular arrhythmia requiring treatment 10. Cardiac arrest (resuscitated) 11. Death (all causes) 12. Hospital readmission (related to pulmonary surgery)
Follow-up Visits and Length of Follow-up	5 years: 30-day and 90-day follow-up visits are scheduled for study assessments
Interim or Final Data Summary
Actual Number of Patients Enrolled	444 (400 subject as per protocol)
Actual Number of Sites Enrolled	22
Patient Follow-up Rate	The follow-up rate at the end of the study was 392 divided by 444= 88%
Final Safety Findings	Slightly lower rates were reported for persistent air leak in ProGel 14.5% vs. control 14.8%, [RR = 0.98 (95%CI: 0.62, 1.56) p = 0.937], and for atrial arrhythmia ProGel 16% vs. control 16% [RR = 0.99 (95%CI: 0.64, 1.55) p = 0.980]. Higher rate was reported for pneumothorax in ProGel 18.1% vs. control 10.5% [RR = 1.72 (95%CI: 1.03, 2.88) p = 0.033], and the association was statistically significant. ProGel group had 1.15 times more subjects with at least one specified adverse event. SAEs that occurred in greater than 3% in either group were hospital readmission 20 per 282 (7%) ProGel and 14 per 162 (9%) control, persistent air leak 23 per 282 (8%) ProGel and 15 per 162 (9%) control, pneumothorax ProGel 18 per 282 (6%) and control 8 per 162 (5%), atrial arrhythmia ProGel 2 per 282 (0.7%) and control 6 per 162 (4%), and death due to all causes 7 per 282 (3%) ProGel and 6 per 162 (4%) control. All other specified SAEs were reported in rates less than 1.5% in both groups. The rest of serious adverse event rates in the two study arms are pretty similar and lower or equal to the rate observed in the original PMA clinical report.
Final Effect Findings	No effectiveness study endpoints were included in the approved protocol.
Study Strengths & Weaknesses	Prospective cohort study design Multi-center decreases potential selection bias and increases generalizability. The demographic distribution of patients reflects the population that requires this type of treatment. Control group included The follow-up rate of 88% is above the 80% that FDA recommends. Study Weaknesses: Non-randomized 44% of PAS treatment arm applications were off-label
Recommendations for Labeling Changes	Labeling changes are recommended based on safety data reported in the final report.
General
Study Status	Terminated
Application Number / Requirement Number	H080002 / PAS001
Date Original Protocol Accepted	01/25/2010
Date Current Protocol Accepted	09/24/2013
Study Name	Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	H070005 / PAS001
Date Original Protocol Accepted	04/13/2017
Date Current Protocol Accepted	02/07/2021
Study Name	AMPLATZER PIVSD Occluder PAS
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the safety and probable benefit of the AMPLATZER PIVSD Occluder in patients undergoing implantation of the PIVSD Occluder following an acute myocardial infarction. This is multicenter, retrospective non-randomized, observational study.
Study Population	The intended population for the AMPLATZER™ PIVSD Occluder are patients with post-myocardial infarct muscular ventricular septal defect (VSD) who are not satisfactory surgical candidates. The study will enroll subjects in two cohorts: First Cohort: All available Emergency and Compassionate PIVSD Occluder subject data from 2011 to end of 2016. All subjects belonging to this cohort must have undergone an attempt to close a post-infarct VSD using the AMPLATZER™ PIVSD Occluder. Second Cohort: The second cohort will be comprised of subjects over the age of 18 who are successfully implanted with a PIVSD Occluder from 2011 onwards. The index procedure must have occurred >6 months prior to enrollment. The subjects must meet following conditions: Subject or subject’s legally authorized representative has provided consent to participate in this study. Subject’s post-procedure echocardiogram is evaluable and can be sent to the echocardiography core laboratory for residual shunt assessment.
Sample Size	First Cohort: All available Emergency and Compassionate PIVSD Occluder subject data from 2011 to the end of 2016. Second Cohort: A total of 30 subjects who have been successfully implanted with PIVSD occluder and have data for the residual shunt assessed by the echocardiography core laboratory post procedure will be enrolled from up to 50 centers in the US.
Key Study Endpoints	Cohort 1: Acute Survival: is defined as survival for at least 24 hours following an attempted PIVSD device implant. Chronic Survival: is defined as survival for at least 183 days post-procedure. Technical Success: Technical success occurs when a subject is successfully implanted with a PIVSD device in the ventricular septal defect. An implant attempt occurs when the delivery system is inserted in the subject’s vasculature. Cohort 2: Acute Closure: defined as the absence of a residual shunt greater than or equal to 3 mm, and will be assessed based on an echocardiogram obtained immediately after successful deployment of the device and up to 7 days post-procedure. Chronic Closure: defined as the absence of a residual shunt greater than or equal to 3 mm at 6 months or later (where 6 months is defined as greater than or equal to 150 days) Chronic Survival: is defined as survival for at least 183 days post-procedure.
Follow-up Visits and Length of Follow-up	6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	Cohort 1- 99 patients Cohort 2- 32 patients
Actual Number of Sites Enrolled	Cohort 1- 64 investigational sites Cohort 2- 16 investigational sites
Patient Follow-up Rate	The data collected in this study is retrospective. Therefore the follow up rate is not relevant to tracking the progress of the study.
Final Safety Findings	Two safety endpoints were analyzed in this post-approval study: acute survival and chronic survival. Acute and chronic survival were defined as survival for at least 24-hours post procedure and for at least 183-days post-procedure, respectively. The primary safety endpoint results were as follows: Acute Survival (Cohort 1): 84.3% (75/89) Chronic Survival (Cohort 1 & 2): 37.2% and 46.4%, respectively
Final Effect Findings	Three effectiveness endpoints were analyzed in this post-approval study: technical success, acute closure, and chronic closure. Technical success was defined as successful implantation of the PIVSD Occluder into the VSD. Acute and chronic closure were defined as the absence of a > 3 mm residual shunt immediately after deployment up to 7 days post-procedure and at 6-months post-procedure or later, respectively. The primary effectiveness endpoint results were as follows: Technical Success (Cohort 1): 76.8% (76/99) Acute Closure (Cohort 2): 53.1% (17/32) Chronic Closure (Cohort 2): 66.7% (4/6)
Study Strengths & Weaknesses	PIVSD is associated with high mortality (>90%) despite optimal medical treatment. There is high mortality rate following surgical repair that ranges between 20% and 65%. Higher postoperative mortality correlates with early surgery (< 7 days) after the diagnosis. Of PIVSD. Subjects included in this study were poor candidates for surgery (indication for treatment with the VSD device). The results of the report demonstrate the Amplatzer™ PIVSD Occluder continues to be a safe alternative to medical therapy and surgical intervention for the repair of a VSD following a myocardial infarction in patients who are considered high risk surgical candidates.
Recommendations for Labeling Changes	Yes, labeling recommended
General
Study Status	Completed
Application Number / Requirement Number	H090002 / PAS002
Date Original Protocol Accepted	11/18/2011
Date Current Protocol Accepted	11/13/2013
Study Name	Enhanced Surveillance Study
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Enhanced Surveillance Study designed to evaluate the safety of BSD-2000 Hyperthermia System. Sites will be contacted on a quarterly basis.
Study Population	Patients with cervical cancer treated with BSD-2000. Patients who have had or not had prior irradiation of the treatment site also will be included. Patients who have had chemotherapy administered also will be included.
Sample Size	No specified sample size or number of clinical sites.
Key Study Endpoints	Evaluation of complaints involving injury and adverse events, including acute and late toxicity associated with hyperthermia and radiotherapy treatment.
Follow-up Visits and Length of Follow-up	Up to 3 years. There are no scheduled follow-up visits for the patients. Adverse events will be captured using the Case Report Forms. The sites will be contacted quarterly for data.
Interim or Final Data Summary
Actual Number of Patients Enrolled	30
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	N/A. No specified follow up per protocol.
Final Safety Findings	There 3 adverse events reported in 3/30 (10%) patients who received radiation + hyperthermia treatment. One AE consisted of pain due to water bolus pressure and hot spot in the vagina during treatment. One AE involved mild blisters that resolved without medical treatment, and 1 AE was determined unrelated with the hyperthermic treatment (appendicitis). A supplemental literature review was provided to support the safety of the device. The AEs adverse events (AEs) reported in the literature included blisters, diarrhea, cystitis, skin burn, pain, nausea, anxiety, hematuria, deterioration of a decubital ulcer, ulceration, local infection from thermometry catheters, sepsis that required antiobiotic therapy, fatigue, rectal bleeding, bolus pressure and vomiting. Toxicity was reported in most studies as being similar between radio+hyperthermia treatment (RHT) and radio treatment (RT) without further specificity. One study reported a grading of 93% good and 13% moderate/severe chronic toxicity in the RHT patient group at 3 years, while another reported toxicity of 12%.
Final Effect Findings	N/A, effectiveness not collected as part of this study. See H090002/PAS003 for effectiveness results of the registry study.
Study Strengths & Weaknesses	The study is all-comers. Although this allows for potentially higher enrollment, the population may not reflect the same population as that of the pivotal study used to support approval of the HDE. Therefore, the safety data may not be directly comparable between the two studies. The lack of enrollment and follow up limits interpretation of the data. Data provided from literature provide more patients for analysis, and therefore additional safety information. However, these data have important limitations. Several studies were retrospective in nature. The evidence provided from retrospective studies does not have as high quality as compared to prospective randomized controlled trials and may have confounding variables or other bias. Examples of these may include (but are not limited to): single site bias, insufficient/ incomplete patient demographic data, non-stratified patient populations, and differences in the length of follow-up. Differences in covariates can introduce biases in the assessment of the device performance, safety outcomes, and study conclusions. The standard of care and complexity of medical therapies and procedures across countries and over time may impact the conclusions from studies from different regions and time periods. Data from the literature were collected by different sources and periods of time. There is the possibility that other descriptive search terms for the device may have resulted in different publications and/or potential missed articles.
Recommendations for Labeling Changes	No
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	H090002 / PAS001
Date Original Protocol Accepted	11/18/2011
Date Current Protocol Accepted	11/13/2013
Study Name	Deep Hyperthermia and Radiation
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Interventional; Open Label; Uncontrolled; Registry
Study Population	Females that are 21 and older that are ineligible to undergo chemotherapy.
Sample Size	All patients treated with the BSD-2000 over the 3-year enrollment period
Key Study Endpoints	1st endpoint - complete tumor response (CR); 2nd endpoints - safety (i.e. adverse events and toxicity) and survival determined from day 0
Follow-up Visits and Length of Follow-up	Up to 36 months after enrollment and expect follow-up completion to be done 72 months following study. Follow-up exams will be performed at 3, 6, 12, 18, 24, and 36 month intervals.
General
Study Status	Completed
Application Number / Requirement Number	P090016 / PAS001
Date Original Protocol Accepted	11/14/2011
Date Current Protocol Accepted	12/07/2012
Study Name	Chemical/Physical Evaluation
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Bench/Lab study to evaluate the chemical/physical reasons that the injection force of Belotero Balance decreases as a function of time during product storage.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	Not applicable. This is a bench/lab study.
Key Study Endpoints	Not applicable. This is a bench/lab study.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	n/a - bench study
Actual Number of Sites Enrolled	n/a - bench study - actual number of batches studied: 3
Patient Follow-up Rate	The ejection force of three device¿s batches was evaluated in the laboratory during 24 months.
Final Safety Findings	¿ Over 24 months at room temperature, the ejection force and dynamic viscosity of the product decrease, but remain within the previously set specifications. From a clinical perspective, then, the material is suitable for a 24 month shelf life. ¿ Because only soluble hyaluronic acid (HA) that is a listed ingredient and not a proprietary ingredient was evaluated and not the crosslinked portion, and because the nature of the soluble HA was variable from time point to time point, it is difficult to draw correlations between the viscosity of the material and the network structure/molecular weight distribution of the product. Generally speaking, physical properties arise from chemical characteristics. In this case, there are multiple factors, chiefly the distribution and degradation of the soluble HA component (and secondarily the apparent burst release of soluble HA), that may ultimately lead to the decrease in material properties.
Study Strengths & Weaknesses	A. Strengths: ¿The evaluation procedures carried out in this study effectively tested stability and ejection force parameters for this device. ¿The study approach was adequate to reveal the behavior and properties of this device at up to 24 months shelf life. ¿The methodology used in this study could be helpful in the evaluation of this class of devices. B. Limitations ¿The methodology used was limited in scope to evaluate soluble HA that is a listed ingredient and not a proprietary ingredient.
Recommendations for Labeling Changes	no (No unexpected findings were reported and no additional information from the PAS is needed in the labeling).
General
Study Status	Completed
Application Number / Requirement Number	H100006 / PAS001
Date Original Protocol Accepted	09/28/2011
Date Current Protocol Accepted	09/28/2011
Study Name	NeuRx DPS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, non-randomized, open-label, interventional study.
Study Population	This study will enroll ALS patients who meet the HDE-approved device indications for use and undergo the surgical implantation procedure to receive the NeuRx DPS System after HDE approval. An important inclusion criterion is that patients must have chronic hypoventilation; an important exclusion criterion is that FVC < 45% predicted at time of surgery.
Sample Size	Based on practical considerations in this small subpopulation of patients with ALS who meet the HDE indications for use, it is expected that 60 participants can be enrolled at 3 to 12 centers over three years. This sample size of 60 participants has 80% power to ensure that the major device-related adverse event rate at 9 months post implant does not exceed 40% (based on peak adverse event rate using same device for spinal cord injury indication [H070003]), assuming the true event rate is 23% (based on IDE), with 5% one-sided alpha. A sample size of 60 patients ensures that there will be at least 48 patients at risk at the beginning of the 6 to 9 months interval to analyze the AE rate at 9 months.
Key Study Endpoints	This study will examine the following safety and probable benefit outcomes of interest: Safety Outcome Measure: Occurrence of major device-related (including procedure-related) adverse events as defined as: Serious capnothorax requiring invasive intervention (such as chest tube placement). Mechanical ventilation for 24 hours or longer post-procedure. Post-procedure extubation failure resulting in permanent tracheostomy ventilation (PTV). Perioperative complication which delays the initiation of NeuRx DPS therapy. Severe discomfort due to stimulation which is unable to be tolerated or resolved and results in interruption or discontinuation of NeuRx DPS therapy. Device malfunction (e.g,. broken wire or stimulator) which interrupts or causes an undesired diminution of NeuRx DPS therapy (e.g., no stimulation in one hemi-diaphragm). Electrode dislodgement from the diaphragm. Wire infection. Any other device- or procedure-related serious adverse event (SAE) that is fatal, life threatening, requires or prolongs hospitalization, or requires intervention to prevent permanent impairment or damage. Probable Benefit Outcome Measure: Survival, defined as time to (a) death or (b) permanent tracheostomy mechanical ventilation (PTV) with discontinuation of pacing. (All deaths and PTV events will be reported regardless of relationship to the device or procedure.)
Follow-up Visits and Length of Follow-up	9 months 0 to 1 month, 1- 3 months, and every 3 months thereafter until post-implant follow-up completion
Interim or Final Data Summary
Actual Number of Patients Enrolled	60 (54 patients implanted)
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	Overall follow-up rate among those enrolled: 78% (47/60) The follow-up rate among those implanted was 87% (47/54).
Final Safety Findings	The highest incidence rate of MDRAEs at 9 and 21 months was due to wire infection [21.7% (95%CI: 12.7, 35.8)], following by device malfunction which interrupts or causes an undesired diminution of NeuRx DPS therapy being [18.3% (95%CI: 9.9, 32.4)] at 9 months and [21.9% (95%CI: 12.2, 37.6)] at 21 months. Adverse events with less than 10% in both time points were, serious capnothorax requiring invasive intervention (such as chest tube placement), perioperative complication which delays the initiation of NeuroRX DPS Therapy, and any other device-or-procedure-related serious AE that is fatal, life threatening, requires or prolong hospitalization. At 9 months the rate for severe discomfort due to stimulation resulting in interruption or discontinuation of NeuRX DPS therapy was 0%, but reporting 4.2% (95%CI: 0.6, 26.1) at 21 months. The composite MDRAEs (patients with at least one MDRAE) was 42.7% (95%CI: 30.4, 57.6) at 9 months, and 47.9% (95%CI: 33.6, 64.7) at 21 months. Patients with severe discomfort due to stimulation resulting in interruption or discontinuation of NeuRx DPS therapy increased from 0% adverse events at 9 months and 4.2% events at 21 months, and device malfunction which interrupts or causes an undesired diminution of NeuRx DPS therapy with 18.3% at 9 months and 21.9% at 21 months. The rest of the incidence rates, were the same at 9 and 21 months. No cases were reported for the rest of the MDRAEs under study (i.e. mechanical ventilation for 24 hours or longer post- procedure, post-procedure extubation failure resulting in permanent tracheostomy ventilation (PTV), and electrode dislodgement from the diaphragm). The frequency (incidence) of major device-related AEs did not increased dramatically toward end of life because the incidence rates at 9 and 21 months slightly increased only for two MDREAs and the composite as explained above. Regarding the secondary objective, there was no significant relationship between survival time and the onset type (bulbar and limb), time from diagnosis to treatment, and use of NIV, riluzole or PEG in patients treated with the device.
Final Effect Findings	No effectiveness study endpoints were included in the approved protocol.
Study Strengths & Weaknesses	Strength: None Weaknesses: Small sample size (60), 78.3% follow-up rate, and no concomitant control group was included.
Recommendations for Labeling Changes	The PAS study design, methods and results must be included in the labeling. Additionally, it should be included the following Serious Adverse events: 3 cases of capnothoraces requiring invasive intervention with a chest tube; all resolved in 1-2 days. 1 case of history of poor pain control precluding the ability to program and use the DPS device. 1 case of pulmonary embolism perioperatively requiring hospitalization and having fatal resolution. 1 case of post-operative spasticity and development of bilateral lung infiltrates requiring 2 bronchoscopies, one with removal of a mucous plug. Table 1: Incidence at 9 and 12 months for MDRAES in N-54 implanted patients (provided interactively on August 10, 2017).
General
Study Status	Completed
Application Number / Requirement Number	H110002 / PAS001
Date Original Protocol Accepted	02/13/2013
Date Current Protocol Accepted	02/13/2013
Study Name	Ext f/u of the Argus II Feasibility Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Extending the Single-armed feasibility study
Study Population	Subjects who have completed participation in the Investigational Phase of this study and who have the Argus II device still implanted are eligible for enrollment in the Post-Approval Phase of this study.
Sample Size	N = 29. Fourteen (14) subjects were enrolled in the Investigational Phase of the study. One of these 14 subjects was explanted, which leaves a maximum of 13 subjects in the U.S. eligible for the post-approval phase of this study. An additional 16 subjects were enrolled in a similar study in Europe. All 16 of these subjects are eligible for participation in the post-approval phase of the study.
Key Study Endpoints	The primary endpoint of the post-approval phase is safety (i.e. the rates of adverse events). The secondary endpoint of the post-approval phase the long-term reliability of the Argus II implant.
Follow-up Visits and Length of Follow-up	Extend the subjects overall participation in the study to 10 years post-implant. During year 5 to 7, every six month; from year 8 to 10 annually. Note the examinations are not exactly the same prior to year 7 and thereafter, because the study undergoing was extended to year 7.
Interim or Final Data Summary
Interim Results	A total of 30 subjects have been enrolled with an implant average implant average of 10.39 +/- 2.84 years (range 1.2 – 12.6 years). Of these, twenty-four subjects have completed full study participation (10 years) and one subject withdrew prior to completing study participation. Four (4) subjects in the study had the Argus II device explanted. The average post-explant duration is 6.6 +/- 4.0 years (range 1.6 – 11.4 years). None unanticipated adverse device events reported.
Actual Number of Patients Enrolled	30 subjects
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	% at 10 Yr- % Follow-up completed (calculated as a percent of expected follow-up) N=30 (enrolled); 1 subject explanted at 1.2 years post-implant N=29 completed 3 years follow-up (100%); 1 subject explanted at 3.5 years, 1 subject explanted at 4.3 years post-implant, 1 subject missed the 4-year and subsequent follow-up visits N=26 completed 5-year follow-up (96%); 1 subject passed away at 6 years post-implant N = 25 completed 7-year follow-up (96%); 1 subject explanted at 9 years post implant, 1 subject withdrew prior to 10-year visit N = 23 completed 10-year follow-up (92%)
Final Safety Findings	The primary endpoint for this study was the rate of device-related adverse events in the post-approval phase. A total of 36 serious and 152 non-serious device- or procedure-related adverse events were observed in the study, starting from 2007 through December 31, 2019. Serious Adverse Events: Conjunctival dehiscence 13% (4/30) Conjunctival erosion 30% (9/30) Corneal Melt - infective 3% (1/30) Corneal opacity 3% (1/30) Endophthalmitis - infective 13% (4/30) Epiretinal membrane 3% (1/30) Hypotony 17% (5/30) Iridis Rubeosis 3% (1/30) Keratitis - infective 3% (1/30) Migration (extra-ocular) of intraocular silicone oil 3% (1/30) Re-tack 7% (2/30) Retinal detachment- rhegmatogenous 10% (3/30) Retinal detachment- tractional and serous 3% (1/30) Retinal Tear 3% (1/30) Uveitis 3% (1/30) Non-serious Adverse Events 360 Circumferential Vitreous Band Traction 3% (1/30) Choroidal detachment 20% (6/30) Choroidal effusion 3% (1/30) Conjunctival congestion 37% (11/30) Conjunctival Cyst 7% (2/30) Conjunctival dehiscence 7% (2/30) Conjunctival erosion 7% (2/30) Conjunctivitis - inflammatory 17% (5/30) Corneal abrasion 3% (1/30) Corneal dryness 3% (1/30) Corneal epithelial defect 3% (1/30) Corneal fold 3% (1/30) Corneal opacity 3% (1/30) Corneal Suture Broken 7% (2/30) Corneal vascularization 7% (2/30) Decrease in light perception 3% (1/30) Elective Revision Surgery 23% (7/30) Epiphora 10% (3/30) Epiretinal membrane 37% (11/30) Fibrosis around Retinal tack 3% (1/30) Fibrosis around tack 3% (1/30) Filamentary keratitis 3% (1/30) Foreign Body Sensation 7% (2/30) Headache 10% (3/30) High IOP 7% (2/30) Hyphema 10% (3/30) Hypotony 27% (8/30) Inflammation -ocular 17% (5/30) Irregular pupil 3% (1/30) Keratic Precipitates 10% (3/30) Nausea 3% (1/30) Nystagmus increase 3% (1/30) Ocular fibrin 3% (1/30) Pain - ocular 60% (18/30) Pre-retinal hemorrhage 3% (1/30) Proliferative Vitreoretinopathy 3% (1/30) Ptosis 7% (2/30) Retinal Break/Tear 3% (1/30) Retinal detachment-tractional 3% (1/30) Retinal Folds 3% (1/30) Retinal Thickening-cystoid macular edema (CME) 13% (4/30) Retinal Thickening-without cystic changes 13% (4/30) Retinoschisis 7% (2/30) Revision Surgery - tack replacement 3% (1/30) Rubeosis 3% (1/30) Scleral graft displacement or reabsorption 3% (1/30) Scleral patch displacement 3% (1/30) Scleritis 3% (1/30) Suture irritation 23% (7/30) Uveitis 20% (6/30) Vertigo 3% (1/30) Vitreous hemorrhage 10% (3/30) No unanticipated adverse events have been reported for this study.
Final Effect Findings	The secondary endpoint for this study was the assessment of the long-term reliability of the Argus 2 System. Out of 30 implanted subjects, two implants failed—each experienced a decline in ability to create and maintain radiofrequency link with the glasses, ultimately leading to total loss of link. One of these failures occurred at 3.9 years post-implant, the other at 4 years post-implant. In addition, four subjects were explanted due to recurrent conjunctival erosion (3), hypotony/subject request (1).
Study Strengths & Weaknesses	The primary strength of this study is the long-term follow up of 30 subjects implanted with the Argus 2 System. This provided almost 300 subject-years of safety and reliability data of a first-in-human device. Study weaknesses include the single-arm design and small sample size of 30 subjects.
Recommendations for Labeling Changes	In the approved Argus 2 Retinal Prosthesis System Product Insert (page 181/379, H110002), reported adverse events, probable benefit, and implant failures should be updated with the outcomes of the “Extended Follow-up of the Argus 2 Retinal Stimulation System Feasibility Protocol (CP-003-001).” Similarly, in the Argus 2 Retinal Prosthesis System Patient Manual (page 340/379, H110002), Clinical Studies should be updated with this information.
General
Study Status	Terminated
Application Number / Requirement Number	H110002 / PAS002
Date Original Protocol Accepted	02/13/2013
Date Current Protocol Accepted	05/13/2020
Study Name	New Enrollment Argus II
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	New Enrollment Post-Approval Study: Multicenter prospective cohort study with Argus II System. Several controls are incorporated into the study. Data collected in the study will be compared with pre-implantation (Baseline) data. In addition, prospective comparisons will be made between the implant and fellow eyes, and by testing subjects visual performance with the Argus II System on and off.
Study Population	Age 25 years or older; both males and females; with severe to profound retinitis pigmentosa; with bare or no light perception in both eyes or with retinal response to electrical stimulation; with previous history of useful form vision
Sample Size	A total of 53 subjects will be enrolled in the study. It is anticipated that 85% of subjects will complete 5 years follow-up. This will provide a sample size of 45 subjects with complete 5 year follow-up. A minimum of 5 and a maximum of 40 centers in the US will participate in this study.
Key Study Endpoints	Primary: Safety (i.e. adverse event rates), with the main safety analysis performed when all subjects have reached 2 years post-implant. Secondary: Visual function, functional vision, and device reliability
Follow-up Visits and Length of Follow-up	5 years Baseline, implant, month 1, 3, 6, 12, 24, 36, 48, 60. Various follow-up assessments including medical and eye exam, functional evaluation will be tested at certain follow-up stages.
Interim or Final Data Summary
Interim Results	A total of 89 device or procedure-related adverse events have been reported to date. Of these, 15 were serious and 74 non-serious. None unanticipated adverse device events reported.
Actual Number of Patients Enrolled	55 subjects
Actual Number of Sites Enrolled	19
Patient Follow-up Rate	77.4&
Study Strengths & Weaknesses	This information will be included in the final report
General
Study Status	Completed
Application Number / Requirement Number	P040046 / PAS001
Date Original Protocol Accepted	02/20/2013
Date Current Protocol Accepted	02/20/2013
Study Name	Core Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	941 patients including 492 primary augmentation, 156 revision- augmentation, 225 primary reconstruction and 68 revision-reconstruction.
Actual Number of Sites Enrolled	47
Patient Follow-up Rate	The follow-up rate at 10 year was highest in the reconstruction group and lowest in the revision-augmentation group. Specifically, the follow-up rate at Year 10 by cohorts were as follows: 66% in the augmentation cohort, 55% in revision-augmentation, 81% in the reconstruction and 77% in the revision-reconstruction.
Final Safety Findings	The most commonly reported complications vary by the indication group. The most commonly reported complications at 10 years by indication group are as follow: Augmentation cohort: Capsular contracture (9.2%), implant malposition (4.7%), breast pain (4.5%) and swelling (4.0%); Revision-augmentation cohort: Capsular contracture (11.9%), implant malposition (9.1%), asymmetry (6.9%) and breast pain (5.2%); Reconstruction cohort: Capsular contracture (14.5%), asymmetry (12.4%), breast pain (8.2%) and wrinkling/rippling (6.2%); Revision-reconstruction: Capsular contracture (26.8%), asymmetry (17.4%), wrinkling/rippling (12.8%) and infection (8.5%); The overall implant rupture rates at 10 years by patient were 11.9% in the augmentation, 13.0% in the revision-augmentation, 8.5% in the reconstruction, and 9.7% in the revision-reconstruction cohorts. The rate of any reoperation by 10 years post-implant was highest in the reconstruction cohort (54.6%), followed by revision cohorts (48.5% in the revision-reconstruction and 47.3% in the revision- augmentation cohorts), and lowest in the augmentation cohort (29.7%). The most frequently reported reason for reoperation varied with the indication. The most common primary reasons for reoperation were asymmetry, capsular contracture, device rupture, implant malposition, need for biopsy, patient request for style/size change, hematoma/seroma, infection, scarring and ptosis. The incidence of breast implant removal by 10 years post-implant was highest in the revision- reconstruction cohort (42.4%), followed by reconstruction cohort (38.3%), revision-augmentation cohort (31.0%) and the augmentation cohort (19.6%). The most common reasons for replacement/removal vary depending on the indication group. The most common reasons for implant replacement and removals are as follows: asymmetry, capsular contracture, device rupture, implant malposition and patient request for style/size change.
Final Effect Findings	The majority of the patients and physicians were satisfied with the surgical outcome at 10 years. In the augmentation cohort, the patient and physician satisfaction was 95% and 96%, respectively, 86% and 85% in the augmentation-revision cohort, 92% and 91% in the reconstruction cohort, 78% and 80% in the revision-reconstruction cohort.
Study Strengths & Weaknesses	One of the study strengths is that the study was a prospective, multicenter study that provides long term data up to 10 years on the safety and effectiveness of the device. The weaknesses of the study were the lack of a comparison group and lack of statistical power to detect rare events due to the small sample size.
Recommendations for Labeling Changes	Yes. The labeling will be updated based on the safety and effectiveness results reported in the final PAS report since these results will provide patients and physicians with long term data (10-years) on the performance of the device.
General
Study Status	Delayed
Application Number / Requirement Number	H120005 / PAS001
Date Original Protocol Accepted	10/10/2013
Date Current Protocol Accepted	08/26/2026
Study Name	New Enroll. PAS for Liposorber LA-15 Sys
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: Multicenter, prospective, single-arm, new enrollment clinical study to evaluate the probable benefit and safety of the LIPOSORBER® LA-15 System Objectives: • The primary objectives of this study are to evaluate the safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 1 month after the final apheresis treatment. • The secondary objectives are to evaluate safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 3 months, 6 months, 12 months, and 24 months after the final apheresis treatment.
Study Population	Inclusion Criteria Adult and pediatric patients with nephrotic syndrome associated with primary focal segmental glomerulosclerosis (FSGS), when the standard treatment options, including corticosteroid and/or calcineurin inhibitors treatments, have been unsuccessful or not well tolerated, and the patient has a glomerular filtration rate (GFR) greater than or equal to 45 ml/min/1.73m2, or the patient is post-renal transplantation. Exclusion Criteria General Exclusion Criteria: 1. Older than 75 years of age in the Adult Study or older than 21 years in the Pediatric Study 2. Parent or patient is unwilling or unable to sign and date the informed consent 3. Pregnant, lactating, or planning to become pregnant prior to completing the study 4. Unable or unwilling to comply with the follow-up schedule 5. Simultaneously participating in another investigational drug or device study 6. Body weight < 15 kg (33.1 lbs.) Medical Exclusion Criteria: 1. Currently being administered ACE inhibitors that cannot be withheld. 2. Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., ARBs) that cannot be withheld on the day of apheresis until after the procedure 3. Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis 4. Hypersensitivity to dextran sulfate, heparin, or ethylene oxide 5. Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications after surgery 6. Extracorporeal circulation therapy with LIPOSORBER® LA-15 System cannot be tolerated due to severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute apoplexy, severe uncontrollable hypertension, or severe uncontrollable hypotension 7. Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease intolerant to apheresis treatment 8. Ongoing diagnosis of Functional thyroid disease other than hypothyroidism due to nephrotic syndrome or Hashimoto's thyroiditis, or liver abnormalities 9. Unresolved systemic or local infection (e.g., Catheter infections or urinary tract infections) that could affect the clinical study outcomes 10. Patients without a history of biopsy-proven FSGS diagnosis 11. Currently receiving or have received treatment with LIPOSORBER® LA-15 System 12. Patients who require any plasmapheresis other than LIPOSORBER® LA-15 System and are unable to discontinue prior to pre-screening, or who are planning to have any plasmapheresis other than LIPOSORBER® LA-15 System 13. Currently undergoing hemodialysis 14. Ongoing diagnosis of End Stage Renal Disease (ESRD)
Sample Size	35 pediatric patients and 35 adult patients (total of 70 patients)
Key Study Endpoints	- The primary probable benefit endpoint is the percent of patients who show complete or partial remission at 1 month after the final apheresis treatment. - The primary safety endpoint is the rate of device-related and procedure-related serious adverse events (SAEs) occurring during the treatment period and up to 1-month follow-up visit. - The secondary objectives are: o to evaluate safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with refractory primary FSGS at 3 months, 6 months, 12 months, and 24 months after the final apheresis treatment. o The secondary safety and probable benefit endpoints include nephrotic condition (complete remission, partial remission, and nephrotic state) including the percentage of patients who obtain complete and partial remission at 3, 6, 12, and 24 months; o incidence of adverse events encountered during the period in which apheresis treatments are given; o incidence of all adverse events and SAEs occurring within 3, 6, 12, and 24 months after the final apheresis treatment; and o laboratory values, including eGFR at baseline, after the last treatment, and at 1, 3, 6, 12, and 24 months after the final apheresis treatment, including percent change from baseline and percentage of patients showing an increase or decrease in each value. The data will be analyzed and presented separately for the pediatric and adult populations.
Follow-up Visits and Length of Follow-up	24 months after final apheresis treatment
Interim or Final Data Summary
Interim Results	Safety: Among adult patients, there were zero AEs and zero SAE during this reporting period. Among pediatric patients, there were 6 new SAEs that occurred in 1 patient: worsening edema, worsening ascites, respiratory distress, sepsis, AKI, and a second occurrence of worsening edema. All events were deemed not related to the Liposorber treatment. Effectiveness: The proportion of pediatric patients in complete or partial remission ranged from 53% (8/15) at 1 month follow-up to 83% (5/6) at 24 months follow-up. The proportion of adult patients in complete or partial remission ranged from 27% (3/11) at 1 month follow-up to 33% (1/3) at 24 months. The small number of pediatric and adult patients, particularly at the later follow-up visits, make it difficult to get a stable estimate of device effectiveness at this time.
Actual Number of Patients Enrolled	29 pediatric and 19 adult enrollments
Actual Number of Sites Enrolled	17 sites
Patient Follow-up Rate	Pediatric: 83% (15/18) at 1 month, 67% (12/18) at 3 months, 56% (10/18) at 6 months, 56% (10/18) at 12 months, and 33% (6/18) at 24 months. Adults: 92% (11/12) at 1 month, 67% (8/12) at 3 months, 58% (7/12) at 6 months, 33% (4/12) at 12 months, and 25% (3/12) at 24 months.
General
Study Status	Completed
Application Number / Requirement Number	H130006 / PAS001
Date Original Protocol Accepted	12/18/2015
Date Current Protocol Accepted
Study Name	HDE Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a follow on study, to the original set of subjects used for the approval of this HDE. The study is a multi-center, prospective, single-arm study in the United States and Europe of subjects with FI. Thirty-five subjects were implanted with the FENIX device in the U.S. (n=15) and Europe (n=20) prior to HDE approval. A total of 24 subjects continue to be enrolled for the extended follow-up period and will be prospectively followed to 5 years after the implant procedure.
Study Population	Subjects (male or female) seeking surgical intervention for fecal incontinence who provided informed consent and met the study inclusion / exclusion criteria were eligible for this study
Sample Size	35 patients implanted. Only 24 patients remain at 60 months.
Key Study Endpoints	There are no statistically derived endpoints for this feasibility study. Effectiveness Bowel Diary • Proportion of study patients achieving at least 50% reduction in FI episodes per week from baseline at 6, 12, 24, 36, 48, and 60 months. • Proportion of study patients achieving at least 50% reduction in FI days per week from baseline at 6, 12, 24, 36, 48, and 60 months. Fecal Incontinence Quality of Life (FIQOL) • Proportion of study patients with improvement in FIQOL score. The four scales of the FIQOL instrument will be analyzed separately (Lifestyle, Coping/Behavior, Depression/Self-Perception, and Embarrassment) Safety Characterized by the adverse events (AEs) experienced with the use of the FENIX System and summarized as incidence rates. Serious device and procedure- related AEs will be summarized separately. Safety was also characterized by physical examination and pelvic X-ray.
Follow-up Visits and Length of Follow-up	5 years 12, 24,36, 48 and 60 months post implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	43 (35 patients implanted)
Actual Number of Sites Enrolled	4
Patient Follow-up Rate	The follow up rate at the different time points is shown below. 43 subjects enrolled 35 subjects implanted 100% (28/28) subjects attended the 1 year follow up visit. 6 subjects were explanted prior to 1 year and 1 exited lost to follow up (LTF) 96.3% (26/27) subjects attended the 2 year follow up visit. One subject completed requirements, bringing the expected to (27) and 1 visit was missed, making the number of visits completed to 26, or 96.3% 100% (24/24) subjects attended the 3 year follow up visit One additional explant, one unrelated death and 1 exit/LTF 95.8% (23/24) subjects attended the 4 year follow up visit One visit was missed 100% (23/23) subjects attended the 5 year follow up visit One subject exited after the 4 year visit.
Final Safety Findings	As shown in Table 43 from the submission, from the 223 AEs reported, there were 30 AEs that were related (or the relationship was unknown) to the device and/or procedure. These were tallied as follows: Impaction or defecatory disorder (8) Pain (5) Bleeding (3) Device Erosion (4) Infection (4) Other (6) Mild Perineal bleeding Mild Rectal Pain Mild and Moderate Constipation Mild Anal Pain Moderate Allergy, inflammation reaction
Final Effect Findings	The sponsor presents data showing the percent reduction in FI episodes per week. Appendix A (page 7 of 77) shows that: 9.1% (2/22) showed no response, at 60 months 91% (20/22) had a greater than 25% decrease in FI episodes at 60 months 73% (16/22) had a greater than 50% decrease in FI episodes at 60 months 64% (14/22) had a greater than 75% decrease in FI episodes at 60 months 32% (7/22) had a 100% decrease in FI episodes at 60 months
Study Strengths & Weaknesses	Length of follow up was 5 years Patients were assessed for safety and efficacy (although the requirement is “probable benefit”). 73% (16/22) had a greater than 50% decrease in FI episodes at 60 months 32% (7/22) had a 100% decrease in FI episodes at 60 months Study Weaknesses This was a single arm a study without a comparator High degree of patient loss by 60 months. 35 patients were implanted, and 24 were left at the end of 60 months. 23-35 = 11. 11/35 = 31% of patients were lost.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the methods and long term data results obtained from PAS All PAS results tables should be included (existing from the approval order) Inclusion of ODS scores, for patients that had an increase in impaction disorder Statement about FIQOL scores for these patients
General
Study Status	Delayed
Application Number / Requirement Number	H130001 / PAS001
Date Original Protocol Accepted	08/24/2015
Date Current Protocol Accepted	08/24/2015
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study is to assess the safety of Lixelle column in patients with (dialysis-related amyloidosis) DRA in the US. The secondary objective of the study is to assess the probable benefit of Lixelle column to increase the 2M reduction rate in a single dialysis session. This is a new enrollment study. This is a prospective study with two arms; DRA patients treated with Lixelle column (treatment arm) and DRA patients treated with conventional hemodialysis(HD) (natural history arm). The PAS will consist of four stages for the two groups. Stages 1, 3 and 4 will be observed in the natural history arm and Stages 1, 2, 3 and 4 will be observed in the study arm.
Study Population	Patients receiving thrice-weekly HD (conventional hemodialysis) and diagnosed as DRA by one or more of the following 2-1 to 2-4 will be included: 2-1. Biopsy of any tissue, showing Congo-red positive amyloid fibrils and immunohistochemical stains consistent with ß2M 2-2. Shoulder ultrasonography showing rotator cuffs greater than 8 mm in thickness, and/or echogenic pads between muscle groups of the rotator cuff 2-3. Two or more diagnoses of the following (1) to (5) (1) Polyarthralgia (2) Carpal tunnel syndrome (3) Trigger finger (4) Dialysis-associated spondylosis ((i) or (ii)) (i) Destructive spondyloarthropathy (DSA) (ii) Spinal stenosis (5) Bone cysts (Bone cysts considered to be caused by other diseases such as osteoarthritis, aneurysmal bone cysts and unicameral bone cysts should be excluded.) 2-4. Biopsy of any tissue, showing Congo-red positive amyloid fibrils, and one diagnosis or surgical history of criterion specified above in 2-3 (1) to (5)
Sample Size	30 DRA patients treated with Lixelle column (study arm) and 10 DRA patients treated with conventional HD. The sample size is based on clinical considerations and is not statistically driven.
Key Study Endpoints	Primary endpoint The primary endpoint is the rate of every SAE in the through 2 years of Lixelle treatment during the study period. The data will be assessed by descriptive statistics and will be compared to the SAE rate observed in the natural history arm. Secondary endpoints There are three secondary endpoints to assess the probable benefit of Lixelle in serum 2M reduction rate in a single Lixelle-treatment: 1. In study arm, 2M reduction rates obtained in Stage 2 (2nd week to 7th week) will be statistically compared with that in Stage 1 (1st week). 2. In study arm, 2M reduction rates obtained in Stage 3 (any week from 46th to 53rd week) will be statistically compared with that in Stage 1. 3. Differences in 2M reduction rates will be statistically compared between Stage 1 and Stage 3 in the natural history arm and study arm respectively.
Follow-up Visits and Length of Follow-up	Patients will be followed for 2 years The follow-up assessments for both groups are as follows: Stages 1 (1st week), 3 (any week from 45th to 52nd week) and 4 (any week from 93rd to 104th week) will be observed in the natural history arm and Stages 1 (1st week), 2 (2nd week to 7th week), 3 (any week from 46th to 53rd week) and 4 (any week from 94th to 105th week) will be observed in the study arm.
General
Study Status	Completed
Application Number / Requirement Number	H150003 / PAS002
Date Original Protocol Accepted	10/02/2020
Date Current Protocol Accepted
Study Name	Flourish Real-World Evidence PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: Continued evaluation of safety and probable benefit after approval of the Flourish device Design: A single-arm, RWE observational study with both prospective and retrospective data collection from patients’ medical records.
Study Population	Patients meeting the following criteria are eligible for participation in the study: 1. Has esophageal atresia (EA) 2. Atretic gap < 4cm 3. Absence of, or repaired tracheoesophageal fistula (TEF) 4. Less than 1 year of age 5. Absence of visible teeth 6. Gastrostomy tract properly sized to accommodate an 18 Fr gastric catheter 7. Absence of gastrostomy site signs of significant infection (significant as determined by physician) 8. Parent or guardian of patient provides informed consent for use of data There is no comparator group in this study.
Sample Size	A minimum of 20 patients will be enrolled.
Key Study Endpoints	Primary outcome measures for continued evaluation of device safety are rates of the following: • Stricture at the anastomotic site leading to the need for dilation or surgery • Peri-anastomotic leaks • Other adverse events and/or complications possibly, probably, or causally related to the device or procedure The secondary outcome measure for evaluation of probable benefit is successful anastomosis formation, which is defined as creation of a lumen connecting the upper esophageal pouch to the lower esophageal pouch. Per the IFU, successful anastomosis formation is confirmed by showing connected flow of contrast agent.
Follow-up Visits and Length of Follow-up	2 years after Flourish treatment There are no prespecified follow-up visits for this study, as patients will be cared for according to the physician’s clinical judgment. Data will be extracted from the medical record through 24 months and will be allocated into intervals of 2 weeks, and 1, 3, 6, 12, 18, and 24 months or until study exit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	21
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	7 patients completed the 2-year follow-up, 1 patient was followed until transfer to another hospital, 12 patients met an early study exit point due to subsequent anastomosis treatment of their esophageal atresia, and 1 patient met a study exit point due to death that was unrelated to the device
Final Safety Findings	Peri-anastomotic leak was reported in 2 patients (18%; 2/11) who achieved successful anastomosis formation
Final Effect Findings	Successful anastomosis formation was achieved in 11 patients (52%; 11/21)
Study Strengths & Weaknesses	Strength: This is a very challenging patient population and Flourish appears to offer benefits to certain patients with acceptable risk. Limitation: The small number of PAS patients limits the generalizability of the study results.
Recommendations for Labeling Changes	Labeling will not be updated since the Flourish device is no longer marketed as of 2023
General
Study Status	Completed
Application Number / Requirement Number	P200049 / PAS001
Date Original Protocol Accepted	08/14/2021
Date Current Protocol Accepted
Study Name	Continued Follow-up of the Amulet IDE Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of the Amulet IDE study to characterize the clinical outcomes annually through 5 years post-procedure of all available subjects who were enrolled in the randomized and roll-in cohorts of the Amulet IDE study.
Study Population	Patients were randomized to the Amulet device or the control Watchman device.
Sample Size	2079 (already enrolled)
Key Study Endpoints	Safety and effectiveness endpoints include: all-cause death, ischemic stroke, systemic embolism, major bleeding (Type 3 or greater per Bleeding Academic Research Consortium), procedure and device related complications, pericardial effusion requiring intervention, and device-related thrombus.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	2079 subjects enrolled (No new enrollment for this study): • 201 roll-ins • 1878 randomized subjects (934 Amulet subjects, 944 subjects
Actual Number of Sites Enrolled	115
Patient Follow-up Rate	Actual follow-up rate at 5-year: Amulet randomized subjects: 89.2% Watchman randomized subjects: 83.3% Roll-in subjects: 89.0%
Final Safety Findings	Subject Deaths: There have been 251 Amulet and 261 Watchman subject deaths adjudicated by the CEC in the randomized group for the ITT population. Fourteen (14) of these deaths have been adjudicated as device-related or as having an unknown relationship to the device (5 Amulet and 9 Watchman). One Amulet subject death and one Watchman subject death were adjudicated as device-related, and the remainder were adjudicated as unknown relatedness to the device. As of the final 5-year visit, 27 deaths have been adjudicated as either related to or possibly related to COVID-19 in the randomized group (11 Amulet, 16 Watchman). Serious Adverse Events (SAEs): A total of 542 Randomized Amulet subjects (58.0%) and 535 Randomized Watchman subjects (56.7%) experienced a SAE. Device-related SAEs occurred in 11.5% Randomized Amulet subjects and 10.1% Randomized Watchman subjects and procedure-related SAEs occurred in 9.0% Randomized Amulet subjects and 8.1% Randomized Watchman subjects. There have not been any reported unanticipated adverse events in the clinical trial. There have been 1233 SAEs in the Randomized Amulet group and 1142 SAEs in the Randomized Watchman group. The most common SAEs for both device groups were congestive heart failure (12.1% Amulet and 11.1% Watchman), gastrointestinal bleeds (10.5% Amulet and 10.5% Watchman), and ischemic stroke (6.1% Amulet and 5.6% Watchman). A total of 149 randomized Amulet subjects experienced a procedure- and/or device-related serious adverse event. Ischemic stroke (5.8%), pericardial tamponade (1.8%), and pericardial effusion (1.6%) were the most common procedure- or device-related SAEs. A total of 143 randomized Watchman subjects experienced a procedure- and/or device-related serious adverse event. Ischemic stroke (5.1%), transient ischemic attack (1.8%), and pericardial tamponade (1.5%) were the most common procedure- or device-related SAEs. Non-Serious Adverse Events: A cumulative total of 401 non-serious adverse events were adjudicated in the randomized Amulet subject group and 351 non-serious adverse events in the randomized Watchman subject group. Epistaxis (4.0%), Gastrointestinal Bleeding (3.1%), and Bruise/ Purpura Simplex (2.8%) were the most commonly adjudicated non-serious adverse events in the randomized Amulet subject cohort. Gastrointestinal Bleeding (3.9%), Epistaxis (3.5%), Bruise/ Purpura Simplex (2.3%), and Hematuria (2.3%) were the most commonly adjudicated non-serious adverse events in the randomized Watchman subject cohort.
Final Effect Findings	A total of 111 subjects experienced one or more components of the effectiveness endpoint: 58 in the Amulet group and 53 in the Watchman group, resulting in Kaplan-Meier estimated rates of 7.4% and 7.1%, respectively. The difference between the two groups was 0.3%. Ischemic stroke had a rate of 7.1% and 6.8% and systemic embolism rates of 0.3% and 0.4% for Amulet and Watchman, respectively.
Study Strengths & Weaknesses	This study follows up the premarket cohort through five years post- procedure and provides longer term safety and effectiveness results of the Amplatzer Amulet LAAO device
Recommendations for Labeling Changes	Yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	H150003 / PAS001
Date Original Protocol Accepted	04/27/2018
Date Current Protocol Accepted	10/02/2020
Study Name	Flourish Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective and Design Objective: continued evaluation of safety and probable benefit post-approval of the Flourish device. Design: a prospective, single-arm, observational clinical study. It is a new enrollment study.
Study Population	A patient is suitable for participation in the study if the patient meets the following criteria: 1. Has esophageal atresia (EA) 2. Atretic gap < 4cm 3. Absence of, or repaired tracheoesophageal fistula (TEF) 4. Less than 1 year of age 5. Absence of visible teeth 6. Gastrostomy tract properly sized to accommodate an 18 Fr gastric catheter 7. Absence of gastrostomy site signs of significant infection (significant as determined by physician) 8. Parent or guardian of patient provides informed consent for use of data No comparator group.
Sample Size	A minimum of 20 patients will be enrolled
Key Study Endpoints	The primary outcome measures for continued evaluation of device safety are the rates of the following: - Stricture at the anastomotic site leading to the need for dilation or surgery - Peri-anastomotic leaks - Other adverse events and/or complications possibly, probably, or causally related to the device or procedure The secondary outcome measure for evaluation of probable benefit is successful anastomosis formation. This is defined as creation of a lumen connecting the upper esophageal pouch to the lower esophageal pouch. Per the IFU successful anastomosis formation is confirmed by showing connected flow of contrast agent.
Follow-up Visits and Length of Follow-up	2 years
General
Study Status	Completed
Application Number / Requirement Number	P160043 / PAS001
Study Name	Cont f/u RESOLUTE ONYX Clinical
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued Follow-up of premarket cohort (Core 2.25mm-4.00mm Clinical Study)
Study Population	Single arm study with Resolute Onyx Stent System
Sample Size	75 subjects (already enrolled)
Key Study Endpoints	The primary safety and effectiveness endpoints is late lumen loss at 8 month post-index procedure. Unpowered secondary endpoints include acute success (device, lesion and procedure), cardiac death, target vessel MI, target lesion revascularization, MACE, target lesion failure, target vessel failure and stent thrombosis.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: 75 RESOLUTE ONYX 2.0 mm Clinical Study: 101
Actual Number of Sites Enrolled	Actual number of study sites enrolled: RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: 15 US sites RESOLUTE ONYX 2.0 mm Clinical Study : 21 US and 3 Japan
Patient Follow-up Rate	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: Subject follow-up compliance remained high through the 30 day, 6 month, 8 month, 12 month, 24 month, and 36 month follow-up visits. A total of 97.1% (67/69) completed their 36-month visit within the protocol defined follow-up window. RESOLUTE ONYX 2.0 mm Clinical Study: A total of 97.0% (98/101) of subjects completed their 30-day visit within the protocol defined follow-up window, 99.0% (100/101) of subjects completed their 6-month visit within the protocol defined follow-up window, 99.0% (100/101) completed their 12-month visit within the protocol defined follow-up window, 96.9% (95/98) completed their 24-month visit within the protocol defined follow-up window, and 100.0% (98/98) completed their 36-month visit within the protocol defined follow-up window.
Final Safety Findings	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: The TLF rate at 36 months is 14.7% (11/75), TVF is 18.7% (14/75), TVMI is 8.0% (6/75), MACE is 21.3% (16/75), and stent thrombosis is 1.3% (1/75). There were 6 deaths; 2 Cardiac and 4 Non-Cardiac Deaths at 36 months. Since the 24-month assessment, at 36 months, there were 3 more cases of TLF, TVF, TVMI, and Death, 5 more cases of MACE, and no cases of stent thrombosis. RESOLUTE ONYX 2.0 mm Clinical Study: The Resolute Onyx 2.0 mm event rates at 36 months post procedure are as follows: 13.9% (14/101) for TLF, 14.9% (15/101) for TVF, 4.0% (4/101) for TVMI, 14.9% (15/101) for MACE, and 0.0% (0/101) ARC definite/probable stent thrombosis. Rate of mortality is 3.0% (3/101), including cardiac mortality of 2.0% (2/101), and non cardiac mortality of 1.0% (1/101). There is no change in deaths, cardiac or non-cardiac from 24 months to 36 months.
Final Effect Findings	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: The TLF rate at 36 months is 14.7% (11/75), TVF is 18.7% (14/75), TVMI is 8.0% (6/75), MACE is 21.3% (16/75), and stent thrombosis is 1.3% (1/75). There were 6 deaths; 2 Cardiac and 4 Non-Cardiac Deaths at 36 months. Since the 24-month assessment, at 36 months, there were 3 more cases of TLF, TVF, TVMI, and Death, 5 more cases of MACE, and no cases of stent thrombosis. ARC/SCAI defined major adverse events up to 1080 days. All MIs were adjudicated using two definitions; the Medtronic extended historical definition and the SCAI definition. Death and stent thrombosis were adjudicated using ARC definitions only. There were four (5.3%) non-cardiovascular deaths and two (2.7%) cardiac deaths, three (4.0%) SCAI defined MIs, and one (1.3%) ARC defined acute definite stent thrombosis. There were no UADEs reported through 36 months. RESOLUTE ONYX 2.0 mm Clinical Study: The primary endpoint of TLF at 12 months was only 5.0%, meeting the pre-specified performance criterion (upper 1-sided 95% CI of 10.1%, compared with the performance goal of 19%, p < 0.001). The 12-month rate of key secondary clinical endpoints included 2.0% TLR, 3.0% TVMI, 5.0% TVF and 5.0% MACE rate. The ITT analysis on principal safety and effectiveness at discharge, as well as at 30 days, 180 days, 360 days, 720 days and 1080 days are summarized in Table 25. Follow-up data demonstrates that the 36-month rate of TLF was 13.9% (14/101), of TVF - 14.9% (15/101), of TVMI - 4.0% (4/101), and of MACE - 14.9% (15/101). There were no cases of stent thrombosis 0.0% (0/101) at 36 months, and there was a total of 3 deaths, including 2 Cardiac Deaths and 1 Non-Cardiac Death. Between 24 and 36 months, there was one additional event of TLF, TVF, and MACE, while the rates of TVMI, stent thrombosis, and death did not change.
General
Study Status	Completed
Application Number / Requirement Number	H160002 / PAS001
Date Original Protocol Accepted	06/19/2017
Date Current Protocol Accepted
Study Name	ANSWER Clinical Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Adjunctive Neurovascular Support for Wide-Neck Aneurysm and Reconstruction (ANSWER) (Revision E): Post-Approval Study of a 365 day follow as part of the approved ANSWER study as a condition of approval per the FDA’s 19 June 2017 HDE approval letter. The study endpoints evaluated at 1 year follow-up are neurological death or stroke, technical success, rate of aneurysm occlusion, device movement or migration, stenosis, rate of incidence of new neurological deficits, and complication rate (neurological and non-neurological). The study endpoints identified above were reviewed and approved in the ANSWER Study Protocol under IDE # G130268. The zero to 180-day clinical data has been submitted, reviewed and approved under HDE # H160002. Per the HDE approval letter the ANSWER Study Protocol would serve as Pulsar’s Post-Approval Study Protocol
Study Population	Subjects who met the protocol entry criteria with at least one bifurcation intracranial aneurysm that is acceptable for minimally invasive treatment who were enrolled under the ANSWER study IDE G130268
Sample Size	34 subjects
Key Study Endpoints	This post-approval study progress report will provide a brief summary of the results including the 1-year follow-up. Primary Endpoints: Safety – neurological death or major ipsilateral stroke in downstream territory to 1 year post-procedure Occlusion – rate of aneurysm occlusion at day zero, 180 days, and 365 days using the Raymond Scale Technical success – device placement success and ability to retain coils within aneurysm Additional Evaluations Incidence of new neurological deficits Complication rate (neurological and non-neurological) Rate of occlusion at 365 days Device movement or migration Stenosis at implant site
Follow-up Visits and Length of Follow-up	1 year post implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	34
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	88% (30/34)
Final Safety Findings	Neurological Death or Major Ipsilateral stroke in downstream territory to 1 year post procedure: 0% (0/28) Results for National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (mRS) through 365 days are below: NIH Stroke Score Pre-Procedure n = 34 Post-Procedure n = 34 30-Day n = 34 180-Day n = 321 365-Day n = 282 0 27 29 31 29 24 1 7 4 3 2 3 2 0 1 0 0 0 3 0 0 0 0 1 4 0 0 0 1 0 >4 0 0 0 0 0 Change from Pre-Procedure Decrease by 1 - 3 5 3 3 No Change - 30 28 28 23 Increase - 1 1 1 2 1 180-day NIHSS not done in 2 subjects: 1 due to declining health with metastatic cancer and 1 due to subject non-compliance with clinical follow-up schedule. 2 365-day NIHSS not done in 6 subjects: 1 due to subject death from metastatic cancer; 1 due to subject declining health from mass effect; 1 oversight with study team and clinic and test not performed; 3 subjects lost to follow-up at 365 days. Note: All 4 subjects that did not have the 365-day NIHSS done due to site oversight or lost to follow- up had NIHSS scores of 0 at all timepoints through 180 days. Table 6. Modified Rankin Scale – mRS mRS Pre-Procedure n = 34 Post-Procedure n = 34 30-Day n = 34 180-Day n = 34 365-Day n= 301 0 20 21 20 21 18 1 14 12 12 9 8 2 0 1 1 2 1 3 0 0 1 1 1 4 0 0 0 1 1 5 0 0 0 0 1 Change from Pre-Procedure Decrease by 1 - 4 4 3 5 No Change - 27 25 25 18 Increase - 3 5 6 7 1 365-day mRS not done in 4 subjects: 1 due to subject death from metastatic cancer; 3 due to lost to follow-up at 365 days. Note: All 3 subjects that did not have 365-day mRS due to lost to follow-up had no change in their mRS scores from pre-procedure through 180 days.
Final Effect Findings	Aneurysm Occlusion: Table 3. Aneurysm Occlusion – Raymond Score Raymond Score Day 0 n = 34 180 Days n= 331 365 Days n = 302 I 18 (53%) 20 (61%) 20 (67%) II 9 (26%) 9 (27%) 7 (23%) III 7 (21%) 4 (12%) 3 (10%) I/II 27 (79%) 29 (88%) 27 (90%) 1One subject (5-004) with a carotid terminus aneurysm had a CTA at 180 days and occlusion data not available on image. Same subject died due to metastatic cancer before the 365-day visit and is not included 365-day occlusion data. 2Three (3) subjects were lost to follow-up at the 365-day visit after multiple contact attempts were made (9-003, 14-002, 14-003) Aneurysm Occlusion by Location: Table 4. Aneurysm Occlusion – Basilar and Carotid Terminus Raymond Score Basilar n = 27 Carotid Terminus n = 61 Basilar n = 242 Carotid Terminus n = 61 180 Day Follow-up 365 Day Follow-up I 15 (55%) 5 (83%) 15 (63%) 5 (83%) II 8 (30%) 1 (17%) 6 (25%) 1 (17%) III 4 (15%) 0 (0%) 3 (12%) 0 (0%) I/II 23 (85%) 6 (100%) 21 (88%) 6 (100%) 1One subject (5-004) with carotid terminus aneurysm had a CTA at 180 days and occlusion data could not be determined. Same subject died due to metastatic cancer before the 365-day visit and is not included 365-day occlusion data. 2Three (3) subjects were lost to follow-up at the 365-day visit after multiple contact attempts were made (9-003, 14-002, 14-003) Technical Success: PulseRider technical success was achieved in 100% of the 34 cases. Treating physicians were able to access the aneurysm, deploy the device at the neck, and detach the device successfully.
Study Strengths & Weaknesses	Study Strengths included the use of a prospective, multi-center study design with study endpoints that included both effectiveness and safety endpoints. They study also included a Clinical Events Committee (CEC) to adjudicate reported serious adverse events and make recommendations to the Sponsor. The study weaknesses included that it was a single arm study (non-randomized) which limits the ability to draw comparisons to alternative treatments, financial conflicts of interest as some of the investigators in the study had a significant payment from Pulsar Vascular, Inc., the study was not statistically powered for hypothesis testing of the safety and probable benefit endpoints, and the mRS was not conducted by an unblinded assessor at the 180 day or 365 day follow-up visits that can introduce bias into this measurement.
Recommendations for Labeling Changes	The revised labeling should include a new section of the label that reflects long-term data from the Post-Approval Study. The labeling supplement should include a summary of the post-approval study design, results, and study strengths and limitations
General
Study Status	Ongoing
Application Number / Requirement Number	H170001 / PAS001
Date Original Protocol Accepted	10/23/2019
Date Current Protocol Accepted	09/04/2020
Study Name	MID-C System Registry PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Registry, multi center, single arm, non-randomized, new enrollment cohort study
Study Population	Child: 2-12 yrs, Adolescent: 13-18 yrs, Transitional Adolescent B (as adults): 18-21 yrs. Adolescent patients with adolescent idiopathic scoliosis (AIS) for treatment of single curves classified as Lenke 1 (thoracic major curve) or Lenke 5 (thoracolumbar/lumbar major curve), having a Cobb angle of 45 to 60 degrees which reduces to less than or equal to 30 degrees on lateral side-bending radiographs, and thoracic kyphosis less than 55 degrees as measured from T5-T12.
Sample Size	Patients implanted with the device in the US within 2 years of FDA’s approval of H17001 should be enrolled in the study. A minimum number of 200 patients will be enrolled in this study,with at least 50 patients enrolled by 24 months, 100 patients enrolled by 36 months, and 200 patients enrolled by 48 months. All patients who are implanted with the MID-C System at a participating site in the US will be asked to participate, unless the patient is seeking treatment at a site where the maximum site enrollment has been reached, until 200 patients are enrolled in the study.
Key Study Endpoints	Safety Endpoints Primary: Serious adverse events, and device or procedure related adverse events Secondary: 1. Rate of adverse events, including by relatedness to device or procedure and severity; and 2. Rate of reoperation, including by type of reoperation. Probable Benefit Endpoints Primary: Maintenance of major Cobb angle less than or equal to 40° 5 years post-surgery Secondary: Annual analysis up to 5 years of the following: 1. Maintenance of major Cobb angle less than or equal to 40° 2. Curve progression no more than 10° of the secondary curve above or below the implant. 3. Composite endpoint analysis (maintenance of major Cobb angle less than or equal to 40° AND freedom from SAEs during MID-C procedure and procedure/device related SAEs following surgery). 4. True failure rate analysis. True failure is defined as conversion to another spinal implant OR major Cobb angle that exceeded 40° at defined follow-up visit OR any curve progression at defined follow-up compared to baseline OR death, OR permanent disability.
Follow-up Visits and Length of Follow-up	60 months (5 years) of individual post-implantation follow-up
General
Study Status	Delayed
Application Number / Requirement Number	H170002 / PAS001
Date Original Protocol Accepted	03/04/2019
Date Current Protocol Accepted	08/26/2026
Study Name	New Enroll PAS LIPOSORBER LA-15 Adults
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: multicenter, prospective, single-arm, new enrollment clinical study to evaluate the probable benefit and safety of the LIPOSORBER® LA-15 System Objectives: The primary objectives of this study are to evaluate the safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 1 month after the final apheresis treatment. The secondary objectives are to evaluate safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with primary FSGS at 3 months, 6 months, 12 months, and 24 months after the final apheresis treatment.
Study Population	Inclusion Criteria Adult and pediatric patients with nephrotic syndrome associated with primary focal segmental glomerulosclerosis (FSGS), when the standard treatment options, including corticosteroid and/or calcineurin inhibitors treatments, have been unsuccessful or not well tolerated, and the patient has a glomerular filtration rate (GFR) greater than or equal to 45 ml/min/1.73m2, or the patient is post-renal transplantation. Exclusion Criteria General Exclusion Criteria: 1. Older than 75 years of age in the Adult Study or older than 21 years in the Pediatric Study 2. Parent or patient is unwilling or unable to sign and date the informed consent 3. Pregnant, lactating, or planning to become pregnant prior to completing the study 4. Unable or unwilling to comply with the follow-up schedule 5. Simultaneously participating in another investigational drug or device study 6. Body weight < 15 kg (33.1 lbs.) Medical Exclusion Criteria: 1. Currently being administered ACE inhibitors that cannot be withheld. 2. Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., ARBs) that cannot be withheld on the day of apheresis until after the procedure 3. Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis 4. Hypersensitivity to dextran sulfate, heparin, or ethylene oxide 5. Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications after surgery 6. Extracorporeal circulation therapy with LIPOSORBER® LA-15 System cannot be tolerated due to severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute apoplexy, severe uncontrollable hypertension, or severe uncontrollable hypotension 7. Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease intolerant to apheresis treatment 8. Ongoing diagnosis of Functional thyroid disease other than hypothyroidism due to nephrotic syndrome or Hashimoto's thyroiditis, or liver abnormalities 9. Unresolved systemic or local infection (e.g., Catheter infections or urinary tract infections) that could affect the clinical study outcomes 10. Patients without a history of biopsy-proven FSGS diagnosis 11. Currently receiving or have received treatment with LIPOSORBER® LA-15 System 12. Patients who require any plasmapheresis other than LIPOSORBER® LA-15 System and are unable to discontinue prior to pre-screening, or who are planning to have any plasmapheresis other than LIPOSORBER® LA-15 System 13. Currently undergoing hemodialysis 14. Ongoing diagnosis of End Stage Renal Disease (ESRD)
Sample Size	35 pediatric patients and 35 adult patients (total of 70 patients)
Key Study Endpoints	The primary probable benefit endpoint is the percent of patients who show complete or partial remission at 1 month after the final apheresis treatment. - The primary safety endpoint is the rate of device-related and procedure-related serious adverse events (SAEs) occurring during the treatment period and up to 1-month follow-up visit. - The secondary objectives are: o to evaluate safety and probable benefit of the LIPOSORBER® LA-15 System in relieving nephrotic syndrome associated with refractory primary FSGS at 3 months, 6 months, 12 months, and 24 months after the final apheresis treatment. o The secondary safety and probable benefit endpoints include nephrotic condition (complete remission, partial remission, and nephrotic state) including the percentage of patients who obtain complete and partial remission at 3, 6, 12, and 24 months; o incidence of adverse events encountered during the period in which apheresis treatments are given; o incidence of all adverse events and SAEs occurring within 3, 6, 12, and 24 months after the final apheresis treatment; and o laboratory values, including eGFR at baseline, after the last treatment, and at 1, 3, 6, 12, and 24 months after the final apheresis treatment, including percent change from baseline and percentage of patients showing an increase or decrease in each value. The data will be analyzed and presented separately for the pediatric and adult populations.
Follow-up Visits and Length of Follow-up	24 months after the final apheresis treatment.
Interim or Final Data Summary
Interim Results	Safety: Among adult patients, there were zero AEs and zero SAE during this reporting period. Among pediatric patients, there were 6 new SAEs that occurred in 1 patient: worsening edema, worsening ascites, respiratory distress, sepsis, AKI, and a second occurrence of worsening edema. All events were deemed not related to the Liposorber treatment. Effectiveness: The proportion of pediatric patients in complete or partial remission ranged from 53% (8/15) at 1 month follow-up to 83% (5/6) at 24 months follow-up. The proportion of adult patients in complete or partial remission ranged from 27% (3/11) at 1 month follow-up to 33% (1/3) at 24 months. The small number of pediatric and adult patients, particularly at the later follow-up visits, make it difficult to get a stable estimate of device effectiveness at this time.
Actual Number of Patients Enrolled	29 pediatric and 19 adult enrollments
Actual Number of Sites Enrolled	17 sites
Patient Follow-up Rate	Pediatric: 83% (15/18) at 1 month, 67% (12/18) at 3 months, 56% (10/18) at 6 months, 56% (10/18) at 12 months, and 33% (6/18) at 24 months. Adults: 92% (11/12) at 1 month, 67% (8/12) at 3 months, 58% (7/12) at 6 months, 33% (4/12) at 12 months, and 25% (3/12) at 24 months.
General
Study Status	Delayed
Application Number / Requirement Number	H200001 / PAS001
Date Original Protocol Accepted	02/17/2021
Date Current Protocol Accepted	12/19/2022
Study Name	Patient Specific Talus Spacer PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study objective is to evaluate the continued safety and probable benefit of the Talus Spacer in commercial use. The Patient Specific Talus Spacer PAS is a prospective, single-arm, multicenter US observational study to provide ongoing safety and probable benefit assessment of the Patient Specific Talus Spacer in treatment of avascular necrosis of the ankle.
Study Population	50 adult subjects who have been diagnosed with avascular necrosis (AVN) in the ankle joint
Sample Size	A minimum number of 50 patients will be enrolled in this study. Of the 50 subjects, a minimum of 20 subjects will receive a Cobalt Chromium Patient Specific Talus Spacer and a minimum of 20 subjects will receive a Titanium (Ti6Al4V) with Titanium Nitride (TiN) coating Patient Specific Talus Spacer. The total sample size is based on both the safety and probable benefit hypotheses, accounts for 10% lost-to-follow-up, and ensures 90% statistical power using an unadjusted chi-square test with a 1-sided type 1 error rate of a = 0.05. The failure rate with device removal or serious device-related adverse event by Year 5 of the patient specific talus spacer is assumed to be lower than the failure rate with a non-union of the comparator, tibiotalocalcaneal fusion with allograft. For patients without failure, a >=20-point improvement on a 100-point scale for the Visual Analog Scale (VAS) pain scale at 5 years compared to baseline is assumed. The sample size for each material group is determined to ensure statistical power for the subgroup analysis.
Key Study Endpoints	Primary Probable Benefit Endpoint: The primary probable benefit endpoint is a clinically significant improvement in pain, as demonstrated by a = 20-point improvement on a 100-point scale for the Visual Analog Scale (VAS) pain scale at 5 years compared to baseline. Patients who undergo an SSSI will be defined as probable benefit endpoint failures. Therefore, a patient will achieve the primary probable benefit endpoint only if they do not undergo an SSSI and they achieve a = 20-point improvement in VAS pain. Primary Safety Endpoint: Based on the need for a subsequent secondary surgical intervention (SSSI) or Device Related Serious Adverse Events (“SAEs”) at 5 years post-procedure. The following secondary safety endpoints will also be assessed: • Adverse events (“AEs”) • Device - or procedure related AEs • Serious AEs (“SAEs”) Additional Analyses: Improvement at 5 years post-procedure compared to Pre-op on: • Ankle ROM; • FAOS for: a. Pain b. Symptom c. Sport/Rec d. Activities of Daily Living (“ADL”); and e. Quality of Life (“QoL”) Other Exploratory Analyses: • X-ray Assessment and Measurements: a. Tibiotalar Alignment b. Talar Tilt Angle c. Boehler’s Angle d. Talar declination angle e. Meary’s angle
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results There have been seven (7) serious adverse events (SAEs) which occurred in five (5) patients. Five (5) of the SAEs are determined to be probably related to the device. There have been fourteen (14) subsequent secondary surgical interventions (SSSI), including two (2) device removals and seven (7) reoperations. Effectiveness Results VAS Pain: mean = 64.1 (N=21; SD=18.3) at pre-op; mean=26.2 (N=14; SD=29.83) at 1 year; mean=20.0 (N=5; SD=29.99) at 2 years; mean=18.0 (N=1) at 3 years. The VAS satisfaction with surgical results at 2 years were as follows: 40.0% (2/5) Good, and 60.0% (3/5) very satisfied (excellent). FAOS Symptom Subscale Scores: mean = 31.4 (N=20; SD=13.27) at pre-op; mean = 62.5 (N=14; SD=22.18) at 1 year; mean=52.9 (N=5; SD=30.45) at 2 years; mean=14.3 (N=1) at 3 years. FAOS Pain Subscale Scores: mean = 31.4 (N=20; SD=15.43) at pre-op; mean = 71.6 (N=14; SD=21.71) at 1 year; mean=66.1 (N=5; SD=26.45) at 2 years; mean=50.0 (N=1) at 3 years. FAOS ADL Subscale Scores: mean = 41.8 (N=20; SD=20.41) at pre-op; mean = 81.3 (N=14; SD=21.23) at 1 year; mean=77.9 (N=5; SD=22.40) at 2 years; mean=72.1 (N=1) at 3 years. FAOS Sport/Rec Subscale Scores: mean = 11.5 (N=20; SD=15.31) at pre-op; mean = 54.6 (N=14; SD=32.01) at 1 year; mean=52.0 (N=5; SD=44.10) at 2 years; mean=0.0 (N=1) at 3 years. FAOS QoL Subscale Scores: mean = 8.8 (N=20; SD=13.95) at pre-op; mean = 53.1 (N=14; SD=26.49) at 1 year; mean=45.0 (N=5; SD=39.38) at 2 years; mean=25.0 (N=1) at 3 years. Ankle ROM Scores: mean = 38.8 (N=20; SD=13.14) at pre-op; mean = 50.0 (N=14; SD=16.33) at 1 year; mean=42.8 (N=5; SD=15.55) at 2 years; mean=30.0 (N=1) at 3 years.
Actual Number of Patients Enrolled	22
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	Follow-up rate with complete data for the primary endpoint: 78.9% (15 actual patients / 19 expected patients) at 12 months post operative; 43.8% (7 actual patients / 16 expected patients) at 2 years post operative; 36.4% (4 actual patients / 11 expected patients) at 3 years post operative.
General
Study Status	Terminated
Application Number / Requirement Number	P200021 / PAS001
Date Original Protocol Accepted	08/20/2021
Date Current Protocol Accepted	05/27/2022
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Neuro Cochlear Implant System Post Approval Study (PAS) is to provide longer-term data on the safety and effectiveness of the Neuro Cochlear Implant System under general conditions of use in the postmarket environment up to a minimum of 3 years post-implantation in adult population (aged 18 yrs and older). It is a prospective multi-center, one arm, non-randomized, open label, repeated measures clinical study.
Study Population	60 adult subjects meeting the inclusion criteria
Sample Size	60
Key Study Endpoints	Primary effectiveness endpoint: The primary effectiveness measures will be the within-subject differences between AzBio scores obtained in Quiet at 12- and 36-months post-surgery with their cochlear implant alone and preoperative, best-aided scores. Secondary Effectiveness endpoints: Within-subject difference between CNC scores obtained in Quiet at 12- and 36-months post-surgery with their cochlear implant alone and pre-operative, best-aided scores. AzBio Sentence scores at 1 month in Quiet Az Bio sentences (Quiet and Noise) and CNC word scores at 3 months, 6 months and 24 months AzBio sentences +10dB SNR and 5dB SNR at 3 months and 12 months (bimodal) Patient reported outcome (PRO) measures including quality of life, listening effort and tinnitus at 6-,12-,24- and 36 months postactivation Scores on a cognitive assessment at 12-24 and 36 months postactivation T and C levels collected at all intervals Electrode impedances collected at all intervals eCAP responses collected in the operating room Surgeon perception of handling of the Neuro Zti and electrode array as well as information related to surgical technique Primary safety endpoint: The primary safety endpoint is the description of the type and frequency of all adverse events and serious adverse events occurring during the study period. All device failures (internal and external parts) will be documented and reported according to the AAMI C186 reporting standard
Follow-up Visits and Length of Follow-up	36 months post-implantation for each subject
General
Study Status	Protocol Pending
Application Number / Requirement Number	H200002 / PAS001
Study Name	Distal Cholangiocarcinoma Study
General Study Protocol Parameters
General
Study Status	Study Pending
Application Number / Requirement Number	P250018 / PAS001
Date Original Protocol Accepted	08/20/2026
Date Current Protocol Accepted	08/20/2026
Study Name	REVEAL New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study is to evaluate the long-term safety and effectiveness of the RefluxStop device in the treatment of Gastroesophageal Reflux Disease (GERD). The study is a single-arm, prospective, multi-center, new-enrollment clinical study.
Study Population	Patients greater than or equal to 18 years old with hiatal hernia size < 3 cm who are diagnosed with acid or non-acid Gastroesophageal Reflux Disease (GERD) who meet the following criteria: - Documented GERD present for > 6 months - Patient has endoscopy verified esophagitis, and/or a 24-hour pH monitoring proven GERD defined as pathologic number of impedance pH reflux episodes of acid or weakly acid and/or pathologic pH <4 for >4.5% of the total time, off PPI therapy for at least 7 days prior to testing.
Sample Size	200 patients will be enrolled at 4-10 sites, with at least 50 % of sites located in the United States and at least half of all RefluxStop procedures performed at U.S. sites. With an expected 12% dropout rate over 5 years, 176 patients will be available for analysis of 5-year endpoints. A 6% dropout rate is expected at 1 year. The study is expected to detect any side effects/ adverse events with high probability even if they are uncommon. For example, an event that occurs in 1 per 100 patients will be detected with a probability of 83% and an event that occurs with a frequency of 1 per 50 patients will be detected with a probability of 97%. Thus, with this sample size, all events that are common and events that are uncommon will be detected with a high probability.
Key Study Endpoints	Primary Safety Endpoint: Incidence of procedure and device related serious adverse device effects (SADEs), serious adverse events (SAEs) and device deficiencies (DDs) at 1 year post RefluxStop implant. Primary Effectiveness Endpoint: Pathologic acid in the lower esophagus measured by 24-hour pH monitoring (total percentage of time pH <4) at 1 year post RefluxStop implant. Secondary Safety Endpoints: - Incidence of procedure- and device-related SADEs, SAEs and DDs at all time points excluding at year 1, comprising month 6 as well as years 2 to 5 - Incidence of procedure- or device-related Adverse Events (ADEs or AEs) at 6 months and annually thereafter up to 5 years Secondary Effectiveness Endpoints: - Subjects with <50% improvement of GERD-HRQL at year 1 compared to baseline - Reduction in GERD-HRQL group score, measured at 6 months and years 1 to 5 compared to baseline - Regular daily PPI usage Due to GERD/acid reflux, with PPI question completed at 6 months and years 1 to 5 (Note: Requirement of at least one episode of terminating the PPI medication for at least 6 weeks at a time point after the 6-month visit. If subject uses PPI at or after the 2-year visit, one more period of PPI drug termination should occur at a time point as of the 2-year follow-up.) - Total percentage of time pH <4 measured by 24-hour pH monitoring at year 1 (mean and standard deviation on group level) - Pathologic 24-hour pH monitoring and on-label device position at year 2-5 - Incidence of inability to belch based on questionnaire at 6 months and annually at years 1 to 5 Other Endpoints: - Contrast swallow x-ray as a surgical control at hospital stay (gastrographin only at hospital stay) and 5 years visit (barium), and in “Subjects with possible acid reflux” (regular daily PPI usage or GERD-HRQL score <50% improved from baseline) which occurs after the year 1 visit (performed once only using barium) Note: The TSC analyzes the surgical procedure and the categorization of the device position to determine Failure risk or Unacceptable as determined by the contrast swallow x-ray of all “subjects with possible acid reflux.” Failure subjects having acid reflux caused by a placement that is too low or too far from esophagus are controlled. - Regurgitation frequency question (episodes per day or week) at 6 months and annually at years 1 to 5 - Functional Lumen Imaging Probe (FLIP) assessment may be performed at the discretion of the Investigator in subjects with persistent dysphagia after 6 months follow-up - In patients with severe gastric emptying problems based on anamnesis, an emptying test may be performed, either gastric emptying scintigraphy or stable isotope breath test may be used - Grade of esophagitis (Grade A, Grade B, Grade C, Grade D) from esophago-gastroduodenoscopy (EGD) at baseline and year 1 - Number of subjects reporting AE = ‘Gastritis’ - New GERD-HRQL and 24-h pH monitoring should be carried out 6 months after any re-surgery has been performed - Patient dissatisfaction due to GERD - Procedure-related operational complications - Length of patients’ hospital stay and length of surgery - Manometry data - Failure indication: Subjects with both objective and subjective indication of potential therapy failure. Indications of therapy failure are pathologic 24-hour pH monitoring, consuming regular daily PPI due to GERD and being dissatisfied due to GERD.
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250041 / PAS001
Study Name	SELUTION4ISR Continued Follow-up Study
General Study Protocol Parameters
Study Population	Adult: At least 22 yrs
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250041 / PAS002
Study Name	SELUTION SLR PTCA DEB Post-Approval Surv Analysis
General Study Protocol Parameters
Study Population	Adult: At least 22 yrs
General
Study Status	Study Pending
Application Number / Requirement Number	P250050 / PAS001
Date Original Protocol Accepted	09/25/2026
Date Current Protocol Accepted	09/25/2026
Study Name	Continued Follow-up of the IDE Study Subjects
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P220013 S028/ PAS001
Study Name	DUAL-AF PAS
General Study Protocol Parameters
General
Study Status
Application Number / Requirement Number	P260007 / PAS001
Study Name	Continued Follow-up of the Premarket Cohort
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P260007 / PAS002
Study Name	New Enrollment Study
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P230005 S002/ PAS001
Study Name	New Enrollment PAS on 105cc Models
General Study Protocol Parameters
Study Population	Adult: At least 22 yrs
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250051 / PAS001
Study Name	REJ-CT-0007 PAS
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250051 / PAS002
Study Name	REJ-CT-0020 PAS
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P210006 S018/ PAS001
Study Name	CHEETAH Registry
General Study Protocol Parameters
General
Study Status	Delayed
Application Number / Requirement Number	P160015 S001/ PAS002
Date Original Protocol Accepted	07/16/2026
Date Current Protocol Accepted	10/16/2026
Study Name	Simulation Study of the AED 3 with CPR Uni-padz
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Delayed
Application Number / Requirement Number	H210002 / PAS001
Date Original Protocol Accepted	07/13/2023
Date Current Protocol Accepted
Study Name	REFLECT Scoliosis Correction System Registry PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this multi-center, prospective, single-arm registry study is to evaluate radiographic and clinical outcomes of patients with idiopathic scoliosis treated with the REFLECT™ Scoliosis Correction System.
Study Population	Inclusion Criteria Patients may be enrolled in the study if all of the following inclusion criteria are met: Diagnosis of progressive idiopathic scoliosis Preoperative major Cobb angle 30°-65° Preoperative flexibility to less than or equal to 30° on side bending radiograph (left or right) Skeletally immature at the time of surgery with Risser sign <5 or Sanders score <8 Osseous structure dimensionally adequate to accommodate screw fixation, as determined by radiographic imaging Failed or intolerant to bracing Signed informed consent and/or assent forms specific to this study Exclusion Criteria Patients cannot be enrolled in the study if any of the following exclusion criteria are met: Prior spinal surgery at the level(s) to be treated Documented poor bone quality, defined as a T-score of -1.5 or less Presence of any systemic infection, local infection, or skin compromise at the surgical site Any medical or surgical condition which would preclude the potential benefit of spinal surgery, such as coagulation disorders, allergies to the implant materials, and patient's unwillingness or inability to cooperate with post-operative care instructions Unwillingness, inability, or living situation (e.g. custody arrangements, homelessness, detention) that would preclude ability to return to the study site for follow-up visits as described in protocol and Informed Consent Active participation in a drug or device study that is more than minimal risk such that participation would confound the measurements of the present study
Sample Size	Number of subjects: 100 patients Assumptions for sample size estimation: N/A Number of sites: 5 Sites location: U.S. sites
Key Study Endpoints	Primary Endpoints The primary endpoints are deformity correction and safety, evaluated at 60 months postoperative, using the following: • Primary probable benefit: maintenance of major Cobb angle less than or equal to 40° • Primary safety: serious adverse events (SAEs) and device- or procedure-related adverse events (AEs) Secondary Outcomes: Secondary outcome measures include the following evaluations at 60 months postoperative, compared to preoperative baseline where applicable: • Curve progression no greater than 10° of any secondary curve above or below the implant, or development of a new curve equal to or greater than 40° Device integrity failures including cord breakage and screw migration Composite endpoint analysis (maintenance of major Cobb angle less than or equal to 40° AND freedom from Serious Adverse Events (SAEs) during the procedure and procedure/device related SAEs following surgery) Analysis of the failure attributable to conversion to another spinal implant OR major Cobb angle that exceeded 40° at defined follow-up visit OR any progression of the major curve at defined follow-up compared to baseline OR death OR permanent disability Mean score of Scoliosis Research Society 22r Patient Questionnaire
Follow-up Visits and Length of Follow-up	Patients will be followed for 5 years with evaluations at the following timepoints: preoperative, intraoperative, immediate postoperative (first erect), 6 weeks, 6 months, 12 months, 24 months, and 60 months. The clinical evaluation schedule with follow-up windows (+/-2wk at 6wk; +/-1mo at 6mo; +/-2mo at 12; +/-4mo at 24 and 60mo) is provided in Appendix I.
General
Study Status	Study Pending
Application Number / Requirement Number	H230002 / PAS001
Date Original Protocol Accepted	03/30/2026
Date Current Protocol Accepted	03/30/2026
Study Name	Cont F/u of the RIVER Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort.
Study Population	All living patients enrolled under “The RIVER Trial.” The RIVER Trial enrolled patients with idiopathic intracranial hypertension (IIH) who failed medical therapy, had a significant stenosis of the venous sinus (> 50% stenosis and pressure gradient greater than or equal to 8 mmHg), and had an upstream venous sinus diameter between 5 mm and 8.5 mm. Patients also had severe headache or vision loss at the time of study enrollment.
Sample Size	39 patients were implanted with the River Stent System in “The RIVER Trial.”
Key Study Endpoints	Long-term follow-up data collected according to the IDE protocol will be used to provide safety and probable benefit information on the durability and safety of treatment using the River Stent System. As stipulated in the IDE protocol, follow-up assessments will include adverse event assessment, contrast enhanced magnetic resonance venography of the stented vessel for absence of significant stenosis or new stenosis, and clinically relevant improvement in the main clinical outcome per specific inclusion criteria for headache or ophthalmic enrollment criteria in “The RIVER Trial.”
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P050052 S162/ PAS001
Date Original Protocol Accepted	03/31/2026
Date Current Protocol Accepted
Study Name	Safety Study to Assess Radiographic Imaging
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To determine if treatment with Radiesse dilute in the décolleté interferes with radiographic imaging of the breast tissue and to assess the safety of Radiesse dilute in the décolleté. Participants will receive three treatments spaced six weeks apart (Week 1, Week 7, and Week 13), with each consisting of injection of 1.5 mL Radiesse diluted 1:2 with sterile saline into the décolleté Imaging will be performed at baseline and 1 month after the third administration.
Study Population	Female participants between the ages of 40 and 65
Sample Size	30
Key Study Endpoints	Any interference of Radiesse dilute in either breast observed in breast ultrasound or mammogram images at Week 17, as assessed by an adjudication committee composed of board-certified radiologists. Occurrence of adverse events (AEs) related to treatment with Radiesse dilute, as reported by the treating investigator throughout the study.
Follow-up Visits and Length of Follow-up	Total participation 60 weeks
General
Study Status	Study Pending
Application Number / Requirement Number	P170027 / PAS002
Date Original Protocol Accepted	04/10/2026
Date Current Protocol Accepted	04/10/2026
Study Name	TherOx PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is an observational, prospective analysis of subjects undergoing primary PCI for AMI and receiving SSO2 Therapy delivered by the TherOx DownStream System or standard of care (PCI only). This study is not blinded. It is open label, both to the treating physician and the subject.
Study Population	The study will prospectively enroll up to 1,125 subjects across three cohorts from up to 40 sites (maximum 10 sites outside the US): 500 control subjects, 500 subjects who received SSO2 Therapy per product label, and up to 125 subjects who received SSO2 Therapy off-label based on clinician judgment for the subject's best interest.
Sample Size	1,125 subjects
Key Study Endpoints	There are two co-primary endpoints. The first co-primary composite endpoint is CV death or HF event at the median timepoint of 1.5 years, and the second co-primary endpoint is infarct size.
Follow-up Visits and Length of Follow-up	24 months
General
Study Status	Study Pending
Application Number / Requirement Number	P250033 / PAS001
Date Original Protocol Accepted	04/02/2026
Date Current Protocol Accepted	04/02/2026
Study Name	Continued Follow-up of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The TRIOMPHE study is a prospective, non-randomized, multi-center clinical investigation designed to evaluate the safety and effectiveness of the NEXUS™ Aortic Arch Stent Graft System for the endovascular treatment of thoracic aortic lesions involving the aortic arch, including chronic dissections, aneurysms, penetrating aortic ulcers (PAU), and intramural hematoma (IMH). It involves continued follow up of IDE subjects.
Study Population	The study enrolled subjects who have thoracic aortic lesions involving the aortic arch.
Sample Size	94 subjects were enrolled in the IDE
Key Study Endpoints	There were two co-primary endpoints, both assessed through 30 days: (1) Device Technical Failure, which captures failure to deliver/deploy/retrieve device components, device occlusion, failed exclusion of the primary entry tear, and unanticipated surgical or interventional procedures; and (2) Clinical Failure, defined as early mortality or occurrence of at least one major adverse event (MAE) — including disabling stroke, permanent paralysis/paraplegia, new-onset renal failure requiring permanent dialysis, aortic rupture, or development of new dissections requiring intervention — through 30 days of the Phase 1 and Index Procedures. Secondary endpoints include a broad range of safety and effectiveness measures assessed at 30 days and at 6, 12, 24, 36, 48, and 60 months, such as all-cause mortality, lesion-related mortality, neurological events, endoleaks, migration, aortic enlargement, false lumen patency, and device integrity.
Follow-up Visits and Length of Follow-up	All implanted subjects will be followed for 60 months (5 years) post-index procedure.
General
Study Status	Delayed
Application Number / Requirement Number	H220001 / PAS001
Date Original Protocol Accepted	07/17/2024
Date Current Protocol Accepted	07/28/2026
Study Name	The TheraBionic P1 Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Non-Randomized, Single-Arm Uncontrolled Study to assess Overall Survival using the TheraBionic P1 system for patients with advanced hepatocellular carcinoma (HCC) who have failed two lines of therapy.
Study Population	Patients with advanced hepatocellular carcinoma (HCC, defined as a liver tumor not eligible for local therapies given the extent of disease or a liver tumor that recurred after local therapy) who have failed at least two lines of therapy or who that are no longer eligible for any line of standard therapy.
Sample Size	Number of subjects: 178 (198 considering 10% attrition rate) Number of sites: 9
Key Study Endpoints	Primary Endpoint: Overall survival will be assessed from the day of TheraBionic treatment initiation until death, or up to 24 months post the start of treatment. Secondary Endpoints: - Patient-reported outcome will be recorded once a week for the first three weeks (3 measurements), then every other week for the next six weeks (3 measurements), then every month afterwards, after the subject starts treatment. The PROs will be administered electronically and/or remotely. - The frequency and nature of patient-reported symptomatic serious adverse device events will be assessed using 10 items from the PROCTCAE item library assessed at every return visit recorded once a week for the first three weeks (3 measurements), then every other week for the next six weeks (3 measurements), then every month afterwards, after the subject starts treatment and at the end of treatment. - Patient-rated pain intensity will be measured using scores from the single item PROMIS Numeric Pain Rating Scale (Pain Intensity 1a) patient-reported outcomes (PRO) - Pain interference will be measured using scores from the Pain Interference Short Form 4a PRO - ECOG Performance Status Scale to measure functional status and ability to carry out activities of daily living. - Overall response rate (ORR) based on physician evaluation - Disease control rate (DCR) based on physician evaluation - Duration of overall response that is measured from CR/PR until the first date of documented recurrent or progressive disease - Duration of overall complete response that is measured from CR until the first date of documented recurrent or progressive disease - Duration of stable disease - Time to radiological progression (TTP) - Progression-free survival (PFS). - Physical function will be assessed using the PROMIS Physical Function Short Form PRO 4a.
Follow-up Visits and Length of Follow-up	Length of follow-up for two years. Baseline and return visits every 7 to 8 weeks: - Oral Exam and ECOG performance status - Review for Calcium Channel Blockers - Serious Adverse Device Events (NCI-CTCAE v5.0) - Serious Adverse Events (NCI-CTCAE v5.0) - PT/INR, CBC, CMP (according to Standard of Care) - Alpha-fetoprotein (only if Screening/Baseline is greater than 30 ng/mL) - Radiologic disease assessment (according to Standard of Care) - ECOG PS (Once every week for 3 weeks(3 Measurements), then every other week for the next 6 weeks (3 Measurements), then every month afterwards) - Device Use Reconciliation - PROMIS Pain Intensity, Pain Interference, Physical Function (Once every week for 3 weeks(3 Measurements), then every other week for the next 6 weeks (3 Measurements), then every month afterwards) - PRO-CTCAE items
General
Study Status	Hold
Application Number / Requirement Number	H240001 / PAS001
Date Original Protocol Accepted	03/20/2025
Date Current Protocol Accepted
Study Name	4WEB Medical Talar Replacement Device PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design: Multi-center, Single-arm, Prospective, Post-Approval Study Study Objective: The primary objective of this clinical investigation is to assess the safety and probable benefit of 4WEB Medical Talar Replacement Device in a commercial use setting.
Study Population	Adults (=22 years of age) who have received the 4WEB Medical Talar Replacement Device under an approved HDE for one of the indications listed on the Instructions for Use (IFU) and who do not have a contraindication.
Sample Size	Number of subjects: 30 Number of sites: Minimum of 5 sites, with no more than 20 subjects enrolled per center. Sites location: USA
Key Study Endpoints	Primary Endpoint Safety: Absence of a subsequent secondary surgical intervention (SSSI) and a device-related serious adverse event (SAE) on the affected joint at five (5) years. • Probable Benefit: Device survivorship at 5 years Secondary Endpoints Safety: • The incidence of device or procedure related Adverse Events (AEs) • Serious Adverse Events (SAEs) Probable Benefit: • Improvement or maintenance of Ankle Range of Motion (ROM) measured at 5 years postop compared to preop (when available) • Improvement in American Orthopaedic Foot and Ankle Outcome Scores (AOFAOS) measured at 5 years postop compared to preop (when available) – Composite score and individual scores for the following subscales o Pain o Function o Alignment Exploratory Endpoints X-ray assessments: When available, x-rays will be used to evaluate the presence of adverse events, proper location of implant without migration, absence of subsidence into calcaneus, and health of surrounding soft tissue: • Tibiotalar Alignment • Talar Tilt Angle • Boehler’s Angle • Talar declination angle1 • Meary’s angle
Follow-up Visits and Length of Follow-up	Frequency of Follow-up Visits: Three (3) months, six (6) months, twelve months and annually thereafter Length of Follow-Up: 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P240022 / PAS001
Date Original Protocol Accepted	04/30/2025
Date Current Protocol Accepted	12/18/2025
Study Name	EVOLYSSE PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design and Objective(s) The post-approval study is a multicenter, prospective, randomized, split face, controlled, double-blind study in adults with Fitzpatrick skin type V or VI desiring correction of moderate or severe nasolabial folds (NLFs) . This study objective is to collect additional safety and effectiveness data on Evolysse Form in darker skin types. To be eligible for the study, subjects were required to have a score of 3 (moderate) or 4 (severe) in both NLFs on the Wrinkle Severity Rating Scale (WSRS).
Study Population	Adult Fitzpatrick type V and VI male and female subjects
Sample Size	Sample Size Number of subjects: Up to 15 Assumptions for sample size estimation: N/A Number of sites: 2 US sites Sites location: US
Key Study Endpoints	Study Endpoints Safety Endpoints - Adverse Events (AE) - AE of Special Interest (AESI; e.g., visual disturbances) - Injection Site Responses (ISR) - Visual assessments (Snellen visual acuity, confrontational visual fields, ocular motility) - Post-treatment pain assessment Effectiveness Endpoints Primary: Independent panel review (IPR) assessments of NLF severity , independently assessed for each side of the face using the validated 5-grade photo numeric WSRS. Secondary: - Blinded evaluator (BE) live assessments on the WSRS - Subject assessment on Global Aesthetic Improvement Scale (GAIS) - Subject assessment on FACE-Q Appraisal of NLFs - Subject assessment on FACE-Q Satisfaction with Outcome
Follow-up Visits and Length of Follow-up	Frequency of Follow-up Visits and Length of Follow-up Subjects receive initial treatment and optional touch-up treatment at 2 weeks if needed to achieve optimal aesthetic outcome. Follow-up visits are at 3 days (safety call) and 6, 12, and 24 weeks after the initial treatment.
General
Study Status	Protocol Pending
Application Number / Requirement Number	P240027 / PAS001
Date Original Protocol Accepted	04/16/2026
Date Current Protocol Accepted
Study Name	SpineSeal Spine Sealant Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	H090002 / PAS003
Date Original Protocol Accepted	11/18/2011
Date Current Protocol Accepted	11/13/2013
Study Name	Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	All-comers registry study
Study Population	Patients with cervical cancer treated with BSD-2000. Patients who have had or not had prior irradiation of the treatment site also will be included. Patients who have had chemotherapy administered also will be included.
Sample Size	No specified sample size or number of clinical sites. Data will be collected on all patients who are treated with the device and agree to participate in the study.
Key Study Endpoints	Primary endpoint: -Rate of complete response (CR), defined as the disappearance of all viable tumor in the irradiated volume. - Local tumor control and duration of local tumor control Secondary endpoints: - Overall survival (defined as death from any cause) at 3 years - Disease free survival - Incidence of adverse events associated with hyperthermia and radiotherapy treatment.
Follow-up Visits and Length of Follow-up	Up to 3 years. Follow-up examinations will be performed at 3, 12, 18, 24 and 36 months intervals.
Interim or Final Data Summary
Actual Number of Patients Enrolled	24
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	3 months: 9/24 (38%) 12 months: 1/24 (4.2%) 18 months: 0/24 (0%) 24 months: 0/24 (0%) 36 months: 0/24 (0%)
Final Safety Findings	There 2 adverse events reported in 2/24 (8.3%) patients who received radiation + hyperthermia treatment. One AE consisted of mild blisters that resolved without medical treatment, and 1 AE was determined unrelated with the hyperthermic treatment (appendicitis).
Final Effect Findings	There were two patient reports of tumor volume reduction. In one patient, tumor dimensions were reduced from W 3.5cm to 1.8cm and L 2.6 cm to 1.5cm. In another patient, tumor dimensions went from 4.5cm to 1.8cm.
Study Strengths & Weaknesses	The registry study is all-comers. Although this allows for potentially higher enrollment, the population may not reflect the same population as that of the pivotal study used to support approval of the HDE. Therefore, the safety and effectiveness data may not be directly comparable between the two studies. The lack of enrollment and follow up limits interpretation of the data. Data provided from literature provide more patients for analysis, and therefore additional safety and effectiveness information. However, these data have important limitations. Several studies were retrospective in nature. The evidence provided from retrospective studies does not have as high quality as compared to prospective randomized controlled trials and may have confounding variables or other bias. Examples of these may include (but are not limited to): single site bias, insufficient/ incomplete patient demographic data, non-stratified patient populations, and differences in the length of follow-up. Differences in covariates can introduce biases in the assessment of the device performance, safety outcomes, and study conclusions. The standard of care and complexity of medical therapies and procedures across countries and over time may impact the conclusions from studies from different regions and time periods. Data from the literature were collected by different sources and periods of time. There is the possibility that other descriptive search terms for the device may have resulted in different publications and/or potential missed articles.
Recommendations for Labeling Changes	No
General
Study Status	Hold
Application Number / Requirement Number	H100002 / PAS001
Date Original Protocol Accepted	09/12/2012
Date Current Protocol Accepted	09/12/2012
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P100040 / PAS001
Date Original Protocol Accepted	04/01/2011
Date Current Protocol Accepted	09/14/2011
Study Name	Captivia Delivery System
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm study to assess the freedom from ARM at five years.
Study Population	The study involves follow-up of the VALOR II cohort. Criteria for being in this study include: age between 18 and 85; a candidate for elective repair of an aneurysm of the descending thoracic aorta; either a fusiform aneurysm with a maximum diameter of at least 5 cm or at least two times the diameter of the non-aneurysmal thoracic aorta, and/or a saccular aneurysm; aneurysm meets the specified anatomic criteria
Sample Size	Based on the need for a statistical power of 80%, using a one-sided 95% confidence level, an estimated ARM free rate of 94%, and a performance goal of 83.6%, the sponsor calculates a required sample size of 117 at five years. Assuming a 15% annual attrition rate, that calculates out to an initial sample size of 160, which is the number of patients that will be followed from the IDE study. Those patients were enrolled from 24 sites.
Key Study Endpoints	Primary Endpoint The primary endpoint of the study is aneurysm-related mortality at five years, defined as: Death from rupture of the fusiform aneurysm or saccular aneurysm/penetrating ulcer or from any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer. If a death occurred within 30 days of any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer, then it is presumed to be aneurysm related. . Secondary Endpoints All-cause mortality Aneurysm rupture Conversions to open surgical repair Endoleaks Secondary endovascular procedures Stent graft migration Loss of stent graft patency, defined as loss of continued blood flow through the treated vessel Major adverse events
Follow-up Visits and Length of Follow-up	Five years
Interim or Final Data Summary
Actual Number of Patients Enrolled	160
Actual Number of Sites Enrolled	28
Patient Follow-up Rate	94%
Final Safety Findings	The majority of aneurysms at all time periods either decrease in size or show no change in size from baseline. From one month to 4 years, 6% or less of aneurysms increased in size. At 5 years the percent of aneurysms increased in size is 11%, much smaller than the percent that decreased in size (48%). These results are consistent with results regarding the consequences of increases in aneurysm size: Low abdominal aortic aneurysm (AAA)-related mortality, no surgical conversions to open surgery since the post- approval study (PAS) began, only one aneurysm rupture since the PAS began, and a rate of secondary interventions for any reason of about only 3% per year. They are also consistent with results regarding the causes of increases in aneurysm size: No stent graft migration or loss of stent graft patency, and only approximately a 5% rate of endoleaks per year following the start of the PAS (compared to 13% in the 12 months of the clinical trial).
Final Effect Findings	Five year aneurysm related mortality rate, by KM analysis is 94.8% (with a lower 95% confidence interval of 91.2%)
Study Strengths & Weaknesses	Strength: Prospective study Device met its performance goal by a large margin (lower bound of 95% confidence interval) Weakness: No concurrent control group No control for potential confounding variables
Recommendations for Labeling Changes	A change in labeling is recommended to update the results of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P100029 / PAS001
Date Original Protocol Accepted	04/20/2011
Date Current Protocol Accepted	04/20/2011
Study Name	Trifecta Valve PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a multi-center, prospective, non-randomized, post-approval study conducted in the United States
Study Population	Subjects previously implanted with a Trifecta prosthetic valve at the selected sites during the IDE clinical investigational study and meet all eligibility criteria for this clinical study will be invited to participate.
Sample Size	The study will enroll approximately 300 subjects enrolled from approximately 6 U.S. sites that enrolled subjects in the Trifecta¿ valve IDE study to result in a minimum of one-hundred-sixty (160) subjects followed for five (5) years from their Trifecta implant procedure.
Key Study Endpoints	Primary Endpoints: Late endocarditis and embolism (linearized) rates as compared to the FDA Draft Replacement Heart Valve Guidance Objective Performance Criteria (OPC). Secondary Endpoints: valve thrombosis, major bleed, all paravalvular leak, major paravalvular leak, reoperation, explants, non-structural dysfunction, structural deterioration, valve related death, embolism, endocarditis, valve thrombosis, major bleed, all paravalvular leak, major paravalvular leak, reoperation, explants, nonstructural dysfunction, structural deterioration and valve-related death, New York Heart Association (NYHA) functional classification status at each interval, and hemodynamic performance at each interval.
Follow-up Visits and Length of Follow-up	Five-years post implant Annual
Interim or Final Data Summary
Actual Number of Patients Enrolled	245
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	94.7%
Final Safety Findings	No Unanticipated Adverse Device Effects (UADE¿s) was reported during the continued follow-up study period. The linearized thromboembolism and endocarditis rates are statistically significantly lower than the FDA 1994 Draft Replacement Heart Valve Guidance Objective Performance Criteria (OPC).
Final Effect Findings	At 5-year visit, over 90% patients maintained at NYHA I level, and valve insufficiency was classified as either none, trivial, or mild for 98.2% of patients.
Study Strengths & Weaknesses	Strength: long-term follow-up (5 years) with over 94.7% of follow-up rate Weakness: The study population consisted of subjects from the premarket cohort. Premarket studies are typically characterized by providers who are exceptionally skilled; and are therefore likely to provide relatively good results
Recommendations for Labeling Changes	Because neither safety nor effectiveness data presented in the final report substantially alter the labeling already approved for the Trifecta Valve, the labeling updates for Trifecta Valve is not recommended
General
Study Status	Completed
Application Number / Requirement Number	P100020 / PAS001
Date Original Protocol Accepted	04/19/2011
Date Current Protocol Accepted	04/19/2011
Study Name	MWP-HPV-159
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	4,291
Actual Number of Sites Enrolled	61
Patient Follow-up Rate	Above 80%
Final Safety Findings	No severe adverse events were reported
Final Effect Findings	A negative HPV result predicted a lower 3-year risk of ¡ÝCIN3 than did a negative cytology result. The low 3-year (cumulative incidence ratio) CIR for a negative HPV result also confirmed the safety of a 3-year interval for HPV primary screening. The follow-up study confirmed the continued high risk of HPV16 or HPV18 infection, with the observation that 1 in 4 women who tested HPV 16+ at Baseline and 1 in 9 who tested HPV18+ at Baseline were diagnosed with ¡ÝCIN3 within 3 years. The follow-up data for the NILM population ¡Ý30 years demostrated safety over 3 years of a negative HPV test at Baseline in the context of adjunct testing. In addition, the data demonstrated a higher risk associated with HPV16+ or HPV18+ results (9.56%).
Study Strengths & Weaknesses	Strengths: Large sample size, high compliance at all follow up years, compliance with exit colposcopy was 88%. Weaknesses: Comparisons of cumulative Incidence rate (CIRs) of high-grade cervical disease between subjects with a positive and those with a negative Cobas HPV tests is only limited to up to 3 years.
Recommendations for Labeling Changes	Labeling incorporating the long term Post approval study were submitted and approved
General
Study Status	Terminated
Application Number / Requirement Number	P000018 / PAS001
Date Original Protocol Accepted	11/03/2000
Date Current Protocol Accepted	02/23/2011
Study Name	Beta-Cath Long Term
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was initially designed as a prospective study. However, due to the inability to prospectively recruit patients, the study design was modified. The current design is a single site retrospective study of the long term safety and effectiveness of the Beta Cath 3.5F system.
Study Population	Patients treated with the BethCath 3.5F System. These patients receive beta radiation to the site of successful percutaneous coronary intervention for the treatment of in-stent restenosis in native coronary arteries with discrete lesions in a reference vessel diameter ranging from 2.7 to 4.0 mm.
Sample Size	200 patients, 1 site
Key Study Endpoints	The primary safety endpoints are: (1) Incidence of device related procedural events and (2) major adverse events at each study point. The primary efficacy endpoints are: 1) device success including successful delivery of source train, return of source train and delivery of intended dose and 2) target vessel revascularization.
Follow-up Visits and Length of Follow-up	Patients will be followed clinically at 6 months, 1, 2, 3, 4, and 5 years post treatment. Due to retrospective enrollment, patients may be enrolled at any of the specified time points and followed for subsequent visits.
Interim or Final Data Summary
Actual Number of Patients Enrolled	One hundred and twenty-eight (128) of 200 required subjects were enrolled.
Actual Number of Sites Enrolled	One (1) site enrolled for this study.
Patient Follow-up Rate	At 5 years the follow-up rates were 91.0% (71/78) for 3.5F PAS 30/40mm group and 92.0% (46/50) for 3.5F PAS 60 mm group.
Final Safety Findings	The safety endpoints for both 3.5F PAS 30/40mm and 3.5F PAS 60mm groups are 1) Incidence of device-related procedural events (Aneurysm) 2) Major Adverse cardiac event (MACE) in-hospital and at 30 days, 6 months, and annually 5 years post -treatment The effectiveness endpoints for both 3.5F 30/40mm PAS and 3.5F 60mm PAS are 1) Device success, including successful delivery of the source train, return of the source train, and delivery of the intended dose, and 2) Target vessel revascularization (TVR) at 6 months and annually, through 5 years posttreatment. Per protocol the 3.5F PAS 30/40mm data were compared to the historical START and START 40/20 Post Approval Studies (which reported long term data for the 5F Beta-Cath 30mm and 40mm Systems), and the 3.5F PAS 60mm data were compared to the historical RENO Long data. Safety: 3.5F PAS 30/40mm Group The reported aneurysm rate at 5 years for the 3.5 F PAS 30/40mm group was 0.0% (0/15). The cumulative Major Adverse Cardiac Events (MACE) rate at 5 years by Kaplan Meier estimate for the 3.5F PAS 30/40mm group was 64.2%. The cumulative MACE rate for 3.5F PAS 30/40mm compared to START Placebo, START Sr- 90 or START 40 Sr-90 was not statistically significant at any of the timepoint.
Final Effect Findings	Effectiveness: 3.5F PAS 30/40mm Group The device success rates for the 3.5F PAS 30/40mm group was 98.7% (77/78). The cumulative target lesion revascularization (TVR) rates at 5 years by Kaplan Meier estimate for the 3.5F PAS 30/40mm group was 48.3%. The cumulative TVR rate was significantly higher in the 3.5F PAS 30/40mm group compared to START Sr-90 [40mm] Group at the following time points: At 3 years, the cumulative TVR rate was 39.7% (31/78) in 3.5F PAS 30/40mm group vs. 16.5% (26/158) in START Sr-90 [40mm] (p< 0.001). At 4 years, the cumulative TVR rate was 46.9% (36/78) in 3.5F PAS 30/40mm group vs. 16.9% (26/154) in START Sr-90 [40mm], (p<0.001). At 5 years, the cumulative TVR rate was 48.3% (37/78) in 3.5F PAS 30/40mm group vs. 19.0% (27/142) in START Sr-90[40mm] (p<0.001). The cumulative TVR rate in the 3.5F PAS 30/40mm group, 39.7 % (31/78), was significantly lower compared to the rate in the START Placebo group, 56.5% (87/154) (p=0.0159) at 3 years only. The cumulative TVR rate in START Sr-90 [30mm] compared to 3.5F PAS 30/40mm group was not statistically significant at any time point. Safety: 3.5F PAS 60mm Group The reported aneurysm rate at 5 years for the 3.5 F PAS 60mm group was 0.0% (0/9). The MACE rate at 5 years for the 3.5F PAS 60mm group was 15.2% (7/46). The MACE rate for RENO-Long data at 6 months, 17.9% (24/134) was significantly higher compared to 3.5F 60mm PAS (< 1year data) 4.0% (2/50), p=0.0160. Effectiveness: 3.5F PAS 60mm Group The device success rate for the 3.5F PAS 60mm group was 100% (50/50). The TVR rate for 3.5F PAS 60mm group at 5 years 6.5% (3/46). The TVR rate for RENO-Long data at 6 months, 14.9% (20/134) was significantly higher compared to 3.5F 60mm PAS data (< 1 year) 4.0% (2/50), (p=0.0435).
Study Strengths & Weaknesses	The study endpoints of MACE, TVR and device-related procedural events (aneurysm) for both 3.5F PAS 30/40mm and 3.5F PAS 60mm groups were collected through 5 years. At 5 years, data was available for assessment of MACE and TVR in over 90% of patients. The study was initially designed as a prospective study but was later modified per protocol to be a retrospective study enrolling patients from a single site. Enrollment in the study could not be completed, and a study based on a single center may have limited generalizability to the general patient population. The retrospective nature of the study designs can introduce recall biases on the assessment of exposure and identification of important endpoints. There were also missing data on follow-up diagnostic catherization in the assessment of safety endpoint, incidence of device-related procedural events (aneurysms).
Recommendations for Labeling Changes	Labeling update is not recommended because subject enrollment could not be completed and there is limited use of the device on label.
General
Study Status	Completed
Application Number / Requirement Number	P020004 / PAS001
Date Original Protocol Accepted	11/06/2002
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The 98-03 study was a multi-center (19 sites), nonrandomized, prospective, concurrent controlled trial, which compared standard open surgical repair (n=99) to endovascular treatment with the EXCLUDER (n=235). The 99-04 study was designed to compare the modified EXCLUDER device to surgical controls with respect to safety and to the original EXCLUDER device with respect to effectiveness. One hundred and ninety three (193) subjects were enrolled between April 2000 and April 2001. Eighty eight (88) additional subjects were enrolled in the continued access protocol
Study Population	Subjects implanted with the Gore EXCLUDER device.The EXCLUDER Bifurcated Endoprosthesis is intended to exclude the aneurysm from the blood circulation in patients diagnosed with infrarenal abdominal aortic aneurysms disease and who have appropriate anatomy inluding: 1) adequate iliac/femoral access, 2) infrarenal aortic neck treatment diameter range of 19-26 inm and a minimum aortic neck length of 15 nim, 3) proximal aortic neck angulation greater than or equal to 60 degrees, and 4) Iliac artery treatment diameter range of 8-13.5 mm and iliac distal vessel seal zone length of at least 10 mm
Sample Size	565 patients, 99 surgical controls
Key Study Endpoints	The primary clinical endpoints included major adverse events and major device events.
Follow-up Visits and Length of Follow-up	Follow-up at 1-month, 3-months, 6-months, 12 months, and annually thereafter, for a total of 5 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	565 patient
Actual Number of Sites Enrolled	19 or more sites
Patient Follow-up Rate	73%
Final Safety Findings	The final analysis showed 81% survival at 5 years in the control group and 70% survival in the combined pre-market cohort. Survival from aneurysm-related mortality at 5 years was 98% in both groups, with no statistically significant difference.
Study Strengths & Weaknesses	The strengths of the study included the prospective cohort study and concurrent control group.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P000025 S084/ PAS001
Date Original Protocol Accepted	12/08/2016
Date Current Protocol Accepted
Study Name	MED-EL EAS Extended f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an extended follow-up of the premarket cohort. The purpose of the study is to evaluate the long term safety and effectiveness of the MED-EL EAS Implant in implanted subjects out to 5 years post-activation. It is a prospective, multicenter, non-controlled, non-randomized study.
Study Population	Up to 68 subjects from the original pivotal study who remain enrolled in the study, implanted with a MED-EL EAS device and have not reached their 5 year post-activation interval will be invited to participate.
Sample Size	The sample size requirements are based on the desire for adequate power for the primary effectiveness endpoint. The hypothesis test is a paired one-sample non-inferiority test of the mean CNC word score. The test will be performed at the one-sided 0.05 alpha level based on a 10% non-inferiority margin. The planned minimum sample size of 55 subjects would yield 90% power for this endpoint, based on an assumed difference of zero and a standard deviation of 25. A higher degree of power would be maintained for a smaller standard deviation.
Key Study Endpoints	Effectiveness endpoints: The primary effectiveness endpoint will be CUNY sentence test score in noise at five years (60 months) post-implantation compared to the 12-month follow-up interval, measured in two conditions: CI alone and EAS in the implanted ear. The secondary effectiveness endpoints will be 1) CNC word score in quiet at five years (60 months) post-implantation compared to the 12-month follow-up interval, measured in two conditions: CI alone and EAS in the implanted ear; and 2) global score on the APHAB questionnaire, completed based responses in the everyday listening condition at five years (60 months) post-implantation compared to the 12-month follow-up interval. Safety endpoints: The primary safety endpoint will be the number and proportion of subjects experiencing device-related adverse events. Expected adverse events include those listed in the original clinical trial protocol, in particular: Profound or total loss of residual hearing Infection or inflammation Vertigo, dizziness, or balance problems Tinnitus Implant migration/extrusion Skin flap problems Device-related or programming problems Uncomfortable sounds during stimulation Temporary pain or numbness Device failure leading to explantation The secondary safety endpoint is residual hearing at five years (60 months) post-implantation that will be summarized and presented as the amount of low-frequency pure-tone average (125, 250, 500, 750, and 1000Hz) shift, the degree of residual hearing, and as a function of the HEARING scale.
Follow-up Visits and Length of Follow-up	5 years post-activation of the device for each subject.
Interim or Final Data Summary
Actual Number of Patients Enrolled	50
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	98% at 5 years* The primary endpoint for this investigation is 5 years post-activation of the MedEl EAS System. As of December 11, 2019, 49 out of 50 enrolled subjects have reached this designated study phase.
Final Safety Findings	A total of eight (8) serious Adverse Events (AEs) occurred during this PAS. Serious AEs in seven (7) subjects, who had significant residual hearing loss in the implanted ear with a low-frequency Pure Tone Average (PTA) across 125-1000 Hz equal or greater than 90 dB HL, were reported during the PAS, but only one (1) was related to internal device failure that was resolved after revision surgery. Five (5) out of seven (7) subjects, who lost residual hearing but still have aidable low-frequency hearing (i.e., threshold less than or equal to 80 dB HL at 125 Hz), are continuing to use the acoustic unit and demonstrate combined electric and acoustic (EAS) benefit. Two (2) out of seven (7) subjects continue to demonstrate benefit with electric-alone stimulation. There were no unanticipated adverse device effects reported. In general, the type and frequency of AEs and serious AEs occurring over the course of this study up to 5 year post-activation interval are mostly related to the loss of residual hearing, which is an anticipated AE. In total, 32% (16 out of 49) subjects lost their residual hearing (PTA across 125-1000 Hz greater than or equal to 90 dB HL) in the implanted ear from post-implant surgery to 5-yr follow-up visit (Note: 9 out of 16 cases occurred within 1-yr follow-up visit).
Final Effect Findings	The mean CUNY (sentence in noise) scores achieved with the MedEl EAS system (i.e., the primary effectiveness endpoint) at the 5-year post activation follow-up is significantly lower than that at the 1-year post activation follow-up. However, for those 39 out of 49 subjects who have aidable residual hearing in the implanted ear (i.e., threshold less than or equal to 80 dB HL at 125 Hz), the CUNY scores still demonstrate an improvement at the 5-year post activation follow-up compared to the pre-operative baseline condition with hearing aids. For those 10 out of 49 who have completely lost residual hearing in the implanted ear, the mean CUNY (sentence in noise) score achieved with the MedEl EAS system at the 5- year post activation follow-up is not superior to that at the pre-operative baseline condition with hearing aids. Through the 5-year post-activation follow-up, the MedEl EAS System improves overall mean CNC (words in quiet) scores and mean AHPAB scores compared with the pre-implant baseline condition and the improvement is sustainable over the five years of follow up.
Study Strengths & Weaknesses	This is a single arm study with no comparator; however, the subjects served as their own control. It is a long-term study (up to 5 years post-implantation) with a high follow-up rate.
Recommendations for Labeling Changes	Yes. A labeling update is recommended to reflect the findings of the study.
General
Study Status	Ongoing
Application Number / Requirement Number	P000025 S104/ PAS001
Date Original Protocol Accepted	10/15/2019
Date Current Protocol Accepted	09/04/2020
Study Name	MED-EL New Enrollment SSD/AHL Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To determine the long-term safety and effectiveness outcomes of cochlear implantation for single-sided deafness and asymmetric hearing loss, 65 subjects will be recruited into this singlesubject, repeated measures study. Twelve of the subjects will be between five and 11 years, 11 months of age, while nine subjects will be between 12 and 17 years, 11 months of age. Six centers across the United States and Canada will recruit subjects into this study. Pre-operative speech perception, quality of life, and localization (where possible) assessments will be conducted. All subjects will receive a MED-EL Cochlear Implant and will subsequently be fit with an FDA-approved audio processor. Post-operative evaluations will occur at three, six, 12, 24, and 36 months post-activation of the CI. Data will be analyzed from the 12-month and 36-month follow-up intervals and compared to baseline data. This is a new enrollment study and the primary objective of this study is to evaluate the long-term effectiveness of cochlear implantation in patients ages five years and older with single-sided deafness or asymmetric hearing loss. The secondary objective of this study is to evaluate the long-term safety of cochlear implantation in patients ages five years and older with single-sided deafness or asymmetric hearing loss.
Study Population	65 subjects with SSD or AHL who are above five years of age will be recruited. Among the 65 subjects, 44 will be adults aged 18 years and older; 12 subjects will be between 5 and 12 years of age; and 9 subjects will be between 12 and 18 years of age. Subjects will be recruited from six investigational sites. SSD/AHL is defined as profound hearing loss (PTA = 90 dB HL across 500, 1000, 2000, and 4000 Hz) and less than or equal to 5% CNC word in quiet score in the ear to be implanted and normal hearing or mild-to-moderate hearing loss (PTA less than or equal to 55 dB HL) in the contralateral ear. Subjects will be implanted with an FDA-approved MED-EL cochlear implant system. After implantation, subjects will be fit with a currently-approved audio processor.
Sample Size	Sixty-five subjects will be enrolled in this study. Of the 65 subjects, 12 will be between the ages of five and 12 years, while nine subjects will be between 12 and 18 years of age. The basis for the sample size calculation is speech in noise performance on AzBio sentences in noise in the speech front, noise to the better hearing ear condition; the pre-operative, best aided condition compared to 12 months post-operative, normal hearing ear and CI. The sample size calculation is based on data from the University of North Carolina clinical trial (G140050) on SSD and AHL subjects. In the SSD group on AzBio, the average pre-operative best aided score was 18.3% (SD=18.2%) and at 12-month testing, the average score with the CI on was 52.6% (SD=21.4%). In the AHL group, subjects reached an average score of 11.9% (SD=17.0%) in the best aided pre-operative condition and at 12-month testing reached an average score of 29.4% (SD=22.6%) with the CI on. Using these data as basis for the sample size calculation, with a power of 90% and an alpha-level of 0.05 for a one-sided Paired sample t-test (or the Wilcoxon signed-rank test for the AHL group because the data were not normally distributed), a total sample size of 43 subjects would be a sufficient sample, but 65 subjects are proposed, to include 21 pediatric subjects between five and 18 years of age, and to account for potential subject loss of 20% over the duration of the study. Specifically, 12 subjects will be recruited between the ages of five and 12 years of age, while nine subjects will be recruited between the ages of 12 and 18 years of age.
Key Study Endpoints	Primary Endpoint: Improvement on speech in noise when speech is presented to the front and noise is presented to the acoustic hearing (contralateral) ear. The pre-operative, best-aided score will be compared to the 12- month and 36-month CI score for AzBio sentences in noise. Improvement is defined as greater than or equal to 10 percentage points. Secondary Endpoints: Speech in noise in two spatial conditions will demonstrate similar performance from the preoperative, best-aided score to the CI score at 12 and 36 months postactivation. AzBio sentence in noise score will be summarized for two conditions: speech and noise presented from the front as well as speech presented to the front and noise presented to the CI ear. Speech perception in quiet will be summarized for the CI ear and the contralateral ear at the preoperative, 12-month, and 36-month intervals. The CI ear is expected to demonstrate improvement (greater than or equal to 10 percentage point change), while the contralateral ear is expected to demonstrate no change. Subjective data will be collected via the Speech, Spatial, and Qualities of Hearing Scale (SSQ) and a Quality of Life questionnaire. Responses will be summarized from the pre-operative, 12-month, and 36-month intervals. Device-related adverse events will be collected and reported throughout the duration of the study. Events will be reported as the number and proportion of subjects experiencing them. Exploratory Analysis: Efforts will be made to collect localization data; however, not every site will have the capability of performing this testing. Subjects will travel to sites with sufficient facilities to test localization, as they are able. When possible, root mean square (RMS) error will be reported from the pre-operative, 12-month, and 36-month intervals.
Follow-up Visits and Length of Follow-up	The study is anticipated to last for six years from enrollment through final data analysis. Individual subject participation will last for approximately 36 months or three years.
General
Study Status	Completed
Application Number / Requirement Number	P000007 S003/ PAS001
Date Original Protocol Accepted	05/09/2003
Date Current Protocol Accepted	05/09/2003
Study Name	Tag Alert
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a real-time aging study of a part of the packaging for the device and will consist of validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	The study will collect data for the validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	All units passed real-time testing
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P860057 S019/ PAS001
Date Original Protocol Accepted	05/09/2003
Date Current Protocol Accepted
Study Name	PERIMOUNT Plus Pericardial Bioprosthesis Model 6900P
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study includes consecutive enrollment of all patients receiving valves.
Study Population	All patients who received valve replacement
Sample Size	All eligible patients who received a mitral valve transplant between 1999 and 2002, a minimum of 150 patients
Key Study Endpoints	NYHA classification pre/post implant (efficacy) and Thromboembolism,Valve thrombosis, Hemorrhage (all and major), Perivalvular leak (all and major), Endocarditis, hemolysis, Structural valve deterioration, Nonstructural dysfunction, Death, reoperation, explant (Safety)
Follow-up Visits and Length of Follow-up	6 months and annually to 8 years
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	209 patients
Actual Number of Sites Enrolled	4 sites
Patient Follow-up Rate	71.3% were followed and alive at 96 months
Final Safety Findings	There was a noteable improvement in New York Heart Association classification and adverse event rate typical for the valve,
Study Strengths & Weaknesses	Adequate follow-up, weaknesses is no hypothesis or sample size calculations
Recommendations for Labeling Changes	None noted, patients were still being followed up until 2010
General
Study Status	Completed
Application Number / Requirement Number	P870077 S013/ PAS001
Date Original Protocol Accepted	05/09/2007
Date Current Protocol Accepted	05/09/2007
Study Name	Tag Alert
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a real-time aging study of a part of the packaging for the device and will consist of validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	The study will collect data for the validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	All units passed real-time testing
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P950024 / PAS001
Date Original Protocol Accepted	09/06/1996
Date Current Protocol Accepted
Study Name	Unipolar Model 4965
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 1-year, multi-center, single arm, prospective and retrospective cohort study. All subjects in the study receive the device.
Study Population	Study Population: The study population includes adults (at least 19 years old) receiving device. Indication: The Medtronic Model 4965 CapSure Epi Steroid-Eluting Unipolar Epicardial Pacing Lead is an epicardial lead designed for pacing and sensing of either the atrium or ventricle.
Sample Size	50 subjects at multiple sites
Key Study Endpoints	Endpoints include freedom from generator and lead-related adverse events and post-market performance of the lead.
Follow-up Visits and Length of Follow-up	There is no specified timeframe for follow-up visits; they occur according to the routine care plan set by each site for all cardiac surgical patients.
Interim or Final Data Summary
Interim Results	There are 4 deaths in 69 enrolled subjects, 2 lead events, and 8 observations to date.
Actual Number of Patients Enrolled	73 subjects
Actual Number of Sites Enrolled	21 centers
Patient Follow-up Rate	51/73 (70%) at one year of follow-up
Final Safety Findings	There were two lead-related complications and six Model 4965 lead observations. A total of 18 deaths were reported. No patient death was considered device- related. However the relatedness of 11 (61%) patient deaths to the Model 4965 could not be determined due to insufficient information.
Final Effect Findings	A total of 98 implanted Model 4965 leads were included in the analysis. The lead-related complication free survival probability at 1-year was 98.8%, with 95% CI (91.8%, 99.8%).
Study Strengths & Weaknesses	A weakness of this study is that enrollment of the 73 participants took almost 14 years 12/1996- 09/2010. Over this time there may have been substantial changes in clinical practice. Additionally, this study was limited by the use of retrospective enrollment, a low follow-up rate, and substantial missingness of data. However the sponsor, will incorporate lead survival data on epicardial leads from the literature, into the labeling to supplement the findings from this study.
Recommendations for Labeling Changes	Yes, labeling updates are being recommended.
General
Study Status	Completed
Application Number / Requirement Number	P010041 S002/ PAS001
Date Original Protocol Accepted	05/09/2003
Date Current Protocol Accepted	05/09/2003
Study Name	Tag Alert
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This is a real-time aging study of a part of the packaging for the device and will consist of validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	The study will collect data for the validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	All units passed real-time testing
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P000023 / PAS001
Date Original Protocol Accepted	01/05/2001
Date Current Protocol Accepted
Study Name	TMJ Fossa-Eminence PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P030054 / PAS001
Date Original Protocol Accepted	06/30/2004
Date Current Protocol Accepted
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was designed to collect, characterize and report on the performance of the device system through three years post-implant.
Study Population	The study included patients rolled over from the pre-market study and newly enrolled post-approval study patients.
Sample Size	1,121 patients, 46 sites
Key Study Endpoints	Endpoints include all-cause mortality for patients implanted with CRT-D or CRT-P systems; Freedom from LV lead or LV lead implant procedure related adverse events; Electrical performance of the LV leads
Follow-up Visits and Length of Follow-up	Patients will be followed every six months for 3 years
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	1127 patients
Actual Number of Sites Enrolled	46 sites
Patient Follow-up Rate	73%
Final Safety Findings	The freedom from all-cause mortality for patients implanted with CRT-D systems is 80% at 3 years. The freedom from LV lead or procedure-related complications is 94% at 3 years. The freedom from system-related complications is 89% at 3 years. The reviews by the lead reviewer and clinical reviewershow that these rates are consistent with expectations and that the 20% mortality is not unexpected given the high proportion of class III and IV heart failure patients.
Study Strengths & Weaknesses	Strength: Large sample size which allows for the examination of rarer events Limitation: Allowance for inclusion of IDE study participants. There was a substantial difference in the major outcomes (death, HF events, etc) between the subjects who were rolled in from the IDE and the newly enrolled PAS subjects (who faired notably worse). This substantial difference seems to be independent of the covariates that were looked at and so it may be concerning. One likely explanation for the difference is of selection bias. The subjects rolled in from the IDE had already been free of death and presumably major events before they enrolled in the PAS and so may have been overall less likely to have events compared to the newly enrolled subjects. But even if selection bias explains the difference, it seems to me that the results for the newly enrolled subjects is a better representation of real world outcomes.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P020045 / PAS001
Date Original Protocol Accepted	04/17/2003
Date Current Protocol Accepted	04/17/2003
Study Name	CryoFACTS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Observational single arm, non-randomized study and literature review
Study Population	Adults referred for ablation of AVNRT.
Sample Size	75 subjects from 10-15 sites Subjects from medical literature
Key Study Endpoints	Device or procedure-related A-V block that persists through discharge; Device or procedure-related A-V block that persists through discharge and requires the insertion of a permanent pacemaker; Acute procedural success, defined as absence of recurrence and non- inducibility of the targeted antrioventricular nodal reentrant tachycardia.
Follow-up Visits and Length of Follow-up	3 months Discharge and three months.
Interim or Final Data Summary
Interim Results	Of the 54 participants, none have had device or procedure related AV block persistent through discharge from the hospital.
Actual Number of Patients Enrolled	75 in study 705 from literature
Actual Number of Sites Enrolled	4
Patient Follow-up Rate	100%
Final Safety Findings	Of the 75 participants, none have had AV block persistent through discharge from the hospital (95% CI = 0-4.8%). There were no subject deaths. Study and literature combined - Permanent AV block: 0% (95% CI=0% - 0.5%)
Final Effect Findings	Acute procedural success has been reported in 71 of the 74 participants (95.9%) for whom ablation was performed. Study and literature combined - Acute procedural success: 93.5% (95% CI=91.5% - 95.1%)
Study Strengths & Weaknesses	Both safety and effectiveness objectives were met by a good margin. Literature review suffers from potential lack of representativeness.
Recommendations for Labeling Changes	None
General
Study Status	Terminated
Application Number / Requirement Number	H080002 / PAS002
Date Original Protocol Accepted	04/06/2010
Date Current Protocol Accepted	09/24/2013
Study Name	Generalizability Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, observational, non-randomized, multi-center study. The study purpose is to confirm the short-term hemodynamic effectiveness results achieved by real world providers are equivalent to the historical control established in the IDE study. Where the percentage of subjects with acceptable TPV hemodynamic function at six months after Melody valve implantation will be assessed.
Study Population	Consecutive subjects at each site will be invited to participate in the study if they meet the indication for the device. This include the eExistence of a full right ventricular outflow tract conduit that was equal to or greater than 16 mm in diameter when originally implanted, and dysfunction ight ventricular outflow tract conduits with a clinical indication for intervention, including moderate or severe regurgitation or stenosis with and ight ventricular outflow tract gradient of at least 35 mmHg.
Sample Size	100 patients, 10-15 sites
Key Study Endpoints	The primary endpoint is the percentage of subjects with acceptable hemodynamic function at six months post-implant.
Follow-up Visits and Length of Follow-up	Follow-up of the clinical endpoints will be conducted at baseline (pre-implant), discharge from the hospital, at six months post-implant, one year, and annually thereafter, until the patient has been followed for five years or until the device has been explanted.
Interim or Final Data Summary
Interim Results	No safety data is available for this study.
General
Study Status	Completed
Application Number / Requirement Number	P000013 / PAS001
Date Original Protocol Accepted	08/16/2003
Date Current Protocol Accepted	08/16/2003
Study Name	Osteonics Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 10-year, multi-center cohort study with three arms. The first arm is comprised of persons who received the ABC Systems I, II total hip replacement. The second arm is the control arm of patients who received the ABC III total hip replacement. The third and final arm is comprised of patients who received the Trident hip replacement. Study success required a Harris Hip Score >70, the absence of device revision or removal and radiographic success. The primary objective of the study is to continue following subjects who were in the Osteonic ABC System premarket clinical trial and the premarket study of the Trident System to evaluate the ongoing safety and effectiveness of the ABC and Trident hip implants through the 5th postoperative year, and the ongoing status of the hip using a questionnaire annually from 6 to 10 years postoperatively. Implanted hips could be unilateral or bilateral and could have an ABC hip on one side and a Trident hip on the other. Radiographic success was defined as the absence of:- progressive radiolucent lines > 2mm in thickness around the entire acetabular, -component, - migration of > 3mm of the acetabular component, - progressive radiolucent lines around the entire femoral component,- progressive subsidence of the femoral component > 5mm
Study Population	Study population is as per device indication. These devices are indicated for patients requiring primary total hip arthroplasty due to painful disabling joint disease of the hip resulting from non-inflammatory degenerative arthritis (osteoarthritis, avascular necrosis, traumatic arthritis, slipped capital epiphysis, pelvic fracture, femoral fracture, failed fracture fixation, or diastrophic variant).
Sample Size	A total of 518 cases [310 ABC Study cases (214 ceramic/96 control), 208 Trident cases] were active in the PAS cohort as of March 12, 2003. Since then, a total of 54 cases have either declined to participate, died, or are been lost-to-follow-up. This PAS report contains data on 274 (185 ceramic/ 89 control) ABC Study cases and 190 Trident cases
Key Study Endpoints	Harris Hip Score >70, the absence of device revision or removal and radiographic success; and radiographic success was defined as the absence of:- progressive radiolucent lines > 2mm in thickness around the entire acetabular component, - migration of > 3mm of the acetabular component, - progressive radiolucent lines around the entire femoral component, - progressive subsidence of the femoral component >5 mm
Follow-up Visits and Length of Follow-up	Follow-ups will be conducted to determine ongoing status of the ABC and Trident hip implants through the 5th postoperative year, and the ongoing status of the hip using a questionnaire annually from 6 to 10 years .
Interim or Final Data Summary
Actual Number of Patients Enrolled	Fully 430 patients were enrolled.
Actual Number of Sites Enrolled	A total of six study sites enrolled patients
Patient Follow-up Rate	Ranged from 80.2% to 88.4% at 10 post-operative years for cases with any follow-up data reviewed or evaluated by an investigator except for those cases who have follow up data for that interval, but either died or were a failure after the data was collected, but prior to completion of the interval being reported.
Final Safety Findings	No significant differences in reported patient satisfaction were observed between the Osteonics ABC, Trident, and control groups.
Final Effect Findings	No statistically significant difference was noted between the proportion of Osteonics ABC patients and control patients with Harris Hip Scores > 80. No statistically significant difference was noted between the proportion of Trident patients and control patients with Harris Hip Scores > 80. A Harris Hip Score > 80 is considered to be a good result.
Study Strengths & Weaknesses	Major strengths of the study include its 10 year duration to examine longer-term device performance and the inclusion of a control group to enhance its scientific rigor. Study weaknesses include the absence of required clinical and radiographic examination during the last 5 years of patient follow-up.
Recommendations for Labeling Changes	Labeling Change Recommended Yes. No statistically significant postoperative difference was noted between the proportion of Osteonics ABC patients and control patients with Harris Hip Scores > 80. No statistically significant difference was noted between the proportion of Trident patients and control patients with Harris Hip Scores > 80. A Harris Hip Score > 80 is considered to be a good result. No significant differences in reported patient satisfaction were observed among the Osteonics ABC, Trident, and control groups.
General
Study Status	Completed
Application Number / Requirement Number	P000029 / PAS001
Date Original Protocol Accepted	09/24/2001
Date Current Protocol Accepted	09/24/2001
Study Name	Deflux Long-Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is an open, non-randomized, multi-center study in 149 children older than 1 year of age using new data collection.
Study Population	Study population is as per device indication: This device is indicated for treatment of children with vesicoureterarle flux (VUR) grades1 11-IVW
Sample Size	The sample size is 149 patients using Deflux. There will be approximately 10-15 sites with each center having approximately 15 patients.
Key Study Endpoints	The primary outcome is grade of reflux according to the VCUG at 3 months after last treatment. The grading is performed by a non-treating physician. Secondary efficacy variable is absence of febrile UTI. There will be 8 visits, including screening, baseline, 3 months, 12 months and once annually for years 2-5. Subjects will be seen by a physician at these time points
Follow-up Visits and Length of Follow-up	There are 6 scheduled follow up visits after the treatment visit. The length of follow up is 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	165 Subjects
Actual Number of Sites Enrolled	12 Sites
Patient Follow-up Rate	18.8% (31/165)
Final Safety Findings	Treatment-emergent adverse events were experienced by 60% of subjects with most events rated as mild or moderate in intensity. The most common TEAEs were urinary tract infection (18%) and micturition urgency (12%). 12% of subjects experienced TEAEs related to the injection or device and 7% experienced a serious TEAE.
Final Effect Findings	Success rate for the primary effectiveness endpoint (Vesico Ureteral Reflux grade at UCUG at 3 months after Deflux treatment) was 66.1% (95% CI 58.3% to 73.2%).
Study Strengths & Weaknesses	Strengths of this study include a prospective design of adequate sample size for evaluation of the short-term (3-month) primary effectiveness endpoint. The main limitation is the low 5-year follow-up rate of 18.8%. However, evaluation of longer-term safety was addressed in an extensive systematic review of the available literature.
Recommendations for Labeling Changes	Labeling changes are recommended based on the safety and effectiveness results of the post- approval study and the longer-term safety of Deflux described in the systematic literature review.
General
Study Status	Completed
Application Number / Requirement Number	P870077 / PAS001
Date Original Protocol Accepted	09/25/1991
Date Current Protocol Accepted	09/25/1991
Study Name	PAS
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P960009 S007/ PAS001
Date Original Protocol Accepted	01/14/2002
Date Current Protocol Accepted
Study Name	VA Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	BMT and DBS: An AE was reported in 82% of the patients (209/255). There were 2056 AE in 209 unique patients. On average, there were 9.8 AEs per patient. The majority occurred in nervous system disorders (65.1%), psychiatric disorders (45.5%), general disorders and administration site conditions (43.9%), injury, poisoning and procedural complications (42.4%), and muscloskeletal and connective tissue disorders (39.6%). DBS Only: An AE was reported in 96.7% of the patients (290/300). There were 6501 AE in 290 unique patients. On average, there were 22.4 AE per patient. The majority of AE were nervous system disorders (92%), injury, poisoning and procedural complications and psychiatric disorders (78.3% each), general disorders and administration site conditions (71.7%), and gastrointestinal disorders (64%). Serious Adverse Events: The SAE dataset contained 107 SAE in 64 unique patients. BMT and DBS : Events from randomization to 6 month visit date. A SAE was reported in 25.1% of the patients randomized (64/255). There were 107 SAE in 64 unique patients with an average of 1.7 SAE per patient who reported a SAE. Within the 107 SAE, 16 were the following infections 12 implant infections and 4 post-operative infections in 13 unique patients. Study population incidence rate is 5.1% (13/255). The 107 SAE were in seventeen SOCs with the most frequent being infections and infestations (7.1 %), nervous system disorders (6.3%), injury, poisoning and procedural complications (5.5%) and general disorders and administration site conditions and psychiatric disorders (3.1%). Gender - There are 208 males and 47 females randomized in this group. The most frequent AEs were implant site infection and fall (3.4% each), postoperative infection and confusional state (1.4% each) and pneumonia, cerebrovascular accident and hallucinations at 1% each in males and implant site infection and air embolism (4.3% each) in females. DBS Only Events in surgical arm from randomization date A SAE was reported in 51% of the patients randomized (153/300). There were 327 SAE in 153 patients with an average of 2.1 SAE per patient. Within the 327 SAE, 27 were the following infections - 23 implant infections and 7 post-operative infections in 23 unique patients. Study population incidence rate is 7.7% (23/300). The most frequent SOCs were injury, poisoning and procedural complications (17.0%), infections and infestations (13.3%), nervous system disorders (13.0%), and psychiatric disorders (9.3%). Gender: There are 250 males and 50 females randomized in this group. The most frequent AEs terms were fall (6.4%), implant site infection (5.2%), medical device complication (4.0%) and pneumonia (3.6%) in males and medical device complication (10.0%), fall and implant site infection (8.0% each), and syncope (6.0%) in females.
Actual Number of Patients Enrolled	299
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	At the 24-month, primary analysis there were 261 completers, for a follow-up rate of 261/299 = 87% follow-up rate. For the 36-month effectiveness analysis there were 159/299 subjects = 53% follow-up rate. For the 36-month safety analysis there were 187/299 subjects = 62.5% follow-up rate.
Final Safety Findings	In terms of safety, no unexpected adverse events occurred. There was not a trend for any of the two stimulation sites to present a significantly higher number of adverse events, including deaths (5/152 subjects GPi, 8/147 STN), suicidality (2 GPi, 3 STN), intracranial hemorrhages (5 GPi, 3 STN), device-related infections (2 GPi, 2 STN) and general paralysis/paresis (12 GPi, 11 STN). AEs were reported in 100% of the patients, while serious AEs (SAEs) were reported in 52% of the subjects randomized to GPi (54/104) as well as 55% of the subjects randomized to STN.
Final Effect Findings	The device showed continued effectiveness at 24-months: the results for the blinded UPDRS III On stim/Off med test are statistically significantly improved from baseline to 24 months for the GPi (11.8 points) and the STN (10.7 points) target sites. At 24 months a minimal clinically important change of 5 points in the UPDRS III measure On stim/Off med was achieved in 66% of GPi subjects and 71% of STN subjects. At 24 months the motor diary demonstrated an increase of 4-5 hours of On time without troublesome dyskinesias, a decrease of approximately 3 hours of On time with troublesome dyskinesias, a decrease of approximately 2 ½ hours of Off time, and an increase of approximately 1 hour of asleep time. The Post-Approval Study also showed an ameliorated quality of life according to one of the measurements adopted but not the others: quality of life was characterized using the PDQ-39, SF-36, and Quality of Well-Being measurements for both 24- and 36-month data sets. The PDQ-39 single index and subscales of mobility, activities of daily living, stigma, and bodily discomfort were statistically significantly improved as compared with baseline for both target sites (-11.2% for GPi and -8.9% for STN in the 24-month ITT data set). The change from baseline for the SF-36 and Quality of Well-Being scores for both target sites were not consistently statistically significantly improved on these general quality of life measures. None of the differences in quality of life outcomes between target sites were considered clinically significant for PDQ-39, SF-36, or Quality of Well-Being. Neuropsychological changes over time through 24 months in 6 domains showed no clinically significant changes from baseline. The only exception to this was the measure of overall cognitive function, which declined in both groups to 24 months, especially in terms of verbal fluency declines. Medication reduction was higher in STN patients at 24 months, compared to Gpi patients: the percent reduction in the average LED (levodopa equivalent dose) from baseline at 24 months was 31.4% for STN and 16.4% for GPi, while at 36 months it was 35.5% for STN and 18.3% for GPi.
Study Strengths & Weaknesses	The major strength of the study: the design was randomized and blinded (independent neurologist or nurse, and subject) to the assigned stimulation site. A major limitation: given the relatively extended follow-up of the study (24 months for the primary effectiveness analysis, 36 months for the secondary, longer term effectiveness analysis and for the safety analysis) the follow-up rates at 36 months were not high (53% for the effectiveness analysis and 62.5% for the safety analysis). This element may have introduced bias in the comparison between the 2 groups randomized to receive STN vs. GPi stimulation sites. The primary effectiveness analysis, both the intention-to-treat and the completer analysis, is not affected by this potential problem: indeed the loss to follow up rate for the primary effectiveness analysis was 13%, showing a good follow up rate.
Recommendations for Labeling Changes	DBS in the PAS Phase II showed continued effectiveness, a safety profile that is not different from expected and that does not differ between the two stimulation sites, with a partially ameliorated quality of life in these patients and a declined overall cognitive function for both stimulation sites. Medication reduction was twice as large in STN patients compared to GPi patients. No major clinical differences emerged between the STN and the GPi in terms of effectiveness, besides a significantly reduced use of medications in STN patients compared to GPi patients. Serious adverse events were reported in 52% of GPi patients and 55% of STN patients. No unexpected adverse events occurred. There was not a trend for either of the two stimulation sites to present a significantly higher number of adverse events, including deaths, suicidality, intracranial hemorrhages, device-related infections and general paralysis/paresis.
General
Study Status	Completed
Application Number / Requirement Number	P000057 / PAS001
Date Original Protocol Accepted	11/19/2001
Date Current Protocol Accepted	09/10/2018
Study Name	Ascension MCPT
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a non-randomized, consecutive enrollment, one-year post-approval study of patients who are treated with the Ascension MCP prosthesis.
Study Population	This device is indicated for use as a total joint replacement of index, long, ring, and small finger metacarpophalangeal (MCP) joints that exhibit symptoms of pain, limited motion, or inadequate bony alignment (i.e., subluxation/dislocation) secondary to articular destruction or degenerative disease related to rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, or post-traumatic arthritis where soft tissue reconstruction can provide adequate stabilization. The study Inclusion Criteria: Patients who have all of the following characteristics are eligible for inclusion: - Index, long, ring, or small finger metacarpophalangeal (MCP) joints that exhibit symptoms of pain, limited motion, or inadequate bony alignment (i.e. subluxation/dislocation) secondary to articular destruction or degenerative disease related-to rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis; or post-traumatic arthritis where soft tissue reconstruction can provide adequate stabilization - Willing to participate in the study - Signed an Informed Consent Form - The means and ability to return for all required study visits Exclusion Criteria: Patients who have any of the following contraindications will be excluded from the study: - Inadequate bone stock at the implantation site - Active infection in the MCP joint - Nonfunctioning and irreparable MCP musculotendinous system - Physical interference with or by other prostheses during implantation or use - Procedures requiring modification of the prosthesis - Skin, bone, circulatory and/or neurological deficiency at the implantation site
Sample Size	100 patients from 4 clinical sites
Key Study Endpoints	Data endpoints include: - MCP range of motion (ROM) - MCP joint ulnar deviation - Pinch and grip strength - Implanted related joint pain - Patient satisfaction - Radiographic appearance (subsidence, migration, and peri-prosthetic bone changes) - Joint position (reduced, subluxed or dislocated) - Complications, adverse events, and post-op procedures.
Follow-up Visits and Length of Follow-up	surgery/immediate post-op, 6 weeks, 12 weeks, 6 months, and 12 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	Overall, 259 joints reported in literature were replaced with the pyrocarbon MCP devices within the period since pre-market approval of this device till the end of August 2017.
Actual Number of Sites Enrolled	This literature review is based on an analysis of available articles containing post-market clinical data relevant to the intended purpose of the Integra Ascension MCP implant, including clinical performance and safety data. The device is evaluated for safety and efficacy, based on data available from the published scientific literature. The scientific literature included in this review is the result of a literature search that covered the period between 19 November 2001 (date of FDA approval of the device) and 28 August 2017 and yielded 12 scientific publications included in the analysis.
Patient Follow-up Rate	The average follow-up well exceeded the 1-year requirement in the CoA in a majority of the articles included.
Final Safety Findings	Adverse Events There were no serious adverse events reported in this scientific literature review that lead to death, birth defect, life-threatening injury/illness, prolonged hospitalization, or permanent impairment of body. There was a 1.9% incidence of joint deformity (including ulnar deviation/drift), a 5.4% incidence of implant subluxation or dislocation, an 8.5% incidence of device revision or removal, a 5% incidence of other soft tissue reoperations, and a 0.4% incidence of synovitis. In sum, there was a 12.7% occurrence of adverse events and an 8.5% rate of revision. Device Revisions There was an 8.5% (22/259) incidence of device revision across the twelve articles identified in this systematic literature review. There were a variety of reasons for device revisions and removals. One device was removed and one revised due to chronic pain (Parker et al. 2006; Wagner et al. 2015). Tendon complications such as contracture and adhesion caused 4 device revisions and 2 removals in Petscavage et al (2011). There were 6 revisions to rectify subluxation, dislocation or instability (Parker et al. 2007; Wagner et al. 2015). Dickson et al (2015) reported 6 revisions for dislocation, fracture and loosening. Finally, two patients underwent device revision surgeries due to dissatisfaction with results, one patient experienced limited range of motion and the other felt his precision pinch had diminished after surgery (Wall & Stern, 2013; Simpson-White and Chojnowski, 2013).
Final Effect Findings	Patient Reported Outcome Patient Satisfaction Seven of the studies (123 patients) reviewed reported patient satisfaction rates. Patient satisfaction rates ranged between 89% to 100% and most patients said they would elect to have the surgery again. Pain Reduction Three studies (59 patients, 127 procedures) reported preoperative and postoperative Visual Analog Scale (VAS) pain scores. The patients in these studies showed an 86% alleviation of pain symptoms, from an average VAS score of 61.4 to an average score of 6.8. The OA patients of Parker et al (2006) had a preoperative average VAS pain score of 73.1 which fell to 8.5 postoperatively. The RA patients of Parker et al (2007) had an average preoperative VAS pain score of 43 which fell to 9 postoperatively. Nunez & Citron (2005) did not perform a statistical comparison of pre- and post-operative pain scores, but did show a decrease in reported pain, from an average VAS score of 68 preoperatively to 3 at the postoperative examination. Objective Measurement Improvement in Mechanical Measures Eleven studies (242 procedures) reported mechanical outcomes of Integra Ascension MCP arthroplasty, as measured by grip strength, pinch strength or range of motion. In summary, across these trials, there was an average 20.3% increase in grip strength (4.7 kg), an average 20.2% increase in arc range of motion (6.3°) and an average 184% increase in oppositional pinch strength (3.8 kg). Device Survival Device survival is defined as the number of devices that remain in patients treated with Integra Ascension MCP devices, at follow-up. All twelve of the publications included in the scientific literature review presented data on device removals and revisions. Average survival at follow-up examination was 95% at 1-year, 93% at 2-years, 85% at 5-years (please note that not all studies reached 5-year follow-up time point).
Study Strengths & Weaknesses	The strength of this literature review is that it includes several articles documenting long-term patient reported outcomes especially subjective pain and patient satisfaction, both of which showed preferable results. Additionally, the average follow-up was higher than what was required in the original approval order. Most studies in this literature review did not have a universal method for post-operation rehabilitation, which can be considered as a study weakness, but because we have seen a good patient satisfaction rate based on this literature review, we think this lack of universal post-op rehab method does not impact our assessment significantly.
General
Study Status	Other
Application Number / Requirement Number	P000049 / PAS001
Date Original Protocol Accepted	04/19/2002
Date Current Protocol Accepted	04/19/2002
Study Name	Prospective VSD Registry
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective registry to evaluate the ongoing occurrence of major complications related to device or procedure, shunt closure status and fracture detection.
Study Population	The CardioSEAL Septal Occlusion System with QwikLoad is indicated for use in adult and pediatric patients with complex ventricular septal defects, which are of significant size that they warrant closure and are considered to be at high risk for standard transatrial or transarterial surgical closure based on anatomical conditions and/or based on overall medical condition. The study population is consistent with the indications for use. It includes patients of all ages with complex ventricular septal defects, who are at high risk for surgical closure due to a high risk anatomical condition or high risk medical condition.
Sample Size	55 patients, 18 sites
Key Study Endpoints	Data collected will include baseline, procedural, and annual follow-up data. This includes demographics, diagnosis, prior procedures, devices used, defect size, and procedural success. The collection of the occurrence of major complications, such as embolization, device explant, or death will be collected annually. Recommended annual evaluations include a history and physical exam, an echocardiogram, and a chest x-ray. A fluoroscopy is recommended if the x-ray is "uncertain".
Follow-up Visits and Length of Follow-up	Annual follow-up will be solicited for a period of 5 years after implantation.
General
Study Status	Completed
Application Number / Requirement Number	P060039 / PAS001
Date Original Protocol Accepted	06/13/2008
Date Current Protocol Accepted	09/12/2014
Study Name	Chronic Extraction
General Study Protocol Parameters
Study Design	Case Control Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to characterize the removability of the Attain StarFixModel 4195 Left Ventricular Lead (StarFix). This study will evaluate the lead removal success in patients that are indicated for left ventricular lead removal.
Study Population	The Attain StarFix Model 4195 steroid eluting, transvenous lead with deployable lobe fixation is intended for chronic pacing and sensing of the left ventricle via the cardiac vein, when used in conjunction with a compatible implantable pulse generator or implantable cardiac defibrillator. The study population consists of subjects of either genders that are indicated for a Model 4195 or a non-Model 4195 Medtronic lead extraction who meet all inclusion criteria are eligible for this study. The baseline date (from Baseline CRF) is designated as the date on which the inclusion criteria are verified and must be within 30 calendar days prior to left ventricular lead extraction attempt. The extraction procedure must occur at least 181 days after implant for subjects included in the primary objective.
Sample Size	120 study subjects (Model 4195 and non-Model 4195 implanted subjects) will be enrolled in the study for the primary objective. A separate cohort of up to an additional 20 subjects with Model 4195 implanted from 90 to 180 days leads will be enrolled, 25 sites
Key Study Endpoints	The primary objective of the study is to compare the removal success of the Model 4195 lead to other Medtronic left ventricular lead models and to test the null hypothesis that the probability of removal of the Model 4195 left ventricular lead is less than other Medtronic left ventricular leads by 20%. The primary end point (extraction success rate) will be first evaluated at the end of three years or when 40 subjects are enrolled in the Model 4195 lead group, whichever comes first.
Follow-up Visits and Length of Follow-up	Subjects will be followed at one month after extraction attempt. The one month follow-up can be completed via in person visit, telephone or data collection from primary care center. Subjects will be exited from the study upon completion of the one month follow-up or after all Adverse Events have been resolved, whichever is later.
Interim or Final Data Summary
Interim Results	As of the time of this report there had been a total of five (5) AEs have been reported, one (1) AE had been adjudicated by the EAC. The adjudicated event was post procedural swelling. At the time of this report seven (7) leads had been returned to Medtronic for returned product analysis. Analysis has been completed on three (3) of the seven leads. No anomalies were found on any of the analyzed leads. One of the returned leads was a 4195 model.
Actual Number of Patients Enrolled	227 subjects
Actual Number of Sites Enrolled	24 centers
Patient Follow-up Rate	89.77%
Final Safety Findings	Extraction success is either: 1) removal of all targeted leads and all lead material from the vascular space, with the absence of any permanently disabling complication or procedure related death; or 2) removal of all targeted leads except for the retention of a small portion of the lead that does not negatively impact the outcome goals of the procedure. This may be the tip of the lead or a small part of the lead (conductor coil, insulation, or the latter two combined) when the residual part does not increase the risk of perforation, embolic events, perpetuation of infection or cause any undesired outcome The observed extraction success rate for model 4195 LV leads implanted greater than 181 days was 92.5% (37/40) compared to a success rate of 98.8% (163/165) for Non Model 4195 Leads.
Final Effect Findings	NA
Study Strengths & Weaknesses	Strength: The high follow-up rate: 89.77% Weaknesses: Limited number of leads studied: 40 Model 4195 leads
Recommendations for Labeling Changes	Yes (Labeling updates has been approved in P060039/S056)
General
Study Status	Completed
Application Number / Requirement Number	P000032 S028/ PAS001
Date Original Protocol Accepted	03/27/2009
Date Current Protocol Accepted	03/27/2009
Study Name	Her Option PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective study to continue follow-up of the premarket cohort. As per approval order, the results of the 2 and 3-year follow-up of the study subjects will be provided.
Study Population	This device is a closed-cycle cryosurgical device intended to ablate the endometrial lining of the uterus in pre-menopausal women with menorrhagia (excessive bleeding) due to benign causes for whom childbearing is complete. The study population is the subjects that were treated premarket.
Sample Size	All premarket subjects
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	106 women
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	At the end of the three year follow-up 51 participants were followed out of 82 treated (62.2%)
Final Safety Findings	Of the 82 subjects treated, 54 subjects (65.9%) were free of any treatment-related complications or side-effects. Only 2 (2.4%) subjects experienced serious adverse events related to study treatment. According to the Sponsor, there were no serious unanticipated adverse events within the study population. The Sponsor reported a reduction of pain/cramping and PMS symptoms following treatment , with 10 and 14 subjects reporting moderate to severe symptoms immediately after the intervention and after 12 months respectively. According to Sponsor incident events of bleeding through onto clothing was reported by 95% of subjects at the baseline assessment. At the 12 month visit, only 8% of subjects reported negative impact on quality of life, and bleed-through incidences were reduced to 23% of subjects
Final Effect Findings	Long term success rates were calculated for the 2-year and 3-year visits and demonstrate a success rate of 56.1% and 54.9% of subjects treated respectively. A percent reduction in menstrual levels from baseline was achieved in 89.4%, 90.9%, and 92.1% of participants after each of the three years of follow-up respectively.
Study Strengths & Weaknesses	This multicenter study was well planned and conducted to evaluate the effectiveness of this surgical device to treat menorrhagia due to benign causes in women for whom childbearing is complete. The study was conducted at seven sites by gynecology specialists with experience in the device and who were familiar with clinical research. As with any other study, there are limitations that need to be pointed out to have a better understanding of the results. Data from 9 censored patients, due to lack of effectiveness of the device, are excluded from the analysis. If these participants were included in the calculation, the effectiveness is estimated at 72.9% (35/48).
Recommendations for Labeling Changes	Labeling should be updated with the results of the study at all evaluation follow-up times in the context of physician and patient.
General
Study Status	Delayed
Application Number / Requirement Number	P050034 / PAS001
Date Original Protocol Accepted	07/01/2010
Date Current Protocol Accepted	12/17/2024
Study Name	IMT PAS 01 New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to assess the safety of the intraocular telescope as measured by the cumulative incidence of patients who within 5 years after implantation experience persistent vision impairing corneal edema (corneal edema leading to persistent loss of best corrected distance visual acuity [BCDVA] >2 lines from pre-surgery baseline level).
Study Population	Adult: >21
Sample Size	Number of subjects: 257 Assumptions for sample size estimation: A total of 257 patients planned for implantation with the intraocular telescope will be enrolled, in order to achieve 150 evaluable patients. Number of sites: 14 Sites location: US
Key Study Endpoints	Safety Endpoints Primary: Primary: the occurrence of persistent vision-impairing corneal edema (corneal edema leading to a persistent loss of BCDVA > 2 lines (> 0.2 LogMAR units) from pre-surgery baseline level at the last available visit). Secondary: Endothelial cell density (ECD) counts and the rate of endothelial cell loss (ECL) in the implanted eye will be evaluated at baseline and postoperative visits. Effectiveness Endpoints Primary: N/A Secondary: N/A
Follow-up Visits and Length of Follow-up	60 months
Interim or Final Data Summary
Interim Results	Safety Results: Adverse Events of Interest: Persistent BCDVA loss > 2 lines from pre-surgery baseline (present at study exit): 4 Inflammatory Deposits or Precipitates on IMT: 9 Device explant: 1 Mean ECD in the Evaluable Cohort prior to surgery was 2,353 cells/mm2. At Months 3, 12, 24, 36, 48 and 60 postoperative, the mean ECD % loss from preoperative baseline was 13%, 13%, 12%, 2%, 14% and 0.3%, respectively. Effectiveness Results: Key effectiveness findings: The primary study outcome was the occurrence of persistent vision-impairing corneal edema (corneal edema leading to a persistent loss of BCDVA > 2 lines from pre-surgery baseline level at the last available visit). Loss of BCDVA > 2 lines was 11% subjects at 12 months, 8%, subjects at 24 months, 18% subjects at 48 months, and 19% subjects at the final visit (60 months).
Actual Number of Patients Enrolled	36
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	36/36 subjects completed 1 month 34/36 subjects completed 3 months 32/35 subjects completed 6 months 28/33 subjects completed 12 months 24/30 subjects completed 24 months 22/27 subjects completed 36 months 18/19 subjects completed 48 months 16/16 subjects completed 60 months 25 missed visits 9 lost to follow up 19 discontinued 0 of 16 leftover subjects are active
General
Study Status	Hold
Application Number / Requirement Number	H080005 / PAS001
Date Original Protocol Accepted	03/10/2011
Date Current Protocol Accepted	01/03/2012
Study Name	Elana Surgical KitHUD
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Post Approval Registry
Study Population	All patients selected for a procedure with the Elana Surgical Kit will be part of the registry study. This will be an 'all comers' registry with no inclusion or exclusion criteria. The registry will collect data of all device uses.
Sample Size	It is expected that a site can select between 3-5 patients on an annual basis. The total expected number of sites in the USA is around 10-15. The total sample size for this registry is set at 80 device uses. The sample size for this study was selected based on the primary endpoint. The total of 80 device uses will provide 80% power for showing the flap retention rate does not exceed 38% under the assumption that the true rate is 22%. The true flap retention rate of 22% is based on the results of an IDE study on 37 device uses.
Key Study Endpoints	Primary endpoint The ability of the Elana Surgical Kit to retrieve a flap (circular disk of tissue) on the tip of the Elana Catheter while creating an arteriotomy. The flap retrieval will be judged successful, if the flap is retrieved on the tip of the Elana Catheter. The flap retrieval will be judged unsuccessful if the flap was either manually retrieved or not retrieved (= flap retention). Secondary measures Mortality and non fatal strokes will be recorded and described.
Follow-up Visits and Length of Follow-up	Post-operative Information will be collected pre-operatively, during the operation and one post operative follow up (>25 days) will be done.
General
Study Status	Completed
Application Number / Requirement Number	P010012 S398/ PAS001
Date Original Protocol Accepted	02/22/2016
Date Current Protocol Accepted	07/07/2020
Study Name	MOUNTAIN PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the MOUNTAIN PAS program is to provide a sustainable mechanism for the collection of data to assess the short and long term performance of Boston Scientific BSC pacing and defibrillation leads. The data sources used to evaluate the ACUITY X4 lead include four existing Real-World Data (RWD) databases and one clinical trial database.
Study Population	All patients added to each database (CMS, Device Tracking, LATITUDE, Complaints database) during the evaluation period will be included in the analyses as specified.
Sample Size	Data from all US centers that contribute data to any of the databases will be used in the analysis.
Key Study Endpoints	The sponsor states that the short-term safety and short- and long-term effectiveness objectives have already been fulfilled through evaluation of clinical trial data. The long-term safety objective has yet to be fulfilled and will be assessed by the Primary Safety Endpoint, Sensitivity Analysis and other analysis specified.
Follow-up Visits and Length of Follow-up	Data will be collected during routine device follow-up and patient care. No additional follow-ups or procedures are required.
Interim or Final Data Summary
Actual Number of Patients Enrolled	ACUITY X4: CMS Fee-for-Service patients with ACUITY X4 leads (N = 34,741) RELIANCE 4-FRONT: CMS Fee-for-Service patients with RELIANCE 4-FRONT leads (N = 10,677) There is no concern for the sample size since this sample size exceeds the minimum 1000 leads required
Actual Number of Sites Enrolled	N/A; This study uses RWD
Patient Follow-up Rate	ACUITY X4: The 34,741 ACUITY X4 leads with fee-for-service coverage at time of implant have been followed for a median of 28.0 months. Chronic follow-up: 33,834 RELIANCE 4-FRONT: The 10,402 RELIANCE 4-FRONT leads with fee-for-service coverage at time of implant have been followed for a median of 20.3 months. Chronic Follow-up: 10,294 No concern for the follow-up sample size. Since this study uses RWE, there is no calculated follow-up rate.
Final Safety Findings	ACUITY X4: The observed primary event-free rate at 5 years equaled 99.5% with a lower confidence limit of 99.4%. There was no signal of accelerating risk of failure. No secondary or tertiary analyses were triggered due to the results of this analysis. The majority of ACUITY X4 Primary Endpoint events occurred in the Malfunction / Breakdown / Mechanical category, with an occurrence rate of < 0.3%. The overall complication-free rate is 97.7% at five years with a lower confidence limit of 97.5%. RELIANCE 4-FRONT: The observed primary event-free rate at 5 years equaled 99.6% with a lower confidence limit of 99.0%. There was no signal of accelerating risk of failure. No secondary or tertiary analyses were triggered due to the results of this analysis. There were 5096 RELIANCE 4-FRONT leads in single-chamber systems that contributed to the analysis of the sensitivity analysis. The observed primary event-free rate at 5 years equaled 98.2% with a lower confidence limit of 97.3%. There was no signal of accelerating risk of failure. No secondary or tertiary analyses were triggered due to the results of this analysis. The sponsor states that the rate of occurence for each diagnosis code category could not be presented due to cell suppression restrictions. All categories had occurrence rates < 0.2%.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study progressed as expected and the sponsor met their endpoints.
Recommendations for Labeling Changes	You have provided a report of the methods, planned analyses and outcomes from the Real World Evidence (RWE) data examination satisfying the Conditions of Approval Studies for ACUITY X4 and RELIANCE 4-FRONT leads. FDA review believes your outcomes are supportive of continued market approval and update of the labeling. FDA also asks that you consider adding the following text and flow charts to your report to help practicing physicians understand the methods and limitations inherent in a RWE approach to showing continued reliability of these leads: 1) Please consider adding a flow chart and plain language text to explain how the most important primary endpoint outcomes related to reliability (for example and not limited to insulation break and electrode conductor fracture) are intended to be detected at the level of detection in each database according to your chosen RWE method. (In other words: What data must be found in each of the linked databases in order to adjudicate that a lead failure is detected? 2) Please add a limitations section explaining any manner in which detection of primary endpoint outcome adverse events may not occur, leading to a falsely normal lead performance adjudication
General
Study Status	Completed
Application Number / Requirement Number	P010012 S436/ PAS002
Date Original Protocol Accepted	07/25/2017
Date Current Protocol Accepted	08/26/2022
Study Name	MANAGE-HF
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	1. To evaluate and optimize HeartLogic Heart Failure Diagnostics clinical integration and the alert management process (Phase I). 2. To evaluate Heart Logic in regards to patient outcomes of death and heart failure hospitalizations (Phase II).
Study Population	Test Device: Phases I and II: ICD and CRT-D devices with HeartLogic turned ON Control Device: Phase II: ICD and CRT-D devices with HeartLogic alerts turned OFF
Sample Size	Between 1700 and 2700 subjects will be enrolled in the study: Phase I: Up to 200 subjects Up to 200 subjects are required in Phase I to build critical knowledge regarding the clinical integration of HeartLogic and the alert management process. Phase II: 1500-2500 subjects The sample size required for Phase II of MANAGE-HF is event-driven. Between 1500 and 2500 subjects will be enrolled in the trial to accrue the necessary number of endpoint events to sufficiently power the primary endpoint. A total of 864 endpoints events from randomized subjects in Phase II are required to sufficiently power the primary endpoint, based on the following assumptions: Expected control group incidence of annual heart failure hospitalization and death = 20% One-sided Alpha = 5% Power = 90% Hazard Ratio = 0.8 Estimated enrollment period = 24 months Expected Follow-up period = minimum of 24 months for last patient enrolled Final sample size will be determined during the study using a sample size re-estimation interim analysis.
Key Study Endpoints	LATITUDE NXT 5.0 System
Follow-up Visits and Length of Follow-up	Follow-Up Schedule: Enrollment Visit Baseline Visit Scheduled follow-up Visits Annual Phone Calls (6, 18,30, 42 months… from baseline) Annual In-Clinic (12,24,36,48 months…from baseline visit) Additional Follow-up Visits HeartLogic Alert Action Visit Additional Subject Interactions (i.e., Not in Response to HeartLogic Alerts) End of Study Visit
Interim or Final Data Summary
Actual Number of Patients Enrolled	Phase 1: 200 subjects Phase 2: 3886 subjects
Actual Number of Sites Enrolled	Phase 1: 29 sites Phase 2: N/A
Patient Follow-up Rate	Phase 1 Rate = 72% 191 completed the baseline visit 144 followed until the last patient enrolled completed their 12- month visit 37 withdrawals 19 subjects died Phase 2: N=1458 patients were included in the analysis, of which 19 died or their device was no longer in service. These were followed for an average of 1.08 years
Final Safety Findings	Phase 1 does not have a safety endpoint Phase 2 does not have a safety endpoint
Final Effect Findings	Phase 1 does not have effectiveness endpoints Phase 2: The observed Sensitivity was 74.5% and an adjusted Sensitivity (95% confidence interval) was 71.3% (65.4%, 76.6%). The False Positive rate (95% confidence interval) was 1.48 (1.42, 1.59).
Study Strengths & Weaknesses	Phase 1: Patients that were included in Phase I of MANAGE-HF were required to meet specific study inclusion and exclusion criteria. This included evidence of worsened heart failure prior to enrollment. In addition, patients with severe kidney impairment or short life expectancy were excluded. Thus, the results are limited to the population that was studied. Furthermore, the small sample size and lack of a control group limits the interpretation of the results. Finally, the study was primarily conducted in the US, and results may vary in other geographies. Phase 2: • The pre-specified endpoints were met. • Analysis was retrospective - The data source for HFE was CMS claims, so there was no event or site monitoring. - Events were not independently adjudicated. - Some results were coarsened due to low numbers as required by CMS reporting policies. - Only US patients are included, and results may be different in other geographies. - Only CMS patients were included, and on average were older with more comorbidities than the patients included in the pre- market (MultiSENSE) study.
Recommendations for Labeling Changes	Phase 1: No labeling changes are recommended. Phase 2: Labeling changes are recommend.
General
Study Status	Completed
Application Number / Requirement Number	P010014 / PAS001
Date Original Protocol Accepted	04/21/2004
Date Current Protocol Accepted	01/04/2013
Study Name	Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, non-randomized study to evaluate two-year post-operative complications among patients implanted with Oxford Meniscal Unicompartmental Knee System and 9-year long-term survivorship of the device.
Study Population	This device is indicated for use in patients with osteoarthritis or avascular necrosis limited to the medial compartment of the knee and intended to be implanted with bone cement. The study population includes patients who are 18 years or older, undergoing primary knee arthroplasty for either Osteoarthritis or Avascular necrosis of the medial compartment of the knee, and meet other inclusion/exclusion criteria will be included in this study.
Sample Size	389 knees
Key Study Endpoints	For Phase 1 (0-2 years), the study endpoint is complications, which is defined as "Any untoward medical occurrence in a patient administered a medical device and which does not necessarily have to have a causal relationship with this treatment. For Phase II, the study endpoint is "removal and/or revision of any component of the device".
Follow-up Visits and Length of Follow-up	In Phase 1, patients will be followed clinically at 6 weeks, 6 months, 1- year and 2- year post-operation. Information gathered includes all adverse events and survival data. In Phase II (3-9 year), only the device survival data will be gathered through patient direct mailing and/or phone call annually.
Interim or Final Data Summary
Interim Results	As of April 2, 2010, there have been 5 deaths reported due to pancreatic cancer (n=1), heart failure (n=1), leukemia (n=1), terminal illness (n=1) and unknown cause (n=1); as well as 11 revisions out of 388 knees implanted.
Actual Number of Patients Enrolled	The patient population includes 354 patients and 388 knees that underwent primary partial knee arthroplasty for either osteoarthritis or avascular necrosis of the medial compartment.
Actual Number of Sites Enrolled	A total of 6 clinical sites enrolled patients in the post-approval study.
Patient Follow-up Rate	The patient post-operative follow-up rates in the study were as follows: 98.2% at 6 weeks, 86.4% at 3 years, 84.2% at 6 years, 82.9% at 8 years and 82.4% at 9 years. The overall follow up rate is 86.8%.
Final Safety Findings	There were 130 complications in 388 knees (16.8 complications/ 100 patient years) from the PAS group and there were 4 complications in 125 knees (1.6 complications /100 patient years) from the historical control IDE group (p-value <0.001). The overall 9-year revision rate is at least 12.4%.
Final Effect Findings	The 9-year cumulative device survivorship for all patients in this post-approval study was 86.56% (95% CI: 82.54, 89.71)
Study Strengths & Weaknesses	Study strengths included an adequate sample size and follow-up rate. A study weakness was the absence of optimal comparability for the collection of complication data between the post-approval study and historical control-IDE groups.
Recommendations for Labeling Changes	The labeling of this device should be updated with the results of this post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P010031 S176/ PAS001
Date Original Protocol Accepted	01/09/2012
Date Current Protocol Accepted	11/22/2013
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Medtronic Post-Approval Network (PAN) is designed to conduct non-randomized, active prospective post-market Surveillance. The Registry is sponsored by Medtronic and is comprised of a global network of hospitals, clinics and clinicians from which reliable ¿real world¿ product safety and patient clinical outcome information is generated. Primary objective: To demonstrate that the complication- free probability is greater than 92.5% at five years post- implant for the high voltage DF4 connector.
Study Population	This study will consist of 1,778 patients implanted with a DF- 4 connector system, enrolled at one of approximately 150 centers globally. Subjects that meet the following inclusion criteria and do not meet any of the following exclusion criteria are eligible for enrollment. Inclusion Criteria ¿ Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements ¿ Subject is implanted with a DF-4 connector system. ¿ Subject within 30 days of implant Exclusion Criteria ¿ Subject who is, or will be inaccessible for follow-up at a site ¿ Subject with exclusion criteria required by local law (Europe, Central Asia [ECA] only) ¿ Complete implant and follow-up data, including any product-related events at implant through the time of enrollment are unavailable
Sample Size	Accounting for attrition, a minimum enrollment of 1778 DF4 connectors are estimated to be required in order to achieve the desired sample size for the primary objective analysis at five years.
Key Study Endpoints	A list of lead-related events eligible to be included in the primary objective: Failure to capture, Failure to sense/ Undersensing, Oversensing, Threshold rise, Abnormal pacing impedance, Abnormal defibrillation impedance (RV and/or SVC coil), Lead insulation breach, Lead conductor fracture, Extra cardiac stimulation, Lead dislodgement, Cardiac perforation, Structural Lead Failure.
Follow-up Visits and Length of Follow-up	Subjects will be followed for a minimum of 5 years from their implant date. Therefore, the expected duration of the DF4 PAS is approximately 7 years. Frequency of f/u is every 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1778
Actual Number of Sites Enrolled	104
Patient Follow-up Rate	38.5%
Final Safety Findings	The complication-free survival probability in this group was 98.6%.
Final Effect Findings	The sponsor presented Pacing Thresholds, Pacing and Defibrillation Impedance, and Sensing data for the subjects who remained in the study at 6 month intervals by lead type associated with the DF4 connector. The results confirm that the electrical performance of the DF4 connector leads is stable over time and within expected ranges.
Study Strengths & Weaknesses	A strength of this study is that the results reflect what is expected to be observed in routine clinical practice. A weakness includes the premature exit of some study sites and patients due to the longer-term nature of the study, thus limiting patient follow-up. Despite this barrier, the primary objective of the study was met, demonstrating the safety and efficacy of the DF4 connector.
Recommendations for Labeling Changes	Yes, completed.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S216/ PAS001
Date Original Protocol Accepted	01/09/2012
Date Current Protocol Accepted	11/22/2013
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Medtronic Post-Approval Network (PAN) is designed to conduct non-randomized, active prospective post-market Surveillance. The Registry is sponsored by Medtronic and is comprised of a global network of hospitals, clinics and clinicians from which reliable ¿real world¿ product safety and patient clinical outcome information is generated. Primary objective: To demonstrate that the complication- free probability is greater than 92.5% at five years post- implant for the high voltage DF4 connector.
Study Population	This study will consist of 1,778 patients implanted with a DF- 4 connector system, enrolled at one of approximately 150 centers globally. Subjects that meet the following inclusion criteria and do not meet any of the following exclusion criteria are eligible for enrollment. Inclusion Criteria ¿ Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements ¿ Subject is implanted with a DF-4 connector system. ¿ Subject within 30 days of implant Exclusion Criteria ¿ Subject who is, or will be inaccessible for follow-up at a site ¿ Subject with exclusion criteria required by local law (Europe, Central Asia [ECA] only) ¿ Complete implant and follow-up data, including any product-related events at implant through the time of enrollment are unavailable
Sample Size	Accounting for attrition, a minimum enrollment of 1778 DF4 connectors are estimated to be required in order to achieve the desired sample size for the primary objective analysis at five years.
Key Study Endpoints	A list of lead-related events eligible to be included in the primary objective: Failure to capture, Failure to sense/ Undersensing, Oversensing, Threshold rise, Abnormal pacing impedance, Abnormal defibrillation impedance (RV and/or SVC coil), Lead insulation breach, Lead conductor fracture, Extra cardiac stimulation, Lead dislodgement, Cardiac perforation, Structural Lead Failure
Follow-up Visits and Length of Follow-up	Subjects will be followed for a minimum of 5 years from their implant date. Therefore, the expected duration of the DF4 PAS is approximately 7 years. Frequency of Follow-up Assessments Every 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1778
Actual Number of Sites Enrolled	104
Patient Follow-up Rate	38.5%
Final Safety Findings	The complication-free survival probability in this group was 98.6%.
Final Effect Findings	The sponsor presented Pacing Thresholds, Pacing and Defibrillation Impedance, and Sensing data for the subjects who remained in the study at 6 month intervals by lead type associated with the DF4 connector. The results confirm that the electrical performance of the DF4 connector leads is stable over time and within expected ranges.
Study Strengths & Weaknesses	A strength of this study is that the results reflect what is expected to be observed in routine clinical practice. A weakness includes the premature exit of some study sites and patients due to the longer-term nature of the study, thus limiting patient follow-up. Despite this barrier, the primary objective of the study was met, demonstrating the safety and efficacy of the DF4 connector.
Recommendations for Labeling Changes	Yes, completed.
General
Study Status	Completed
Application Number / Requirement Number	P010031 S344/ PAS001
Date Original Protocol Accepted	09/25/2013
Date Current Protocol Accepted	09/25/2013
Study Name	LIA in Non-MDT Leads Surveillance Update Analysis
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This analysis plan is created to leverage data that is already available as part of the Medtronic CareLink remote management system. An RV LIA trigger requires 2 of 3 components to be satisfied within 60 days: abrupt pace sense impedance change, frequent extremely short R-R intervals, and rapid non-sustained VT episodes. The save-to-disk file associated with each of these alert (RV LIA or impedance nominal threshold) triggers, and any associated data from DRS and/or GCHS, will be reviewed by the lead failure adjudication committee to determine the cause of the RV LIA alert or impedance nominal threshold crossing.
Study Population	This is a retrospective analysis of existing data from CareLink. Among the large number of patients and clinics that use CareLink to manage their devices, there are some that have already been implanted with a combination of an RV LIA enabled device and an RV defibrillation lead not manufactured by Medtronic. There are three Medtronic sources of information that will be used to support this analysis: X Data Warehousing and Analytics Services (DWAS) X Device Registration System (DRS) X Global Complaint Handling System (GCHS) The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013.
Sample Size	As there are no hypotheses being tested for this analysis, there are no powered sample size estimates. However, two requirements were identified to determine the sample size and timing of the analysis. First was to ensure the amount of lead follow-up is at least the size of the PMA analysis (11,052 RV LIA years of follow up across both St. Jude and Boston Scientific leads) and secondly the analysis will occur after PMA approval. Current estimates are that the RV LIA years of follow-up since the PMA cut off of October 4, 2011 has already been exceeded with approximately 14,500 years of RV LIA enabled follow-up. Therefore, assuming event rates remain the same as in the PMA cohort, it is expected at 77 additional lead events will be included in this study which is 28% more than the 60 true lead events observed across both manufacturers in the PMA analysis. The data cut off for analysis will be the first day after PMA approval in which the RV LIA enabled years of follow-up is greater than 11,050 years of follow-up.
Key Study Endpoints	There are three Medtronic sources of information that will be used to support this analysis: Data Warehousing and Analytics Services (DWAS) Device Registration System (DRS) Global Complaint Handling System (GCHS) The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013. Primary Objective: To summarize the number of lead failure events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads). Secondary Objective: To summarize the number of other detected events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads).
Follow-up Visits and Length of Follow-up	No follow-up visits and length of follow-up
Interim or Final Data Summary
Actual Number of Patients Enrolled	5753 devices
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	The incidence of right ventricular (RV) Lead Integrity Alert (LIA) trigger or impedance nominal threshold during the post-approval period was low in St. Jude Medical (STJ) Riata/Durata leads and Boston Scientific (BSX) Endotak leads (0.725% per device year in STJ leads and 1.23% per device year in BSX leads). The majority of identified triggers classified as lead failure events (LFEs) or other detected events (ODE) were detected by only the RVLIA criterion in both STJ and BSX leads. These findings were consistent with events identified during the original analysis supporting the PMA labeling language for RV LIA use with Non- Medtronic leads.
Study Strengths & Weaknesses	Strength: Large sample size; Weakness: Retrospective data analysis. Lack of data presented to support advance warning of RV LIA relative to lead failure events. No data available on the positive predictive value or negative predictive value.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P100026 / PAS001
Date Original Protocol Accepted	11/14/2013
Date Current Protocol Accepted	09/05/2014
Study Name	Continued F/u -Long Term Treatment (LTT)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	The population enrolled included 57 subjects from the feasibility study and 173 subjects from the pivotal study, for a total of 230 subjects.
Actual Number of Sites Enrolled	The total number of sites enrolled in the study was 33.
Patient Follow-up Rate	A total of 70.4% of the enrolled population reached the study conclusion (162/230 subjects).
Final Safety Findings	As of the final data cutoff (May 1, 2018) 77% of the subjects in the LTT study had reported a serious adverse event (SAE) regardless of the relationship to the device (177/230 subjects). The most common categories of all SAEs were EEG monitoring (63 events in 19.1% of subjects; 44/230) and implant site infection (29 events in 11.3% of subjects, 26/230). The SUDEP rate was calculated for the events that occurred while subjects’ neurostimulators were programmed to deliver responsive stimulation, and includes 5 deaths where SUDEP was determined to be “definite” or “probable.” Between the feasibility, pivotal, and LTT studies, these subjects accumulated 1895.2 patient implant-years, for a definite or probable SUDEP rate of 3.2 per 1000 patient implant-years. The frequency of AEs was comparable to the incidence of AEs reported in the PMA. Whether device-related or not, 99.1% of subjects experienced at least one AE (229/230, 3128 total events). Of these, 56.1% of subjects experienced an event that was determined to be related to the device (129/230). Reasons for explantation and analysis of devices returned revealed no concerns related to the device. There were no unanticipated adverse device effects (UADE) reported in the LTT study.
Final Effect Findings	The median percentage reduction in disabling seizures improves over time. After one year, the intent-to-treat (ITT) population experienced a median reduction of 31.5% (in 229 subjects), which increases to 75% at the end of nine years (in 178 subjects). The responder rate also improves over time. After one year, 33.2% of subjects were considered responders (76/229) increasing to 71% after nine years (117/178). Compared to baseline, there were improvements over the entire 9-year follow-up in overall QOLIE and epilepsy-targeted and cognitive factors related subscales. In the mental health and physical health factors, the improvement observed in the first 2-4 years post-implant were not sustained, and returned to baseline over the 9-year period.
Study Strengths & Weaknesses	One hundred sixty-two subjects reached the protocol-defined completion of the LTT study, from an initially enrolled population of 230. These 162 subjects have at least nine years of experience with the system. A study weakness is that subjects were able to modify antiepileptic medications; this PAS was not designed to evaluate the contribution of factors such as this to long term safety or effectiveness.
Recommendations for Labeling Changes	no
General
Study Status	Completed
Application Number / Requirement Number	P010031 S513/ PAS001
Date Original Protocol Accepted	02/01/2016
Date Current Protocol Accepted
Study Name	MR conditional Tachy Therapy Systems Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P010031 S563/ PAS001
Date Original Protocol Accepted	03/24/2017
Date Current Protocol Accepted
Study Name	MPP PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	A global, prospective, observational, multi-center study following patients implanted with a CRT Quad system and enrolled in the Product Surveillance Registry per the expected standard of care practices of their care provider. The study requires regular reporting of CRT response assessments. Data capture will be reflective of real-world clinical practice in terms of how physicians assess a patients’ response to CRT and what actions they may take to improve response. The study provides an estimate of the nonresponder rate and estimates the proportion of patients who are converted from a non-responder to a responder with the use of the MPP feature.
Study Population	Patients who are considered non-responders to traditional CRT. The patient population is its own control group.
Sample Size	A sample size of 1250 patients assuming 20% of the patients are identified as a surviving CRT non-responder, of which 50% have MPP enabled produces a 95% confidence interval width of 16.5%, if the MPP responder rate is 30%. The primary objective will be analyzed when a sample size of 118 CRT non-responders with MPP enabled is achieved or at 3 years after the approval of the MPP feature whichever comes first.
Key Study Endpoints	To estimate the proportion of MPP therapy responders among patients who did not respond to standard CRT therapy.
Follow-up Visits and Length of Follow-up	duration of the study
Interim or Final Data Summary
Interim Results	Number of IRB Approvals 80 IRB approvals Number of study sites enrolled 80 Clinical Sites Number of subjects enrolled 1515 Subjects Enrolled Data Quality/Inconsistencies 45 study exits (not including deaths), 11 deviations Key Safety Findings 90 deaths 41 of these events were due to cardiac death. There were 149 (of 184 adjudicated) reported Heart Failure Events and 115 heart Failure hospitalizations.
Actual Number of Patients Enrolled	1514 patients
Actual Number of Sites Enrolled	71 sites
Patient Follow-up Rate	The overall follow-up rate was 92.1%
Final Safety Findings	There were no HF hospitalizations after MPP enabled for the four subjects in the primary objective cohort. There was one death of subject in the primary objective cohort after MPP enabled, this was assessed as not system-related.
Final Effect Findings	Primary Objective: To estimate the proportion of MPP therapy responders among patients who did not respond to standard CRT therapy and had MPP programmed “on • 581 (38.4%) of the 1514 enrolled patients completed a CRT response assessment between 3-9 months post CRT implant AND prior to MPP enabled (if enabled). • A total of 108 (18.6%) patients were identified as non-responders to CRT therapy • Seven (7) patients had the MPP functionality turned on subsequent to the visit. Of the seven (7) patients reported to have MPP programmed on at least three months post implant, four (4) maintained MPP enabled for at least three additional months as evidenced in their device data and therefore contribute to the primary objective analysis cohort. Secondary Objectives: Summarize patient baseline characteristics including but not limited to NYHA class, QRS duration, bundle branch morphology, LV lead implant location, etc. • Of the enrolled 1514 patients, 1026 patients (67.8%) received a CRT-D device while 488 patients (32.2%) received a CRT-P. The majority of patients enrolled were NYHA class II (27.4%) or III (37.0%), and NYHA class was missing for 30.1%. For 1292 patients QRS was assessed and average QRS duration was 154.3 ms with a standard deviation of 30.8. Around half of the patients had left bundle branch block (52.3%). The majority of LV leads were implanted in the left ventricle posterior lateral vein (30.3%) or the left ventricle lateral (marginal) vein (27.7%).
Study Strengths & Weaknesses	There were far fewer patients than expected to fall under the primary objective analysis cohort. As there were only four (4) patients, the utilization rate was too low to analyze. The low utilization rate was confirmed by real-world MPP usage rates from the Medtronic CareLink network. This study provided general descriptive information of CRT-D and CRT-P utilization among different NYHA class patients as well as data on the average QRS duration and lead placement during implantation. This is unrelated to the investigational device (MPP)
Recommendations for Labeling Changes	Yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P960009 S219/ PAS001
Date Original Protocol Accepted	10/12/2018
Date Current Protocol Accepted	08/03/2022
Study Name	DBS for Epilepsy New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study “Medtronic Deep Brain Stimulation (DBS) Therapy for Epilepsy Post-Approval Study (EPAS)” will be an interventional, global, prospective, multicenter, open-label, new enrollment, single arm, two-phases (CMM and CMM+DBS) study design to evaluate the long-term safety and effectiveness of Medtronic DBS Therapy for epilepsy on seizure reduction in subjects newly implanted with the DBS device (Activa™ PC Neurostimulation System or PerceptTM PC Neurostimulation System) + current medical management (CMM) following an initial period of 3 months of CMM only. Subjects will then be clinically eligible for the DBS device + CMM. Those meeting implant criteria will undergo DBS implant +CMM. The CMM phase is the 3-month period prior to the CMM Month 3 Visit. The CMM phase is expected to start at the time of enrollment (CMM Month 0 Visit) for most subjects but may start prior to enrollment for subjects with a pre-existing diary. Pre-existing diary data must be documented in the medical record, must be robust in that the data allows the subject to meet the eligibility criteria, and be collected only after study consent is obtained. In the case of pre-existing diary, CMM Month 0 and CMM Month 3 visits may be conducted on the same date. The DBS + CMM phase starts with the Implant Visit and includes the Stimulation Activation Visit followed by 3-month Visit intervals until the DBS + CMM Month 12 Visit. After completing the DBS + CMM Month 12 Visit, visit follow-up becomes annual until three years of follow-up are complete. The subject will discontinue from the study following the completion of the DBS + CMM phase at 36 months.
Study Population	The intended study population is subjects 18 years and older diagnosed with epilepsy characterized by focal-onset seizures that are refractory to at least 3 AEDs.
Sample Size	to power this objective, approximately 140 enrollments (based on 35% pre-implant attrition) and no more than 90 implanted subjects (based on a maximum of 20% post-implant attrition or missing diary data) may be necessary to obtain approximately 72 subjects with follow-up data at 3 years.
Key Study Endpoints	Safety Endpoints Primary Effectiveness: To demonstrate that the total seizure frequency during CMM is reduced by 40% after 3 years of DBS + CMM. This will be demonstrated though a percentage reduction in seizures which is statistically non-inferior to 40% from pre- implant to 3 years post-implant in patients treated with the DBS system, utilizing a margin of 10%. Secondary: Secondary Effectiveness Objectives: 1. To demonstrate that the total seizure frequency assessed during the CMM phase is reduced after 12 months of DBS + CMM 2. To demonstrate that the disabling seizure frequency assessed during the CMM phase is reduced after 12 months of DBS + CMM 3. To demonstrate that the frequency of seizures originating in the temporal lobe assessed during the CMM phase is reduced after 12 months of DBS + CMM Secondary Safety Objective: 4. To characterize the Sudden Unexpected Death in Epilepsy (SUDEP) rate
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	29
Actual Number of Sites Enrolled	11
General
Study Status	Hold
Application Number / Requirement Number	H190001 / PAS001
Date Original Protocol Accepted	10/04/2021
Date Current Protocol Accepted	10/16/2023
Study Name	HALO-FHII PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objectives of the summative usability evaluation are to: 1. Demonstrate that the device can be used by representative intended users under simulated and actual use conditions, without producing patterns of failures that could result in a negative clinical impact to patients or harm to users or patients; 2. Demonstrate that the device design, representative training and labeling are effective in mitigating all use-related risks to an acceptable level; 3. Demonstrate that no new use-related hazards or hazardous scenarios have emerged, and evidence supports that benefits outweigh the residual use-related risks; and 4. Demonstrate that operators are able to prepare the solvent mixture correctly, including verification of the mixture
Study Population	1. Age: 18+ years old 2. Gender: Male or Female 3. Education: Undergraduate degree 4. Experience: unrestricted 5. Primary Duties: Performs laboratory procedures, including preparing and testing specimens and recording results 6. Training: on-the-job instrument training, aseptic technique, blood/plasma handling procedure 7. Hearing: unrestricted 8. Vision: corrected vision or no impairments 9. Permissible impairments: appropriate to the job 10. Language: English 11. Cultural Background: unrestricted
Sample Size	The sample will consist of trained HDL Therapeutics professionals, N=5.
Key Study Endpoints	The summative usability study data collection and analysis is intended to provide sufficient and appropriate data to facilitate identification and understanding of the root causes of any use failures or problems that occur, including usability issues. The root cause analysis is intended to identify causes that are related to the design of the system, the system labeling (including IFU), and the training of test participants. Only the completion of the task without any observed use difficulties, use errors, or assistance from the moderator will be deemed a successful outcome. All other outcomes will be considered degrees of failure for which the moderator will observe and report the nature of the issues in greater detail. A failure can be classified as any assistance provided by the moderator to a test participant for any specific task, beyond what is provided during the training session. A failure can also result if the participant performs a task incorrectly and does not request help. The acceptable range for the number of attempts for this system is three. There will be a limit of 3 times a participant can attempt a task.
Follow-up Visits and Length of Follow-up	The follow-up will be immediately after the 8 hour training evaluation.
General
Study Status	Completed
Application Number / Requirement Number	P010041 / PAS001
Date Original Protocol Accepted	06/24/2002
Date Current Protocol Accepted	06/24/2002
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A five-year clinical study was designed and included two cohorts: 1) A retrospective cohort of patients who were eligible for inclusion in this study, were part of the IDE studies and received an aortic SAV valve between January 1991 and December 1992 at three Canadian sites, and 2) A prospective cohort of newly enrolled patients who received an aortic SAV valve implant after the May 24, 2002.
Study Population	The study population consisted of all eligible patients who were contacted for follow-up from the pre-market study #99-03 and agreed to participate and a new group of eligible patients who received SAV valve implants after May 24, 2002 (study #2007-07). There were six sites.
Sample Size	160 patients, 6 sites.
Key Study Endpoints	There were four outcome variables: (1) Cardiovascular complications: Assessed according to 1996 Society of Thoracic Surgeons Guidelines; (2) Valve-induced hemolysis: based on findings of the complete blood count (red blood cell count, white blood cell count, platelet count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, serum lactate dehydrogenase); (3) Patient functional classification: using New York Heart Association (4) Hemodynamic performance (Doppler echocardiographic study): All echocardiograms were performed via the transthoracic mode. The echocardiography data contained the following variables: mean pressure gradient, peak pressure gradient, effective orifice area (calculated by continuity equation), effective orifice index (effective orifice area divided by BSA), and performance index (EOA / in vitro EOA).
Follow-up Visits and Length of Follow-up	Annual postoperative evaluations are performed on all patients of both cohorts, by the investigator. Types of follow-up methods used are office visit and telephone follow-up performed by the investigator. If the patient was seen at his/her primary care physician's office, medical records were requested by the investigator to collect data for the study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Three-hundred twenty-one (321) subjects were enrolled.
Actual Number of Sites Enrolled	Six (6) study sites were enrolled.
Patient Follow-up Rate	At 5-years there was a 67% follow-up rate.
Final Safety Findings	At 1 year, freedom from valve-related re-operations with explantation was 99.67%. At 5-years, the freedom from all reoperations with explants is 99.0% ± 0.7%., and at18-years, the freedom from all (valve-related) reoperations with explant is 78.5 ± 10.3%.
Final Effect Findings	NYHA Functional Class 1-year interval: preoperative and postoperative NYHA data were available for 194 patients. Of these patients, 87.6% showed improvement, 10.3% showed no change and 2.1% worsened in their NYHA functional class 4- to 5-year interval: data were available for 196 patients. Of these patients, 87.2% improved, 11.2% showed no change, and 1.6% worsened. 10- to 11-year interval: data were available for 91 patients. Of these patients, 87.9% improved, 9.9% were the same, and 2.4% worsened. 14- to 15-year interval: data were available for 54 patients. Of these patients, 83.3% improved, 13.0% were the same as their preoperative status and 3.7% worsened.
Study Strengths & Weaknesses	The losses to follow-up are minimal and at least 67% of participants have been contacted at each time point up to 5 years. This rate is acceptable given the age and comorbidities of the population. Although the study protocol states the length of follow-up is 5-years, there are study participants that have been followed for much longer.
Recommendations for Labeling Changes	Updated labeling requested from the sponsor should reflect the post-approval study safety and effectiveness data for the SAV valve. The post-approval study data should be presented separately from the original PMA data that reflect the data upon which the PMA application approval was based.
General
Study Status	Hold
Application Number / Requirement Number	P060017 / PAS001
Date Original Protocol Accepted	10/29/2007
Date Current Protocol Accepted	10/29/2007
Study Name	PPC Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a clinical study to estimate the positive predictive concordance between the breast lymph node assay and histology as routinely practiced i.e., routine hematoxylene and eosin histology of sentinel lymph node(s), and when available, routine histology of non-sentinel axillary lymph nodes. The positive predictive concordance value is defined as the proportion of breast lymph node assay positive subjects with histologically detectable breast cancer metastases.
Study Population	Study Population: Breast cancer patients. Indication: The device is indicated as an in vitro diagnostic test for the rapid detection of greater than 0.2 mm metastases in nodul tissue removed from the sentinel lymph nodes biopsies of breast cancer patients.
Sample Size	1,000 female or male patients to include a minimum of 246 breast lymph node positive patients, 4 sites
Key Study Endpoints	The primary endpoint is the efficacy endpoint as measured as a metric that uses the less thorough reference. The metric is the positive predictive concordance between the breast lymph node assay and histology as routinely practiced i.e., routine hematoxylene and eosin, histology of sentinel lymph node(s), and when available, routine histology of non-sentinel axillary lymph nodes.
Follow-up Visits and Length of Follow-up	Follow-up was not required for this study.
General
Study Status	Completed
Application Number / Requirement Number	P010062 / PAS001
Date Original Protocol Accepted	06/07/2007
Date Current Protocol Accepted	06/07/2007
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort study conducted in two phases: the Treatment Phase and the Regression Phase. During the Treatment Phase each subject was seen for a Diagnostic Fit Visit, at which time eligibility was assessed, informed consent obtained, and eligible subjects were enrolled into the study. Enrolled subjects were assessed for study lenses and the lenses were ordered. The subjects were scheduled for a Lens Dispensing Visit and a 24-Hour Lens Evaluation Visit. The subjects wore their study lenses on an overnight wear basis. Subjects returned for the 24-Hour Lens Evaluation Visit, and data was evaluated to determine if the subject was a viable candidate to continue the Treatment Phase. If the subject was eligible, the Investigator scheduled follow-up visits. Daily disposable lenses (Bausch and Lomb SofLens one day disposable lenses, known as "maintenance lenses") were dispensed to provide supplemental visual correction during the day as needed for the Ortho-K lens adaptation period. The Regression Phase began after the 3-Month or Exit Visit. Subjects returned for follow-up visits either 5 hours after lens removal on the same day as the 3-Month Visit, or the next day after wearing the Ortho-K lenses the previous night (5 hours after lens removal). They then returned for a 24-Hour Visit, a 3-Day Visit, and a 1-Week Visit. If the subject was discontinued prior to the 3-Month Visit after wearing Ortho-K lenses, he/she was also followed through the same Regression Phase schedule.
Study Population	The lenses are indicated for use in the reduction of myopic refractive error in non-diseased eyes. The lenses are indicated for overnight wear for the temporaly reduction of myopia up to 5.00 diopters with eyes having astigmatism up to 1 .50 diopters. The lenses may only be disinfected using a chemnical disinfection system. The study population is as per device indication.
Sample Size	150 subjects (both eyes), 9 sites
Key Study Endpoints	The primary endpoints were measured during the Regression Phase of the study, as follows: - The proportion of eyes that achieve manifest refractive spherical equivalent (MRSE) within +/- 0.50 and +/- 1.00 diopter (D) of pretreatment, - The proportion of eyes that achieve keratometry within 0.50 and +/- 1.00 D of pretreatment, - The proportion of eyes with best spectacle corrected; (BSCVA) within 1 line and 2 lines of pretreatment, - The time required to achieve 20/40 or worse uncorrected visual acuity (VA) and the time required to achieve -1.00D or worse MRSE
Follow-up Visits and Length of Follow-up	1. One week ± 3 days, AM VISIT WITHIN 2 HRS OF LENS REMOVAL 2. One month ± 1 week, AM VISIT WITHIN 2 HRS OF LENS REMOVAL If refraction is stable in both eyes, make an appointment for cessation of treatment, i.e., removal of lenses. This appointment should be not more than 7 days from the date of' this visit. Patients should continue to wear lenses overnight, removing them during the daytime hours and should not remove lenses the morning of the next scheduled office visit. Lens removal shall be in-office. Or, if not stable 2. Two months ± 2 weeks, AM VISIT WITHLN 2 HRS OF LENS REMOVAL If refraction is stable in both eyes, make an appointment for cessation of treatment, i.e. removal of lenses. This appointment should be not more than 7 days from the date of this visit. Patients should continue to wear lenses overnight, removing them during the daytime hours and should not remove lenses the morning of the next scheduled office visit. Lens removal shall be in-office. Or if not stable 3. Three months ± 2 weeks;. AM V ISIT WITHIN 2 HRS OF LENS REMOVAL If reaction is stable in both eyes, make an appointment for cessation of treatment, i.e., removal of lenses. This appointment should be not more than 7 days from the date of this visit, Patients should continue to wear lenses overnight, removing them during the daytime hours and should not remove lenses the morning of the next scheduled office visit. Lens removal shall be in-office. Or, if not stable Discontinue from Regression Study if both eyes are not stable at 3 months. 4. Post cessation of treatment A. Zero Time-Office visit for- initial lens removal. Should be am visit (8&9am). B. Noon - Same date as lens removal (3-4 hrs post lens removal). C. After Hours - Same dale as lens removal (8-10 hrs post lens removal). D. Day 1 - Next day after lens removal (22-32 hrs post lens removal). E. Day 2 - (45-57 hrs post/lens removal). F. Day 3 - (68-82 hrs post lens removal). G. 1 Week - (6-9 days post lens removal).
Interim or Final Data Summary
Actual Number of Patients Enrolled	138
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	70%
Final Safety Findings	There were no adverse events related to the study product. Three eyes reported to have a grade 3 slit lamp finding during the Treatment Phase (2 eyes completed, 1 eye discontinued) and no reports of a grade 4 slit lamp finding during the Treatment Phase
Final Effect Findings	At the initial diagnostic visit, none (0%) of the eyes achieving stability had uncorrected visual acuity (UCVA) of 20/20 or better and only 12 eyes (6.5%) had UCVA of 20/40 or better. By the end of the Treatment Phase, 3-Month Visit, most eyes that achieved stability had an MRSE that was between -1.00D and +1.00D (177 eyes/ 96.2%). The refractive change from pretreatment resulted in excellent uncorrected distance visual acuity where 144 eyes (78.2%) had UCVA of 20/20 or better and 184 eyes (100%) had UCVA of 20/40 or better. Following lens removal, the stability of the vision was good during the day. At the 5-Hour Visit in the Regression Phase, there were 141 eyes (76.6%) that had UCVA of 20/20 or better and 182 eyes (98.9%) with 20/40 or better. While the MRSE regressed toward the pretreatment MRSE as the Regression Phase continued, there were still 121eyes (66.5%) with UCVA of 20/40 or better at the 24-Hour visit and 52 eyes (28.6%) were 20/20 or better. Although the there was no study requirement for eyes that achieved stability to be followed until complete return to pretreatment status, 128 of 184 eyes (69.6%) had regressed within ± 0.50D of pretreatment MRSE and 172 of 184 eyes (93.5%) had regressed within ± 1.00D of pretreatment MRSE by the 1-Week Regression Phase Visit. The BSCVA comparison of pretreatment to the final Regression Phase demonstrated that 177 eyes (97.8%) had no change (96.7%) or improved a line (1.1%) from the pretreatment BSCVA. The results demonstrated that subject¿s eyes were able to return to pretreatment values.
Study Strengths & Weaknesses	A strength of this study was the large sample size, which was enough to properly evaluate the safety of this device. However, lack of a control group limits interpretation of study results because findings could be due to factors related or unrelated to the device. The follow up rate was only 70%, increasing the likelihood for biased results as usually subjects that remain on the study may differ from those that are lost to follow-up.
Recommendations for Labeling Changes	It is recommended that the label be updated to reflect the long-term results. The post-approval study design, methods, safety and effectiveness results should be included in the labeling from both phases (i.e., treatment and regression phases).
General
Study Status	Completed
Application Number / Requirement Number	P020004 S006/ PAS001
Date Original Protocol Accepted	06/02/2004
Date Current Protocol Accepted	06/02/2004
Study Name	Long Term Follow up
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a multi-site, non-randomized, combination prospective and retrospective observational cohort study to evaluate the performance of the Gore Excluder abdominal aortic anuerysm Endoprosthesis Low Permeability device in the primary treatment of infrarenal abdominal aortic aneurysms. This evaluation will assess the incidence of aneurysm volume increase and morphology over time in subjects treated with the device.
Study Population	Patients were randomly selected from the 98-03 Pivotal Trial who were treated with the original GORE EXCLUDER device and had a CT scan performed at 24 months
Sample Size	140 subjects and 120 controls, 9 sites
Key Study Endpoints	Device related adverse events, aneurysm diameter, aneurysm volume, death, and conversions.
Follow-up Visits and Length of Follow-up	Endpoints are to be assessed at are to be assessed at baseline, post-procedure, at one month, six months, one year and two years post-procedure.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	139 patients
Actual Number of Sites Enrolled	8 sites
Patient Follow-up Rate	89%
Final Safety Findings	The final analysis showed very good device performance
Study Strengths & Weaknesses	Weakness: 1) Combination of retrospective and prospective data made interpretation somewhat difficult; 2) Small number of sites; Strength: Subjects and controls were well matched.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P020004 S123/ PAS001
Date Original Protocol Accepted	02/29/2016
Date Current Protocol Accepted
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study consists of the extended follow-up data out to 5 years for subjects enrolled in the IBE 12-04 clinical study and continued access.
Study Population	Subjects with a common iliac or aortoiliac aneurysm, who have appropriate anatomy to accommodate the device and fit the study selection criteria.
Sample Size	64 unique subjects in the IDE cohort and 18 subjects in the continued access cohort.
Key Study Endpoints	Data will be provided on the following: a summary of the number of patients for whom data are available and the rates of adverse events, such as aneurysm-related mortality, aneurysm rupture, secondary endovascular procedures, conversion to open surgical repair, endoleak, aneurysm enlargement, prosthesis migration and patency, and losses of device integrity.
Follow-up Visits and Length of Follow-up	5 years Annual
Interim or Final Data Summary
Actual Number of Patients Enrolled	The initial cohort enrolled 65 subjects (of which 63 subjects underwent the IBE procedure) and the continued access cohort enrolled 35 subjects.
Actual Number of Sites Enrolled	The initial cohort had 29 investigational sites and the continued access cohort had 20 investigational sites.
Patient Follow-up Rate	The follow up rate for the initial cohort in the 5-year window was 80% (36/45) with any clinical follow-up and 71.1% (32/45) with CT imaging (66.7% (30/45) with contrast). The follow up rate for the continued access cohort in the 5-year window was 73.9% (17/23) with any clinical follow-up and 69.6% (16/23) with CT imaging (all of which were contrast).
Final Safety Findings	The primary safety endpoint result for all eligible initial cohort subjects (n=62) within 30 days of the initial procedure is as follows: 100% were free from all primary safety endpoint events, including: death, stroke, myocardial infarction, bowel ischemia, paraplegia, respiratory failure, renal failure and conversion to open surgical repair. Additional 5-year safety results are as follows: 68.3% of initial cohort subjects and 71.4% of continued access subjects undergoing the IBE procedure experienced a serious adverse event during the study. 9 initial cohort subjects and 8 continued access subjects died during 5-year follow-up. Deaths were not procedure or device related, and there were no aneurysm-related mortality events. 11.5% of initial cohort (IC) subjects and 14.3% of continued access (CA) experienced a device-related serious adverse event, including type IA endoleak (2.9% CA), type II endoleak (3.3% IC; 2.9% CA), stent graft infection (2.9% CA), aortic dissection rupture (2.9% CA), device occlusion (1.6% IC; 22.9% CA), iliac artery dissection (1.6% IC), and access-related complications such as groin hematoma (1.6% IC), incision site infection (1.6% IC), and vascular pseudoaneurysm (1.6% IC).
Final Effect Findings	Primary and secondary effectiveness endpoint results for all eligible initial cohort subjects (n=61) implanted with both IBE Device components at 6 month follow up are as follows: Primary Effectiveness Endpoint 95.1% of subjects were free from an effectiveness endpoint event through 6 month follow up. Individual endpoint component results include: 100% of subjects were free from complete loss of blood flow in the leg of the IBC or IIC due to thrombus or device failure as assessed by an independent core laboratory, 100% of subjects were free from reintervention of either IBE Device component due to Type 1B or Type III endoleak as determined by the CEC, and 95.1% of subjects were free from reintervention of either IBE Device component in order to re-establish patency due to 60% occlusion or greater as determined by the CEC. Secondary Effectiveness Endpoint 100% of subjects were free from new onset buttock claudication arising from the side of the body treated with the IBE Device through 6 month follow up.
Study Strengths & Weaknesses	Observed study performance was sufficient to meet separate, hypothesis-tested performance goals centered on safety and effectiveness. A secondary effectiveness focused on new onset buttock claudication on the IBE-treated side of the body showed freedom from event through six months post-procedure. Device safety and effectiveness was demonstrated with clinical data through 6 months post procedure. Follow-up data collected after this time point (up to 5 years) showed continued safety and effectiveness in the longer term. However, study conduct showed a high rate of screen failures that were primarily based on anatomical eligibility, such as common iliac artery lumen diameter, indicating that a portion of an aortoiliac or common iliac artery patient population may not be able to be treated with the IBE Device in an on-label fashion. The study population was heavily represented by Caucasian males and data in female or non-White populations is limited. Treatment of a bilateral aneurysm patient population was limited.
Recommendations for Labeling Changes	Labeling will be modified to reflect the findings of the post-approval study.
General
Study Status	Terminated
Application Number / Requirement Number	P020006 / PAS001
Date Original Protocol Accepted	12/27/2007
Date Current Protocol Accepted	12/27/2007
Study Name	Enteryx
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post-approval study was to assess the long-term safety and effectiveness of the device, both in subjects undergoing a single treatment and in subjects who are retreated with additional injections of Enteryx. Subjects were enrolled into one of two groups (Part A - new subjects, or Part B -subjects enrolled under the IDE study). The primary effectiveness endpoint was elimination of proton pump inhibitor (PPI) medication use.All subjects would be followed for adverse events, medication injection for three years after the last Enteryx procedure. Subjects enrolled in Part A would also be contacted by the investigational site at least quarterly to obtain current adverse event information.
Study Population	Study population is as per device indication. This device is indicated for endoscopic injection into the region of the lower esophageal sphincter, for the treatment of gastroesophageal reflux disease (GERD) symptoms in patients responding to and requiring daily pharmacological therapy with proton pump inhibitors.
Sample Size	A total of 220 patients were enrolled in Part A of the Post-Approval Study. One hundred and sixty nine (169) completed the 12-month visit, 125 completed the 24-month visit and 12 have completed the 36-month visit. Twenty-five (25) patients are either lost to follow-up or have formally withdrawn from the study. One hundred and eighty three (183) patients were active at the time study was terminated. A total of 90 patients were enrolled in Part B of the Post-Approval Study. The 12-month visit was conducted under the IDE, eighty seven (87) patients completed the 24-month visit and 79 completed the 36-month visit. Nine patients are either lost to follow-up or have formally withdrawn from the study.
Key Study Endpoints	The primary effectiveness endpoint was elimination of proton pump inhibitor (PPI) medication use.All subjects would be followed for adverse events, medication injection for three years after the last Enteryx procedure. Subjects enrolled in Part A would also be contacted by the investigational site at least quarterly to obtain current adverse event information.
Follow-up Visits and Length of Follow-up	Subjects enrolled in Part A would also be contacted by the investigational site at least quarterly to obtain current adverse event information. Total of 3-yearsof follow-up
Interim or Final Data Summary
Interim Results	Study was terminated. See final results
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	Since the 2006 FDA report (P020006/R5), there were five new reports of a severe adverse events. All five were Device Related Adverse Events in participants of study Part A. Four cases were in patients that were not retreated or prior to retreatment, and one after retreatment. The severe adverse events included one case of pain retrasternal/chest pain, one case of nausea, one case of vomiting, and two cases of dysphagia/odynophagia. Four cases were resolved and one was ongoing as of report date (2006). In Part B of the study, 7 out of 90 patients had device related AEs including four patients with mild retrosternal/chest pain, dysphagia/odynophagia, fever, epigastric pain/abdominal pain, or heartburn, and 3 patients with moderate dysphagia/odynophagia, nausea, or vomiting.
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	None, product was recalled.
General
Study Status	Completed
Application Number / Requirement Number	P020024 / PAS001
Date Original Protocol Accepted	05/14/2003
Date Current Protocol Accepted	05/14/2003
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was intended to evaluate long term safety and effectiveness issues that may not have been adequately addressed during the clinical investigation.
Study Population	The AMPLATZER Duct Occluder is a percutaneous, transcatheter occlusion device and is indicated for the non-surgical closue of patent ductus arteriosus. The only requirement for enrollment into the Post-Approval Study was prior enrollment in the Phase II patent ductus arteriosus clinical investigation.
Sample Size	435 patients. 20 sites
Key Study Endpoints	No endpoints were specified.
Follow-up Visits and Length of Follow-up	A follow-up visit at either five, six, or seven years was considered to be a "final" follow-up visit. If a subject has already completed a five year visit, they would not return for a six or seven year visit. However, a subject who missed their five year follow-up could be re-consented and seen after the five year window ends for a final follow-up at six or seven years. Subjects unwilling or unable to return for an office visit had the option of a phone interview.
Interim or Final Data Summary
Actual Number of Patients Enrolled	435 patients
Actual Number of Sites Enrolled	20 sites
Patient Follow-up Rate	35%
Final Safety Findings	All remaining patients had demonstrated complete closure of the ductus.
Study Strengths & Weaknesses	Strengths: It is very difficult to conduct long term follow-up in this pediatric population. Therefore, any attempt to gather long term data on this group is to be applauded. Weaknesses: Very poor follow-up.
Recommendations for Labeling Changes	There were no recommendations for changes to the labeling based on the results of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P000053 S005/ PAS001
Date Original Protocol Accepted	02/07/2007
Date Current Protocol Accepted	02/07/2007
Study Name	Registry AMS MC-0611
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The sponsor has created a registry-based study that will include all patients who have received an AUS 800 or AUS 800 with IZ at a US-based site subsequent to October 13, 2006. It is a passive surveillance system where information is voluntarily submitted to AMS by the implanting physician and is tied to credit for new devices under warranty. The purpose of the registry is to evaluate the long-term performance of the AUS 800 compared to the AUS 800 with IZ by evaluating infection, mechanical component and system failures and surgical revision. The study hypothesis is that there is equal survival time (based on device replacement due to infection or mechanical failure) for IZ impregnated versus unimpregnated devices.The objective of this post-approval registry is to evaluate the long term performance of the AMS 800 against the long term performance of the AMS 800 with InhibiZone as it relates to rate of infection, mechanical component or system failures and surgical revision rates.
Study Population	Study population is as per device indication. This device is used to treat urinary incontinence due to reduced outlet resistance (intrinsic sphincter deficiency) following prostate surgery.
Sample Size	All comers registry
Key Study Endpoints	Primary endpoint is device replacement surgery
Follow-up Visits and Length of Follow-up	There are no follow up visits in this study; the entire study will include 5 years of follow up for each patient.
Interim or Final Data Summary
Actual Number of Patients Enrolled	17,063 subjects
Actual Number of Sites Enrolled	2,240 sites
Patient Follow-up Rate	There was no formal follow�]up in this registry�]based study. The post�]approval study included patients who were implanted with the AMS 800 device between October 14, 2006 and July 31, 2012 and those receiving revisions on a previously implanted AMS 800 device through July 31, 2012.
Final Safety Findings	Infection Free Rates For the overall system, the infection free rates were not significantly different between the Inhibizone (IZ) and non�]Inhibizone (non�]IZ) groups in the Original surgery group (98.26% vs. 98.22%) and in the Revision surgery group (96.77% vs. 96.48%). For specific components, there were also no statistically significant differences in infection free rates between the IZ and non�]IZ devices in both Original and Revision surgery groups. Mechanical Malfunction Free Rates For the overall system, in the Original Surgery Group, the IZ group had a significantly lower malfunction free rate than the non�]IZ group (93.47% vs. 95.22%, P=0.003). However, in the Revision Surgery Group, the malfunction free rate was not significantly different between the IZ and non�]IZ groups (92.85% vs. 92.81%, P>0.05). For the Components analysis, in the Original Surgery Group, the difference in malfunction free rates for the Pump and Balloon were not statistically significant, but the differences in malfunction free rates for the cuff [IZ 98.40% vs. non�]IZ 99.04%, P=0.007] and the Not Specified Component [IZ 97.11% vs. non�]IZ 98.16%, P=0.03] were statistically significant. In the Revision Surgery Group components analysis, there were no statistically significant differences in malfunction free rates.
Final Effect Findings	For both the Original Surgery Group and the Revision Surgery Group, the 5�]year revision free rate from any cause was higher in the IZ group compared to the non�]IZ group but the difference was not statistically significant [Original Surgery Group: (IZ 78.94% vs. non�]IZ 77.79%; difference=1.15%; log rank test P= 0.191); Revision Surgery Group: (IZ 73.85% vs. non�]IZ 72.04%; difference=1.81%; log rank test P= 0.933)].
Study Strengths & Weaknesses	Strengths An all�]comers Registry�]based study with large, representative study sample Weaknesses There is no formal follow�]up plan, which may contribute to bias and underreporting of events. In addition, the database does not record events (e.g., infection) that are successfully treated without a surgical explant procedure, i.e., if no implanted system component change occurs or no surgical device adjustment occurs, the study did not record the (infection) event in the database. Therefore, the reported adverse event rates may be lower than the actual rate experienced by participating patients.
Recommendations for Labeling Changes	Labeling change recommended to include long�]term safety and effectiveness data from the registry�]based study.
General
Study Status	Completed
Application Number / Requirement Number	P020014 S012/ PAS001
Date Original Protocol Accepted	06/15/2007
Date Current Protocol Accepted	06/15/2007
Study Name	ESS-305
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational cohort study. A new cohort of patients and physicians will be enrolled to collect procedural data on ESS305. Data from the Study for Newly Trained Physicians (completed September 2005) will be used as the comparator. The protocol also includes collection of adverse events data.The purpose of this post-approval clinical study is to determine the following: 1. Bilateral placement ofthe ESS305 micro-insert at first attempt; 2. Comparison of bilateral placement success between NewlyTrained physicians and Experienced physicians 3. Identification of factors predictive of failure to achieve bilateral placement ofthe ESS305 micro-insert al first attempt; 4. Evaluation of aspects ofthe ESS305 design that may impact bilateral placement rate; 5. Hysteroscopy time to perform the procedure 6. Adverse device effects; and 7. Adverse procedure events.
Study Population	Study population is as per device indication. This device is indicated for permanent birth control (female sterilization) by bilateral occlusion of the fallopian tubes in adult women seeking permanent birth control.
Sample Size	657 women enrolled - protocol states 20 sites enrolled patients
Key Study Endpoints	Study endpoints include: (1) bilateral micro-insert placement rate, (2) identification of factors predictive of micro-insert placement failure, (3) evaluation of aspects of the ESS305 design that may impact bilateral placement rate; and (4) hysteroscopy time to perform the procedure.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	584 women
Actual Number of Sites Enrolled	76
Patient Follow-up Rate	81.60%
Final Safety Findings	The sponsor reported only 6 adverse events occurred during and after the Essure placement procedure (6 out of 584). All reported events were minor with the exception of one case. The subject was hospitalized after hysteroscopy resulted in a uterine perforation by the hysteroscope. The sponsor claims the Essure device did not cause the injury to the patient. None of these events represent unanticipated adverse device effects.
Study Strengths & Weaknesses	The study is well designed to evaluate the placement rate among newly trained physicians at first attempt, when implanting the device in women seeking permanent sterilization.
Recommendations for Labeling Changes	Update labeling with the results of the study in the context of patient and physician labeling.
General
Study Status	Completed
Application Number / Requirement Number	P020014 S017/ PAS001
Date Original Protocol Accepted	02/24/2012
Date Current Protocol Accepted	09/29/2016
Study Name	Essure/post-NovaSure PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm multi-center prospective observational study
Study Population	Women aged 21-50 with Essure micro inserts properly placed (confirmatory hysterosalpingogram) seeking treatment for menorrhagia.
Sample Size	A minimum of 220 female subjects relying on Essure micro- inserts seeking treatment for menorrhagia (i.e. NovaSure) at up to 30 US sites.
Key Study Endpoints	Primary: Occurrence of confirmed pregnancy at 1 year and 3 years among subjects relying on Essure micro-inserts for permanent birth control when NovaSure is performed. Secondary: Incidence of adverse events (AEs) and/or complications associated with the performance of NovaSure in the presence of Essure micro-inserts, reported during follow-up visits.
Follow-up Visits and Length of Follow-up	3 years One week post NovaSure procedure, then one, two, and three year post-endometrial ablation Phone Call
Interim or Final Data Summary
Actual Number of Patients Enrolled	220 women with successful bilateral Essure insert location and tubal occlusion were enrolled, from which 215 met all the eligibility criteria. Among the 215 eligible women, 211 women had NovaSure attempted, and 209 women underwent the NovaSure endometrial ablation treatment. Out of all enrolled women (n=220), 11 women exited the study prior to a NovaSure treatment attempt (n=4), after NovaSure was attempted but before undergoing treatment (n=2) or were screening failures (n=5).
Actual Number of Sites Enrolled	25 sites were included in the study. Subjects were enrolled from 18 sites.
Patient Follow-up Rate	Out of all enrolled patients (220 women), 174 women completed the study (79.1%). Out of the women who underwent a NovaSure treatment, 83.3% (174/209) completed the study. There were 35 women who discontinued from the study and 11 lost to follow-up. For each post-endometrial ablation visit, out of all eligible women (n=215), the follow-up rates were: 1-week: 97.2% 1-year: 92.6% 2-year: 86.5% 3-year: 81.4%
Final Safety Findings	There were 211 women who had NovaSure attempted and make up the primary safety analysis cohort. A total of 398 events were reported in 116/211 subjects (55.0%) from the primary safety cohort. There were 28 serious adverse events (SAEs) in 18 subjects and 370 non-serious adverse events in 113 subjects. The AEs occurring in greater than or equal to 2% of subjects were pelvic pain (28 subjects, 13.3%); vaginal discharge (15 subjects, 7.1%); urinary tract infection (12 subjects, 5.7%); vaginal hemorrhage (10 subjects, 4.7%); heavy menstrual bleeding, dysmenorrhea, and nausea (9 subjects, 4.3% each); abdominal pain (7 subjects, 3.3%); procedural pain and uterine spasm (6 subjects, 2.8% each); and fatigue, uterine hemorrhage, and vulvovaginal pruritus (5 subjects, 2.4% each). SAEs are a subset of all the reported AEs. The SAEs occurring in more than 2 subjects were pelvic pain (5 subjects, 2.4%) and heavy menstrual bleeding (2 subjects, 0.9%). One (n=1) subject (0.5%) died due to congestive cardiac failure; the death was assessed as not related to the Essure device, NovaSure device, or NovaSure procedure. None of these events represent unanticipated adverse device effects and the events are consistent with available data for Essure and NovaSure.
Final Effect Findings	No pregnancies were reported at any timepoint in the study. The 95% upper Bayesian credible interval was 1.23% and 1.33% at 1 year and 3 years, respectively, which meets the predetermined study success threshold of 2.1% and 2.8% at 1 year and 3 years, respectively.
Study Strengths & Weaknesses	The study was designed to provide the pregnancy rate in women with successful bilateral Essure insert location and tubal occlusion who underwent NovaSure endometrial ablation treatment, with a confidence interval of 95%. One strength of the study is the high observed follow-up rate. A limitation of the study is the data collection through phone call follow-up visits, instead of a clinical exam.
Recommendations for Labeling Changes	Not applicable. On December 31, 2018, Bayer stopped selling and distributing the Essure device in the United States. As of December 31, 2019, all unused Essure units should have been returned to Bayer so that they are no longer available for implantation. The most recent labeling from 2018 includes warning and precautions about performing endometrial ablation of the uterus in patients with Essure inserts. The most recent labeling indicates that investigations are ongoing to understand contraception rates in women with successful bilateral Essure insert location and tubal occlusion who underwent NovaSure endometrial ablation treatment. This post-approval study provides information on the subject population described above. In this post-approval study, the self-reported pregnancy rate among study participants relying on Essure micro-inserts for permanent birth control when NovaSure was performed was 0% at 1 year and 0% at 3 years. These post-approval study findings support the information already included in the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P020014 S041/ PAS001
Date Original Protocol Accepted	07/29/2015
Date Current Protocol Accepted	04/28/2016
Study Name	Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is the continuation of the premarket study (Use of Transvaginal Ultrasound to Confirm Essure Micro-insert Placement in Women: Demonstration of Effectiveness) utilized to support P020014/S041. The study is a prospective, multi-center, international study of women seeking permanent contraception. The objectives of the study are to evaluate the effectiveness of the Essure procedure when the TVU/hysterosalpingogram (HSG) algorithm is used for confirmation testing, evaluate the intent-to-treat reliance rate 3 months following TVU/HSG confirmation test algorithm, and evaluate subject satisfaction with the TVU confirmation test.
Study Population	Women, aged 21 to 44 years of age, seeking permanent contraception
Sample Size	620 patients were enrolled.
Key Study Endpoints	The two co-primary endpoints of the study are to evaluate the occurrence of confirmed pregnancy among subjects relying on Essure inserts for birth control on the basis of the TVU/HSG algorithm at 1-year post-alternative contraception and to evaluate the intent-to-treat reliance rate 3 months following TVU/HSG confirmation test protocol. The secondary endpoints of the study are to evaluate subject satisfaction with TVU and to evaluate the occurrence of confirmed pregnancy at 10 years among subjects relying on Essure inserts for birth control on the basis of the TVU/HSG algorithm. Enrollment is complete. Data to be collected will include the following: a. Reliance rate (complete at time of approval) b. Pregnancies and outcomes c. Adverse Events d. Device removal (added 2016)
Follow-up Visits and Length of Follow-up	Subjects will be followed for 10 years post-device placement.
Interim or Final Data Summary
Actual Number of Patients Enrolled	620 women enrolled into the study, from which 597 (96.3%) underwent an Essure placement attempt. Among the 597 women who underwent an Essure placement attempt, 582 (97.5%) achieved bilateral placement and 547 (91.6%) were told to rely on Essure for birth control following the 3-month post-placement visit.
Actual Number of Sites Enrolled	20 sites were included in the study, 12 sites in the US and 8 sites outside the US.
Patient Follow-up Rate	Out of all enrolled patients (620 women), 236 (n=236) women completed the study (38.1%). Out of the women who were told to rely (n=547), 236 women completed the study (43.1%). For each annual visit after approval, out of all subjects who were told to rely (n=547), the follow-up rates were: 2-year: 86.3% 3-year: 83.4% 4-year: 73.5% 5-year: 65.8% 6-year: 53.6% 7-year: 48.3% 8-year: 47.0% 9-year: 45.0% 10-year: 43.1%
Final Safety Findings	There were 597 women who had an Essure procedure attempted and make up the primary safety analysis cohort. A total 1,987 events were reported in 406/597 subjects (68.0%) from the primary safety cohort throughout the 10-year follow-up duration. There were 146 serious adverse events (SAEs) in 85 subjects. The AEs occurring in greater than or equal to 5% of subjects were heavy menstrual bleeding (95 subjects, 15.9%), pelvic pain (60 subjects, 10.1%), dysmenorrhea (52 subjects, 8.7%), abdominal pain (34 subjects, 5.7%), urinary tract infection (34 subjects, 5.7%), arthralgia (32 subjects, 5.4%), back pain (32 subjects, 5.4%), abnormal uterine bleeding (31 subjects, 5.2%), headache (31 subjects, 5.2%), and uterine leiomyoma (30 subjects, 5.0%). SAEs are a subset of all the reported AEs. There were 146 SAEs reported in 85 subjects. The only SAE occurring in greater than or equal to 1% of subjects was pelvic pain (9 subjects, 1.5%). Four (n=4, 0.7%) subjects died due to cardiac arrest, colon cancer, stroke, or an unknown cause. The deaths were assessed as not related to the Essure device. None of these events represent unanticipated adverse device effects and the events are consistent with available data for Essure.
Final Effect Findings	Out of the 582 women who had bilateral placement of Essure, 547 were told to rely (94%). Overall, there were 4 pregnancies that occurred among all study subjects. In the first year, there were 3 reported pregnancies, which were reported at the time of approval. A fourth pregnancy occurred 16 months after the subject was told to rely. Overall, the study pregnancy rate was 0.78% (lower control limit 1.55%) at the end of the study. Out of the subjects that received transvaginal ultrasound confirmation testing (n=528), 520 women were satisfied with the transvaginal ultrasound test (98.5%). Subject comfort was reported as excellent, very good, or good by 521/528 subjects (98.7%). One subject did not provide a response for subject comfort. The study protocol was modified in early 2016 to add the capture of device removal events. The cumulative probability of device removal for all subjects for any reason at 10 years is reported as 19.5% (95% confidence interval range is 15.3-23.5%). The cumulative probability of device removal for any reason at 10 years for US subjects and OUS subjects is 20.9% (95% confidence interval range is 15.1-26.3%) and 17.6% (95% confidence interval range is 11.5-23.2%), respectively. The study was not originally designed to collect data on device removal; as the protocol was modified during the ongoing study, some events were captured retrospectively and patient outcomes data are unavailable. Removals reported in the rate above include all removals, regardless of the reason for removal (for example, adverse event, concomitant with another gynecologic surgery, subject request). Therefore, the removal rates reported do not reflect removals due to device complications alone, which may be a lower rate.
Study Strengths & Weaknesses	The study was designed to provide the pregnancy rate in women told to rely on Essure for permanent contraception after confirmation using the TVU/HSG algorithm confirmation test. The results include data from both inside the US and outside the US. One strength of the study is the long-term follow-up duration to monitor pregnancy occurrence in women told to rely on Essure for permanent contraception. A weakness of the study is the lost to follow-up rate by the end of 10 years of follow-up. The lost to follow-up rate may be in part due to COVID-19 related challenges, and other external factors.
Recommendations for Labeling Changes	Not applicable. On December 31, 2018, Bayer stopped selling and distributing the Essure device in the United States. As of December 31, 2019, all unused Essure units should have been returned to Bayer so that they are no longer available for implantation. The most recent labeling from 2018 includes instructions for completing confirmation testing using TVU or HSG and the co-primary endpoint results. This post-approval study provides information on the confirmation test methods discussed above. In this post-approval study, the findings support the information already included in the labeling.
General
Study Status	Other
Application Number / Requirement Number	P000049 S016/ PAS001
Date Original Protocol Accepted	03/05/2009
Date Current Protocol Accepted	03/05/2009
Study Name	Fatigue & Corrosion Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a fatigue testing study. The study should assess corrosion potential and passivation layer before and after fatigue testing out to a 10 year equivalent of the device.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	This is a fatigue testing study. The study should assess corrosion potential and passivation layer before and after fatigue testing out to a 10 year equivalent of the device.
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P020014 / PAS002
Date Original Protocol Accepted	11/04/2002
Date Current Protocol Accepted	11/04/2002
Study Name	5 year follow up
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Extended follow-up (5 years) of premarket study cohorts: The Phase II Study and the Pivotal Study (formerly known as STOP). The Phase II Study was a prospective, multi-center, international study of women seeking permanent birth control. There were sites in the US, Australia, Belgium, and Spain. The Pivotal Trial was designed as a multi-center, non-randomized, single-arm, international study of women seeking permanent contraception. The study was conducted in the U.S., Europe, and Australia.
Study Population	Adult women seeking permanent birth control. The study included participants of the premarket cohorts (Phase II and Pivotal Trial), ages 21 to 45 years old.
Sample Size	Phase II Study: 269 women enrolled Pivotal Trial: 657 women enrolled
Key Study Endpoints	Phase II Study: Study primary objectives were to evaluate: Essure micro-insert placement rate, woman¿s tolerance and recovery from the micro-insert procedure, safety of the micro-insert procedure, woman¿s tolerance of the implanted micro-inserts, long-term safety of the implanted micro-inserts, and effectiveness of the micro-inserts in preventing pregnancies. Pivotal Trial: Primary study endpoints: prevention of pregnancy, safety of the micro-insert placement procedure, and safety of the micro-insert wearing. Secondary endpoints included: participant satisfaction with the micro-insert placement procedure, participant satisfaction with micro-insert wearing, bilateral micro-insert placement rate; and development of a profile for an appropriate candidate for the Essure procedure.
Follow-up Visits and Length of Follow-up	For both studies, women were followed at: 1 week-post device placement (PDP), 3 months PDP, 3, 6, and 12 months post-alternate contraception (PAC); and yearly through 5 years, as part of the post-approval study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Phase II Study: 269 women enrolled from which, 227 underwent a micro-insert placement procedure. The remaining 42 women voluntarily withdrew, were excluded at the time of screening, or were enrolled into the Pivotal trial instead. There were 2 sites in the US (44 women), 1 site in Australia (130 women), 1 site in Belgium (28 women) and 1 site in Spain (25 women). Pivotal Trial: A total of 657 women were enrolled in the study; of those, 518 underwent the Essure procedure and 453 women achieved bilateral occlusion 3 months post-procedure (4 unilateral placements). These 453 include 6 women that were followed for safety only.
Actual Number of Sites Enrolled	Phase II Study: 5 sites Pivotal Trial: 13 sites
Patient Follow-up Rate	Phase II Study: 86.3% at 1-year; 85.5% at 2-year; 80.2% at 3-year; 77.5% at 4-year; 75.3% at 5-year. Pivotal Trial: 97.5% at 1-year; 92.0% at 2-year; 89.4% at 3-year;85.2 at 4-year; 81.6% at 5-year
Final Safety Findings	Phase II Study: Long-term Safety: Adverse events after the day of the procedure occurred in 9% of the women; 5% of these events were related to period pain, and ovulatory pain or changes in menstrual function. The other adverse events included: perforations (7), expulsion (1), unsatisfactory device location (1), and a retained micro-insert fragment (1). The perforations accounted for 3% of the patients that underwent the procedure. Four perforations were identified at the 3-month post-procedure evaluation; one was identified at the 18-month post-procedure evaluation. One additional case was of a peritubal perforation noted on gross examination following device removal due to pain. A seventh case was discovered when the woman had laparoscopic hysterectomy, the right device had perforated the tube. Six of the seven women that suffered perforations had the micro-insert located in the peritoneal cavity. In four of these women the device was removed successfully, in one woman the device was left in the peritoneal cavity. For the case of a retained micro-insert fragment, the event occurred during an attempt to remove the device that resulted in the broken distal ball tip. At the time of final report submission, there have been no reports of clinical sequelae for this case. Pivotal Trial: Adverse events that initially prevented reliance by the woman on Essure occurred in 21 (4.5%) women. These were primarily Micro-insert expulsions following original Micro-insert placement that was out-of-specification. Nine of the women who experienced an expulsion chose to undergo a second placement procedure, and all were successful. Therefore, adverse events that ultimately prevented reliance occurred in only 12 women (2.6%). The most frequently reported adverse events reported in the first year that did not prevent the woman from relying on Essure, but were rated by the Investigator as at least "possibly" related to Essure, were back pain (6.2/1000 women-months), abdominal pain/cramps (2.6/1000) and dyspareunia (2.5/1000 women-months). All other events occurred at less than 2.5/1000 women-months of wearing.
Final Effect Findings	In both studies, no pregnancies were reported while relying on Essure for contraception.
Study Strengths & Weaknesses	The studies were limited in that there were no comparison groups. Both were designed to provide the pregnancy rate with the precision around it (95% Confidence Interval). Another limitation is the length of follow-up. Both studies were designed to provide an estimate of pregnancy rate out to 5 years; after which point there is no precise data on effectiveness and safety of the device, from these two studies. One of the strengths of the studies is the observed follow-up rates. The study provides a precise estimate of the pregnancy rate at 5 years
Recommendations for Labeling Changes	Yes, label was updated to include the 5-year performance data
General
Study Status	Completed
Application Number / Requirement Number	P020018 S005/ PAS001
Date Original Protocol Accepted	06/09/2005
Date Current Protocol Accepted	06/09/2005
Study Name	Postmarket Surveillance Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	A low occurrence of deployment problems was reported. No problems were reported for over 90% of the cases in each deployment category. All 151 implanted Zenith Renu AAA Ancillary Grafts were deployed successfully (i.e., successful delivery and deployment of the device and successful removal of the delivery system). One hundred eleven (111) cases were identified with endoleaks prior to or during the procedure. Of those cases with endoleak, 96 were proximal type I endoleaks. The vast majority of new endoleaks at follow-up have been identified as type II. The sponsor concludes that it is likely many had been previously overlooked, misidentified, or masked by other existing endoleaks during review at earlier time periods.
Actual Number of Patients Enrolled	151
Actual Number of Sites Enrolled	95
Patient Follow-up Rate	60%
Final Safety Findings	One case of Renu migration occurred at 36 months after implantation. One occlusion was identified at the 24-month time period.. Death beyond 30 days of the initial procedure occurred in 43 cases. Twenty-nine cases were determined to be unrelated to endovascular repair. Of the 14 remaining cases, 5 have been adjudicated as related to endovascular repair (i.e., procedure, technique, pre-existing graft, and/or Renu-related) and 9 are unable to be adjudicated due to insufficient information from the site (no additional information is able to be collected).
Final Effect Findings	One hundred eleven (111) cases (73.5%) were identified with endoleaks prior to or during the procedure. Of those cases with endoleaks, 96 were proximal type I endoleaks. There were 26 new type II endoleaks at one month and one remained at 60 months.
Study Strengths & Weaknesses	The sponsor reports that 91 patients reached an endpoint at 5 years. Although the follow-up rate therefore is only 60%, there are enough patients with 5 year endpoint information since the conditions only required 100 patients to be enrolled.. The study provides additional information that can be used for updated labeling.
Recommendations for Labeling Changes	Yes. The labeling supplement should include a summary of the post-approval study design, results, and study strengths and limitations. In addition, sponsor should provide not only rates in the revised labeling, but reasons for secondary interventions and conversions, as well as contributing factors or causes of death. Finally, the labeling should highlight the endoleak data from the post-approval study.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P040023 / PAS001
Date Original Protocol Accepted	05/03/2005
Date Current Protocol Accepted	05/03/2005
Study Name	Duraloc Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a prospective, uncontrolled multi-center study that is designed to evaluate the long-term safety and effectiveness of the Duraloc Option Ceramic Hip. However, because of the lack of progress on the original PAS, FDA asked the sponsor to redesign the PAS. The PAS was revised per a FDA letter dated 7/14/09. The new protocol is not approved yet [Aug 13, 2010]. The description presented here is for the old study
Study Population	Study population as per device indication. This device is indicated for non-cemented use in primary total hip arthroplasty in skeletally mature patients with non-inflammatory degenerative joint disease (NIDJD) such as osteoarthritis, avascular necrosis, congenital hip dysplasia, and post-traumatic arthritis.
Sample Size	A total of 250 patients 10 clinical centers
Key Study Endpoints	Key endpoints include device survival, Harris Hip Score, and radiographic assessment. During the final 5 years of patient follow-up, patients will only complete a mailed outcomes questionnaire that will inquire regarding device survival and patient satisfaction.
Follow-up Visits and Length of Follow-up	Each patient will be followed for 10 years. During the first 5 years of patient follow-up, patients will undergo clinical and radiographic examination as well as complete an outcomes questionnaire.
General
Study Status	Completed
Application Number / Requirement Number	P020024 S052/ PAS001
Date Original Protocol Accepted	01/11/2019
Date Current Protocol Accepted
Study Name	Continued FU of IDE/CAP cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of IDE pivotal and continued access cohorts. The objective of this study is to evaluate the safety and effectiveness of the AMPLATZER Piccolo Occluder annually through 3 years post-procedure.
Study Population	Patients with a patent ductus arteriosus. The study is comprised of two cohorts: patients = 2 kg and patients > 2 kg in weight. The majority of subjects are less than 2 years old.
Sample Size	The premarket study enrolled a total of 50 subjects, 18 in the = 2kg cohort and 32 in the > 2kg cohort.
Key Study Endpoints	The primary safety endpoint for the study is the rate of major complications through 180 days after an attempted ADO II AS device implant. Major complications are defined as device or procedure-related adverse events resulting in any of the following: o Death o Life-threatening adverse event o Persistent or significant disability/incapacity, and/or o A major open surgical intervention performed by a surgeon under general anesthesia The primary effectiveness endpoint is the rate of effective closure of the ductus arteriosus among patients with a successful ADO II AS implant as assessed by the presence of either a Grade 0 or Grade 1 shunt at the six-month follow-up by transthoracic echocardiography. The secondary endpoint is the rate of significant obstruction of the pulmonary artery or aorta through the 6-month follow-up visit per the following definitions: 1. Significant obstruction of the left pulmonary artery is defined as less than 30% flow to the left lung by lung perfusion scan or a peak instantaneous gradient in left pulmonary artery =35 mmHg by echocardiogram if lung perfusion scan is not available. OR 2. Significant obstruction of the aorta is defined as a gradient of =20 mmHg in the aortic isthmus by invasive aortic catheterization or a mean gradient =20 mmHg in the aortic isthmus by echocardiogram if invasive aortic catheterization is not available. In addition, the study will record implant success, major and minor complications, death, and adverse events.
Follow-up Visits and Length of Follow-up	Follow up will continue annually through 3 years post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	IDE Pivotal Cohort (IDE): The study enrolled a total of 50 subjects in the IDE cohort. CAP Cohort (CAP): The study enrolled a total of 150 CAP cohort subjects at 9 investigational sites in the US.
Actual Number of Sites Enrolled	IDE Cohort - 8 investigational sites in the U.S. CAP Cohort - 9 investigational sites in the U.S.
Patient Follow-up Rate	IDE Pivotal Cohort: 42/46 (91.3%) completed the 36-month visit CAP Cohort: 114/136 (83.8%) completed the 36-month visit
Final Safety Findings	Primary Safety Endpoint (IDE & CAP) is defined as the rate of major complications through 180 days after an attempted Amplatzer Piccolo Occluder implant. IDE: Zero (0.0%, 0/50) major complications were reported No deaths were reported. CAP: Four subjects weighing = 2 kg (2.8%, 4/144) experienced a major complication. Zero subjects weighing > 2 kg (0%, 0/144) experienced a major complication. Six subjects with a successful implant withdrew before 180 days without an event and are excluded from the analysis. CAP: Death: There were nine deaths reported among CAP cohort subjects. Eight subject deaths were adjudicated as not related to the device or implant procedure.
Final Effect Findings	Primary Effectiveness Endpoint (IDE & CAP) is defined as the rate of effective closure of the ductus arteriosus among patients with a successful Amplatzer Piccolo Occluder implant at the 6-month follow-up by transthoracic echocardiography (TTE) as assessed by the Echocardiography Core Laboratory. IDE: All subjects (100%, 46/46) with an evaluable echocardiogram achieved effective closure at 6 months. CAP: All subjects = 2 kg, and 98.2% of subjects > 2 kg achieved effective closure at 6 months post-procedure, for an overall rate of effective closure of 99.2% (128/129). Secondary Endpoint (IDE & CAP) is defined as the rate of significant obstruction of the pulmonary artery or aorta through the 6- month follow-up. IDE: One of the 41 evaluable subjects (2.4%, 1/41) had significant obstruction of the aorta. CAP: No subject (0%, 0/130) had significant obstruction of the LPA or aorta.
Study Strengths & Weaknesses	A strength of both studies (IDE & CAP) is that both studies followed the subjects through 3 years post-procedure and provides longer term safety and effectiveness results of the Amplatzer Piccolo Occluder device. A weakness of both studies (IDE & CAP) is that both studies are single-arm (non-randomized) studies.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and efficacy results from these studies.
General
Study Status	Ongoing
Application Number / Requirement Number	P170032 / PAS001
Date Original Protocol Accepted	03/29/2021
Date Current Protocol Accepted	03/20/2026
Study Name	PAS1 - PostMarket Surveillance-Long Term Safety
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the trial is to collect long-term safety and effectiveness information on the WovenEndobridge (WEB) Aneurysm Embolization System in the endovascular treatment of wide-necked aneurysms located at the middle cerebral artery (MCA) bifurcation, internal carotid artery (ICA) terminus, anterior communicating artery (AComm) complex, or basilar artery apex.
Study Population	Subjects with wide-necked intracranial aneurysms located at the at the middle cerebral artery (MCA) bifurcation, internal carotid artery (ICA) terminus, anterior communicating artery (AComm) complex, or basilar artery apex.
Sample Size	180 Subjects Enrolled (US)
Key Study Endpoints	1. Key effectiveness outcome is the proportion of subjects with adequate aneurysm occlusion at one year after treatment. 2. Key safety outcome includes the proportion of subjects with death of any nonaccidental cause or any major stroke* within the first 30 days after treatment or major ipsilateral stroke or death due to neurologic cause from day 31 to the 1 year after treatment. *Major stroke is defined as an ischemic or hemorrhagic stroke resulting in an increase of 4 points or more on the National Institutes of Health Stroke Scale
Follow-up Visits and Length of Follow-up	30day, 6 month, 12 month, then annually to 5 years.
General
Study Status	Completed
Application Number / Requirement Number	P170032 / PAS002
Date Original Protocol Accepted	12/31/2018
Date Current Protocol Accepted
Study Name	PAS2 - WEB-IT Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multicenter, international interventional cohort.
Study Population	The study population is comprised of subjects with intracranial wide-neck aneurysms located at arterial bifurcations.
Sample Size	The sample size is 200 patients.
Key Study Endpoints	Study endpoints include adequate aneurysm occlusion, death, major stroke and additional neurological deficit.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	150 subjects enrolled in the study at the time of database extraction, and 123 subjects remaining in the study and being followed for 5 years.
Actual Number of Sites Enrolled	21 U.S. sites and 6 OUS sites
Patient Follow-up Rate	clinical follow up rate >90% for all scheduled visits. The 5-yr cumulative Imaging follow-up is 55%.
Final Safety Findings	Twenty-seven (27) aneurysm retreatments occurred during this study involving 23 subjects. There were no unanticipated adverse events (UADEs). There have been no events of re-bleed of previously ruptured treated index aneurysms or new bleeds from unruptured treated index aneurysms for the study. There were no reported device- or procedure-related serious adverse events later than the 30 day follow up visit. Between 1 year and 5 year, there have been twelve (12) events classified as AEs of Special Interest, all adjudicated as unrelated to the WEB device.
Final Effect Findings	Primary effectiveness endpoint has been evaluated in the 12-month IDE study and is not the focus of this PAS review.
Study Strengths & Weaknesses	Strength: A prospective and long-term study with clinical follow-up rate for ITT population above 90%. Weaknesses: Single arm study not controlling for confounding factors. Imaging follow-up rate is low.
Recommendations for Labeling Changes	Recommend Labeling update to include long-term study results from the PAS.
General
Study Status	Hold
Application Number / Requirement Number	H040006 / PAS001
Date Original Protocol Accepted	09/05/2006
Date Current Protocol Accepted	09/05/2006
Study Name	Abiocor Artificial Heart
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective multi-center single armed study. The goal of the study is to continue to gather clinical data on the AbioCor to permit the continued assessment of its clinical performance while in clinical use.
Study Population	Study Population: Patients in severe biventricular heart failure and who are not transplant candidates; not supportable by a left ventricular assist device alone; are less than 75 years old; require multiple inotropic support; not treatable by left ventricular assist device destination therapy; not weanable from biventricular support, if applicable. Indication: Biventricular heart failure.
Sample Size	25 patients, 10 sites
Key Study Endpoints	The following outcomes will be assessed: 1) Adverse events: including neurologic events, infection, bleeding, renal dysfunction, liver dysfunction, thrombosis, and respiratory events, 2) Quality of life using the Kansas City Cardiomyopathy Questionnaire and the EuroQol will be administered on a monthly basis while in the hospital and every three months after discharge from the hospital, 3) Characterization of patient activity and interaction with family will be monitored by the patient caregiver, 4) CVA events due to thromboembolism, 5) Discharge history to hotel, intermediary facility, or home, and readmission to hospital, 6) Functional status instruments, including distance walked and ventilatory oxygen uptake measurements, and 7) Neurological assessment, including NIH stroke scale, modified Rankin scale, and a battery of cognitive function tests
Follow-up Visits and Length of Follow-up	Post-discharge, patients will be contacted every three months. Patients will be followed until death (while on the device) or other outcome (e.g. elective termination by family, device malfunction, etc).
General
Study Status	Completed
Application Number / Requirement Number	P990020 / PAS001
Date Original Protocol Accepted	09/28/1999
Date Current Protocol Accepted	09/28/1999
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was a multi-center prospective clinical trial that involved 19 sites. The first five subjects enrolled at each site were enrolled in the surgical arm of the study. All following sequential enrollments received the AneuRx stent graft.
Study Population	Patients were candidate for surgical repair of an infrarenal aortic or aorto-iliac aneurysm.
Sample Size	923 patients, 16 sties
Key Study Endpoints	The primary endpoint was aneurysm related mortality at 5 years. Secondary endpoints included 1) Delivery success, 2) Deployment success, 3) Stent graft migration, measured by CT, angiography, ultrasound, or pathological analysis, 4) Aneurysm exclusion, evidence of blood flow around or through the stent graft into the aneurysm, 5) Stent graft patency, evidenced by CT, angiography, ultrasound or pathological analysis, 6) Device integrity, 7) Mechanical integrity, 8) Major morbidity (rupture, conversion, and major adverse events, and 9) Mortality.
Follow-up Visits and Length of Follow-up	Follow-up was scheduled at 1 month, 6 months, and 1 year post-procedure, then every 6 months for the duration of the implant, up to 5 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	931 patients
Actual Number of Sites Enrolled	16 sites
Patient Follow-up Rate	75%
Final Safety Findings	Late aneurysm-related mortality accelerated in years 4 and 5 and was very high compared to open surgical controls.
Study Strengths & Weaknesses	Strength: Prospective follow-up design; Weakness: A literature control group that lacked some important information was used as a comparison group for the primary endpoint.
Recommendations for Labeling Changes	We recommended that labeling changes be made to reflect the high aneurysm-related mortality rate in later years. Review of the labeling change is currently being done.
General
Study Status	Completed
Application Number / Requirement Number	P860057 S023/ PAS001
Date Original Protocol Accepted	04/07/2005
Date Current Protocol Accepted	04/07/2005
Study Name	Carpentier Edwards PAS
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a bench testing study. It is a real-time aging for the other two models namely, 3000TFX, 6900PTFX, 2700TFX and 2800TFX.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	Data will collected from: 1) tissue relaxation studies of zero timeand accelerated aged tissues, 2) histological evaluation of real-time aged whole valves, 3) real-time aged whole valve hydrodynamic testing, and 4) real-time aged whole valve structural integrity testing
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P040036 / PAS001
Date Original Protocol Accepted	08/11/2006
Date Current Protocol Accepted	08/11/2006
Study Name	NaviStar Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, observational, multi-site, non-randomized, single arm study (please expand). This study is designed to provide additional, corroborative safety data for the NAVISTAR THERMOCOOL catheter for the treatment of subjects with sustained, monomorphic VT or incessant VT associated with coronary artery disease.
Study Population	All patients who are considered for a radio frequency ablation procedure for drug refractory sustained, monomorphic or incessant ventricular tachycardia associated with coronary artery disease and who are eligible for treatment by a study investigator are to be screened, and then included in the study if they meet the inclusion and exclusion criteria.
Sample Size	249 total subjects and 224 evaluable subjects, 18 sites
Key Study Endpoints	Endpoints include: 1) One-year all cause mortality, 2) Cardiovascular-specific adverse event at one week, 3) cardiac perforation, 4) pericardial effusion with hemodynamic compromise, 5) pulmonary embolus, 6) complete heart block, 7) stroke, 8) acute myocardial infarction, 9) new acute severe mitral or aortic regurgitation, 10) deep venous thrombosis, arterial dissection or injury that requires surgical treatment, and 11) death.
Follow-up Visits and Length of Follow-up	Follow-up period will be three years, with follow-up visits every 6 months.
General
Study Status	Completed
Application Number / Requirement Number	P020012 / PAS001
Date Original Protocol Accepted	10/27/2006
Date Current Protocol Accepted	10/27/2006
Study Name	Study P521-01
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, non-randomized, non-controlled post-approval study.
Study Population	Subjects who agree to participate and are consecutively treated with Artefill in nasolabial folds (NLF). All subjects must have a negative Artefill skin test prior to treatment.
Sample Size	The sample size is 1,000 subjects who agree to participate and are consecutively treated with ArteFill in nasolabial folds. There are to be 25 investigational sites.
Key Study Endpoints	Endpoints include the incidence of granuloma, incidence of serious unanticipated adverse events (including their severity and relation to the implant product), incidence of anticipated adverse events at each follow-up, and subject's assessment of satisfaction characterized by using a five point non-parametric scale at each follow-up.
Follow-up Visits and Length of Follow-up	5 years Patients will be evaluated at baseline before treatment is administered. Follow-up starts at the completion of treatments. The first follow-up visit is at a 3 months after the last treatment, and then using a mail patient questionnaire the sponsor will assess adverse events and subject's satisfaction with treatment at the following intervals from the last treatment: 6, 12, and 18 months, and then 2, 3, 4 and 5 years. at the end of 5 years of follow-up, a final office visit is conducted. During the follow-up period, if a subject indicates the presence of a potential adverse event of a questionnaire, the sponsor or its representative will contact the investigator caring for that subject. For serious adverse events related to the treatment, the investigator will contact the subject to schedule an appointment to have the event evaluated clinically at the site in a timely manner.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,008
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	87% at 5 years
Final Safety Findings	Granulomas were encountered in 17 of 1,008 subjects (1.69%). A total of 887 adverse events (AEs) were noted among 416 (41.3%) treated subjects. There were 177 AEs among 118 (11.7%) treated subjects that were considered device�]related. In general, the majority of these events were typical of dermal fillers, mild in severity and resolved during the study period. A total of 101 serious adverse events (SAEs) were noted among 75 (7.4%) treated subjects. In addition to the 7 deaths, there were 94 other SAEs. The 94 other serious adverse events included one event of difficulty breathing, shortness of breath, or tightness in the chest, four events of severe illness or trauma, 43 other local complications, and 46 other systemic complications. None of these SAEs were determined to be device�]related.
Final Effect Findings	Subject satisfaction remained high throughout the study. The majority (>83%) of subjects were very satisfied or satisfied (scored 1 or 2 on the 5�]point scale) with their treatment outcome at the 5� year follow ]up.
Study Strengths & Weaknesses	This is a prospective, multicenter study that provides long term data up to 5 years on the safety and effectiveness of the device. The follow ]up rate at 5 years was relatively high (87%). The weakness of the study was the lack of a comparison group.
Recommendations for Labeling Changes	The labeling will be updated based on the 5� year safety and effectiveness results reported in the PAS final report.
General
Study Status	Completed
Application Number / Requirement Number	P020014 S006/ PAS001
Date Original Protocol Accepted	07/22/2004
Date Current Protocol Accepted	07/22/2004
Study Name	HSG Evaluation Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P860057 S016/ PAS001
Date Original Protocol Accepted	11/29/2001
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, observational, non-randomized, multi-center study of the Carpentier-Edwards pericardial bioprostesis.
Study Population	Subjects were eligible for participation if they required mitral valve replacement, were average or better operative risk, and did not meet criteria for exclusion.
Sample Size	209 subjects, 7 sites
Key Study Endpoints	Adverse event rate, New York Heart Association classificatioin, Hemodynamic performance
Follow-up Visits and Length of Follow-up	Participants were followed at discharge, 6 months and 1 year and annually thereafter.for 7 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	209 patients
Actual Number of Sites Enrolled	7 sites
Patient Follow-up Rate	71%
Final Safety Findings	Final report indicates acceptable device performance
Study Strengths & Weaknesses	Strength: Prospective cohort study
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P070027 / PAS001
Date Original Protocol Accepted	04/15/2008
Date Current Protocol Accepted	11/05/2008
Study Name	Vitality Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, one armed, non-randomized, observational, multi-site study. The purpose of this study is to examine, through the endpoints established in this protocol, the long-term safety and effectiveness of the Talent Abdominal Stent Graft System, in a post-approval environment.This study incorporates the Test Group from the Talent Abdominal PMA (eLPS cohort), consisting of 166 subjects. In addition, 94 new subjects will be prospectively enrolled to compliment the PMA subjects. All subjects are followed for a total of 5 years following initial implantation.
Study Population	Subjects will include patients diagnosed with an abdominal aortic or aorto-iliac aneurysm that are considered candidates for endovascular repair, per the FDA approved indications for use. The stent graft is indicated for the endovascular treatment of abdominal aortic aneurysms with or without iliac involvement having: 1) Iliac/femoral access vessel morphology that is compatible with vascular access techniques, devices, and/or accessories; 2) - A proximal aortic neck length of > 10 mm; 3) Proximal aortic neck angulation < 60 ; 4) Distal iliac artery fixation length of > 15 mm; 5) An aortic neck diameter of 18-32 mm and iliac artery diameters of 8-22 mm; and 6) Vessel morphology suitable for endovascular repair.
Sample Size	166 subjects from the premarket cohort, 94 new subjects from 20-30 sites
Key Study Endpoints	Primary endpoint: Freedom from aneurysm-related mortality at 5 years. Death from rupture of the abdominal aortic aneurysm or from any procedure intended to treat the abdominal aortic aneurysm. If a death occurred within 30 days of any procedure intended to treat the abdominal aortic aneurysm, then it is presumed to be aneurysm related.
Follow-up Visits and Length of Follow-up	Subjects are followed at 1-month, 6-months, 12-months, 24 months, 36 months, 48 months, and 60 months post-implant. Total duration of follow-up is 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	260
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	72.7%
Final Safety Findings	There were three aneurysm-related deaths in the first 30 days, two more in year one, one in year two, and one in year three. The Kaplan-Meier estimate for freedom from AAA-related mortality was 97.0% at five years (lower 95% limit of confidence interval at five years was 95.0%). There were very few aneurysm ruptures, conversions to open surgery, problems with stent graft patency, integrity, or migration, Type I and III endoleaks have remained at less than 3% annually combined.
Final Effect Findings	Technical implant success was 98%
Study Strengths & Weaknesses	Although mortality, aneurysm-related mortality, and secondary procedures were found to be higher than that in males, and although the major adverse event rates were found to be higher in non-whites than in whites, the sample sizes for females (n = 33) and non-whites (n = 19) were far too small for adequate statistical comparisons of these variables.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P020056 / PAS003
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Focus Group
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Actual Number of Patients Enrolled	There were 29 augmentation participants and 23 reconstruction participants.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A, There was no follow-up of focus group participants.
Final Safety Findings	N/A, There are no safety findings.
Study Strengths & Weaknesses	The strength of the study was that the focus groups included augmentation and reconstruction patients. The weakness of the study was that the participants many not be representative of all breast implant patients.
Recommendations for Labeling Changes	Changes were made to the Patient Planner based on the recommendatin of the focus groups. These changes included changing the order of text in the planner and making the planner available on-line.
General
Study Status	Terminated
Application Number / Requirement Number	H140001 / PAS001
Date Original Protocol Accepted	01/23/2015
Date Current Protocol Accepted	01/23/2015
Study Name	Impella RP Prospective Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, multicenter single -arm study enrolling new patients.
Study Population	Patients with right ventricular failure in need of hemodynamic support. Patients in RVF will be supported with the Impella RP until recovery, transplantation or implantation with a long-term device. Patients that meet all eligibility criteria
Sample Size	30 consecutive patients enrolled from up to 15 US sites. The sample size of 30 subjects for the Impella RP follows the same rationale used in the CentriMag PAS that had a sample size of 25 patients with RVF of all causes. The rationale for choosing a sample size of 25 patients for the CentriMag PAS was based on the following: First, the original study cohort included 24 RVAD patients. Thus, the CentriMag clinical trial and postmarket study populations were nearly identical in size, and the nature of the patients enrolled into the PAS were anticipated to be similar to those included in the original clinical trial. Additional consideration in selecting a sample size of 25 relates to the timeline of the original study. The 24 patients enrolled into the original trial took approximately 4 years to enroll. Approximately 16% of the patients who receive an implantable LVAD require an RVAD. Thus, the rate of enrollment has been historically slow. The enrollment of 25 patients was expected to be performed in a similar timeframe during which the practice of medicine was expected to be relatively comparable and the results meaningful. The sample size of 30 subjects for the Impella RP PAS is 20% higher than the CentriMag RVAS post-market study.
Key Study Endpoints	Data collected in the PAS will be based on institutional standards of care for the patient population. Data will be collected on Case Report Forms (CRFs). Source documents include, but are not limited to, death certificate, autopsy report, laboratory reports, operative report, echocardiograms, ultrasound report, angiograms, cardiac catheterization logs and cardiac catheterization reports, patient discharge report. Primary: Survival at 30 days post device explant or hospital discharge (whichever is longer), or to induction of anesthesia to a longer term therapy, including a heart transplant or an implant of a surgical RVAD. Secondary: Safety Rates of the following major adverse events measured at hospital discharge or to induction of anesthesia to a longer term therapy (including a heart transplant or an implant of a surgical RVAD): Death (any cause of death and cardiac death) Major Bleeding Hemolysis Pulmonary Embolism Survival only will be assessed at 30 days (± 10 days) and 180 days (± 30 days). Other adverse events Device failures and malfunctions Secondary Probable benefit Improvement in hemodynamic parameters Cardiac Index Central Venous Pressure LVAD flows after initiation of Impella RP support. Major adverse events (MAEs) will be reviewed, adjudicated and categorized by the Clinical Events Committee.
Follow-up Visits and Length of Follow-up	180 days post explant 30 days and 180 days
General
Study Status	Ongoing
Application Number / Requirement Number	P020056 / PAS008
Date Original Protocol Accepted	08/03/2015
Date Current Protocol Accepted	08/25/2016
Study Name	Natrelle and 410 Combined Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). This Combined Cohort study was designed as part of the re-design of the LARGE PAS. This is a smaller cohort study to primarily address safety outcomes (i.e., including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problems, effects on mammography, effects on patient satisfaction with breasts and psychosocial well-being, and silicone subject compliance with magnetic resonance imaging (MRI) recommendations. This re-structured PAS, once completed as designed, would satisfy the post-approval requirements for both the Natrelle® (P020056) and Natrelle® 410 (P040046) silicone breast implants. The Round Responsive and Style 410 implants will be compared with saline implants or national norms. In addition, information gained from the NBIR will help strengthen the general understanding of implantation rates and certain risks associated with breast implants.
Study Population	Subjects who have received Allergan silicone gel-filled breast implants or saline implants will be eligible to participate in the study. INCLUSION: Subjects must meet all of the following inclusion criteria at the time of surgery: 1) Female, age 18 years or older (age 22 or older for breast augmentation subjects) 2) Exhibit fluency and literacy in English or Spanish EXCLUSION: Subjects who meet any of the following criteria are not eligible for enrollment in the study: 1) Are transgender 2) If a saline implant subject, have a current or past unilateral or bilateral silicone gel-filled breast implant 3) Investigator decision that subject is not a suitable candidate for a long-term observational study CONTINUATION (BIFS ARM ONLY): Subjects are eligible to continue in the BIFS arm if they meet all of the following criteria: 1) Have complete baseline and years 1, 2, 3, and 4 follow-up questionnaires available (including the Satisfaction with Breasts and Psychosocial Well-Being modules of the BREAST-Q). Saline reconstruction and revision reconstruction do not need to have complete BREAST-Q questionnaires at baseline. 2) Meet all enrollment criteria, specifically the minimum age requirements for silicone implants (18 or older for reconstruction subjects and 22 or older for augmentation subjects), and were free of all target diseases at baseline 3) Are enrolled at a site that is selected in the cluster sampling to continue in the BIFS arm under Amendment 5.
Sample Size	2,000 subjects with Allergan Round Responsive silicone gel filled breast implants and 245 subjects with saline implants selected from the Breast Implant Follow-up Study (BIFS) cohorts, and 530 newly enrolled Style 410 highly cohesive silicone breast implants. The BIFS continuation arm will be targeted to include 20 saline revision augmentation, 11 saline reconstruction, and 11 saline revision-reconstruction subjects. If the cluster sampling results in insufficient subjects from these groups, additional subjects (who would otherwise not qualify for the BIFS arm) will be selected from continuing sites at random to meet the targets.
Key Study Endpoints	Adverse events (including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problem, effects on mammography, effects on satisfaction with breasts and psychosocial well�]being, and silicone subject compliance with MRI recommendations.
Follow-up Visits and Length of Follow-up	10 years Subject questionnaire will be collected annually. Office visits at Year 1, 4 and 10 for participants enrolled in the device group.
Interim or Final Data Summary
Actual Number of Patients Enrolled	BIFS-ARM: 2,257 subjects (2,000 Round Responsive subjects; 257 Saline Control subjects)
Actual Number of Sites Enrolled	BIFS-ARM – 172 sites
Patient Follow-up Rate	BIFS-ARM: Completion of annual questionnaire for Round Responsive subjects: Year 1: 100% Year 2: 100% Year 3: 100% Year 4: 100% Year 5: 83.5% Year 6: 79.6% Year 7: 77.8% Year 8: 74.2% Year 9: 72% Year 10: 66.7% Completion of annual questionnaire for saline subjects: Year 1: 100% Year 2: 100% Year 3: 100% Year 4: 100% Year 5: 86.4% Year 6: 80.9% Year 7: 77.8% Year 8: 72.4% Year 9: 75.1% Year 10: 68.5%
Final Safety Findings	BIFS-ARM: Through 10 years, the study did not identify any new safety findings. No relationship with silicone breast implants and rare diseases was identified. Risks of implantation in the post-market environment were consistent with observations from the pre-market Core Clinical Study that established the safety profile of NATRELLE® Silicone-Filled Breast Implants.
Final Effect Findings	BIFS-ARM: On the 100-point BREAST-Q scale, median satisfaction with breasts was 31.0 for both the silicone and saline cohorts at baseline. Median scores were 77.0 and 74.0 for the silicone and saline cohorts at year 1. Median scores were 74.0 and 73.5 for the silicone and saline cohorts at year 4. Median scores were 73.0 and 70.5 for the silicone and saline cohorts at year 10. Median psychosocial well-being scores at baseline were 55.5 for silicone subjects and 50.0 for saline subjects. Median psychosocial well-being scores were 96.5 and 93.0, respectively for silicone and saline subjects at year 1. At year 4, median psychosocial well-being scores were 85.0 for silicone and 82.0 for saline subjects. At year 10, median scores were 76.0 and 73.0, respectively for the silicone and saline cohorts.
Study Strengths & Weaknesses	Pending
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P010013 S041/ PAS001
Date Original Protocol Accepted	02/01/2013
Date Current Protocol Accepted	01/04/2022
Study Name	NovaSure PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single-arm, multi-center study
Study Population	Premenopausal women greater than or equal to 18 years old with menorrhagia due to benign causes for whom childbearing is complete and have received an Essure Permanent Birth Control System
Sample Size	Up to 21 sites, 318 patients
Key Study Endpoints	1. Primary Endpoint: Removal of an Essure micro-insert with the NovaSure device 2. Secondary Endpoints: 2.1. AEs during and/or immediately following the NovaSure procedure; 2.2. AEs up to 1 month after the NovaSure procedure
Follow-up Visits and Length of Follow-up	1 Month 1 Follow-up assessment
Interim or Final Data Summary
Actual Number of Patients Enrolled	16
Actual Number of Sites Enrolled	16
Patient Follow-up Rate	Out of all enrolled patients (148), 127 patients completed the study (85.8%). Out of the women who underwent a NovaSure treatment, 95.4% (127/133) completed the study. There were 15 patients who were screened after enrollment and 6 lost to follow-up.
Final Safety Findings	Note: The original study enrolled 127 patients that underwent NovaSure post Essure placement and completed the study. Data from the original study was supplemented with data from Bayer Pharma AG’s study (P020014/S017/PAS001) with a comparable patient population. Supplemental data provided from the Bayer study included 211 treated patients, bringing the total number of patients evaluated with these two data sets (Hologic and Bayer) to 338. Please see the P020014/S017/PAS001 database for more details. Outcomes below are broken down by study. Removal of Essure Inserts with NovaSure Device: There were no inadvertent removals of an Essure micro-insert due to snagging on the NovaSure array in both Hologic’s and Bayer’s studies. AEs During and/or Immediately following NovaSure Procedure and up to 1 Month following the Procedure: Hologic Study A total of 102 events were reported in 48/127 subjects (37.8 %). There were 0 serious adverse events (SAEs). Among 102 adverse events (AEs), 72 events were during and/or immediately following the NovaSure procedure and 30 events were up to 1 month after the NovaSure procedure. The AEs occurring in greater than or equal to 2% of subjects were uterine spasm (28 subjects, 22.0%); vaginal hemorrhage (24 subjects, 18.9%); vaginal discharge (19 subjects, 15.0%); abdominal pain (6 subjects, 4.7%); nausea (3 subjects, 2.4%); and vomiting (3 subjects, 2.4%). Bayer Study Data from the Bayer study did not distinguish between events immediately after the procedure or up to 1 month following, as initial follow up was recorded at 1 month. A total of 94 events were reported in 53/211 subjects (25.1 %) within 1 month from the NovaSure procedure. There were 4 SAEs in 3/211 subjects within 1 month from the NovaSure procedure. The AEs occurring in greater than or equal to 2% of subjects were vaginal discharge (12 subjects, 5.7%); pelvic pain (9 subjects, 4.3%); vaginal hemorrhage (8 subjects, 3.8%); uterine spasm (6 subjects, 2.8%); abdominal pain (6 subjects, 2.8%); nausea (6 subjects, 2.8%); and procedural pain (5 subjects, 2.4%).
Final Effect Findings	There were no key endpoints related to the effectiveness of the NovaSure device.
Study Strengths & Weaknesses	The study enrollment did not meet original sample size (318). While supplemental data were provided from the Bayer study which had a similar patient population, there were differences in protocol between the two studies that may impact poolability (e.g., initial follow up timepoint, primary endpoint). Therefore, caution should be taken with interpretation of the combined results.
Recommendations for Labeling Changes	None, the NovaSure labeling approved in S041 that required this PAS already includes information regarding potential thermal injury following ablation in patients with Essure inserts.
General
Study Status	Completed
Application Number / Requirement Number	P030011 S011/ PAS002
Date Original Protocol Accepted	05/16/2012
Date Current Protocol Accepted	11/27/2015
Study Name	INTERMACS Companion
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This is a two armed (partially retrospective and partially prospective), multi center, non randomized, cohort registry study that uses the INTERMACS Registry to compare performance of the TAHt when supported with the Companion 2 Driver System vs. performance of the TAH�t when supported with the CSS Console. The primary endpoint will be the comparison of the positive outcome rate for TAHt patients initially supported with the Companion 2 Driver System compared to the positive outcome rate for patients initially supported with the CSS Console (concurrent cohort). Positive outcome will be assessed at both three and six months post-implant, and is defined as transplant, transfer to Freedom Driver, or continuing on implant driver support. The hypothesis is that the C2 Driver is non-inferior in positive outcome rate to the CSS Console by a margin of 10 percentage points.” “Secondary Objectives will be to provide descriptive statistics on enrollment, adverse events, and outcomes for all TAHt patients enrolled in the INTERMACS registry. Additionally, the positive outcome rate for all patients initially supported with the Companion 2 Driver System will be compared to the positive outcome rate of all patients initially supported with the CSS Console (cumulative cohort).
Study Population	Patients in the INTERMACS Registry who are implanted with the TAH�t and used the C2 Driver System as their initial driver. There will be 2 control groups used for comparison. One consists of all Patients in the INTERMACS Registry who are implanted with the TAH�t who used the CSS Console (cumulative cohort). The other consists only patients in the INTERMACS Registry who were implanted with the TAH�t after The C2 Driver System began to be used June 2012 (concurrent cohort).
Sample Size	The study will be composed of 200 patients supported by the Companion 2 Driver System and all INTERMACS Registry patients supported by the CSS Console at the time that the sample size for the C2 Driver System reaches 200.
Key Study Endpoints	The data will be collected as defined in the INTERMACS Protocol. The primary endpoint of survival rate at 3 and 6 months post implant will be evaluated according to the hypothesis mentioned above. Secondary objectives include the analysis of the same hypothesis except the comparing the C2 Driver System to the cumulative CSS console cohort.
Follow-up Visits and Length of Follow-up	4 years Per INTERMACS Registry (1 week, 1 month, 3 month, 6 month and every 6 months thereafter).
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 200 Companion 2 (C2) Driver and 89 CSS Console users were enrolled in the concurrent cohort; a total of 225 C2 Driver and 268 CSS Console users were enrolled in the cumulative cohort.
Actual Number of Sites Enrolled	A total of 57 INTERMACS clinical sites contributed data. (Database Closure Date for the Final Report: June 30, 2017)
Patient Follow-up Rate	The follow up rate through six months is 99.5% for C2 Driver users and 100% for CSS Console users (*only one patient, who was initially supported by the C2 Driver, was lost to follow-up.)
Final Safety Findings	Mortality Data: The positive outcome (“survival”) rate in concurrent cohort: At 3 months: 65.5% for C2 Driver users (lower bound of 95% confidence interval=58.5%) vs. 77.5% for CSS Console users. The non-inferiority was not met. At 6 months: 60.0% for C2 Driver Users (lower bound of 95% confidence interval=52.9%) vs. 74.2% for CSS Console users. The non-inferiority was not met. For patients who did not achieve positive outcome (“no survival”), all occurrences were due to death. The survival rate in concurrent cohort, stratified by pre-implant circulatory rescue intervention: Patients with rescue intervention: 1. At 3 months: 58.4% for C2 Driver users vs. 79.2% for CSS Console users 2. At 6 months: 55.8% for C2 Driver users vs. 72.9% for CSS Console users Patients without rescue intervention: 1. At 3 months: 69.9% for C2 Driver users vs. 75.6% for CSS Console users 2. At 6 months: 62.6% for C2 Driver users vs. 75.6% for CSS Console users The survival rate in cumulative cohort: At 3-months: 66.2% for C2 Driver users vs. 82.5% for CSS Console users At 6-months: 60.6% for C2 Driver users vs. 78.4% for CSS Console users Neurological Adverse Events: The proportion of patients with neurological adverse events in concurrent cohort: Through 3 months: 31.0% for C2 Driver users vs. 13.5% for CSS Console users Through 6 months: 31.5% for C2 Driver users vs. 14.6% for CSS Console users The difference in neurological adverse events appeared to be driven mainly by the difference in cerebrovascular accident (CVA) for the two groups. The proportion of patients with CVA events (concurrent cohort): CVA through 3 months: 26.5% for C2 Driver users vs. 7.9% for CSS Console users (P<0.0001) CVA through 6 months: 27.0% for C2 Driver users vs. 7.9% for CSS Console users (P<0.0001) The proportion of patients with CVA events (concurrent cohort), stratified by pre-implant circulatory rescue intervention: Patients with rescue intervention: 1. CVA through 3 months: 26.0% for C2 Driver users vs. 6.3% for CSS Console users 2. CVA through 6 months: 26.0% for C2 Driver users vs. 6.3% for CSS Console users Patients without rescue intervention: 1. CVA through 3 months: 26.8% for C2 Driver users vs. 9.8% for CSS Console users 2. CVA through 6 months: 27.6% for C2 Driver users vs. 9.8% for CSS Console users Other Adverse Events: The study also compared the occurrence of eleven other adverse events in patients initially supported with the C2 driver to those initially supported with the CSS Console. These adverse events were: arterial non-CNS thromboembolism, bleeding, device malfunction, hepatic dysfunction, infection, pericardial drainage, psychiatric episode, renal dysfunction, respiratory dysfunction, venous thromboembolism and wound dehiscence. There was no statistically significant difference in the occurrence of these eleven adverse events between C2 driver users and CSS Console users through 3 months and through 6 months.
Study Strengths & Weaknesses	Strength: The follow-up rate was high in the study; the data source used in the study represented real-world data. Weaknesses: The study reported higher mortality and CVA adverse events for patients initially supported by C2 Driver System than those initially supported by the CSS Console. However, we do not know the causes for these observed differences. The summary results did not adjust for potential confounding factors, such as patient characteristics or device characteristics. The existing data in INTERMACS Registry are limited in that detailed device characteristics (e.g. driver operating parameters, driver history, previously reported driver issues) and comprehensive patient pre-implant characteristics were not captured. Furthermore, the study was not powered to detect a significant difference between C2 driver group and CSS Console group for the secondary adverse event endpoints.
Recommendations for Labeling Changes	Yes. It is recommended that the label be updated to reflect the higher rates of unsuccessful outcomes and neurological adverse events in the C2 driver group compared to CSS Console group.
General
Study Status	Completed
Application Number / Requirement Number	P020016 / PAS001
Date Original Protocol Accepted	09/21/2005
Date Current Protocol Accepted	09/21/2005
Study Name	Long-term Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a follow-up of the pre-market study patients.
Study Population	Study Population: All patients remaining at approval of device. Indication: For reconstruction of the temporomandibularjoint.
Sample Size	150 patients, 8 sites
Key Study Endpoints	The primary endpoints include quality of life, jaw pain, jaw function and, maximum interincisal opening, patient satisfaction and implant removal.
Follow-up Visits and Length of Follow-up	Patients will be followed for 3-years post implant. The follow-up schedule was not noted.
Interim or Final Data Summary
Actual Number of Patients Enrolled	288
Actual Number of Sites Enrolled	Not stated
Patient Follow-up Rate	91%
Final Safety Findings	Of the enrolled patients, 98.4% of known patients retained the implant at three years. However, there are 32 patients lost to follow-up and 12 with no response. If all patients lost to follow-up or with no response were included as failures at 3 years, survival of device implant would remain over 90%, indicating reasonable assurance of safety.
Study Strengths & Weaknesses	The strength of the study is that there is adequate follow-up. The weaknesses of the study is that there were no hypothesis or sample size calculations.
Recommendations for Labeling Changes	There were no recomendations were made for labeling changes.
General
Study Status	Completed
Application Number / Requirement Number	P980022 S012/ PAS001
Date Original Protocol Accepted	12/27/2006
Date Current Protocol Accepted	12/27/2006
Study Name	PXX/GS041/A
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a randomized controlled trial, in which one arm receives the device with human albumin serum sensor and the other arm receives the device with bovine albumin serum sensor.
Study Population	Study Population: Patients aged 18 to 65 years, previously diagnosed with type 1 diabetes, and currently using an insulin pump or multiple daily injections. Indication: The device is used in patients with diabetes as a continuous glucose monitoring system in conjunction with a standard home blood glucose meter.
Sample Size	78 patients, 4 sites
Key Study Endpoints	The clinical endpoints to be measured consist of capillary blood glucose concentration as measured by the One-Touch Ultra Meter, and glucose values calculated from sensor signals measured by the Guardian RT System. The safety endpoints consist of device effects and frequency of device complications associated with the Guardian RT System. Data collection consited of a download the continious glucose monitoring system and glucose meter data as well as interview the patient at office visits.
Follow-up Visits and Length of Follow-up	After enrollment, subjects will be followed by phone calls on day 3, day 18, and day 21. On day 30s the end of study, subjects will return all study supplies to the site, and data will be uploaded to a computer for analysis and review.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	78
Actual Number of Sites Enrolled	4
Patient Follow-up Rate	80%
Final Safety Findings	A total of five adverse events were reported across 4 subjects during the study. All reported complete recovery. Two of the subjects experienced skin disorders (rash and/or itching); one subject experienced a hypoglycemic event, which was considered severe (the subject showed complete recovery after treatment with concomitant medications); and one subject experienced a syncopal episode (subject passed out after inserting a sensor) and withdrew from the study.
Study Strengths & Weaknesses	Strength: The study was designed as a randomized controlled trial.
Recommendations for Labeling Changes	There were no recomendations made for labeling changes.
General
Study Status	Ongoing
Application Number / Requirement Number	P030011 S011/ PAS003
Date Original Protocol Accepted	06/25/2025
Date Current Protocol Accepted
Study Name	Companion 2 Driver System PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The Post-Approval Study is a registry-based, multi-center, prospective, new enrollment of all comers. It will provide a confirmatory assessment of both short-term and long-term safety and effectiveness of the 50cc SynCardia temporary Total Artificial Heart (TAH-t) is a post- approval setting.
Study Population	The patient whose de-identified data will be used in this study will be representative of the patient population with irreversible biventricular failure at imminent risk of death and extends across all subpopulations that were implanted with the TAH-t for the following indication: The TAH-t System is indicated for use as a bridge to transplantation in cardia transplant-eligible candidates at risk of imminent death from biventricular failure. Inclusion Criteria All patients greater than or equal to 19 years of age who receive a legally utilized MCSD implanted at an INTERMACs – activated center. (NOTE: Patients implanted before the cetner activation data are not eligible for participation in INTERMACS.) Exclusion Criteria 4. Patients who receive a MCSD, which is not legally utilized 5. Patients who are < 19 years of age 6. Patients who are incarcerated persons (prisoners).
Sample Size	Number of subjects: 24 Assumptions for sample size estimation: Number of sites: All sites participating in the SYS INTERMACS/PEDIMACS Registry will be eligible to participate in the study. Sites location: All sites are US.
Key Study Endpoints	Safety Endpoints Primary: • Survival outcome (being alive and continuing TAH-t support or having received a transplant). • Rate of stroke through three-months, six-months and two-years. Secondary: • Rates of device malfunction (pump and driver) and rates of adverse events Effectiveness Endpoints Primary: • Time on device (implant to outcome) Secondary: • Rates of device exchange (pump and driver, other than for routine schedule service) Note: TAH malfunctions (device failures) will be documented, investigated, and reported under applicable regulatory requirements, as necessary.
Follow-up Visits and Length of Follow-up	TAH-t patients are followed according to the STS INTERMACS/PEDIMACS Registry Protocol at: • One week • One month • Three months, and • Six months post-implant and Will continue to be followed every six months thereafter until 2 years post implant if the patient remains on TAH-t support.
General
Study Status	Completed
Application Number / Requirement Number	P180007 / PAS001
Date Original Protocol Accepted	03/01/2019
Date Current Protocol Accepted	09/01/2021
Study Name	EMPROVE Extension Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is designed as continued, prospective, long-term follow up of the EMPROVE pre-market cohorts. The objective is to evaluate the long-term safety and effectiveness of the Spiration Valve System for the treatment of severe emphysema. This will be an observational study for long-term follow-up of the EMPROVE Trial pre-market patient cohort with no planned interventions
Study Population	All active (enrolled and not withdrawn) subjects continuing long-term (beyond 1 year) follow-up in protocol CPR-03434.
Key Study Endpoints	Primary Safety: All serious adverse events and non-serious adverse events related to the device or procedure will be assessed at annual follow-up visits by seriousness, severity, and relatedness. Effectiveness Observations: The following effectiveness assessments will be undertaken at annual follow-up visits: Spirometry St. George’s Respiratory Questionnaire (SGRQ) SF-36 COPD Assessment Test (CAT) Modified Medical Research Council dyspnea scale (mMRC) Quality of Well Being (QWB) questionnaire
Follow-up Visits and Length of Follow-up	Control group subjects will be followed annually through 2 years. Treatment group subjects will be followed annually through 5 years. a1 antitrypsin deficiency subjects (a separate non-randomized treatment cohort) will be followed annually through 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	172
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	99% for treatment arm at 5 years. 85% for control arm at 2 years.
Final Safety Findings	Composite safety endpoint: Treatment group = 12.5% at 5 years; Control group = 20% at 2 years.
Final Effect Findings	Primary endpoint = FEV1 improvement 0.098 liters at 6 months in comparison with the control group. At 2 years the FEV1: Improvement between Treatment and Control groups = 0.085 liters on average (95% BCI: 0.016 – 0.153), with a posterior probability of superiority > 0.9923. At 5 years the FEV1: Improvement is 0.049 liters (0.049 -/+ 0.247).
Study Strengths & Weaknesses	The sponsor has conducted a randomized controlled multi-center trial with 5-year follow up for treatment arm, but only 2-year follow up for control arm, following the approved protocol. In addition, control subjects were not blinded and were immediately aware of their assignment to the control group upon randomization, and therefore suffered a 15% drop-out rate.
Recommendations for Labeling Changes	There are no new or unexpected findings in or conclusions drawn from this Final Report which would suggest that a labeling update is necessary.
General
Study Status	Ongoing
Application Number / Requirement Number	P180007 / PAS002
Date Original Protocol Accepted	05/21/2019
Date Current Protocol Accepted	08/20/2026
Study Name	SVS [STRIVE] Post-Market Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the PAS registry study registry is to collect safety and effectiveness data in a post-approva1 setting for the Spiration Valve System (SVS). The SVS will be used as intended and in accordance with FDA-approved labeling. This post-market study is a single-arm, prospective, multi­ center Registry. It is designed to assess 36-month safety and effectiveness of this FDA approved product in a post-approval setting, and to support the continued assessment of Spiration Valve System therapy for the treatment of severe emphysema in the United States.
Study Population	The population will be comprised of subjects with severe emphysema and evidence of low collateral ventilation, such as fissure integrity.
Sample Size	150 subjects at a minimum of 10 sites and up to 40 sites.
Key Study Endpoints	Primary Safety: Incidence of pre­ specified thoracic adverse events of special interest {TAEsSI) through 12 months following the first implantation procedure, including but not limited to acute asthma or bronchospasm; acute exacerbation of COPD, airway injury from valve placement, valve migration, or airway stenosis from a valve, hemoptysis, pneumonia, pneumothorax, and respiratory failure that requires mechanical intervention. Secondary Safety: (a) 45-day pneumothorax rate. (b) Survival rate over 24 months compared to the EMPROVE study control cohort
Follow-up Visits and Length of Follow-up	All enrolled Subjects who undergo the SVS procedure will be monitored for outcome data from baseline through 3 years post-first implant.
Interim or Final Data Summary
Interim Results	Safety Results As only 99/150 (66%) subjects have been enrolled to date and only 41 have reached 12-month safety timepoint, no conclusions can be drawn about device safety. Effectiveness Results As only 99/150 (66%) subjects have been enrolled to date and only 2 have reached 36-month effectiveness timepoint, no conclusions can be drawn about device effectiveness.
Actual Number of Patients Enrolled	99
Actual Number of Sites Enrolled	16
Patient Follow-up Rate	99% (30/99 (40%) of subjects were withdrawn post-procedure.
General
Study Status	Completed
Application Number / Requirement Number	P030016 S001/ PAS001
Date Original Protocol Accepted	03/07/2019
Date Current Protocol Accepted	07/19/2019
Study Name	Visian Toric ICL New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this PAS is to evaluate the long term (i.e. 24 months) clinical performance of the Visian TMICL with respect to rotational stability, refractive and visual outcomes, and ocular adverse event (AE) rates. This is a new enrollment, prospective, multicenter, open-label, single arm, post approval study.
Study Population	Subjects will be selected from each clinical site’s patient population. Patients meeting all of the following criteria will be considered suitable study subjects. All subjects enrolled in this clinical study will meet the requirements under the indications for use outlined in the package insert directions for use (DFU) for the FDA approved lenses and additional eligibility criteria. (refer below): Inclusion Criteria (each eye to be implanted) 1. Subjects 21 through 45 years old at time of surgery. 2. Moderate to high myopia with spherical equivalent ranging from -3.0 D to less than or equal to -15.0 D (in the spectacle plane) and cylinder in the range of 1.0 D to 4.0 D (in the spectacle plane). 3. Stable refractive history within 0.5 D for both spherical equivalent and cylinder for 1 year prior to implantation. 4. Anterior chamber depth (ACD) 3.0 mm or greater, when measured from the corneal endothelium to the anterior surface of the crystalline lens. 5. Meet minimum endothelial cell density (ECD) requirements for age and ACD. 6. Correctable (CDVA) to at least 20/40 in the eye to be treated; and absent of ocular pathology (except that myopic degeneration is allowed). 7. Able to read, understand and provide written informed consent on the Institutional Review Board (IRB) approved Informed Consent Form (ICF). 8. Able and willing to return for scheduled follow-up examinations after surgery. Exclusion Criteria (each eye to be implanted) 1. Younger than 21 or older than 45 years of age. 2. With true ACD < 3.00 mm*. 3. Anterior chamber angle less than Grade III as determined by gonioscopic examination. 4. Do not meet the minimum ECD as defined in the “Minimum Endothelial Cell Density for Age and True ACD*” table below. 5. Unstable or worsening nearsightedness. 6. History or clinical signs of iritis/uveitis. 7. Diabetic retinopathy. 8. Glaucoma. 9. History of previous eye surgery. 10. Serious (i.e., life threatening), acute, chronic or systemic, nonophthalmic disease or illness that would increase the operative risk, confound the outcome(s) of the study or which may preclude study completion. 11. Progressive sight threatening disease or other previous or current ocular conditions, other than myopia, that may predispose for future complication. 12. Diagnosis of ocular hypertension (high eye pressure). 13. Insulin-dependent diabetes. 14. Pseudoexfoliation. 15. Pigment dispersion. 16. Spherical equivalent less than -3.0 D or greater than -15.0 D (in the spectacle plane) of nearsightedness; cylinder (spectacle plane) less than 1.0 D and greater than 4.0 D. 17. Pregnant or nursing women, or those who plan to become pregnant over the course of this clinical study or has another condition with associated fluctuation of hormones that could lead to refractive changes. 18. Involved in another clinical study or who may have been involved in a different clinical study within 30 days prior to this clinical study or will be involved in a different clinical study within 30 days of beginning this study.
Sample Size	124 subjects who meet all eligibility criteria will be offered consecutive enrollment in the study to result in a sample of 100 eyes. Calculations provide 95% power to reject the null hypothesis that >10% of eyes will exhibit >5º rotation and to allow for losses of 10% per year. In addition, a minimum of 14 subjects requiring a Toric ICL cylinder power of 3.5 or 4.0 diopters will be enrolled.
Key Study Endpoints	Primary Endpoint: The primary endpoint for this study is rotation of less than or equal to five degrees between 18 and 24 months postoperative. The endpoint will be met if at least 90% of the treated eyes rotate less than or equal to five degrees between 18 and 24 months postoperative (i.e., less than or equal to 10% of eyes exhibit >5º rotation). Secondary Endpoints The following additional endpoints will be evaluated: Absolute rotation between visits. Absolute rotation <5 degrees, <10 degrees, <20 degrees, and <30 degrees from the intended orientation at each visit. Absolute rotation from the intended orientation at each visit. Postoperative manifest refraction spherical equivalent and cylinder at each visit. Ocular AE rates assessed in implanted eyes.
Follow-up Visits and Length of Follow-up	24 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	125
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	89.7% of total eyes at Visit 9 (208/232); 7 subjects (14 eyes, 6.0%) lost to follow-up; 14 subjects (24 eyes, 10.0%) discontinued from the study
Final Safety Findings	A total of 136 ocular Adverse Events (AEs) have been reported in 83 eyes (35.8%) and a total of 35 ocular Serious Adverse Events (SAEs) in 29 eyes (12.5%) of 22 subjects have been reported in the study to date. No deaths or Unanticipated Adverse Device Effects (UADEs) have been reported in the study. The most frequently reported postoperative AE to date is increased IOP (44 events in 37 eyes, 15.9%).
Final Effect Findings	The primary endpoint for this study will be met if at least 90% of the treated eyes rotate = 5 degrees (º) between 18 and 24 months postoperative. All (100.0%) of the primary eyes exhibited rotation = 5 degrees between the 18-and 24-Month postoperative. The mean (± standard deviation) lens rotation between the 18-and 24-Month Postoperative Visits is 0.3° (0.19°). 99% of all implanted TICLs were placed within ± 3.0 degrees of intended axis of orientation on day 0. Lens rotation from the intended axis of greater than 5° occurred in 8 primary eyes (6.4%) of 8 subjects (subject 05-007 experienced 2 events of significant rotation OS), and 7 fellow eyes (6.5%) of 7 subjects in this study. Mean (SD) preoperative MRSE for all subjects enrolled was -8.79 (2.41) D, and mean (SD) preoperative manifest refractive cylinder was -2.06 (0.86) D with a range of 1.00 D to 4.00 D. At the Month 1 Visit, mean (SD) MRSE was -0.20 (0.38) D, and mean (SD) MR cylinder was -0.54 (0.42) D. Mean MRSE remained stable throughout the study (Month 24) and a slight reduction (-0.41 [0.44] D) in mean cylinder was observed.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P030016 S035/ PAS002
Date Original Protocol Accepted	05/20/2022
Date Current Protocol Accepted
Study Name	CP22-01 Postmarket Evaluation of the EVO ICL
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This new enrollment, prospective, multi-center, single arm PAS study will be conducted at up to 10 clinical sites in the United States (US). The study is designed to evaluate the success of the EVO Physician Certification Program in reducing the rate of early IOP increases at 1 – 6 hours after implantation of EVO/EVO+ ICL lenses by surgeons who have been trained and certified under the EVO Physician Certification Program.
Study Population	Subjects aged 21 to 45 years implanted with EVO/EVO+ ICLs in both eyes, in accordance with the product labeling and the eligibility criteria.
Sample Size	The study will enroll a minimum 200 subjects (i.e., 200 primary eyes and 200 fellow eyes). Assumptions include: • The proportion of primary eyes that will reach or exceed an IOP of 30 mmHg is 6% and the proportion of primary eyes that will reach or exceed an IOP of 40 mmHg is 1%. These estimates are based on Study CP19-01 data (as presented in PMA P030016/S035) from investigators who followed the instructions in the proposed EVO Physician Certification Program regarding removal of OVD, i.e., used a minimum of 10 – 20 cc of irrigation solution. • The proportion of fellow eyes reaching these thresholds for increased IOP will be equivalent to the rates found in the primary eyes. • No more than 10% loss to follow-up in this 2-week study. For a single sample exact binomial test with a two-tailed alpha of 0.05 to demonstrate that a hypothesized rate of 6% is significantly lower than 15.3% for IOP spikes = 30 mmHg with 98% power, a sample of 181 eyes would be required. Demonstrating that the rate of IOP spikes greater than or equal to 40 mmHg is significantly lower, given a hypothesized rate of 1% vs the Study CP19-01 rate of 7%, a sample size of 181 primary eyes of 181 subjects will achieve 96% power. Power to achieve both endpoints can be conservatively estimated by the product of the two powers, .98 times .96, or 94%. Analysis of fellow eye rates would also be conducted, and results would be used to support the findings of the two primary eye analyses.
Key Study Endpoints	The primary endpoint is the proportion of primary (i.e., first implanted) eyes that have IOP greater than or equal to 30 mmHg and IOP greater than or equal to 40 mmHg at 1 – 6 hours postoperatively. The secondary endpoint is the proportion of fellow eyes that have IOP greater than or equal to 30 mmHg and IOP greater than or equal to 40 mmHg at 1 – 6 hours postoperatively. Other safety endpoints include the following: 1) the proportion of fellow eyes that have IOP greater than or equal to 30 mmHg at 1 - 6 hours postoperatively 2) the proportion of fellow eyes that have IOP greater than or equal to 40 mmHg at 1 - 6 hours postoperatively 3) Rates of increased IOP in primary and all (primary + fellow) eyes attributed to retained OVD 4) Rates of increased IOP in primary and all eyes attributed to other causes (e.g., pupillary block, steroid response, etc.) 5) Rates of all categories of AEs (in primary and in all eyes) 6) Device deficiencies 7) Distribution of lens vault measured by OCT 8) Slit lamp findings and distributions of gradings (e.g., of anterior chamber cells and flare) 9) Notable ophthalmoscopy findings 10) UDVA and CDVA (uncorrected and corrected distance visual acuity) 11) Instances of loss of greater than or equal to 10 letters of CDVA from baseline, along with analyses of the causes.
Follow-up Visits and Length of Follow-up	Length of follow-up will be two weeks post-implantation of the fellow eye
Interim or Final Data Summary
Actual Number of Patients Enrolled	205
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	The Applicant reports that 402 of 408 eyes were available for analysis at Visit 4 (for each eye), 10-18 days after surgery. The 6 eyes not available were categorized as "Missing at scheduled visit but seen earlier/later," meaning 0 eyes were lost to follow-up.
Final Safety Findings	The primary study endpoint was the proportion of primary (i.e., first implanted) eyes that had Intraocular Pressure (IOP) greater than (or equal to) 30 mmHg, and greater than (or equal to) 40 mmHg at 1-6 hours postoperatively. The analysis of the primary study endpoint was based on the superiority of the proportion of primary eyes that have IOP greater than (or equal to) 30 mmHg and IOP greater than (or equal to) 40 mmHg at 1 – 6 hours postoperatively compared with the outcomes of Study CP19-01 (IDE G191084), which reported 15.3% (50/327) primary eyes with IOP greater than (or equal to) 30 mmHg, and 7.0% (23/327) primary eyes with IOP greater than (or equal to) 40 mmHg. In the current study, 7.3% (15/205) and 2.0% (4/205) of primary eyes presented with IOP greater than (or equal to) 30 mmHg and IOP greater than (or equal to) 40 mmHg, respectively, at the 1-6 hour postoperative visit. Based on these results, the incidence of IOP greater than (or equal to) 30 mmHg and IOP greater than (or equal to) 40 mmHg in primary eyes is significantly lower than that reported in Study CP19-01. The secondary study endpoint is the proportion of fellow eyes that had IOP greater than (or equal to) 30 mmHg and greater than (or equal to) 40 mmHg at 1-6 hours postoperatively. Per protocol, analysis of fellow eye rates was used to support the findings of the two primary eye analyses. In the current study, 7.9% (16/203) and 3.0% (6/203) of fellow eyes presented with IOP greater than (or equal to) 30 mmHg and IOP greater than (or equal to) 40 mmHg, respectively, at the 1-6 hour postoperative visit. Based on these results, the incidence of IOP greater than (or equal to) 30 mmHg and IOP greater than (or equal to) 40 mmHg in fellow eyes is significantly lower than that reported in original PMA Study CP19-01.
Final Effect Findings	The objective of this clinical trial was to assess the rate of early Intraocular Pressure (IOP) increases following implantation of EVO ICL lenses compared to Study CP19-01 (IDE G191084). Data that were analyzed relating to effectiveness included accuracy of refractive correction and visual acuity outcomes during the postoperative follow-up (10-18 days after surgery). The Manifest Refraction Spherical Equivalent (MRSE) was within 0.50 Diopters (D) in 84.6% (345/408) and within 1.00 D in 98.5% (402/408) of all eyes at Visit 4 (10-18 days). In addition, 99.8% (407/408) of eyes with preoperative Corrected Distance Visual Acuity (CDVA) 20/20 or better achieved Uncorrected Distance Visual Acuity (UDVA) 20/40 or better and 96.6% (394/408) of eyes reported no change or improvement of CDVA at Visit 4 (10-18 days) compared with preoperative values. These outcomes are comparable with those observed in pre-approval Study CP19-01. The accuracy of refractive correction, achievement of high levels of UDVA with preservation of CDVA with EVO ICL lenses are comparable to the early postoperative results achieved in Study CP19-01.
Study Strengths & Weaknesses	All study endpoints were met, all milestones were achieved, and no subjects were lost to follow-up. The majority of protocol deviations were minor, and appropriate corrective actions were introduced for major deviations. All adverse events were categorized as anticipated.
Recommendations for Labeling Changes	None.
General
Study Status	Completed
Application Number / Requirement Number	P030004 / PAS001
Date Original Protocol Accepted	07/21/2005
Date Current Protocol Accepted	07/21/2005
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is to continue following for 3 years post-embolization those patients from the PMA study who received Onyx LES but did not have their AVM completely, surgically resected
Study Population	This device is indicated for presurgical embolization of brain arteriovenous malformations. The post-approval study includes patients from the PMA study who received Onyx LES but did not have their AVM completely, surgically resected
Sample Size	17
Key Study Endpoints	MRI/CT scan results and adverse events
Follow-up Visits and Length of Follow-up	Annually for 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	17
Actual Number of Sites Enrolled	Not mentioned
Patient Follow-up Rate	53%
Final Safety Findings	There were 14 adverse events occurred in 4 Onyx patients and a total of 10 adverse events occurred in 5 n-BCA treated patients who have completed the minimum 3 year follow-up.
Study Strengths & Weaknesses	Prospective f-u up to 3-year. No control, only limited to part of IDE subjects.
Recommendations for Labeling Changes	None
General
Study Status	Hold
Application Number / Requirement Number	P040052 / PAS001
Date Original Protocol Accepted	12/18/2007
Date Current Protocol Accepted	12/18/2007
Study Name	CHOICE Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study consists of consecutive patients for whom a MonoGen Pap Test is performed at the participating laboratories constitute the MonoGen Pap Test arm of this study. These patiens will be compared to historical Pap smear slides from the same laboratories.
Study Population	Study Population: Patients 18 years or older, with a Pap test and a minimum of 400 HSIL. There were also 360 patients who have an accompanying colposcopy/biopsy results. Indication: The MPPT is intended for use in collecting and preparing cervical-vaginal cytology specimens for Pap stain-based screening for cervical cancer, its precursor lesions, and other cytologic categories and conditions defined by the 2001 Bethesda System for Reporting Results of Cervical Cytology.
Sample Size	400 HSIL patients and 360 patients with an accompanying colposcopy/biopsy, 3 sites
Key Study Endpoints	Data will be collected on the MonoGen Pap test results for MPPT patients and Pap smear results will be obtained from the control patients. The endpoint includes cervical cytology results from cervical-vaginal cytology specimens using both MPPT method for the prospective arm and PS method for the historical arm. For cases with cytologic diagnosis of HSIL+ from both MPPT and PS arms, comparative data from histological examination (colposcopy and, if appropriate, biopsy) will be collected.
Follow-up Visits and Length of Follow-up	Follow-up was not required for this study.
Interim or Final Data Summary
Interim Results	The study was terminated early because the sponsor does not intend to market the device.
General
Study Status	Terminated
Application Number / Requirement Number	P040028 / PAS001
Date Original Protocol Accepted	03/16/2006
Date Current Protocol Accepted	03/16/2006
Study Name	LUMA
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a multi-center single-arm internally controlled trial that will enroll approximately 950 subjects at up to 9 clinical study sites to assess LUMA's ability to detect significantly more subjects with CIN 2/3+ compared to colposcopy alone
Study Population	Study population is as per device indication. This device is indicated for use as an adjunct to colposcopy for the identification of high-grade disease (CIN 2, 3+) in women referred to colposcopy with a Pap test result of atypical squamnous cells (ASC), low-grade squamous intraepithelial lesion (LSIL), highgrade squamous intraepithelial lesion or cancer (HSIL+). PAS required oversampling of women younger than 21 years.
Sample Size	800 evaluable women at 9 sites
Key Study Endpoints	Each patient will be evaluated with colposcopy first and then with LUMA. Primary object is to assess the relationship between subject age and the performance of LUMA as adjunct to colposcopy for detection of CIN 2,3+. Secondary objective will be to assess relationship between colposcopists' experience and performance of LUMA. Method for data collection included physician visit for colposcopy and subsequent biopsy.
Follow-up Visits and Length of Follow-up	There is no follow up in this study. Subject complete participation within 20 minutes.
General
Study Status	Completed
Application Number / Requirement Number	P010015 / PAS001
Date Original Protocol Accepted	08/28/2001
Date Current Protocol Accepted	08/28/2001
Study Name	Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a non-randomized multi-center registry. The purpose of this study is to characterize the postmarket performance of the InSync Model 8040 (InSync), InSync III Model 8042 (InSync III), Attain LV leads (Models 2187, 2188, OTW 4193, OTW 4194), InSync ICD Model 7272, InSync Marquis Model 7277, InSync II Marquis Model 7289, InSync Maximo Model 7303, and InSync Sentry Model 7297.
Study Population	Study Populaton: Patients from the completed Multicenter InSync Randomized Clinical Evaluation (MIRACLE), U.S. InSync III trials, and patients implanted after market release approval of the InSync, InSync III CRT, and CRT-D systems may be enrolled into the InSync Registry.
Sample Size	Up to 2000 patients may be enrolled to obatin 1000 patients with 3 years of follow-up, 150 sites
Key Study Endpoints	The primary endpoints include 1) mortality and cause specific mortality, 2) Left ventricular sensing: biventricular pacing impedance, biventricular R wave amplitude (sensing), and LV pacing voltage threshold, and 3) lead-related complications.
Follow-up Visits and Length of Follow-up	Clinical data is collected at baseline and then every 6 months for 36 months or until explant or death.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,999
Actual Number of Sites Enrolled	99
Patient Follow-up Rate	One-thousand and fourteen patients reached 3 years follow-up and attrition is 49.3%. Of the 985 study exits, 450 (46%) were patient deaths.
Final Safety Findings	The event-free proportion at 3-years was 89.5% with 425 patients at risk. The 36-month estimate is 89.8% with 555 patients at risk.
Final Effect Findings	The proportion of patients with elevated thresholds through 36-months was 15.96% (models 2187/2188/4193/4194) and 8.02% (model 4194). The proportion of patients with elevated thresholds through 36-months was 15.96% (models 2187/2188/4193/4194) and 8.02% (model 4194). The proportion of patients with impedance out of range was 0% through 36 months for both lead models. The proportion of patients with an R-wave out-of-range through 36-months was 1.01% (models 2187/2188/4193/4194) and 0.63% (model 4194).
Study Strengths & Weaknesses	One-thousand and fourteen patients reached 3 years follow-up and attrition is 49.3%. Of the 985 study exits, 450 (46%) were patient deaths. The high attrition introduces bias into the study results and limits the external validity.
Recommendations for Labeling Changes	Yes, the sponsor will be asked to include a summary of the post-approval study methods and results specifically presenting a frequency histogram of various lead capture outcome values for the InSync registry to be included in the manuals for the applicable devices
General
Study Status	Completed
Application Number / Requirement Number	P870056 S015/ PAS001
Date Original Protocol Accepted	08/22/2003
Date Current Protocol Accepted
Study Name	Tag Alert
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a real-time aging study of a part of the packaging for the device and will consist of validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	The study will collect data for the validation of the Sensitech brand TagAlert Temperature Alarm Indicator (high and low) with programming over time
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	All units passed real-time testing
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status
Application Number / Requirement Number	P030053 / PAS002
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Device Failure Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The Device failure study is still ongoing. The data is submitted to the FDA in PMA Annual Reports.
Study Population	All explanted devices are to be returned to Mentor and analyzed and tested
Sample Size	All returned devices are analyzed.
Key Study Endpoints	An analysis was performed on the following categories to identify specific trends correlating to device failures: device type, size, clinical variables, visual observations, in-vivo time, surgical approach, device placement, incision size, pocket irrigation usage. Explanted devices underwent the following physical testing to assess the physical characteristics of the explanted devices: tension set, joint strength, ultimate elongation, gel cohesion.
Follow-up Visits and Length of Follow-up	There is no patient follow-up in this study
General
Study Status	Completed
Application Number / Requirement Number	P030053 / PAS003
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Informed Decision Process
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The Informed Decision Process study is a random survey of physicians on an annual basis to determine the success of the informed decision process provided to woman who is seeking breast implants surgery
Study Population	Each year, a random selection of 50 physicians are targeted for a survey to determine the success of the patient informed consent process.
Sample Size	A total of 50 physicians surveyed each year
Key Study Endpoints	Survey is administered to 50 physicians and asks questions on the level of understanding a patient has after consulting the Allergan patient planner.
Follow-up Visits and Length of Follow-up	There are no follow up visits in this study
Interim or Final Data Summary
Interim Results	There is no interim device safety Information from this study
Actual Number of Patients Enrolled	The Informed Decision Process consisted of yearly surveys. Each year a different sample was selected for the survey. These are the results for 2011 annual report. 54 surveys were returned. Per the condition of approval, the sponsor did administer the survey to a random selection of 50 physicians.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	The majority of respondents (94.2%) said the Informed Decision Brochure was of value in helping patients to understand the risks and benefits of implant surgery.
Study Strengths & Weaknesses	The sample of physicians was chosen randomly, which is a strength of the study. However, the observational, cross-sectional design of the study does not allow for any hypothesis testing. The results are descriptional only.
Recommendations for Labeling Changes	Mentor has no current plans to change the Informed Decision Process based on the survey results.
General
Study Status	Completed
Application Number / Requirement Number	P020056 / PAS002
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Core
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Interim or Final Data Summary
Actual Number of Patients Enrolled	715 patients including 455 primary augmentation, 147 revision-augmentation, 98 primary-reconstruction and 15 revision-reconstruction patients.
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	The follow-up rates for each cohort varied, but the overall rate was above 65% at Year 10. The follow-up rate was highest in the revision-reconstruction group and lowest in the revision-augmentation group. Specifically, the follow-up rate at Year 10 by cohorts were as follows; 66.8% in the augmentation cohort 63.8% in the revision-augmentation, 75.4% in the reconstruction and 80.0% in the revision-reconstruction cohort.
Final Safety Findings	The most commonly reported complications for all cohorts include capsular contracture, breast pain, swelling, symmetry, wrinkling and implant malposition. The overall implant rupture rates by patient were 9.5% in the augmentation, 6.3% revision-augmentation, 27.2% in the reconstruction, and 6.7% in the revision-reconstruction cohort. The rate of any reoperation by 10 years post-implant was highest in the reconstruction cohort (71.5%), followed by revision cohorts (46.7% in the revision-reconstruction and 46.0% in the revision-augmentation cohorts), and lowest in the augmentation cohort (36.1%). The most frequently reported reason for reoperation varied with the indication. The most common primary reasons for reoperation were asymmetry, capsular contracture, device rupture, implant malposition, need for biopsy, patient request for style/size change and ptosis. Specifically for the revision-reconstruction patients, nipple complications were reported as the most common reason for reoperation. The incidence of breast implant removal by 10 years post-implant was highest in the reconstruction cohort (53.8%), followed by in the revision-augmentation cohort (32.4%), in the augmentation cohort (18.6%) and in the revision-reconstruction cohort (13.3%). The most common reasons for replacement/removal vary depending on the indication group. The most common reasons for implant replacement and removals are as follow: Asymmetry, capsular contracture, device rupture, implant malposition and patient request for style/size change.
Final Effect Findings	Majority of the patients and physicians were satisfied with the surgical outcome. In the augmentation cohort, the patient and physician satisfaction was 93% and 94%, respectively, 84% and 83% in the augmentation revision cohort, 84% and 86% in the reconstruction cohort, 72% and 80% in the revision-reconstruction cohort
Study Strengths & Weaknesses	One of the study strength is that the study is a prospective, multicenter study that provides long term data up to 10 years on the safety and effectiveness of the device. The weaknesses of the study were the lack of a comparison group and lack of statistical power to detect rare events due to the small sample size
Recommendations for Labeling Changes	The labeling will be updated based on the safety and effectiveness results reported in the final PAS report.
General
Study Status	Completed
Application Number / Requirement Number	P030022 / PAS001
Date Original Protocol Accepted	12/17/2004
Date Current Protocol Accepted	12/17/2004
Study Name	Reflection Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center prospective follow-up study that continues to follow through their 10th post-implantation year several cohorts of subjects enrolled in the original IDE study.
Study Population	This device is indicated for use in patients requiring primary tectal hip arthroplasty due to non-inflammatory arthritis (degenerative joint disease) such as osteoarthritis, avaseular necrosis, or traumatic arthritis. The study population consist of four cohorts: (1) Randomized Non-inflammatory Arthritis (RNIA) cohort; (2) the Randomized Inflammatory Arthritis (RIA) cohort; (3) the Revision Hip (RR) cohort , and (4) the Continued Access Cohort (CAC) cohort. The sponsor indicated that not all of the CAC hips will be followed through 5 years, only those necessary to obtain the 100 unilateral C/C hip minimum per Sample size and power calculations are not provided in protocol.
Sample Size	(1) Randomized Non-inflammatory Arthritis (RNIA) cohort includes 156 ceramic-on-ceramic (C/C) hips and 117 ceramic-on-polyethylene (C/P) hips that served as a control group. (2) the Randomized Inflammatory Arthritis (RIA) cohort includes 17 ceramic-on-ceramic hips and 11 ceramic-on-polyethylene hips. (3) the Revision Hip (RR) cohort includes 4 ceramic-on-ceramic hips and 3 ceramic-on-polyethylene hips. (4) The Continued Access Cohort (CAC) cohort includes of 159 ceramic-on-ceramic hips. The sponsor indicated that not all of the CAC hips will be followed through 5 years, only those necessary to obtain the 100 unilateral C/C hip minimum per Sample size and power calculations are not provided in protocol.
Key Study Endpoints	The first five years of patient follow-up include clinical and radiographic examination. Endpoints include device revision and the determination of a Harris Hip Score. The final 5 years of follow-up is limited to a brief questionnaire. Endpoints encompass patient satisfaction and the incidence of device revision.
Follow-up Visits and Length of Follow-up	Patients are seen annually for clinical and radiographic examinations during the first five years of follow-up and then receive questionnaires annually during the last 5 years of follow-up.
Interim or Final Data Summary
Interim Results	No significant differences in questionnaire responses regarding hip removal, patient satisfaction, or plans to remove the hips in the next year were observed between the ceramic-on-ceramic and ceramic-on-polyethylene groups during years 6 through 10 of patient follow-up. .
Actual Number of Patients Enrolled	The study population consisted of 364 ceramic-on-ceramic hips and 144 ceramic-on- polyethylene hips.
Actual Number of Sites Enrolled	A total of 9 clinical sites enrolled study subjects.
Patient Follow-up Rate	The follow-up rate in the study at 10 years was 71.1% for the ceramic-on-ceramic hip group and 47.2% for the ceramic-on-polyethylene group.
Final Safety Findings	There was no statistically significant difference at 10 post-operative years in device survival between the ceramic-on-ceramic group, 91.1% and the control ceramic-on-polyethylene group, 90.2%, p = 0.66.
Final Effect Findings	Tabulation of postcard responses at 6, 7, 8, 9 and 10 year intervals revealed that consistently more than 90% of respondents were satisfied with their hip throughout the follow-up years of the study in both treatment groups. At the 10 year interval 92.0% (206/224) of subjects in the C/C group and 93.3% (56/60) of subjects in the C/P groups reported that they were satisfied with their hip.
Study Strengths & Weaknesses	An important study strength was the inclusion of a concurrent control group. A study weakness was the sub-optimal follow-up rates for both the ceramic-on-ceramic and ceramic-on-polyethylene groups. The follow-up rate at 10 years was 71.1% for the ceramic-on-ceramic group and 47.2% for the ceramic-on-polyethylene group. The low follow-up rates are a potential source of bias in the study as the device experience for the patients who were lost to follow-up may have differed from their counterparts who remained in the study.
Recommendations for Labeling Changes	The labeling should be changed to reflect the data noted above.
General
Study Status	Completed
Application Number / Requirement Number	P940016 / PAS001
Date Original Protocol Accepted	09/19/1997
Date Current Protocol Accepted	09/19/1997
Study Name	Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a multicenter patient registry. All patients who receive H.E.L.P. therapy will be enrolled into the study. Data for all patients will be collected, a mortality report will be submitted quarterly, and a report including all other data collected (demographic and clinical) will be submitted annually to the FDA. There is no hypothesis to test for this PAS.
Study Population	All patients who are treated with the Heparin-Induced Extracorporeal Lipoprotein Precipitation (H.E.L.P.) System. H.E.L.P. is a low density lipoprotein cholesterol (LDL-C) apheresis system, indicated for use in performing LDL-C apheresis to acutely remove LDL-C from the plasma of the following high risk patient populations for whom diet has been ineffective and maximum drug therapy has either been ineffective or not tolerated: Group A - Functional Hypercholesterolemic Homozygotes with LDL-C > 500 mg/dl; Group B - Functional Hypercholesterolemic Heterozygotes with LDL-C > 300 mg/dl; and Group C - Functional Hypercholesterolemic Heterozygotes with LDL-C > 200 mg/dl and documented coronary heart disease (CHD). Documented CHD is defined as having one or more of the following: a prior documented myocardial infarction (MI); a prior coronary artery bypass graft surgery (CABG); a prior percutaneous transluminal coronary angioplasty (PTCA) with or without atherectomy or coronary artery stent placement; and significant angina pectoris with a positive thallium or other heart scanning stress test.
Sample Size	N/A
Key Study Endpoints	Data Collection includes: Occurrence of death (cardiovascular or non-cardiovascular deaths); Occurrence of cardiovascular events (MI, stroke, unstable angina, transient ischemic attack (TIA), congestive heart failure, pulmonary embolism, arrhythmia, peripheral vascular disease, hypertension); Occurrence of surgical or non-surgical intervention procedure or the treatment of artherosclerotic cardiovascular disease (eg. CABG). Frequency and severity of CHD symptoms, Use of CHD medications for treatment of the following: angina, heart failure, arrhythmias, hypertension, hyperlipidemia, Use of lipid-lowering medications and other cardiovascular medications concomitantly, Laboratory assessments: lipids, lipoprotein, CBC, Activated clotting time Coagulation labs, blood chemistry , Quality of life assessments (SF-36), Occurrence of serious or unanticipated adverse events reported during treatment, Occurrence of other serious illnesses, Full physical exam ,Pregnancy test (females), smoking history
Follow-up Visits and Length of Follow-up	Any patients receiving at least 3 months of H.E.L.P. therapy will be followed for two years after discontinuation of therapy.
Interim or Final Data Summary
Actual Number of Patients Enrolled	113
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	N/A
Final Safety Findings	No adverse events occurred more tan 1%, but there were 148 AEs, 49% being device related. Sufficient evidence of safety over the 10 years of the study.
Final Effect Findings	The device lowered cholesterol at least 50% on average
Study Strengths & Weaknesses	Strengths, all those exposed to device were included in the registry, weaknesses, no specified hypotheses, no sample size calculation, no comparator
Recommendations for Labeling Changes	none
General
Study Status	Completed
Application Number / Requirement Number	P010001 / PAS001
Date Original Protocol Accepted	02/03/2003
Date Current Protocol Accepted
Study Name	Ceramic Transcend Hip
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	There is No PAS study protocol for this examination. As per approval order the sponsor agreed to provide long term (i.e., 5 years) data for a minimum of 175 procedures selected from the original PMA complete follow-up cohort and 25% of N=630 Continued Access Procedures. A minimum of 175 procedures were to have completed the Hip Survey and underwent independent radiographic review at a minimum of 5 postoperative years.
Study Population	This device is indicated for primary total hip arthroplasty in skeletally mature patients with non-inflammatory degenerative joint disease such as osteoarthritis, avascular necrosis, congenital hip dysplasia, and traumatic arthritis. The study population is subjects from the premarket cohort.
Sample Size	175 Patients
Key Study Endpoints	Used the Ceramic TRANSCEND Hip Study Survey form and A-P and lateral radiographs of the implanted hip. Questions on the Ceramic TRANSCEND Hip Study Survey Form: 1. Is your artificial hip in place? Yes or No; If not, when was it removed? 2. How well do you feel your artificial hip is functioning?; Excellent, good, fair, poor; 3. Have you had x-rays taken of your hip in the last year? Yes or No; 4. Do you expect to have your hip implant removed or replaced in the immediate future? Yes or No; If yes, when?___________________; Name of doctor who will remove or replace your hip implant_________________
Follow-up Visits and Length of Follow-up	Required continued follow-up through 5 years with annual assessments.
General
Study Status	Completed
Application Number / Requirement Number	H070004 / PAS001
Date Original Protocol Accepted	10/07/2008
Date Current Protocol Accepted	05/22/2009
Study Name	Centrimag PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, one-armed, multi-center observational study. This study will include data from 25 consecutive patients from the participating clinical centers with acute nght ventricular failure from any cause requiring use of the CentnMag RVAS to sustain life Patients may be enrolled from two populations The first population will include any patient in need of an RVAD that is not participating in the Levitronix pivotal study entitled, "Levitronix CentnMag VAS Failure-to-Wean from Cardiopulmonary Bypass Trial" The second population will include patients who have been enrolled in the Levitronix pivotal trial and subsequently enrolled into this post approval study Patients enrolled in the pivotal study will already have a CentnMag RVAS in place
Study Population	The study population includes patients implanted with the dentrimag device. The CentriMag RVAS is intended to provide temporary circulatory support for up to 14 days for patients in cardiogenic shock due to right ventricular failure. It is intended for use in patients with a body surface area of 1.4 m2 or greater.
Sample Size	25 consecutive patients implanted with the device will be followed from device implant to device removal, and 30 days post RVAD removal.
Key Study Endpoints	The primary endpint in patients who recover and do not go on to transplantation or use of a long-term device includes survival to 30 days post-support or to hospital discharge, whichever is longer. In patients who do not recover and are bridged to transplant or a long-term system the primary endpoint is survival to induction of anesthesia for implantation of a long-term device or heart transplant.
Follow-up Visits and Length of Follow-up	Clinical endpoints will be recorded at baseline, 3 days post-implant, prior to explant, and 30 days post-removal of the device.
Interim or Final Data Summary
Actual Number of Patients Enrolled	25
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	100%
Final Safety Findings	Central venous pressure, mean arterial pressure, and cardiac index increased a little on-pump, but returned to baseline by 2 days post-�pump. BUN and total bilirubin increased on-pump, but returned below baseline within 30 days post-pump.
Final Effect Findings	Success rate (Survival to 30 days, transplanted, or bridged to artificial heart): 72%
Study Strengths & Weaknesses	Strengths: Prospective follow-up study 100% follow-up Performance goal met by large margin (72% vs. 10% performance goal) Weaknesses: None significant
Recommendations for Labeling Changes	NONE
General
Study Status	Completed
Application Number / Requirement Number	P030025 S021/ PAS001
Date Original Protocol Accepted	09/24/2008
Date Current Protocol Accepted	09/24/2008
Study Name	5 year clinical outcomes
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was a prospective, randomized, controlled, multicenter, double-blind safety and efficacy study. Patients were randomized in a 1:1 ratio to receive either the TAXUS Express Slow-Release paclitaxel-eluting stent system or an uncoated Express control stent. Randomization included stratification by clinical site, target lesion length (<18 mm versus >18 mm), and the presence or absence of medically treated diabetes mellitus. The primary objective of this study was to further evaluate the safety and effectiveness of the TAXUS Express Paclitaxel-Eluting Coronary Stent System in long lesion lengths, small and large vessel diameters and with multiple overlapping stents in the treatment of de novo coronary artery lesions.
Study Population	The device is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries >2.25 to <4.0mm in diameter in lesions < 28mm in length.
Sample Size	1108 patients, 70 sites
Key Study Endpoints	Primary endpoint for this study is the rate of ischemia-driven target vessel revascularization at 9 months after the index procedure.
Follow-up Visits and Length of Follow-up	All patients were followed at 30 days, were to completed a 9-month follow-up evaluation, which included angiographic assessmen and followed annually through 5 years post index procedure.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	1172 patients, 586 Control and 586 Taxus
Actual Number of Sites Enrolled	70 sites
Patient Follow-up Rate	83%
Final Safety Findings	At the 5 year endpoint of the study, the TAXUS treatment group exhibited a statistically significant excess of MI compared to the Control treatment group (5.6% in Control vs. 9.3% in TAXUS). In addition, the "Cardiac death and MI" rates across time though 5 years were statistically significantly different for the TAXUS group (13.5%) relative to the Control group (8.6%). The overall MACE rates (cardiac death, myocardial infarction [MI], and TVR rate) over time through 5 years were comparable between the TAXUS (30.6%) and Control groups (33.6%). The Cardiac death rates over time through 5 years were not statistically significantly different between the TAXUS (5.3%) and Control groups (3.6%). The per protocol stent thrombosis rates were similar between the two groups through 5 years (1.9% for TAXUS vs. 0.7% for Control). From 4 to 5 years, there were no ST events per protocol in either treatment group. The rates for all death through 5 years were comparable in the TAXUS (10.2%) and Control groups (8.5%). The serious adverse events rates through 5 years were comparable between the TAXUS and Control groups (71.1% in TAXUS vs. 73.4% in Control).
Study Strengths & Weaknesses	Strengths: Five year clinical follow-up was completed in 83.1% of all patients enrolled and eligible for follow-up (871/1048). Weaknesses: The main area of concern is the higher MI rate in the TAXUS versus the control group
Recommendations for Labeling Changes	The high rates of MI and cardiac death or MI at five years in TAXUS patients compared to BMS patients with a visually assessed RVD > 2.5 mm and lesion length >26 mm with > 2 planned stents are notable. The sponsor has been asked to include this data in the label.
General
Study Status	Completed
Application Number / Requirement Number	P030025 S021/ PAS002
Date Original Protocol Accepted	09/24/2008
Date Current Protocol Accepted	09/24/2008
Study Name	Fatigue/Matter Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a simulated use particulates testing, 10-year equivalent pulsatile particulates on a curve testing, 10-year equivalent pulsatile fatigue on a curve testing.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	This is a simulated use particulates testing, 10-year equivalent pulsatile particulates on a curve testing, 10-year equivalent pulsatile fatigue on a curve testing.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	N/A, This is a bench testing study.
Actual Number of Patients Enrolled	NA
Actual Number of Sites Enrolled	NA
Patient Follow-up Rate	NA
Final Safety Findings	NA
Final Effect Findings	NA
Study Strengths & Weaknesses	NA
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P030028 / PAS002
Date Original Protocol Accepted	09/10/2004
Date Current Protocol Accepted	09/10/2004
Study Name	ECD Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective study that extends the follow-up of the premarket study for safety and efficacy of the ARTISAN Myopia lens. Study subjects will be followed out to five year postoperative data as follows:1) Subjects implanted in 2000 and 2001 will be asked to participate in the study extension to acquire all available four and five year data within the next two years (from PMA approval 2004).
Study Population	As per device indication. The device is indicated for the reduction or elimination of myopia in adults with myopia ranging from -5 to -20 diopters with less th:in or equal to 2.5 diopters of astigmatism at the spectacle plane and whose eyes have an anterior chamber depth greater than or equal to 3.2 millimeters; and,- patients with documented stability of refraction for the prior 6 months, as demonstrated by spherical equivalent change of less than or equal to 0.50 diopters. Study population consists of the premarket cohort.
Sample Size	A total of 503 eyes were implanted during this time period (282 first eyes and 221 second eyes).
Key Study Endpoints	Data collected will include:* Uncorrected distance visual acuity* Manifest refraction* Best corrected distance visual acuity* lop* Endothelial cell count (images to be read by single reading center)* Complications and adverse events, including but not limited to: Cataract formation, Retinal detachment rates, Comeal decompensation, Chronic uveitis, Persistent elevated lOP requiring medication, Secondary surgical interventions (lens exchanges, explants, etc.)
Follow-up Visits and Length of Follow-up	These subjects will be asked to return for yearly follow-up until live year data has been acquired for each eye implanted.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Number of eyes available for analysis at enrollment (pre-operative): 1,139
Actual Number of Sites Enrolled	37 doctors participated at one site.
Patient Follow-up Rate	Available eyes for analysis post-implantation, compared to baseline (i.e., before implantation): 89.8% at 6 months 90.7% at 1 year 83.9% at 2 years 67.3% at 3 years 42.5% at 4 years 39.0% at 5 years
Final Safety Findings	Eyes greater than or equal to 30% loss ECD, compared to baseline, among eyes with readable images: two (1.4%) at 6 months, 1 (0.7%) 1 year, 4 (3.2%) 2 years, 4 (4.5%) at 3 years, 1 (2.6%) at 4 years and none at five years. These percentages were calculated after comparing each one to the earliest available postop reading. When preop data is unavailable does not accurately reflect patient conditions (i.e., the data points at different intervals are weighted differently). According to the sponsor, after thorough review of all patient files, no adverse events (or serious complications) were reported that may have contributed to the ECD loss. A comparison of cumulative complications/adverse events during PMA (N = 662) and PAS (N = 702) show the following results: DESCRIPTION PMA PAS n (%) n (%) Cataract 21( 3.17) 11( 1.57) Glaucoma 0( 0.00) 6( 0.85) Significant Corneal Problems 20 ( 3.02) 11( 1.57) Significant Glare 142(21.45) 129(18.38) Retinal Detachment 4( 0.60) 7( 1.00) Lens Exchange 9( 1.36) 3( 0.43) Preventive Lens Repositioning 14( 2.11) 20( 2.85) Lens Dislocation/Reattachment 5( 0.76) 8( 1.14) Lens Explant 10( 1.51) 3( 0.43) Other Eye Disease 58( 8.76) 24( 3.42) The sponsor presented results from seven published articles. Among these publications, a 10 year retrospective single cohort study in 89 implanted eyes provided complementary clinical information: The mean spherical equivalent (SE) after 10 years was -0.70±1.00 diopters (D; range, -4.00 to 2.00 D), with no significant change in mean SE between 1, 6, and 10 years. At 10 years, 68.8% of all eyes were within 1.0 D of the intended correction. At 10 years, 31.2% (n = 24) gained 1 or more Snellen lines of BCVA and 2.6% (n = 2) lost more than 2 Snellen lines of BCVA; 93.3% reached a BCVA of 20/40 or better, and 82.0% reached a UCVA of 20/40 or better. The mean intraocular pressure remained stable and was 15.5±3.5 mmHg (range, 7-25 mmHg) at 10 years (Nayyirih G. et al. 2007, Ophthalmology; 114:1133-1142).
Final Effect Findings	Effectiveness is not a part of the post-approval study requirement and therefore it is not reported by the sponsor.
Study Strengths & Weaknesses	Strengths: a. Large initial sample size Weaknesses: a. No control or comparison group was included. b. The number of participating subjects reduced considerably during follow-up: The number of eyes with readable images dropped from 504 eyes at 2 years postop to 422 eyes (83.7%) at 3 years in the pre-approval phase. After that, the number of eyes with readable images declined substantially to 204 eyes (40.5%) and 170 eyes (33.7%), at 4 and 5 years respectively as compared to 2 years postop (504 eyes). This sample size reduction increased the likelihood of selection bias: Lost to follow-up subjects tend to have relatively worse safety outcomes, and thus the results of the study may reflect a potential underestimation of the incidence of long-term safety issues related to this device.
Recommendations for Labeling Changes	Labeling should include a brief description of the study objectives, design, study population, key study endpoints, study visits, length of follow-up, total number of enrolled study sites and subjects, follow-up rate, safety results, and study strengths and weaknesses.
General
Study Status	Completed
Application Number / Requirement Number	P860057 S042/ PAS001
Date Original Protocol Accepted	11/03/2009
Date Current Protocol Accepted	11/03/2009
Study Name	Clinical Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	258
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	98% For the 258 patients implanted with the Magna Ease aortic valve, mean follow-up was 6.2 ± 2.4 years, range of follow-up was 0 – 8.2 years, and total cumulative follow-up was 1597.6 patient-years. There were 1576.6 late patient-years of follow-up for the implanted patients.
Final Safety Findings	The study device was found to meet all Objective Performance Criteria with the exception of Bleeding (All and Major) in which the upper 95% confidence limit was above 2xOPC (3.4 vs 2.8 for All Bleeding and 1.9 vs 1.8 for Major Bleed). This results are acceptable when considering the cause of bleed for affected patients. The Kaplan-Meier rate for Freedom from Structural Valve Deterioration (SVD) was 90.1% at 8 years.
Final Effect Findings	At all follow-up timepoints out to 8 years 93.9% of patients were NYHA Class I or Class II. At 8 years, 88.6% of patients had trivial or none regurgitation and 10.2% of patients had mild regurgitation. No patients were reported with severe regurgitation at any timepoint. Of patients that had regurgitation, most were central regurgitation rather than perivalvular.
Study Strengths & Weaknesses	Strengths of the study included the overall follow-up of patients through mid-term durations (8 years) to collect 1576.6 late patient-years of follow-up for the implanted patients. Weaknesses of the study include that the study was a single-arm trial which is true for most recent surgical valve studies. Additionally, the final dataset was limited by missing echocardiograms for various timepoints throughout the study.
Recommendations for Labeling Changes	The sponsor should update their labeling to reflect the results obtained in the completed study.
General
Study Status	Completed
Application Number / Requirement Number	P030016 / PAS003
Date Original Protocol Accepted	12/22/2005
Date Current Protocol Accepted	12/22/2005
Study Name	Axial Lengths
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This clinical study is a prospective cohort, two-center, non-randomized study. The objective of this clinical investigation is to assess the effect of the STAAR Myopic Implantable Collamer Lens (Visian ICL) on the measurement of axial length of the eye to determine whether the ICL effects this measurement. This analysis is important for future cataract extractions in patients with an ICL so that the correct IOL power is implanted.
Study Population	Study population is as per device indication: This device is indicated for adults 21-45 years of age: * to correct myopia ranging from -3.0 diopters to < - 15.0 diopters with less than or equal to 2.5 diopters of astigmatism at the spectacle plane; * to reduce myopia ranging from greater than -15.0 diopters to - 20.0 diopters with less than or equal to 2.5 diopters of astigmatism at the spectacle plane; and,* with an anterior chamber depth (ACD) 3.00 mm or greater, and a stable refractive history within 0.5 diopter for i year prior to implantation.
Sample Size	30 eyes (30 patient)
Key Study Endpoints	Axial length of the eye
Follow-up Visits and Length of Follow-up	baseline & 1 month
Interim or Final Data Summary
Interim Results	Study is completed. See Final Results
Actual Number of Patients Enrolled	30
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	100%
Final Safety Findings	24 of the 30 patients were from Site 1 and 6 patients were from site 2. Eleven were male and 19 female, 29 were Caucasian and one Asian. Safety Summary: No adverse events were observed during the study. Effectiveness Summary: The ICL power of the lens implanted averaged -10.68D (range -3.50 to -16.00). The pre-op axial length averaged 27.30mm (range 23.69 to 34.32) and the post-op axial length averaged 27.28mm (23.72 to 34.51). The average difference in axial length measurements is -0.02mm (range-0.23 to + 0.19).
Study Strengths & Weaknesses	One of the strenghts is that this was a prospective study. However, the length of follow-up up was just one month post-treatment.
Recommendations for Labeling Changes	Labeling should be updated to include a summary of the post-approval study design, results, and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P080006 / PAS001
Date Original Protocol Accepted	04/07/2009
Date Current Protocol Accepted	04/07/2009
Study Name	Elution
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will provide the complete elution profile data for the tip and ring at 50 rpm and 100 rpm from all the lots that are manufactured during the first post-approval year. Based on the elution data provided in this report, a decision on the rotation speed and/or the acceptance criteria for the tip and ring will be made by the Agency. Elution profile data for the tip and ring at 50 rpm and 100 rpm from all the lots that are manufactured during the first post-approval year
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	Elution profile data for the tip and ring at 50 rpm and 100 rpm from all the lots that are manufactured during the first post-approval year
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A This is a bench testing study.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P080006 / PAS002
Date Original Protocol Accepted	04/07/2009
Date Current Protocol Accepted	12/05/2013
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study utilizes the Medtronic¿s Post-Approval Network Product Surveillance Registry (PSR) designed to conduct non-randomized, active prospective post-market Surveillance. The Registry is sponsored by Medtronic and is comprised of a global network of hospitals, clinics and clinicians from which reliable ¿real world¿ product safety and patient clinical outcome information is generated.
Study Population	The study will consist of patients rolled over from the pre-market study and patients newly enrolled in the postapproval study all tracked within the System Longevity Study sponsor registry. These are patients indicated for chronicpacing and sensing in the left ventricle via thecardiac vein, when used in conjunction with a compatible Medtronic Cardiac Resynchronization Therapy system.
Sample Size	1778 patients, 60 sites
Key Study Endpoints	The endpoints include the complication free rate will be estimated based on the chronic (> 30 days post implant) clinical adverse events including 1) failure to capture, 2) failure to sense, 3) Undersensing, 4) Threshold rise, 5) Oversensing, 6) Abnormal pacing impedance, 7) Lead insulation breach, 8) Lead conductor fracture, 9) Extracardiac stimulation, 10) Cardiac perforation, 11) Lead dislodgement, and 12) Structural Lead Failure.
Follow-up Visits and Length of Follow-up	Patients will be followed every six months for 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1847
Actual Number of Sites Enrolled	124
Patient Follow-up Rate	52.41%
Final Safety Findings	The Chronic Performance Post-Approval Study met the primary endpoint demonstrating that the Medtronic Attain Ability 4196 lead-related complication-free rate is greater than 92.5% at five years implant with a 95.68% complicate-free rate at five years with a lower 2-sided confidence bound of 94.47% and an upper 2-sided confidence bound of 96.63%.
Final Effect Findings	As of R073, there were a total of 82 threshold rises at implant and 133 threshold rises at follow-up. Of those, 72 threshold rises from 31 different leads were reported as lead related complications, including 22 were counted against the complication-free survival estimate (CFSE) based on the study protocol definition. There were 20 impedances out of range at implant and 9 impedances out of range at follow- up. One impedance out of range was reported as a lead related complication.
Study Strengths & Weaknesses	The Chronic Performance PAS met the primary endpoint and provided long-term data. However, the final attrition rate was higher than the initially anticipated attrition rate (71% vs 40%).
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P910023 S154/ PAS001
Date Original Protocol Accepted	01/13/2009
Date Current Protocol Accepted	09/09/2010
Study Name	SJ4 PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	There were 34 device-related complications in 22 patients in the PAS study. Of the 34 complications, 13 have been classified as right ventricular lead or SJ4 connector related complications.
Actual Number of Patients Enrolled	1701
Actual Number of Sites Enrolled	58
Patient Follow-up Rate	78.01%
Final Safety Findings	The 95% Lower Confidence Bound (LCB) for the freedom from complications using the Kaplan-Meier method at 5 years was 95.5%.
Final Effect Findings	The mean RV lead capture threshold is less than 1 V for all follow-up visits.
Study Strengths & Weaknesses	1) Large sample size of 1701 subjects 2) Long-term follow-up for 5 years) Weakness: 2) Study deviation rate of 14.39% per visit
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P030031 S011/ PAS001
Date Original Protocol Accepted	11/24/2009
Date Current Protocol Accepted	11/24/2009
Study Name	CABANA Trial
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to provide long term data on the incidence of stroke in paroxysmal atrial fibrillation patients treated with Thermocool catheters compared to patients treated with antiarrhythmic drugs, in the CABANA Trial
Study Population	Study Population: The proposed study is a subgroup analysis of data to be collected in the CABANA Trial. Study subjects included in the subgroup analysis will include all PAF patients treated with Thermocool catheters and all PAF patients treated with AADs. Indication: For the treatment of paroxysmal atrial fibrillation.
Sample Size	A total of 3000 patients will be randomized in a 1:1 fashion to a strategy of catheter ablation (n=1500) vs. drug therapy for either rate or rhythm control (n=1500) in the CABANA Study. The sponsor anticipates that 375 (33%) patients in the ablation arm will be PAF patients treated with Thermocool catheters (33% x 75% x 1500), and 500 patients in the AAD arm will be PAF patients (33% x 1500).
Key Study Endpoints	The primary endpoint for this subgroup analysis is the incidence of stroke. The sponsor will also analyze other endpoints from the CABANA Trial such as total mortality, serious bleeding and cardiac arrest.
Follow-up Visits and Length of Follow-up	Patients in the trial will be randomized, treated, and followed up for a median of 3 years. Follow-up in all patients will occur at 3, 6, and 12 months during the first year, and every 6 months thereafter, with clinic visits.
Interim or Final Data Summary
Interim Results	No safety data is available for this study.
Actual Number of Patients Enrolled	The number of patients for this subgroup analysis was 702 among the total 2,204 patients enrolled for the CABANA Trial. The 702 included 226 paroxysmal atrial fibrillation (PAF) patients randomized to the ablation arm and treated with Biosense Webster ThermoCool ablation catheters and 476 PAF patients randomized to the drug arm.
Actual Number of Sites Enrolled	For this subgroup post-approval study (PAS), the ThermoCool ablation arm enrolled patients in 94 sites, and the drug arm in 56 sites among the 126 sites for the CABANA trial.
Patient Follow-up Rate	The follow-up rates in the drug and ThermoCool ablation arms are 85.9%, and 91.6%, respectively.
Final Safety Findings	Primary: The primary endpoint for this subgroup PAS is the incidence of stroke in ThermoCool ablation and drug treated PAF patients enrolled in the CABANA trial. The subgroup study results show that there is no statistically significant difference in the incidence rates of any stroke between the ablation and drug arms, i.e., 2.7% vs. 2.7%; hazard ratio of 0.93; 95%-CI of [0.34, 2.57]; and p=0.895. Therefore, the study met the primary endpoint, i.e., the ablation therapy is non-inferior to the drug therapy for treating PAF patients. Secondary: The ablation arm shows statistically significant improvement over the drug arm for the following secondary endpoints: 1) for all-cause mortality or cardiovascular hospitalization, 49.6% vs. 58.4%, 95%-CI of [0.55, 0.86], p=0.001; 2) for cardiovascular hospitalization, 46.9% vs. 55%, 95%-CI of [0.54, 0.86], p = 0.001; and 3) for recurrent AF, 47% statistically significant reduction of AF, hazard ratio of 0.53, 95%-CI of [0.40 0.70], p<0.0001).
Study Strengths & Weaknesses	This subgroup study was a randomized trial utilizing 2,204 PAF patients enrolled in the multi-center CABANA trial for providing long-term data in the incidence of stroke in the PAF patients. While one-to-one randomization was done for the CABANA trial but not for the subgroup PAS, sampling from the CABANA trial population is still a strength in this subgroup study since confounding is reduced/minimized by randomization.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P030031 S086/ PAS001
Date Original Protocol Accepted	06/01/2018
Date Current Protocol Accepted
Study Name	VISITAG SURPOINT PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm study. Primary safety and effectiveness endpoints will be compared to pre-determined performance goals. This is a new enrollment study.
Study Population	Subjects (age 18 years or above) undergoing electrophysiology mapping and RF ablation with STSF and ST catheter for treatment of antiarrhythmic drug refractory symptomatic paroxysmal AF.
Sample Size	A total of 330 subjects (280 treated with STSF catheter with EPU and 50 treated with ST catheter with EPU) enrolled from up to 45 U.S. sites.
Key Study Endpoints	Primary effectiveness endpoint: Freedom from documented (symptomatic and asymptomatic) atrial fibrillation, atrial flutter and atrial tachycardia (AF-AFL-AT) (hereinafter collectively referred to as “atrial tachyarrhythmias") recurrence (episodes = 30 secs on TTM or continuously recorded on the standard 12-leads ECG or Holter) during the eval period (Day 91-365) & freedom from the following failure modes: Acute procedural failure, including: Failure to confirm entrance block in all pulmonary veins at the end of procedure • Repeat ablation failure, including: o >1 repeat ablation procedures during the 3-Month Blanking Period (Day 0-90) after the index ablation procedure. Any repeat ablation procedure during the evaluation period. • DC cardioversion for AF-AFL-AT following the 3-month blanking period • Surgical treatment for AF-AFL-AT after the index ablation procedure. • AAD failure: Taking a new AAD for AF, a previously failed AAD at a greater than the highest ineffective historical dose or starting an AAD for AF during the evaluation period. Primary safety endpoint: Any PAE occurring within 7 days following an AF ablation procedure (including the initial and repeat procedures) using the STSF-ST catheter with EPU, except atrio-esophageal fistula and PV stenosis, which may also be considered as primary adverse events if occurring greater than 7 days post the ablation procedure. PAE include the following conditions: - Death - Atrio-esophageal fistula - Cardiac Tamponade*+-Perforation+ - Myocardial infarction (MI) - Stroke - Cerebrovascular accident (CVA) †, †† - Thromboembolism - Transient Ischemic Attack - Diaphragmatic paralysis - Pneumothorax - Heart block - PV stenosis* - Pulmonary edema (Respiratory Insufficiency) - Vagal Nerve Injury - Pericarditis - Major vascular access complication-bleeding Hemodynamic compromise or instability is defined as Systolic BP < 80 mm Hg. + Cardiac Tamponade-Perforation occurring within 30 days of the AF ablation process will be considered Primary AEs † Subjects with non-focal global encephalopathy will not be reported as a stroke without unequivocal evidence based upon neuroimaging studies. Modified Rankin score assessments should be made by certified individuals.
Follow-up Visits and Length of Follow-up	1 year
Interim or Final Data Summary
Actual Number of Patients Enrolled	333 signed informed consent, 310 treated (261 with Thermocool SmartTouch SF (STSF), 49 with Thermocool SmartTouch (ST))
Actual Number of Sites Enrolled	35 investigational sites in United States and outside United States
Patient Follow-up Rate	95.5% STSF and 92.9% ST
Final Safety Findings	Overall, the data provided suggest a reasonable assurance of safety and effectiveness of the device use with the SFST and ST catheters in Tag Index-guided PV isolation for the treatment of PAF.
Final Effect Findings	The results of the planned interim analysis suggest that the PAS has met the pre-specified early success criteria. Both the primary effectiveness and safety performance goals were met in the STSF subjects.
Study Strengths & Weaknesses	see above
Recommendations for Labeling Changes	Labeling updated with additional information on usage of VISITAG SURPOINT feature with specified catheters (P030031/S110).
General
Study Status	Completed
Application Number / Requirement Number	P020026 / PAS001
Date Original Protocol Accepted	04/24/2003
Date Current Protocol Accepted	04/24/2003
Study Name	Bench Testing
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	n/a
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	n/a
Final Effect Findings	n/a
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	no
General
Study Status	Completed
Application Number / Requirement Number	P030031 / PAS001
Date Original Protocol Accepted	12/19/2005
Date Current Protocol Accepted	12/19/2005
Study Name	Navastar Thermocool
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was a multi-center, observational, one-armed prospective cohort study of patietns with atrial flutter treated with the device.
Study Population	Subjects from several different centers with symptomatic typical atrial flutter who meet the inclusion/exclusion criteria. It is indicated for catheter-based cardiac electrophysiological mapping (stimulating and recording), and when used with the Stockert 70 generator, for the treatment of Type I atrial flutter in patients age 18 or older.
Sample Size	291 subjects at 21 sites
Key Study Endpoints	The primary effectiveness endpoint was confirmation of complete bidirectional conduction block across the subeustachian isthmus at a minimum of 30 minutes following the last radio frequency application. Success was considered to be 88% effectiveness, with a one-sided 95% lower confidence bound of 80%. The primary safety endpoint was the percentage of subjects experiencing cardiovascular specific adverse events within seven days of the ablation procedure. Success was considered to be a CSAE no greater than 2.7%, with one-sided 95% confidence level no greater than 7%.
Follow-up Visits and Length of Follow-up	One month, one year, and annually thereafter for a total follow-up of 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	291 patients
Actual Number of Sites Enrolled	21 sites
Patient Follow-up Rate	100%
Final Safety Findings	Cardiac specific adverse events occurred in 4 of 267 subjects (two complete heart blocks, one pulmonary embolus, one myocardial infarction) in the safety cohort (1.5%). The upper one-side 95% confidence bound was 3.6%. All cardiac specific adverse events occurred in the primary group, in which the rate was 1.7% (upper 95% bound of 3.8%). Only one of the 4 was determined to be related to the device or the procedure. All 4 resolved. There were no deaths or unanticipated adverse events.
Study Strengths & Weaknesses	The strength of the study was the excellent follow-up and prospective cohort study design.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P020026 S017/ PAS001
Date Original Protocol Accepted	08/17/2009
Date Current Protocol Accepted	10/10/2014
Study Name	CYPHER MINI
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multi-center, non-randomized, postmarket surveillance study.
Study Population	Study subjects with ischemic heart disease, due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing PCI with stent placement and no contraindications to prolonged DAPT and who have received at least one 2.25 mm CYPHER stent during the course of the study. The study population enrolled in this postmarket surveillance study will supplement the 2.25mm CYPHER data collected from the CYPHER Elite randomized trial. The intent is to combine the data from the CYPHER Elite randomized trial to have a total sample size of 160 patients. This trial is expecting to enroll 160 subjects in which approximately 24 of the subjects will come from the CYPHER Elite trial. Subjects with de novo atherosclerotic coronary artery lesions that are treated with a 2.25mm stent will be eligible for study participation. Subjects must meet all eligibility criteria for inclusion into the study.
Sample Size	A total of 160 patients with de novo coronary artery lesions that are treatable with a 2.25 mm stent and meet all other inclusion and exclusion criteria will be enrolled into this study. The clinical outcomes and safety data from this protocol will be pooled for analysis with the 2.25mm CYPHER control data from the CYPHER ELITE Stent IDE clinical study, (IDE G070140). With a sample size of 142, a one-sided ÷2 test using a nominal significance level of 0.05 will have approximately 90% power to reject the null hypothesis when the observed CYPHER 2.25mm TLF rate at 12 months is 21.0%. Assuming a 10% attrition rate over 12 months, enrollment is set at 160 patients. The 160 patients will be a combination of those patients enrolled in this post-market study and those enrolled in the control arm of the Cypher Elite trial.
Key Study Endpoints	Primary Endpoints The primary endpoint of this study is target lesion failure (TLF) defined as clinically-driven target lesion revascularization, target vessel myocardial infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel at 12-months post-procedure. Secondary Endpoints 1.Procedural endpoints: −Lesion success −Device success −Procedure success 2. Clinical endpoints at 12 months post procedure and yearly to 33 months post procedure: −Target lesion revascularization (TLR) −Target vessel revascularization (TVR) −Target vessel failure (TVF) and its individual components −Composite endpoint of all deaths or MI −Composite endpoint of cardiac death or MI −Major adverse cardiac events (MACE) (death, Q wave or WHO-defined non-Q wave myocardial infarction, emergent bypass surgery, or repeat target lesion revascularization) and its individual components 3. Safety endpoints: −Stent thrombosis events (acute, sub-acute, late, very late) (using both ARC and ¿Protocol¿ definition) −Bleeding events −Death (cardiac and non-cardiac) −Myocardial Infarction (Q wave or WHO-defined non-Q wave) −Stroke (hemorrhagic and non- hemorrhagic)
Follow-up Visits and Length of Follow-up	All subjects enrolled in this study will be followed for 33 months. Follow- up visits are at 30 days, 6 months, one year, and annually to 33 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Three hundred twenty seven subjects were enrolled (20 subjects from CYPHER ELITE and 307 subjects from CYPRESS) in the CYPRESS study 2.25mm Stent Sub-Group.
Actual Number of Sites Enrolled	One hundred sixty (160) sites were approved by Cordis to participate in study. One hundred thirty-nine (139) received IRB approval, were initiated in the clinical study, and enrolled patients.
Patient Follow-up Rate	76.76% (251/327) through 33 months
Final Safety Findings	Protocol-defined major bleeding occurred in 5.5% (14/255) of the patients by 33 months. Using the GUSTO definition, severe bleeding was reported in 2.4% (6/253) of all randomized patients. Using the TIMI definition, the rate of major bleeding was 3.9% (10/254) at 33 months. A total of 5.5% (14/253) experienced all-cause death [cardiac: 3.9% (10/253); non-cardiac: 1.6% (4/253)], and 7.3% (19/259) experienced myocardial Infarction (Q wave or non-Q wave).
Final Effect Findings	The overall TLF rate was 18.8% (49/261) comprised of clinically driven TLR rate of 13.0% (34/261), target vessel MI rate of 6.2% (16/257) and cardiac death rate of 3.6% (9/253). Note: Cardiac deaths included only cardiac deaths that were related to the target vessel or an unknown vessel. By 33 months, MACE occurred in 21.3% (56/263) of the patients with 5.5% (14/253) experiencing all- cause death [cardiac: 3.9% (10/253); non-cardiac: 1.6% (4/253)], 7.3% (19/259) experiencing MI (Q wave or non-Q wave), 0.0% (0/253) patients undergoing emergent CABG and 13.0% (34/261) undergoing clinically driven TLR. Note: cardiac deaths include all deaths of cardiac causes including death related to a non-target vessel and cardiac death not related to a coronary artery disease. The overall TVF rate at 33 months was 23.7% (62/262). Through 33 months post-procedure stroke was reported in 2.0% (5/255) of the patient. The rate of definite/probable ARC-defined stent thrombosis at 33 months was 2.4% (6/255).
Study Strengths & Weaknesses	This study provides longer term (33 months) safety and effectiveness results of the 2.25 mm CYPHER Stent among United States patients. A weakness of the study is that lost to follow-up was less than 80%. This study confirmed the safety and effectiveness results of the premarket data on the 2.25 mm CYPHER Stent System.
Recommendations for Labeling Changes	Labeling changes are not recommended since this device is no longer on the market.
General
Study Status	Completed
Application Number / Requirement Number	P030050 S002/ PAS002
Date Original Protocol Accepted	07/28/2009
Date Current Protocol Accepted	05/01/2018
Study Name	Clinical PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a 5-year prospective, open-label, multi-center study to be conducted in the United States in 35 clinical sites. The overall objective is to assess the post market safety of SCULPTRA Aesthetic in immune-competent subjects when used as a single regimen for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in persons with Fitzpatrick skin types I-VI.
Study Population	Immuno-competent male or female subjects 18 to 75 years of age with NLF contour deficiencies and other facial wrinkles as defined by WAS criteria.
Sample Size	With 604 evaluable subjects, the study has 80% power to ensure that the upper limit of the observed one-sided 95% confidence interval for the percentage of subjects with any injection site nodule and/or papule adverse event in 5 years will be less than 21% assuming that the actual percentage is p=17% (according to the 17% rate of nodule and/or papule from premarketing study DL6049-0301. The 21% upper bound rate is based upon agreements with FDA). With 604 evaluable subjects, the study has 99% power to ensure that the upper limit of the observed one-sided 95% confidence interval for the percentage of subjects with any adverse event of interest other than nodule or papule in 5 years will be less than 3% assuming that the actual percentage is p=0.1% (according to the 0% rate of adverse event of interest other than nodule or papule from premarketing study DL6049-0301. The 3% upper bound rate is based upon agreements with FDA). The study with 604 evaluable subjects will have an overall power close to 80% to achieve positive results for both the primary hypothesis tests because of 99% power for the second primary hypothesis test. To ensure sufficient representation of dark skin subjects, the study will have at least 15 subjects with Fitzpatrick skin types IV and 85 subjects with Fitzpatrick skin types V-VI. Assuming an annual dropout rate of 7% (30% in 5 years), the study will enroll approximately 863 subjects (at least 22 with Fitzpatrick skin type IV and 122 with Fitzpatrick skin type V-VI) in order to have a total of 604 evaluable subjects at the end of the study (at least 15 with Fitzpatrick skin type IV and 85 with Fitzpatrick skin type V-VI). When all subjects have completed two years of follow-up, the drop-out rate and other assumptions will be evaluated, and if necessary, additional subjects will be enrolled.
Key Study Endpoints	The co-primary safety endpoints are: ¿ The percentage (incidence rate) of subjects with any injection site nodule and/or papule over 5 years. ¿ The percentage (incidence rate) of subjects with any of the following injection site events over 5 years: ¿ Hypertrophic scarring ¿ Keloid formation ¿ Changes in the skin pigmentation at the site of injection compared to adjacent skin ¿ Granuloma (confirmed by a biopsy) ¿ Skin necrosis ¿ Hypersensitivity reactions ¿ Unexpected change in wrinkle contour The injection site adverse events listed above are defined as adverse events of interest in this study. The secondary safety endpoints are: ¿ The percentages (incidence rate) of subjects with any injection site nodule and/or papule; the percentage of subjects who experienced any adverse events of interest other than injection site nodule or papule over 2 years; location and intervention for any adverse events of interest; adverse event severity, duration, time to onset, relationship to Sculptra® Aesthetic and relationship to injection procedure during the course of the study. The secondary efficacy endpoints are: ¿ Change from baseline to post-treatment follow-up time points in the Global Assessments Scores (WAS) at Month 6, Month 13, and Years 2, 3, 4, and 5. ¿ Investigator/Subject GAS at Month 6, Month 13, and Years 2, 3, 4, and 5.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	867
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	76.2% (661/867) at Year 5
Final Safety Findings	In the intent-to-treat population (ITT, n = 867), the overall incidence rate of injection site nodules and/or papules (NPs) was 28.5% for subjects treated with Sculptra® Aesthetic in all treated facial areas (nasolabial folds, cheek folds, marionette lines, and chin crease). The incidence rates of NPs in each anatomic area were 19.0% (nasolabial folds), 5.4% (cheek folds), 27.2% (marionette lines), and 3.6% (chin crease). The overall incidence of adverse events of interest (AEIs) other than NPs was 1.0% of subjects treated with Sculptra® Aesthetic in all treated facial areas. Among subjects who completed Year 5 of the study (n = 661), the overall incidence rate of injection site NPs was 31.5% and the overall incidence rate of AEIs other than NPs was 0.9%. The overall incidence of NPs by treatment area were 21.0% (nasolabial folds), 6.3% (cheek folds), 29.1% (marionette lines), and 3.9% (chin crease). No trend of increasing NPs was observed with increasing number of Sculptra® Aesthetic injection sessions.
Final Effect Findings	In all four anatomic locations, statistically significant changes from baseline (p<0.001) in average Wrinkle Assessment Scale (WAS) scores were observed at all timepoints through 5 years. However, the reductions (i.e., benefit) appeared to diminish over time. The overall mean change in the WAS score from baseline for nasolabial folds was -1.76, -1.73, -1.61, -1.19, -0.85, and -0.53 at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively. Investigators reported overall improvements from baseline using the Global Aesthetic Improvement Scale (GAIS) in 99.5%, 99.3%, 96.4%, 91.2%, 81.5%, and 68.8% of the subjects at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively. Subjects reported overall improvements from baseline using the GAIS of 97.4%, 97.4%, 91.7%, 86.5%, 74.4%, and 66.3% at the Month 6, Month 13, Year 2, Year 3, Year 4, and Year 5 visits, respectively.
Study Strengths & Weaknesses	One study strength is that it was a prospective and multicenter investigation that provided long term data up to 5 years on the safety and effectiveness of the device. Weaknesses of the study include a high lost-to-follow-up rate (23.8%) and considerable site-to-site variability (0 – 79.1%). In addition, direct comparison of the incidence of NPs between the post-approval study and the original pivotal study is difficult due to differences in the collection and reporting of adverse events and because the original pivotal study
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P030050 S034/ PAS001
Date Original Protocol Accepted	01/21/2022
Date Current Protocol Accepted
Study Name	Sculptra HF PAS
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To validate that Sculptra training material reduces use-related risk to an acceptable level. Design: Test participants will be provided with Sculptra training materials and asked to review the materials. Following training, the participant will exit the study room and a training decay period of one hour will commence. During the decay, the participant will be asked to complete distractor tasks (e.g., complete surveys, puzzles, etc., that are unrelated to Sculptra). Test sessions will be conducted at a research facility in a room set up to simulate a room in a medical spa and will include a table with supplies for reconstituting and a separate area with patient bed where the participant will administer injections to a simulated skin pad placed on the bed. Study participants may sit or stand, based on preference. During a test session, participants will be asked to complete one simulated use scenario. In the scenario, the participant will reconstitute Sculptra then inject prepared Sculptra into an injection pad. Critical tasks related to reconstitution and injection will be evaluated.
Study Population	Device group: Licensed aesthetic injector (RN/NP/PA or MD/DO) experienced with injecting facial fillers. Comparator group: None.
Sample Size	15
Key Study Endpoints	Evaluation of critical tasks related to correctly reconstituting and injecting Sculptra.
Follow-up Visits and Length of Follow-up	None
Interim or Final Data Summary
Actual Number of Patients Enrolled	15
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	None
Final Safety Findings	The results from this study show participants were able to reconstitute and inject, following self-guided training, with only a one use-issue attributed to IFU and other use issues attributed to other factors.
Final Effect Findings	All participants correctly answered all eight knowledge task questions.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Labeling should be updated to include pictures of the filler after reconstitution to ensure that users are able to adequately understand and execute the reconstitution procedure correctly.
General
Study Status	Completed
Application Number / Requirement Number	P210005 / PAS001
Date Original Protocol Accepted	09/20/2022
Date Current Protocol Accepted
Study Name	Continuation Study - SAIL-101-PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the long-term safety of the IC-8 Apthera IOL. Design: Structure: Prospective, multi-center, open-label, single-group, post-approval follow-up study of subjects previously implanted with the IC-8 Apthera IOL in the IC-8 Apthera IOL IDE study (G180075). Sites: 21 U.S. clinical sites that participated in the IC-8 Apthera IOL IDE study. Duration: Approximately 18 months to allow for 12 months of enrollment and 6 months to conduct the 3-year post IC-8 Apthera IOL implantation visit. Administration: There is no active treatment in this study. Visit Schedule: All subjects will undergo one scheduled visit: the 3-year post IC-8 Apthera IOL implantation visit.
Study Population	The study population will include patients previously implanted with the IC-8 Apthera IOL in the IC-8 Apthera IOL IDE study (G180075). There are no Exclusion criteria for this study. All subjects that participated in the US IDE (G180075) are intended to be reconsented to participate in this study. Subjects are eligible for the study if they meet the following Inclusion criteria: Inclusion Criteria: 1. Enrolled in IDE G180075 study and implanted with the IC-8 Apthera IOL; 2. Able to comprehend and have signed a statement of informed consent; 3. Availability, willingness, ability and sufficient cognitive awareness to comply with examination procedures and study visit(s)
Sample Size	No. of subjects: All 343 IC-8 Apthera IOL subjects are intended to be re-consented. Sample size is based on the number of subjects who participated in the pivotal study G180075. No. of sites: 21 Sites location: US
Key Study Endpoints	Co-Primary Safety Endpoints: • Rates of secondary surgical interventions (pars plana vitrectomy, explant, laser treatment, etc.) • Rates of other serious adverse events (as described in ISO 11979-7 historical grid) • Rates of ocular adverse events, including but not limited to the adverse events described in the ISO 11979-7 historical grid • Rates of subjective visual disturbances Additional Safety Endpoints: Other parameters that will be collected and evaluated for safety in the study include but are not limited to the following: • Monocular best-corrected distance visual acuity (BCDVA) • Rate of IOL removals
Follow-up Visits and Length of Follow-up	1 visit at year 3. Total length of follow-up: 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	196 (one subject failed screening, leaving 195 eligible subjects, all of whom completed the study)
Actual Number of Sites Enrolled	21
Patient Follow-up Rate	100% of enrolled subjects were accounted for.
Final Safety Findings	Safety Results: Eleven of 195 (5.6%) IC-8 eyes had a total of 15 SSIs through 3 years. The SSIs in IC-8 eyes were secondary YAG capsulotomy (n=7), retinal detachment repair (n=1 eye with 2 reported events), vitrectomy (n=1), IOL exchange (n=1), and other (n=4). Two eyes had SSIs related to the optical properties of the IC-8 IOL (IOL exchange [n=1] and secondary YAG capsulotomy [n=1]). Ten of the 11 IC-8 eyes with SSIs had successful surgical interventions. Two of 195 (1.0%) fellow eyes had a total of 2 SSIs through 3 years. Both SSIs were categorized as other and both were successful. The IC-8 IOL eyes had more secondary YAG capsulotomies than fellow IOL eyes (7 vs 0; [95% CI: 1.0, 6.2]). No eyes in either group had SSIs performed as treatment for an adverse event.
Final Effect Findings	N/A
Study Strengths & Weaknesses	Only 195 of the potential 343 subjects were enrolled into the study.
Recommendations for Labeling Changes	The year-three rate of YAG capsulotomies in eyes implanted with the IC-8 Apthera IOL was 4%, while the rate in the control eyes was 0%.
General
Study Status	Completed
Application Number / Requirement Number	P030050 / PAS001
Date Original Protocol Accepted	08/17/2009
Date Current Protocol Accepted	08/17/2009
Study Name	Long Term Registry
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is an five year, open-label, multi-center study to evaluate the long-term safety of Sculptra in HIV-infected patients with facial lipoatrophy by Fitzpatrick skin type and by gender, which will be assessed by the incidence and severity of concomitant illnesses (adverse events). Each subject will be enrolled into one of the four groups at baseline: (a) female with Fitzpatrick skin types I-III; (b) female with Fitzpatrick skin types IV-VI; (c) male with Fitzpatrick skin types I-III; and (d) male with Fitzpatrick skin types IV-VI. Patients will be treated with Sculptra (4-6 treatment sessions to reach optimal correction) at 4 to 6 week intervals.
Study Population	This device is indicated for use in immune-competent subjects as a single regimen for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. The study population includes patients with HIV-associated lipoatrophy.
Sample Size	300 patients, 20 sites
Key Study Endpoints	Effectiveness endpoints are the clinical presentation of lipoatrophy (James scale) and physician and subject satisfaction on the device based on questionnaire and photographic comparison before and after the previous visit. Safety endpoints include (1) Incidence and severity of concomitant illnesses and the usage and indications of concomitant medications at baseline, yearly follow-up visits, and unscheduled visits that are not mandated by protocol; (2) Incidence and severity of AEs, including hypertrophic scars or keloids at the yearly follow-up visits and unscheduled visits that are not mandated by protocol; (3) Information regarding any additional Sculptra administered at the yearly and unscheduled visits that are not mandated by protocol. In addition, subject-reported QOL/body image will be collected validated QOL and body image questionnaires.
Follow-up Visits and Length of Follow-up	Subjects will have a follow-up visit at one year post baseline (approx 6 months post last treatment), and then yearly office visits for a total of 5 years
Interim or Final Data Summary
Interim Results	Preliminary data has shown Sculptra to have a reasonable effectiveness and safety profile at approximately two year after initial treatment.
Actual Number of Patients Enrolled	296
Actual Number of Sites Enrolled	18
Patient Follow-up Rate	81.4%
Final Safety Findings	87.2% of subjects reported treatment emergent adverse events (TEAEs) during the 5�]year study. The majority of TEAEs were mild or moderate in severity (19.0% and 42.1% respectively). The most frequently reported SOC categories were: Infections and Infestations (60.0%), General Disorders and Administrative Site Conditions (43.1%), and Gastrointestinal Disorders (34.1%). One subject reported a TEAE of hypertophic scar or keloid. Seventy six subjects (26.2%) reported serious TEAEs and 17 subjects (5.9%) died during study. None of the SAEs or deaths was related to either the injection procedure or study medication.
Final Effect Findings	There was statistically significant improvement in clinical presentation of facial lipoatrophy at all follow�up time�points (all p<0.001). Significant reductions in mean James scale scores at 1 Year (�-1.4) was either maintained or slightly reduced for the remainder of follow�]up (�-1.4, �-1.1, �-1.1, and �-1.1 at 2, 3, 4, and 5 Years, respectively). Overall, the proportion of subjects with Grade 1 facial lipoatrophy (almost normal) increased from baseline (11.5%) to Year 1 (81.3%) and was maintained or slightly reduced for the remainder of follow�up (79.2%, 61.1%, 58.3%, and 60.1% for the 2, 3, 4, and 5 Year time�points, respectively). Mean change in James Scale scores from baseline by gender and Fitzpatrick skin type were consistent with the overall results.
Recommendations for Labeling Changes	Update labeling to include 5 year data from the post approval study
General
Study Status	Completed
Application Number / Requirement Number	P920023 / PAS001
Date Original Protocol Accepted	05/06/1996
Date Current Protocol Accepted
Study Name	Urolume PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objectives were to assess the incidence, duration and severity of positive urine cultures, incontinence and post-void dribbling, to assess changes in sexual dysfunction and global function, and to assess the number of retreatments.
Study Population	Study population is as per device indication. Urinary stent indicated for use in men with recurrent bulbal urethral stricture, prostatic obstruction secondary to benign prostatic hyperplasia (BPH), or detrusor external sphincter dyssynergia over age 60 or under age 60 who are poor surgical candidates and who have prostate glands at least 2.0cm in length.
Sample Size	110
Key Study Endpoints	Incidence, frequency and severity of the following: urinary tract infection (measured by culture), incontinence, and post-void dribbling. Changes in sexual function, global assessment and number of retreatments
Follow-up Visits and Length of Follow-up	At 6-weeks, 6-months, 1year and 2year post-stent placement
Interim or Final Data Summary
Actual Number of Patients Enrolled	72 enrolled but 61 patients treated
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	78.7
Final Safety Findings	Negative urine culture at 2 years: 76.2% (95% CI 71.7% - 80.7%). Stress incontinence: 18.5% (10/54) at baseline and 72.2% (39/54) at final evaluation (either at 1- or 2-year visit). Patient bothered by stress incontinence: 31% (13/42) not bother at 2 years vs. 81.4% (48/59) at baseline (p-value<0.001). Urge incontinence: 42.6% (23/54) at baseline and 59.3% (32/54) at final evaluation. Patient bothered by urge incontinence: 48.8% (20/41) not bother at 2 years vs. 55.9% (33/59) at baseline (p-value>0.05). Overflow incontinence: 16.7% (9/54) at baseline and 46.3% (25/54) at final evaluation. Patient bothered by overflow incontinence: 64.3% (27/42) not bother at 2 years vs. 83.1% (49/59) at baseline (p-value<0.05). Post void dribbling: 63% (34/54) at baseline and 72.2% (39/54) at final evaluation. Patient bothered by post void dribbling: 35.7% (15/42) not bother at 2 years vs. 33.9% (20/59) at baseline (p-value<0.05). Patients’ responses indicated no negative effects because of stent placement on sexual function. Global assessment (If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?): Roughly 55.7% of patients reported new satisfaction with their urinary status. The probability of patients remaining free from re-treatment for recurrent strictures or reobstruction within the stented area in the study was greater than 90% through the 1-year evaluation and approx. 87% at the 2-year follow-up.
Study Strengths & Weaknesses	Low precision of estimate since a 72-patient study has a 81% precision and a CI that is 124% wider compared to the planned 110-patients study.
Recommendations for Labeling Changes	As per PAS closing letter: Labeling should be revised to include the long term follow-up, safety information and adverse events, including information regarding the proportion of explants observed during the post-approval study, which his twice that identified in the literature
General
Study Status	Delayed
Application Number / Requirement Number	H230003 / PAS001
Date Original Protocol Accepted	01/12/2024
Date Current Protocol Accepted	03/27/2024
Study Name	Total Talus Replacement (TTR) PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design: Multicenter, single arm, prospective, post-approval study Study Objective: The objective of this study is to provide ongoing safety and probable benefit assessment of the restor3d TTR implant through evaluation of clinical and radiographic data.
Study Population	Adults (greater than or equal to 22 years of age) who have received a restor3d Total Talus Replacement device under an approved HDE for one of the indications listed on the Instructions for Use (IFU) and who do not have a contraindication.
Sample Size	50 subjects will be enrolled in this post approval study. The study will include a minimum of 5 US centers, with a maximum of 20 patients at any 1 site.
Key Study Endpoints	Primary Endpoint: A composite endpoint will be used to evaluate safety and probable benefit of the TTR device at 5 years. • Safety: Absence of a subsequent secondary surgical intervention (SSSI) and a device-related serious adverse event (SAE) on the affected joints at 5 years. • Probable Benefit: Joint salvage with the restor3d device still in place at 5 years Secondary Endpoints (evaluated based on comparison of postoperative scores to baseline scores): Safety: • Procedure-related SAE at 5 years post implantation • Device or procedure related adverse events (AEs) Probable Benefit: • Pain improvement on the 11 – point Pain Numeric Rating Scale (NRS) • Improvement of maintenance in Ankle Range of Motion (ROM) • Improvement in Foot and Ankle Outcome Scores (FAOS)-Composite • Improvement in FAOS – Subscale, individually, on the following subscales o Pain subscale o Symptoms subscale o Sports/Recreation subscale o Quality of Life (QoL) subscale o Activities of Daily Living (ADL) subscale Exploratory Endpoints: • The following x-ray assessments will be performed to evaluate: o Presence of adverse events, proper location of implant without migration, absence of subsidence into calcaneus, and health of surrounding soft tissue o Tibiotalar Alignment o Talar Tilt Angle o Boehler’s Angle o Talar declination angle o Meary’s angle. • Soft tissue attachment sites will be defined as the number of cases provided with soft tissue attachment sites and the number of cases where soft tissue attachment sites were used. Device-related AEs and SAEs will be analyzed to determine if there is a relationship between use of the soft tissue attachment site and the rate of AE/SAE occurrences. • Preference questions (e.g., if the patient would choose to undergo this procedure again if given the option) will be asked to participants, annually.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	3
Actual Number of Sites Enrolled	1
General
Study Status	Completed
Application Number / Requirement Number	P170002 S026/ PAS001
Date Original Protocol Accepted	12/13/2023
Date Current Protocol Accepted	10/18/2024
Study Name	TEO-PAS-2302
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a randomized, controlled, double-blinded, within-subject (split-face), multicenter, prospective study to investigate whether RHA1-M with mepivacaine is non-inferior to RHA1 with lidocaine in terms of injection site pain felt by the subject during injection
Study Population	Adults 22 years of age or older; cohort will include at least 10% of Fitzpatrick Skin Types V & VI
Sample Size	20
Key Study Endpoints	The primary endpoint is injection site pain during injection into the upper perioral rhytids assessed immediately following injection with RHA1-M with mepivacaine (using a 100 mm VAS) compared to the injection site pain felt during injection into the contralateral upper perioral rhytids assessed immediately following injection(s) with RHA1 with lidocaine. Safety endpoints: Adverse events; visual assessment, neurological assessment, lip functionality
Follow-up Visits and Length of Follow-up	The follow-up will be for 30-65 days
Interim or Final Data Summary
Actual Number of Patients Enrolled	20
Actual Number of Sites Enrolled	3
Patient Follow-up Rate	100%
Final Safety Findings	The clinical evaluation of RHA Redensity formulations containing either lidocaine or mepivacaine demonstrated consistently favorable safety profiles, with no significant differences observed between the two anesthetic options including for subjects with FST V and VI. Both products were well tolerated across all study populations, with no reported deaths, serious adverse events (SAEs), unexpected adverse device effects (UADEs), or study withdrawals due to adverse events (AEs) or adverse device effects (ADEs). No adverse events of special interest (AESIs) were identified.
Final Effect Findings	The study results demonstrated that RHA Redensity with mepivacaine (RHA Redensity Mepi) was non-inferior to RHA Redensity with lidocaine in terms of reducing injection pain.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	To update the labeling to integrate the Post Approval Study results for subjects with Fitzpatrick V and VI in effectiveness and safety sections.
General
Study Status	Completed
Application Number / Requirement Number	P170002 S030/ PAS001
Date Original Protocol Accepted	02/29/2024
Date Current Protocol Accepted	02/29/2024
Study Name	Teoxane Lip Fullness Scale (TLFS) PAS
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS consists of 2 non-interventional studies, i.e. a photographic and a live validation of the 5-grade photonumeric TLFS scale. The objective of this protocol is to guide the photographic and the live validations of the 5-grade TLFS to be used as a validated instrument for the assessment of the lip fullness. The scale validation will allow for verification of the repeatability and reproducibility of the scale.
Study Population	At least 200 individual subjects will be photographed by a qualified photographic image services vendor (Canfield Scientific) to collect a subset of subject’s representative of full ranges of lip fullness with a broad diversity of age, gender, ethnicity/race and Fitzpatrick skin phototype, in order to create a pool of appropriate participants for photographic assessment, live assessment, or both. For the live Validation, a minimum of 80 and a maximum of 150 subjects will be selected to participate to the 2 sessions of the live validation (2 weeks apart). Subjects will be selected by one member of the Scale Working Group from the pre-screened subjects. They will be selected to be approximately equally distributed between the 5 grades of the TLFS. However, the live subjects will not be assigned a true grade. The selected subjects will include Fitzpatrick Skin type from I to VI. Subjects may participate in both photographic and live scale validations. In addition, two other sets of different photographs will be selected from the photo collection: one Training Set and one Certification Set. These 2 Sets will include different photographs from each other, and different from the Validation Set (used for the Photographic Scale Validation). The Training Set will be used for training the scale validators (members of both Photographic and Live Scale Validation Groups) and future raters. The Training Set will include at least 3 photographs for each grade, as well as the full range of Fitzpatrick skin types.
Sample Size	Number of subjects: 200-350 (200 photograph + 80-150 live, but subjects may participate in both) Assumptions for sample size estimation: Not provided Number of sites: Not provided Sites location: Not provided -Distribution across each point/grade on the scale. There will be an approximative balance distribution between each grade, i.e., there will be approximately the same number of photographs for each of the 5 grades. -Demographic: At least 20% of subjects with Fitspatrick Skin Type (FST) IV-VI At least 10% of subjects with FST V/VI including subjects with FST V and FST VI At least 10% of subjects of Hispanic ethnicity At least 3% of subjects of Asian descent Of note: there are no FDA specific requirements for stratification by grade and by FST, and by ethnicity in this validation protocol.
Key Study Endpoints	To demonstrate the photographic validity (i.e. repeatability and reproducibility) of the scale. To demonstrate the live validity (i.e., repeatability and reproducibility) of the scale.
Interim or Final Data Summary
Actual Number of Patients Enrolled	323
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	N/A
Recommendations for Labeling Changes	Yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P020056 / PAS001
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	08/03/2015
Study Name	BIFS (Large PAS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	* NOTE: The PAS001 (BIFS Large PAS) were revised and replaced with two ongoing PASs, i.e. PAS007 (Re-Op Phase, i.e. the NBIR arm selected for Re-Op study), and PAS008 (Natrelle and 410 combined cohort). 55,279 The evaluable subjects by indications are summarized in table below: Subjects by Indication 39,069 Silicone 14,487 Saline augmentation 28,365 (72.6%) 13,379 (92.4%) revision augmentation 5,662(14.5%) 896 (6.2%) reconstruction 4,386(11.2%) 171 (1.2%) revision reconstruction 656(1.7%) 41 (0.3%)
Actual Number of Sites Enrolled	873
Patient Follow-up Rate	The follow-up rates from year 1 to 8 are 70.2%, 74.8%, 74.4%, 69.4%, 60.5%, 55.1%, 50.8%, and 63.2% for Silicone cohort, and 46.1%, 53.8%, 60.9%, 58.6%, 52.9%, 46.0%, 42.0%, and 50.0% for Saline cohort, respectively. . Follow-up rate is calculated as [actual observed subjects/(yearly cohort - completed study without data in visit window)].
Final Safety Findings	Deaths There were 367 deaths (311 silicone and 56 saline) reported, which represents 0.7% of the analyzed population with a calculated event rate of 25 per 10,000 subject years. The most common cause of death was breast cancer (0.2%). Less than 0.1% of subjects in each cohort committed suicide. None of the deaths were related to the implant. Very rare adverse events All collected data (including any data on events occurring through Year 7) encompassing a total of > 157,000 observed subject years. For augmentation, reconstruction, and revision-augmentation cohorts, no event rate was twice as high in silicone subjects compared to national norms. Higher standard incidence ratios (SIRs) were observed in the revision-reconstruction cohort for scleroderma, Sjogren’s syndrome, and dermatomyositis/polymyositis. Rare target adverse events All collected data (including any data on events occurring through Year 7) encompassing a total of > 157,000 observed silicone subject years and > 14,000 observed saline subject years. No adverse event demonstrated an increased risk (adjusted risk ratios) associated with the NATRELLE Silicone-filled Breast Implants compared to saline breast implants since all the 90% confidence interval included 1.0. Local complications The Year 5 Kaplan Meier rates for local complications as well as rates of reoperation and implant removal with and without replacement are compared with Allergan’s Core study. In the Augmentation, Reconstruction, and Revision-Augmentation cohorts, no rate was higher in the BIFS study compared to the Core Study. Higher local complication rates were observed in the Revision-Reconstruction cohort that had smaller sample sizes (699 in BIFS study and 15 in Core study). The Kaplan-Meier estimated cumulative incidence rates at 5 years for less frequent, but severe complications were infection (0.3%-1.9%), rupture (1.4%-2.6%), removal without replacement (1.1%-2.4%). Rheumatologic Signs & Symptoms There was no clear pattern to reports of rheumatologic signs and symptoms, although there were ~500 possible events in silicone vs less than 5 events occur in saline, and some symptoms occurred more frequently in the silicone cohort compared to the saline cohort, even after an age-adjusted analysis.
Final Effect Findings	A total of 12,758 (32.6%) Silicone subjects and 1,393 (9.6%) saline subjects completed the year 4 questionnaire. On the 100-point BREAST-Q scale, median satisfaction with breasts was 33.3 for both the Silicone and Saline cohorts at baseline and improved to 94.4 in both cohorts at year 1. At year 4, the median satisfaction with breasts decreased slightly to 88.9 for both cohorts. The medians of psychosocial well-being scores were 66.7 for Silicone and 58.3 for Saline at baseline and improved to 97.2 for each cohort at year 1. At year 4, psychosocial well-being scores were 91.7 for Silicone and 88.9 for saline.
Study Strengths & Weaknesses	Strength: This is a large cohort study. Weakness: The follow-up rates are low (~40-60% from years 5-8) and the percentages of censoring/missing data are high (94% saline and 54% Silicone at year 1). Missing data and/or loss to follow-up introduce study bias and limit the interpretation of the study results.
Recommendations for Labeling Changes	Due to very low follow-up rates after 5 years post-implant, labeling changes are not recommended
General
Study Status	Completed
Application Number / Requirement Number	P050033 / PAS001
Date Original Protocol Accepted	04/29/2008
Date Current Protocol Accepted	04/29/2008
Study Name	Elevess CTA Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a 24-week, multi-center, single arm prospective cohort study. All subjects in the study receive the device.
Study Population	The device is indicated for injection into the mid to deep dermis for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. The study population includes Fitzpatrick skin types V, V, and VI.
Sample Size	100 subjects, 9 sites
Key Study Endpoints	Endpoints include observed and reported adverse events at each visit and in a subject diary. Specific safety endpoints include keloid formation and pigmentation change at the site of injection.
Follow-up Visits and Length of Follow-up	Treatment visits will be conducted every 14 days until optimal cosmetic correction is obtained. Follow-up visits will take place at 2, 6, 12, and 24 weeks after the last injection.
Interim or Final Data Summary
Actual Number of Patients Enrolled	122
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	96%
Final Safety Findings	Of the 122 patients enrolled, a total of 100 were included in the analysis. (1) No keloids were observed at the injection site during the 24-week follow-up. (2) Ten (10%) subjects experienced 13 occurrences of mild hyperpigmentation, none requiring treatment or medical intervention. The incidence of injection site discoloration is 23 per 100 person years, which is greater than that observed in the pivotal clinical study. (3) A total of 47 (47%) experienced a total of 95 adverse events. All local adverse events were attributed to the device. From patient diaries, 80% of patients reported some type of injection site reaction, all reactions were mild and the most common reactions were swelling bruising and redness. The most serious adverse events were abcesses or cysts at the site of injection requiring further surgical or medical intervention. Rare adverse events were also reported: disfigurement (6 reports), facial nerve palsy (1 report), impaired vision (1 report), swollen lymph nodes (1 report). Specific device related events that were higher in the post-approval study than the pivotal study include injection site discoloration (10% vs. 1.4%), induration (5% vs. 0.5%), nodule (4% vs. 1%) and pain (4% vs. 1%).
Final Effect Findings	Not applicable
Study Strengths & Weaknesses	Strengths: The high follow-up rate of 96% for 100 subjects minimizes the potential bias that might arise due to losses to follow-up. None of the patients who were lost to follow-up discontinued participation due to adverse events. The most often reason for discontinuation cited was person/family reasons. Because the methods of injection, dose and intended use for Hydrelle in this study are similar to the approved use, it was possible to compare the incidence of patient and physician-reported adverse outcomes in the current study with those observed in the pre-market pivotal study. Data collected on volume of injection and number of touch-ups allowed evaluation of trends in association between these variables and the study endpoints. Weaknesses: Given the small sample size within each site, no conclusions can be drawn about the impact of device dose on the adverse events. The small sample size at each study site also limited the ability to interpret the results of analyses of the association between all adverse events and Fitzpatrick skin type. There were a significant number of protocol deviations mostly involving observations outside of the study window (61of 107 protocol violations).
Recommendations for Labeling Changes	Yes, to update the AEs for Fitzpatrick skin types IV-VI
General
Study Status
Application Number / Requirement Number	P030053 / PAS001
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	10/01/2014
Study Name	Large PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The Large PAS for the MemoryGel® Silicone Breast Implant was an observational prospective cohort study (10 years of follow-up), originally designed to address very rare adverse events with the target enrollment goal of 41,900 MemoryGel® and 1,000 saline patients. Mentor® met patient enrollment goals, but the study was limited by low follow-up rates. The Large PAS was re-designed (listed as Revised/Replaced on the PAS webpage) with: a re-operation data collection phase (Re-op Phase), a smaller cohort study, and a case-control studies requirement. The smaller cohort study and Re-Op Phase are ongoing and the description of study objectives and designs can be found in the PAS webpage under OSB Lead-MemoryGel and Shape Glow Study and OSB Lead-Re-Op Phase. The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put-on hold while the systematic literature review was conducted. The systematic literature review demonstrated insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value. The FDA continues to monitor these rare adverse events using other postmarket surveillance tools and real-world data (e.g. NBIR, PROFILE, MDRs)
Study Population	Study Population consists of women who receive MemoryGel and saline breast implants for augmentation, revision-augmentation, reconstruction and revision-reconstruction . This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
Sample Size	41,900 MemoryGel and 1,000 saline patients
Key Study Endpoints	Baseline data will be collected from the study subjects using patient self-administered questionnaire during the visit for preoperative evaluation. For MemoryGel patients, information on local complications including reasons for re-operation with or without removal of breast implants and reasons for removal, results of MRI evaluations, and results of rheumatologic or neurological evaluations will be collected during scheduled follow-up and on an interim/unscheduled basis, as needed.
Follow-up Visits and Length of Follow-up	3 surgeon visits (1, 4-6 and 9-10 years post-implantation) and 10 annual follow-up questionnaire completed by participants during 10 years of study
Interim or Final Data Summary
Interim Results	A total of 42,928 female patients (41,911 MemoryGel, 1,017 saline) were enrolled. Through May 1, 2010, the Year 1 follow-up rate of surgeon visit for MemoryGel participants was 22.8%; the Year 1, 2, 3 follow-up rates of patient questionnaire were 21.4%, 24.3%, 23.0% for MemoryGel and 5.9%, 7.3% , 16.7% for saline participants respectively. The follow-up rates were too low to provide meaningful safety information at this time.
Actual Number of Patients Enrolled	A total of 41,452 MemoryGel participants were enrolled in the study. Enrollment by indication was: 26,173 primary augmentation participants, 8382 revision-augmentation participants, 5023 primary reconstruction participants, 1761 revision-reconstruction participants, and 113 participants with missing indication information.
Actual Number of Sites Enrolled	2,342
Patient Follow-up Rate	At year 7, the overall follow-up rate was 20.1%. Follow-up rate by indication was: 19.2% primary augmentation group, 17.6% revision-augmentation group, 27.9% primary reconstruction group, 22.7% revision-reconstruction group, and 22% missing indication group.
Final Safety Findings	Participant Reported Complications and Reoperations For MemoryGel participants in the primary augmentation cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 35.9% for any complication or reoperation, 3.3% for breast infection, 19.6% for breast pain related to implants, 8.7% for capsular contracture Baker Grade II, 7.2% for capsular contracture Baker Grades III/IV, 0.7% for MRI confirmed rupture, 8.2% for suspected rupture, 6.2% for implant removal, and 11.7% for reoperation. For MemoryGel participants in the revision-augmentation cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 50.8% for any complication or reoperation, 4.0% for breast infection, 25.0% for breast pain related to implants, 20.2% for capsular contracture Baker Grade II, 18.0% for capsular contracture Baker Grades III/IV, 2.8% for MRI confirmed rupture, 14.2% for suspected rupture, 12.5% for implant removal, and 18.9% for reoperation. For MemoryGel participants in the primary reconstruction cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 53.4% for any complication or reoperation, 6.3% for breast infection, 29.6% for breast pain related to implants, 12.3% for capsular contracture Baker Grade II, 12.7% for capsular contracture Baker Grades III/IV, 2.2% for MRI confirmed rupture, 12.5% for suspected rupture, 15.9% for implant removal, and 24.7% for reoperation. For MemoryGel participants in the revision-reconstruction cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 58.5% for any complication or reoperation, 5.9% for breast infection, 27.8% for breast pain related to implants, 16.1% for capsular contracture Baker Grade II, 18.3% for capsular contracture Baker Grades III/IV, 2.6% for MRI confirmed rupture, 15.6% for suspected rupture, 17.4% for implant removal, and 26.6% for reoperation. Reasons for Reoperation Among MemoryGel participants the Kaplan-Meier estimated cumulative incidences through seven years following implantation of participant reported reoperation are 11.7% for primary augmentation participants, 18.9% for revision-augmentation participants, 24.7% for primary reconstruction participants, and 26.6% for revision-reconstruction participants. Among primary augmentation participants, the two most frequent reasons for reoperation (at the procedure level) were capsular contracture Baker Grades II/III/IV (26.8% of procedures) and patient requested size change (21.0%). Among revision-augmentation participants, the two most frequent reasons for reoperation were capsular contracture Baker Grades II/III/IV and patient requested size change (31.1% and 19.9% of procedures, respectively). Among primary reconstruction participants, the two most frequent reasons for reoperation were asymmetry (22.1%) and capsular contracture Baker Grades II/III/IV (20.0%). Among revision-reconstruction participants, the two most frequent reasons for reoperation were asymmetry and capsular contracture Baker Grades II/III/IV (24.4% and 21.4%, respectively). Reasons for Explantation In the two augmentation cohorts, the most frequent reason for explantation during the seven years after implantation was patient requested size change (58.9% and 44.8% of procedures among participants in the primary augmentation and revision-augmentation cohorts, respectively). In the two reconstruction cohorts, the most frequent reason for explantation was asymmetry (26.4% and 31.2% of procedures among participants in the primary reconstruction and revision-reconstruction cohorts, respectively). Due to word limits, the safety results are continued in the effectiveness section below.
Final Effect Findings	There were no study objectives related to effectiveness. The information that follows is a continuation of safety findings. Types of Additional Procedures Among MemoryGel participants having reoperations during the seven years after implantaton, the most frequent type of procedure in each cohort and overall was implant removal with or without replacement with any device (48.9% of procedures overall). Also frequent in each of the cohorts were capsulectomy (12.3% of procedures overall), pocket adjustment (8.2% of procedures overall), and open capsulotomy (7.5% of procedures overall). Connective Tissue Disease and Fibromyalgia Among all MemoryGel participants, there were a total of 349 new cases of rheumatoid arthritis (incidence rate per 10,000 person-years of 32.2), 46 new cases of scleroderma (incidence rate = 4.2), 66 new cases of SLE (incidence rate = 6.0), 62 new cases of Sjögren?s disease (incidence rate = 5.7), 204 new cases of other CTDs (incidence rate = 18.8), and 307 new cases of fibromyalgia (incidence rate = 28.4). Cancer Overall, 532 MemoryGel participants without a history of cancer at baseline experienced newly diagnosed cases of cancer. There were 116 participants with newly diagnosed cases of breast cancer, 5 with lung cancer, 3 with brain cancer, and 408 with other types of cancer, including 65 with melanoma. The incidence rates (per 10,000 person-years) were 63.8, 13.9, 0.6, 0.4, and 48.9 for all types of cancer, breast cancer, lung cancer, brain cancer, and other cancers, respectively. The incidence rate (per 10,000 person-years) was 7.8 for melanoma. Neurological Disease There were a total of 394 new cases of neurological disease among MemoryGel participants. There were 47 new cases of multiple sclerosis, 17 of myositis, and 332 of other types of neurological diseases. The incidence rates (per 10,000 person-years) were 35.8, 4.3, 1.5, and 30.7 for all types of neurological diseases, multiple sclerosis, myositis, and other neurological diseases, respectively. The most common ?other neurological diseases? included epilepsy, headache, peripheral neuropathy, stroke, trigeminal neuralgia, and tumor. Rheumatological and Neurological Signs and Symptoms Overall, the estimates of mean post-baseline prevalence for MemoryGel participants were highest for persistent non-traumatic joint pain (estimate = 12.9%) and persistent sleep disorders at night (estimate = 25.8%). Reproduction and Offspring Overall, a total of 3133 post-operative pregnancies have been reported among MemoryGel participants. Among them, there were a total of 501 miscarriages or stillbirths (16.0%), with 416 miscarriages (13.3%) and 85 stillbirths (2.7%). Overall, a total of 1710 offspring have been reported among MemoryGel participants. Among these, there were 234 premature births (13.7%), 155 low birth weight babies (9.1%), and 194 babies that required neonatal intensive care (11.3%). There were no reported births of children with cleft lip, neural tube defect, or pyloric stenosis. There was one reported birth of cleft palate and one of esophageal deformity. There were 25 reported births (1.5% of births) with other birth defects or congenital malformations. Suicide There have been a total of 173 known deaths among the MemoryGel participants. There have been 5 known suicides among these 173 deaths. Anaplastic Large Cell Lymphoma There has been one confirmed case of Anaplastic Large Cell Lymphoma (ALCL) in a Large PAS participant. MRI Compliance and Rupture At years 1, 2, 3, 4, 5, 6, and 7, only 3.4%, 4.7%, 5.2%, 5.5%, 4.9%, 4.5%, and 4.4%, respectively, of MemoryGel participants reported having had an MRI since completing their last questionnaire. Overall, of the 2051 MemoryGel participants with an MRI, there were 132 participants (6.4%) with rupture.
Study Strengths & Weaknesses	Overall, there are a total of 255,541 person-years of follow-up among MemoryGel participants. However, results are difficult to interpret due to the very low follow-up rate. Loss to follow-up can introduce study bias and limits the interpretation of the study results, as those that remain in the study may not be comparable to those that were lost. FDA and the sponsor have agreed to replace the original LARGE study requirement with a new study design to fulfill the condition of approval. It should also be noted that not all reported cases of CTD or neurological diseases were confirmed as board-certified diagnosed cases. Therefore, the current cases reported in this study (self-reported by participants as diagnosed by a board-certified specialist, rheumatologist or neurologist) may not represent the actual rate.
Recommendations for Labeling Changes	Due to very low follow-up rate, labeling changes are not recommended.
General
Study Status	Completed
Application Number / Requirement Number	P030016 / PAS002
Date Original Protocol Accepted	12/22/2005
Date Current Protocol Accepted	12/22/2005
Study Name	Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a a prospective cohort to continue follow-up of the original PMA Cohort of eyes.
Study Population	Study population is as per device indication. This device is indicated for adults 21-45 years of age: * to correct myopia ranging from -3.0 diopters to < - 15.0 diopters with less than or equal to 2.5 diopters of astigmatism at the spectacle plane; * to reduce myopia ranging from greater than -15.0 diopters to - 20.0 diopters with less than or equal to 2.5 diopters of astigmatism at the spectacle plane; and,* with an anterior chamber depth (ACD) 3.00 mm or greater, and a stable refractive history within 0.5 diopter for i year prior to implantation.
Sample Size	526 eyes (294 subjects)
Key Study Endpoints	Safety Endpoints: Specular microscopy (Endothelial Cell Density count), Secondary ICL Related Surgical Procedures (ICL Removal/Cataract Extraction, ICL Replacement, ICL Repositioning), Crystalline lens evaluation (Lens Opacity), Complications/Adverse Reactions, Intraocular Pressure (IOP) change, Biomicroscopy, Gonioscopy. Effectiveness Endpoints: Best Spectacle, Corrected Visual Acuity (BSCVA) over time, Best Spectacle Corrected Visual Acuity (BSCVA) in Patients with Preop BSCVA 20/20 or Better, Comparison of Preoperative BSCVA to 5 Year Postoperative BSCVA, Change in BSCVA, Uncorrected Visual Acuity (UCVA) - Distance, Manifest Refraction Spherical Equivalent (MRSE)
Follow-up Visits and Length of Follow-up	6, 12, 18, 24, 36, 48, and 60 months
Interim or Final Data Summary
Interim Results	Study Final Report received and it is still under FDA Review. Some results: The cell loss between baseline and the three -month visit was 2.2% and between three - month and one- year visit was 0.8%. Over the following two consecutive years, the rate of cell loss appeared to increase, however very slightly, from 2.2% between one and two years postoperatively to 2.9% between two and three years postoperatively. After the three year period, cell loss declined to -2.6% between 3 and 4 years and -2.1% between 4 and 5 years.
Actual Number of Patients Enrolled	294
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	65.3%
Final Safety Findings	Percent change of Endothelial cell loss from baseline to 3 years was 8.18% (SD 7.5%); from baseline to 4 years was 10.1% (SD 8.5%); and from baseline to 5 years was 13.9% (SD 8.7%). Endothelial cell loss over time in persons with extremely high myopia is unknown. Other safety findings for adverse events show none exceeding FDA grid except retinal detachment of 0.6% (FDA grid 0.3%), and surgical reintervention of 4.4% (FDA grid 0.8%). However, surgical reinterventions were not shown to have an impact on safety or efficacy. Other Complications Postoperatively Intraocular Pressure (IOP)>25 mmHg during follow-up or an increase of >10 mmHg over preoperative took place in 14 cases through 5 years (only 7 persisted at last visit) which is 2.7% of the Visian ICL PMA cohort. Only 2 cases (0.4%) in the entire cohort were diagnosed with ocular hypertension and started on pressure lowering medication. No cases (0.0%) in this study exhibited optic nerve or visual field changes characteristic of glaucoma.
Final Effect Findings	Visual Acuity The postoperative results demonstrated that the Visian ICL can provide full correction for high myopia up to -15D and only partial correction up to -20D. UCDVA= Uncorrected Distance Visual Acuity, Snellen Where emmetropia was the goal (+0.50D) and Pre-op Best Spectacle Corrected Visual Acuity (BSCVA) was better than or equal to 20/20, the rate of UCDVA at first year is 66.5%, third year 59.2% and fifth year 52.7%. BCDVA= Best Corrected Distance Visual Acuity, Snellen Eyes with Preoperative BCDVA 20/20 or better, the rate at first year is 95.3%, third year 96.6% and fifth year 96.2%.
Study Strengths & Weaknesses	The study uses the original IDE cohort following study subjects who had already completed two years of follow-up; therefore long-term data (5-years) is available sooner (as opposed to having newly enrolled subjects). This is the only PAS sub-study that collected ECD data. However, the five year follow-up rate of 65.3% is less than optimal. Biases could have been introduced due to lost to follow-up; which, can limit the generalizability of study results.
Recommendations for Labeling Changes	Yes. Update labeling with long-term data (5-year).
General
Study Status	Completed
Application Number / Requirement Number	P050016 / PAS002
Date Original Protocol Accepted	07/03/2007
Date Current Protocol Accepted	11/04/2008
Study Name	New Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a multi-center, prospective cohort study. The first null hypothesis of the study is that the 24 month cumulative revision rate is more than 0.126. The second null hypothesis is that the 24 month composite clinical success rate is less than 0.81.
Study Population	Study population is as per device indication.
Sample Size	The sample size is 160 procedures.
Key Study Endpoints	For both primary efficacy endpoints (freedom from revision and composite clinical success), the primary objective will be met by way of estimation using 95% exact binomial confidence intervals. Device survival will be illustrated by life tables and the plotting of a Kaplan-Meier curve.
Follow-up Visits and Length of Follow-up	Patients will be evaluated preoperatively, and at 6 weeks, 6 months, 12 months and 24 months postoperatively. The length of patient follow-up is two years.
Interim or Final Data Summary
Interim Results	Good-excellent Harris Hip Scores were obtained by 95.2% of study participants at 6 post-opertaive months and 97.4% at 12 post-operative months. Two cases of femoral neck fracture were reported.
Actual Number of Patients Enrolled	A total of 147 patients and 160 hips were enrolled in the study.
Actual Number of Sites Enrolled	A total of six study sites enrolled patients into the study.
Patient Follow-up Rate	Follow-up in the study was 81.8% at 24+months.
Final Safety Findings	The percentage of study subjects who achieved Composite Clinical Success (CCS), 92.5%, in the unilateral analysis groups for the Post-Approval (PAS) study was higher than that for the Pre-Market study, 90.6%.
Final Effect Findings	A pronounced increased in Harris Hip Scores, a measure of device effectiveness, was observed post- operatively. The mean Harris Hip Score pre-operatively was 53.9 for unilateral patients and 60.2 for bilateral patients. The mean Harris Hip Score at 24+ post-operative months was 96.1 for unilateral patients and 93.5 for bilateral patients.
Study Strengths & Weaknesses	A strength of the study was that it was appropriately powered for the study endpoints. An additional strength of the study was the fact that a broad cross-section of clinical sites participated in the study. A study weakness was the absence of a concurrent control group.
Recommendations for Labeling Changes	Labeling changes are recommended. The sponsor should be instructed to submit a labeling change supplement for the post-approval study that encompasses the findings regarding the post-approval study that are delineated above.
General
Study Status	Completed
Application Number / Requirement Number	P030053 / PAS004
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Adjunct Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	The Adjunct study is a 5-year study, in which patients will be followed at 1, 3, and 5 years postoperatively to assess satisfaction and occurrence of local complications.
Study Population	The study population is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
Sample Size	number of study sites: 2,958; 12,811 reconstruction patients were implanted with 23,090 implants
Key Study Endpoints	Safety endpoints include clinical complications such as infection, seroma, implant rupture and capsular contracture at 1 ,3, 5 years of follow-up and rheumatologic/immunologic symptoms and connective tissue disorders at 3, 5 years of follow-up
Follow-up Visits and Length of Follow-up	3 follow-up visits during 5 years of study (1, 3, 5 years post-implantation)
Interim or Final Data Summary
Interim Results	A total of 136,609 patients implanted with MemoryGel breast implants for reconstruction and revision-reconstruction were enrolled in the Adjunct study. The overall patient follow-up rates at 1, 3 and 5 years were 35.7%, 24.0% and 16.0% respectively.
Actual Number of Patients Enrolled	147,585
Actual Number of Sites Enrolled	4,684
Patient Follow-up Rate	44.0% at 1 year, 24.7% at 3 years, 13.8% at 5 years
Final Safety Findings	The 3 most commonly reported complications using the Kaplan-Meier cumulative incidence estimates at 5 years were: asymmetry (18.6%), wrinkling (9.9%), and Capsular Contracture, Baker III/IV (8.3%) in the Reconstruction Cohort; asymmetry (23.7%), wrinkling (14.3%), and Capsular Contracture, Baker III/IV (11.7%) in the Revision-Reconstruction Cohort; wrinkling (12.3%), asymmetry (11.4%), and Capsular Contracture, Baker III/IV (9.2%) in the Revision- Augmentation Cohort. The most common reasons by cohort for removal were: capsular contracture (36.4%), infection (13.2%), and patient request for size and implant change (10.5%) in the Reconstruction Cohort; capsular contracture (37.4%), leakage/rupture/ deflation (12.2%), and infection (11.5%) in the Revision-Reconstruction Cohort; capsular contracture (36.1%), leakage/rupture/ deflation (16.1%), and patient request for size and implant change (10.3%) in the Revision-Augmentation Cohort. The Kaplan-Meier cumulative rupture rates at 5 years were: 1.8% in the Reconstruction Cohort; 3.6% in the Revision-Reconstruction Cohort; 3.5% in the Revision-Augmentation Cohort. Bilateral implantation, white, infra-mammary surgical approach and sub-glandular surgical approach showed a higher risk of rupture, and reconstruction, smooth surface implant, high profile implant, high education and sub-muscular surgical placement showed a lower risk of rupture. Rheumatoid arthritis was the most common patient-reported rheumatic disease at 0.6%. Fibromyalgia and Raynaud's phenomenon were the most commonly reported rheumatic syndromes at 0.8% and 0.5% respectively.
Final Effect Findings	N/A
Study Strengths & Weaknesses	A large number of patients were enrolled in the adjunct study. However, the study was originally designed to address the public health needs of reconstruction and revision patients before device approval and to gather safety data regarding short-term post-implant complications under a limited clinical protocol without follow-up goals. The overall patient follow-up rates at 1, 3 and 5 years in this final report were only 44.0%, 24.7% and 13.8% respectively. The poor patient compliance significantly limited meaningful interpretation of the available safety results.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P030053 / PAS005
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Core
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	The Core study is a 10-year prospective, open-label, multi-center cohort study to evaluate the safety and effectiveness of MemoryGel breast implants
Study Population	The study populaiton is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
Sample Size	1000 patients at up to 40 sites
Key Study Endpoints	Safety endpoints include point prevalence on a per patient and per device basis of rates of occurrence of all adverse events and time to occurrence of the complication; Effectiveness endpoints include patient satisfaction measured by validated quality of life questionnaires and change in breast size measured by both bra and cup size and the chest/bust circumference.
Follow-up Visits and Length of Follow-up	11 follow-up visits (6 months and annually 1-10 years after surgery) during 10 years of study
Interim or Final Data Summary
Interim Results	A total of 1,008 female patients (including 552 Augmentation, 145 Revision-Augmentation, 251 Reconstruction, and 60 Revision-Reconstruction patients) were enrolled in the Core study. The overall follow-up rate was 64.4% at 7 years. The top 3 7-year Kaplan-Meier cumulative incidence rates of complications were any operation (19.3%), Baker III, IV capsular contracture (10.3%) and ecxplantation with or without replacement (7.2%) for augmentation patients; any operation (36.9 Baker III, IV capsular contracture (23.3%) and ecxplantation with or without replacement (20.1%) for revision-augmentation patients; any operation (36.8%), ecxplantation with or without replacement (19.8%) and Baker III, IV capsular contracture (14.0%) for reconstruction patients; any operation (38.9 Baker III, IV capsular contracture (29.4%) and ecxplantation with or without replacement (26.0%) for revision-reconstruction patients.
Actual Number of Patients Enrolled	1,008
Actual Number of Sites Enrolled	48
Patient Follow-up Rate	62% at 10 years
Final Safety Findings	For the Primary Augmentation cohort, the 10-year Kaplan-Meier estimated cumulative incidence rates for the key complications at the patient level were: capsular contracture III/IV, 12.1%; infection, 1.6%; explantation with or without replacement, 11.6%; explantation with replacement with study device, 7.4%; and any reoperation, 25.5%. The most frequently reported primary reasons for reoperation were capsular contracture II/III/IV (25.4% of reoperations) and breast mass (10.6% of reoperations). For the Revision-Augmentation cohort, the rates were: capsular contracture III/IV, 24.4%; infection, 1.4%; explantation with or without replacement, 24.1%; explantation with replacement with study device, 13.6%; and any reoperation, 43.6%. The most frequently reported primary reason for reoperation was capsular contracture II/III/IV (30.4% of reoperations). For the Primary Reconstruction cohort, the rates were: capsular contracture III/IV, 20.5%; infection, 6.2%; explantation with or without replacement, 33.4%; explantation with replacement with study device, 19.8%; and any reoperation, 49.0%. The most frequently reported primary reasons for reoperation were asymmetry (16.6% of reoperations), capsular contracture II/III/IV (14.0% of reoperations), rupture (12.7% of reoperations), and breast mass (10.8% of reoperations). For the Revision-Reconstruction cohort, the rates were: capsular contracture III/IV, 36.9%; infection, 0%; explantation with or without replacement, 37.8%; explantation with replacement with study device, 24.8%; and any reoperation, 50.7%. The most frequently reported primary reasons for reoperation were capsular contracture II/III/IV (23.4% of reoperations) and breast mass (12.8% of reoperations). Overall, the most frequently reported reasons for explantation through 10 years were size change, capsular contracture II/III/IV, and rupture. Based on the MRI cohort, the overall Kaplan-Meier estimated cumulative rupture rates at 10 years were 27.9% and 18.5% for patients and implants, respectively
Final Effect Findings	The overall mean changes in circumferential chest size were positive and statistically significant. The overall mean bra cup size increase from baseline across all follow-up visits was 1.8 cup sizes and was statistically significant. At the 10-year follow-up visit, overall 97.6% of patients indicated they would make the same decision to have breast implant surgery.
Study Strengths & Weaknesses	One of the study strengths is that the study is a prospective, multicenter study that provides long term data up to 10 years on the safety and effectiveness of the device. The weaknesses of the study were the lack of a comparison group and lack of statistical power to detect rare events due to the small sample size.
Recommendations for Labeling Changes	The labeling will be updated based on the 10-year safety and effectiveness results reported in the Core PAS final report.
General
Study Status	Completed
Application Number / Requirement Number	P030053 / PAS006
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Focus Group
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The Focus Group study is a one time study designed to evaluate how easily patients understand the information in the informed decision brochure about the risks associated with the use of slicone breast implants. A total of 35 women participated in one of four group interviewers for the study. Two discussion groups were conducted for women considering breast implants for augmentation and two group interviews were conducted with women considering breast implantssfor reconstruction. Each group was composed of eight to ten women. A trained female moderator led the discussion groups, which were each abouat 2 hours long. Respondents received a $150 honorarium in return for their time. Group interviewrs were conducted in a professional resaraevh facilities that alloesd for observation and audio recording.
Study Population	The study population is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
Sample Size	35 women in one of each of 4 groups. Two were held in Dallas, Texas and two in San Francisco, California. These sites were selected based on the volume of breast implant surgeries condcuted in these areas.
Key Study Endpoints	The study used two methods of data collection: discussion groups and a self-administered survey-- to capture both group level and individual level data. A female moderator led each discussion group using a discussion guide prepared in advance by the contracted research firm with the assitance of Mentor Corporation. Two versions of the brochure were tested, one designed for augmentation patients and one designe for reconstruction patients. Endpoints included respondents' reactions to the overall layout oand format of the brochures, content ordering, and iollustrations and tables.. Data were collected on respondents' comprehesnion and perceived relevance of the content. Throughout the discussion, data were gathered on respondents' suggestions for improvements.
Follow-up Visits and Length of Follow-up	No Follow-up required
Interim or Final Data Summary
Interim Results	Study is completed. See Final Results
Actual Number of Patients Enrolled	35 women distributed over 4 groups.
Actual Number of Sites Enrolled	2 (San Francisco and Dallas)
Patient Follow-up Rate	not applicable
Final Safety Findings	No safety findings. Key findings reported by sponsor are summarized here. Overall reaction to both versions of brochures tested was positive. Group discusions and self-administered survey indicate that solid understanding of the information in brochures. Respondents all agreed that brochure was more comprehensive than anything else they had seen. Respondents had difficulty understanding particular points in the brochure. Misost respondents interpreted the informtion on MRIs for the detection of silent ruptures to mean that MRIs were recommended as replacements for mammography. Many respondents perceived that silicone breast implnats are fragile and prone to rupture. Many were alarmed by this and teh combination of the fact that most ruptures are silent. A few respondents concluded that the true purpose of the brochure was to protect Mentor, rather than inform patietns about breast implant surgery. Respondents reported taht most of the information did not help them weigh the relative importance of risks and complications associated with breast implants. Brochure fell short of provideing infiormation on the benefits of breast implants and did not acknowledge the deeply personal benefits of body image and self-esteem, especially for women who lose their breast to cancer.
Study Strengths & Weaknesses	Discussion groups are useful for exploring attitudes, knowledge and beliefs. Readers should be cautious in intrepreting the data and in making generalizations about the target population as a whole. Given the qualitative nature of the data, they suggest general tendencies but can not be considered definitive. The study is limited by its small sample size and the selection of a non-probablistic sample.
Recommendations for Labeling Changes	Add information clearly describing differences between restoration, replacement, reconstruction, and revision early in the main body of the brochure. add informtion on Organize information on potential complications based onteh likelihood of occurrence and calling attention to the relative importance of each possible outcome. Provide more information about benefits. provie more qualitative information (personal testimony, caes histories) to help women make more informed decisions. Include more illustrations, visual white space, color and bolding. mke illustrations, larger, darker, ,orerealistinc and more clearly labelled.
General
Study Status	Terminated
Application Number / Requirement Number	P030053 / PAS007
Date Original Protocol Accepted	04/18/2014
Date Current Protocol Accepted	04/18/2014
Study Name	Breast Implant Case Control Studies
General Study Protocol Parameters
Study Design	Case Control Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee link met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put on-hold while the systematic literature review was conducted. The systematic literature review showed insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value. The FDA continues to monitor for these rare adverse events using other postmarket surveillance tools and real-world data (e.g. MDRs MDRs, NBIR, PROFILE).
Study Population	Women in Denmark, Germany, and the United Kingdom with the studied rare diseases (i.e., rare CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma) as cases and women without any of the 5 studied rare diseases from the same countries as controls.
Sample Size	For each of the 5 case]control studies, 1,150 cases of women diagnosed with studied rare disease identified from the specialized medical centers and cancer registries in Denmark, Germany and the UK will be enrolled. A total of 5,000 females identified from the same neighborhood as cases without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
Key Study Endpoints	Data will be collected by using questionnaires as well as electronic information provided by the cancer registries/tumor centers. The same questionnaires will be used for cases and controls. The participating women will fill in the questionnaires on potential confounders (e.g., life] style related covariates) and exposure to breast implants. Similar questionnaires have been successfully used in previous case]control studies with self]administered questionnaires.
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P020056 / PAS007
Date Original Protocol Accepted	01/16/2015
Date Current Protocol Accepted	01/16/2015
Study Name	Re-Op Phase
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). This Re-Op Phase Study requirement was designed as part of the re-design of the LARGE PAS for the Natrelle® Silicone Gel Breast Implant. In this Re-Op Phase, data will be collected when subjects with Natrelle® silicone breast implants have secondary surgical procedures/re-operations. This requirement will serve as a bridge between the Large PAS and NBIR.
Study Population	The NBIR arm consists of subjects implanted with round responsive devices or saline devices who were originally enrolled in the BIFS study but were not selected to remain in the smaller 10-year follow-up cohort study (BIFS arm).
Sample Size	37,390 subjects with Natrelle silicone gel-filled breast implants and 14,995 subjects with saline-filled breast implants.
Key Study Endpoints	Implant removal and reoperation rates; Reasons for reoperation.
Follow-up Visits and Length of Follow-up	The follow-up data will be collected when the participant requires a secondary procedure/reoperation.
Interim or Final Data Summary
Actual Number of Patients Enrolled	50,584 subjects
Actual Number of Sites Enrolled	953 sites
Patient Follow-up Rate	n/a (no active follow up); follow up for 10 years total
Final Safety Findings	There were a total of 190 reoperations reported in the NBIR arm of the BIFS-001 Study. In the Silicone cohort, reoperations were reported for 180 subjects (0.5%). In the Saline cohort, reoperations were reported for 10 subjects (<0.1%).
Final Effect Findings	Not assessed
Study Strengths & Weaknesses	Data was passively collected, as there was no active follow up in the study. Patients were only followed up if they required a reoperation. This was only recorded in the study if the patient followed up with the original surgeon and that information was submitted. - By the end of the study, there were only 318 sites that were active (653 sites were inactive). Approximately 20,000 patients were considered “completed due to site closure.” If the site was closed or inactive, even if a patient received a reoperation, it would not have been reported. - The reported reoperation rates in this study do not seem to be consistent with other previous studies. Given the passively collected data, this suggests that there is missing data, which is a significant limitation to this study.
Recommendations for Labeling Changes	The significant limitations of the study design given the fact that this was passive surveillance should be mentioned as a caveat of the study data. Interpretation of this study data is limited given the amount of missing data.
General
Study Status	Completed
Application Number / Requirement Number	P030053 / PAS009
Date Original Protocol Accepted	01/16/2015
Date Current Protocol Accepted	08/28/2020
Study Name	Re-Op Phase
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). This Re-Op study requirement was designed as part of the re-design of the LARGE PAS for the MemoryGel® breast implants. In this Re-Op Phase of the study, data will be collected when the subjects with MemoryGel® breast implants have secondary surgical procedures/re-operations. This Re-Op Phase will serve as a bridge between the Large PAS and NBIR.
Study Population	Women with MemoryGel breast implants who were enrolled in the Large PAS.
Sample Size	41,900
Key Study Endpoints	Implant removal and reoperation rates; Reasons for reoperation.
Follow-up Visits and Length of Follow-up	The follow�]up data will be collected when the participant requires a secondary procedure/reoperation.
General
Study Status	Completed
Application Number / Requirement Number	P080006 S073/ PAS001
Date Original Protocol Accepted	12/10/2014
Date Current Protocol Accepted	12/10/2014
Study Name	Post-Approval Study Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	see p080006/S068 for all results
General
Study Status	Terminated
Application Number / Requirement Number	H100004 / PAS001
Date Original Protocol Accepted	12/16/2011
Date Current Protocol Accepted	07/27/2012
Study Name	All Comers Registry
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will be an all-comers prospective registry
Study Population	Patients implanted with the EXCOR Pediatric VAD per indications for use
Sample Size	49 patients (39 for complete follow-up), 10 to 50 sites
Key Study Endpoints	Primary safety: serious adverse event rates of Major Bleeding Cardiac Arrhythmias Pericardial Fluid Collection (with and without Tamponade) Hemolysis Hepatic Dysfunction Hypertension Major infection Myocardial Infarction Neurological Dysfunction Psychiatric Episode Renal Dysfunction Respiratory Failure Right Heart Failure Arterial Non-CNS Thromboembolism Venous Thromboembolism Wound Dehiscence Other Primary effectiveness: transplant, recovery of left ventricular function or death
Follow-up Visits and Length of Follow-up	24 months post-implant Pre-implant, Discharge, Post-implant at 3 & 6 weeks, 3, 6, 12, and 24 months
General
Study Status	Completed
Application Number / Requirement Number	P080012 / PAS001
Date Original Protocol Accepted	05/03/2012
Date Current Protocol Accepted	07/12/2022
Study Name	Prometra Programmable Pump System
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, non-randomized, open-label, multicenter study, which will include subjects from the premarket study cohorts and new enrollment of subjects receiving the device in the postmarket.
Study Population	Group A: Active prospective study subjects. Group B: Subjects previously enrolled in the premarket trials PUMP I or PUMP II will be offered voluntary participation in the post-approval study. Subjects in Group B will be followed for a total of five years, which includes all time enrolled in the previous PUMP study.
Sample Size	400 patients
Key Study Endpoints	Primary endpoint is to assess long-term occurrence and safety as a result of granuloma formation. Secondary endpoints are to assess the long-term device performance including: -Pump failure, including time to occurrence, type, and number of occurrences -Pump battery life The additional endpoint will include: -Device-related adverse events -Device-related serious adverse events -The effect of race and ethnicity on granuloma formation -The effect of alternative drugs on granuloma formation
Follow-up Visits and Length of Follow-up	5 years Subjects shall be seen at least once every 90 days (± 30 days) from the date of implantation (Group A) or enrollment (Group B) throughout the study
Interim or Final Data Summary
Actual Number of Patients Enrolled	400
Actual Number of Sites Enrolled	28
Patient Follow-up Rate	N/A
Final Safety Findings	The extremely low number of confirmed granuloma formation during the course of this study provides reasonable and continued assurance of the long-term safety of the Prometra Programmable Infusion System.
Final Effect Findings	The extremely low number of occurrences of pump failure and low battery life provides reasonable and continued assurance of the longterm device performance of the Prometra Programmable Infusion System.
Study Strengths & Weaknesses	The majority of study deviations were due to out-of-window visits (60.10%), with the least deviations (12.86 %) due to patients not signing the informed consent. However, baseline protocol demographics showed that minority enrollment percentages were only around 5%, rendering it difficult to truly determine the effects of race on granuloma formation.
Recommendations for Labeling Changes	There are no recommendations for labeling changes.
General
Study Status	Hold
Application Number / Requirement Number	P080012 / PAS002
Date Original Protocol Accepted	05/04/2012
Date Current Protocol Accepted	05/04/2012
Study Name	Extended Use Stability Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is a non-clinical study.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	16 pumps will be used in this study.
Key Study Endpoints	The stability of the Infumorph solution in the Prometra infusion pumps will be assessed for a period of 90 days and that stability will be assessed for multiple refills (on a 90 day cycle) for a period of 10 years. The pump flow rate will also be assessed during this study as sample volumes removed will be measured versus the expected quantities.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
General
Study Status	Completed
Application Number / Requirement Number	P080012 / PAS003
Date Original Protocol Accepted	05/04/2012
Date Current Protocol Accepted	05/04/2012
Study Name	Leachables Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a non-clinical study.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	8 Prometra pumps will be used in this study.
Key Study Endpoints	Leachables Testing The leachables study will use eight (8) Prometra pumps as required in the condition of approval. The solutions will be placebo solutions at the appropriate corresponding pHs. At each time-point pumps will be emptied of their contents through the catheters and 15 mLs of solution will be used for leachable testing. Pumps will then be refilled with 22 mL of placebo solutions. This schedule mimics actual use of the pumps (dispensing and refilling) and will allow sufficient sample for the leachables testing. Controlled Extraction Study The control extraction studies will involve the evaluation of extraction solutions of the materials of the Prometra pumps that come into contact with the drug product formulation. The accelerated extractions will be done using an Accelerated Solvent Extraction. The solvents to be used for extraction are purified water, water adjusted to pH 9.5, isopropanol, and hexane. The materials of the pump will be extracted in each of these solvents at reflux for 24 hours.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A - Bench Study
Actual Number of Sites Enrolled	N/A - Bench Study
Patient Follow-up Rate	N/A - Bench Study
Final Safety Findings	All the test results met the acceptance criteria for Leachable and Extractables for all the time periods throughout the study.
Final Effect Findings	Effectiveness Results In all study reports test parameters in the test samples were not found to be significantly different from previously tested time points.
Study Strengths & Weaknesses	The sponsor was consistent in their testing of trace metals, and where present, provided literature and rationale as to why their presence was not harmful. The sponsor should have communicated all protocol changes prior to implementation of such changes.
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P030027 / PAS001
Date Original Protocol Accepted	01/07/2003
Date Current Protocol Accepted	01/07/2003
Study Name	Ceramic Transcend Hip
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	Final Study Report received and under FDA review [Aug 6, 2010]
Actual Number of Patients Enrolled	1778
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	49,3% in PMA cohort
Final Safety Findings	94.1% device survival at 5 years
Final Effect Findings	94.1% device survival at 5 years
Study Strengths & Weaknesses	Poor follow-up rate, lack of Harris Hip Score
Recommendations for Labeling Changes	TBD
General
Study Status	Completed
Application Number / Requirement Number	P040001 / PAS001
Date Original Protocol Accepted	12/08/2006
Date Current Protocol Accepted	12/08/2006
Study Name	LTOS Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Long-Term Outcomes Study (LTOS) is a prospective, multi-center study of patients who received the X-STOP device in the pre-market trial, crossover study (COS) or continued access program (CAP).
Study Population	The study population is comprised of patients aged 50 years and older who have lumbar spinal stenosis, suffers symptoms of neurogenic intermittent claudication, have moderately impaired physical function, and are able to relieve their symptoms when they bend forward or flex their spines. This device is indicated for treatment of patients aged 50 or older suffering from neurogenic intermittent claudication secondary to a confirmed diagnosis of lumbar spinal stenosis (with X-Ray, MRI, and/or CT evidence of thickened ligamentum flavum, narrowed lateral recess and/or central canal narrowing). The X STOP is indicated for those patients with moderately impaired physical function who experience relief in flexion from their symptoms of leg/buttock/groin pain, with or without back pain, and have undergone a regimen of at least 6 months of nonoperative treatment. The X STOP may be implanted at one or two lumbar levels in patients in whom operative treatment is indicated at no more than two levels.
Sample Size	The sample size is 155 potential patients who participated in the IDE.
Key Study Endpoints	The primary effectiveness endpoint is treatment response, defined as follows:- Clinically significant improvement (by at least 5 points) in the Symptom Severity (SS) Domain of the ZCQ compared to the preoperative baseline.-Clinically significant improvement (by at least 0.5 points) in the Physical Function (PF) domain of the ZCQ compared to the preoperative baseline score -Patient satisfaction with treatment defined by Patient Satisfaction score at the five-year postoperative evaluation.- No additional surgery for lumbar stenosis performed.- No dislodgement of the implant. - No device-related complications. Secondary effectiveness endpoints encompass mean individual ZCQ domain scores and mean SF-36 scores.Radiographic examination will permit the assessment of the maintenance of distraction. Distraction will be maintained if the distance between the spinous processes is not reduced by more than 4 mm from the distance observed at the six-week clinical assessment.
Follow-up Visits and Length of Follow-up	The duration of patient follow-up will be 5 years. The follow-up schedule for the study is delineated below:- 24 months following initial enrollment for those patients actively participating in either the CAP or COS at the time of LTOS study initiation- 36 months for all CAP/COS patients following enrollment into their original IDE study- 48 months for all CAP/COS patients following enrollment into their original IDE study - 60 months for all CAP/COS patients following enrollment into their original IDE study, > 60 months, for all Pivotal Trial patients following their IDE study enrollment into the X-STOP group. All patients in the Pivotal Trial have already reached their fifth postoperative year; therefore they will have in excess of 60 months device experience at their next follow-up visiT. At every office visit, patients will complete the ZCQ and the SF-36 prior to physician examination. Patients will undergo a complete clinical examination with emphasis on the neurological assessment for strength, reflexes, sensation, and pain related to the diseased intervertebral space. Radiographic examination, anterior/posterior (AP) and lateral x-rays, will be performed on all LTOS patients at their 5 year postoperative visit. Radiographic examination will also be performed on LTOS patients at 24 months. Data collected from the radiographic examinations will include the position of the X-STOP, the status of the X-STOP, the status of the spinous process, laminae and facets, and the distance between the tips of the spinous processes.
Interim or Final Data Summary
Interim Results	Radiographic findings for 63 subjects are provided. Radiographs were assessed for maintenance of distraction, device positioning, device condition, and status of the spinous process, laminae, and facets. As previously reported in the first amendment to the 24-month interim report, two subjects (subjects 01-022 and 01-024) declined to participate in the radiographic examination portion of the 60-month clinical follow-up. Neither of these subjects reported any adverse events, as shown in Tables 8 and 9. Per the March 27, 2009, amendment to the 24-month interim study status report (P040001/R011), Medtronic has contacted the core radiographic lab to review film quality and radiographic evaluation procedures to improve interpretation of LTOS data. In four subjects, the 12-month radiographic assessment was used as baseline in lieu of the 6-week radiographic assessment, as 6-week films were not available (subjects 01-002, 01-006, 01-008, 05-002).
Actual Number of Patients Enrolled	A total of 69 study subjects were enrolled.
Actual Number of Sites Enrolled	A total of six study sites were enrolled.
Patient Follow-up Rate	The follow-up rate for enrolled patients was 97.1%.
Final Safety Findings	A total of 56 patients were analyzed radiographically at the 5-year postoperative assessment (29 had single-level implants and 27 had multilevel implants). In those with single-level implants, 27/69 (39.1%) patients maintained distraction for at least 5 years. In those with multilevel implants, 23/69 (33.3%) patients maintained distraction at all levels for at least 5 years The most commonly reported adverse events were lumbar spinal stenosis (LSS, 7.2% of patients overall; 7.3% of patients in the target cohort and 7.1% patients in the safety cohort) and arthralgia (5.8% of patients overall; 7.3% of patients in the target cohort and no patients in the safety cohort).
Final Effect Findings	The treatment success rate was 45.5% (25/55) for the target cohort and 42.9% (6/14) for the safety cohort. Patients in the target cohort showed statistically significant improvements in the domains of bodily pain, general health, physical component, physical functioning, role-emotional, role physical, social functioning, and vitality scores as measured by the SF-36 at 5 years post- implantation. Patients in the safety cohort showed statistically significant improvements from baseline in the domains of bodily pain, physical component, physical functioning, role physical, and vitality scores.
Study Strengths & Weaknesses	Strengths of the study include the duration of follow-up and the conduct of radiographic examinations. Study weaknesses include the retrospective coding of adverse events and limited sample size,
Recommendations for Labeling Changes	Yes, labeling change is recommended to provide long-term, five year data regarding device safety and effectiveness, including clinical results and radiographic findings.
General
Study Status	Terminated
Application Number / Requirement Number	P040001 / PAS002
Date Original Protocol Accepted	11/21/2005
Date Current Protocol Accepted	10/24/2014
Study Name	COAST Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This Medtronic Spine LLC-sponsored, prospective, multicenter longitudinal five-year study of X-STOPPK implant usage in LSS patients is designed to supplement pre-market safety and effectiveness data with information on longer-term device performance in a population of patients with moderately impaired physical function at preoperative baseline (i.e., an indicated population) who elect to undergo X-STOPPK surgery.
Study Population	The study population was comprised of patients aged 50 years and older who have lumbar spinal stenosis, suffers symptoms of neurogenic intermittent claudication, have moderately impaired physical function, and are able to relieve their symptoms when they bend forward or flex their spines. This device is indicated for treatment of patients aged 50 or older suffering from neurogenic intermittent claudication secondary to a confirmed diagnosis of lumbar spinal stenosis (with X-Ray, MRI, and/or CT evidence of thickened ligamentum flavum, narrowed lateral recess and/or central canal narrowing). The X-STOP is indicated for those patients with moderately impaired physical function who experience relief in flexion from their symptoms of leg/buttock/groin pain, with or without back pain, and have undergone a regimen of at least 6 months of nonoperative treatment. The X-STOP may be implanted at one or two lumbar levels in patients in whom operative treatment is indicated at no more than two levels.
Sample Size	The sample size required within the protocol is 240 patients.
Key Study Endpoints	This study was designed primarily to evaluate long-term treatment response to the X-STOPPK implant in LSS patients with moderately impaired physical function at baseline. Treatment success in an individual patient (i.e., a responder) was defined by seven separate criteria at the two-year postoperative evaluation, as follows: Clinically significant improvement (by at least 0.5 points) in the Symptom Severity (SS) domain of the ZCQ compared to preoperative baseline Clinically significant improvement (by at least 0.5 points) in the Physical Function (PF) domain of the ZCQ compared to preoperative baseline Patient satisfaction with treatment (defined as a Patient Satisfaction [PS] score <2.5) No additional surgery for lumbar stenosis performed Maintenance of distraction No dislodgement of the implant No device-related complications Sustained treatment success in a responder was defined as continued success at the five-year postoperative evaluation as defined above. Secondary endpoints included scores from the SF-36, ODI, and NRS, as well as incidence rates of adverse events, device failures, and secondary surgeries.
Follow-up Visits and Length of Follow-up	Safety and effectiveness data was assessed at baseline and annually through five (5) years postoperatively. Office visits were scheduled preoperatively, and at 6 weeks and, 1, 2, 3, 4, and 5 years postoperatively. Clinical/neurological and radiographic examination was performed during each office visit. A baseline patient history (including medication usage) was taken, and concomitant medications were recorded at each postoperative follow-up visit. In addition, patients were asked to complete the following questionnaires prior to consultation with their physicians or their staff at each postoperative visit: Zurich Claudication Questionnaire (ZCQ), Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and SF-36 Health Survey. At the 2-, 3-, 4- and 5-year office visit, patients were also asked two questions assessing the value of surgery and the overall improvement in the quality of life postoperatively.
Interim or Final Data Summary
Interim Results	The mean change in baseline symptom severity score was 0.97 at 6 post-operative weeks and 1.01 at 12 post-operative months. Five study subjects experienced device migration and 2 subjects suffered spinous process fracture.
Actual Number of Patients Enrolled	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons. 162 patients were enrolled.
Actual Number of Sites Enrolled	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons. 20 sites participated in enrollment.
Patient Follow-up Rate	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons. The follow-up rate of expected subjects is 91.53% and 91.67% at the 24-month and 60-month visit, respectively. The attrition rate due to death, lost to follow-up and withdrawal is 5.56% and 27.16% at the 24-month and 60-month visit, respectively.
Final Safety Findings	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons. Adverse Events (AEs) Summary: Through August 15, 2014, a total of 814 adverse events were reported by 132 (81.5%) patients. The most common category of AEs was musculoskeletal and connective tissue disorders, reported by 88 (54.3%) patients and the most commonly reported adverse event was back pain, reported by 36 (22.2%) patients. Within this set of AEs, thirty-two events were reported for 18 (11.1%) patients to be implant-related while 51 events reported in 27 (16.7%) patients were classified as X-STOP procedure-related. The most frequently reported implant-related AE was device removal reported in 10 (6.2%) patients. The most frequently reported procedure-related AEs were incisional site pain in 7 (4.3%) patients, and spinal fracture in 6 (3.7%) patients. Serious Adverse Events (SAEs) Summary: Through August 15, 2014, a total of 210 serious adverse events have been reported by 65 (40.1%) patients. Within this set of SAEs, 26 events were reported for 15 (9.3%) patients to be implant-related while five events reported in 3 (1.9%) patients were classified as X-STOP procedure-related. Subsequent Lumbar Surgery There were 39 secondary surgery forms completed in thirty-two (19.8%) patients with 28 (17.3%) patients reporting X-STOP removal. Success Rates Overall success rates for the study participants were observed as follows: 12 months, 44.8%; 24 months, 30.9%; and 60 months, 24.2%.
Final Effect Findings	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons.
Study Strengths & Weaknesses	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons.
Recommendations for Labeling Changes	These results are from the 96-month interim report (Aug 15, 2014) This summary is not a final analysis as the study was terminated prior to study completion due to volunatary withdrawal of the PMA by the sponsor for business reasons.
General
Study Status	Completed
Application Number / Requirement Number	P040002 / PAS001
Date Original Protocol Accepted	10/29/2004
Date Current Protocol Accepted
Study Name	Long Term/Pivotal Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study included all surviving endovascular patients from the original pivotal study cohort. There were no hypotheses was proposed to evaluate long-term (5-year) safety and effectiveness.
Study Population	The Endologix, Inc. Powerlink System is an endovascular stent graft and delivery system that is indicated for endovascular treatment of abdominal aortic aneurysms.
Sample Size	192 endovascular sten graft patients and 66 control patients across 15 sites
Key Study Endpoints	The primary effectiveness endpoint was all cause mortality. Primary safety endpoint was the incidence of major adverse events including: death, myocardial infarction, coronary intervention, respiratory failure, aneurysm rupture, kidney failure, secondary procedures, conversion to open surgical repair, stroke, blood loss, prosthesis migration, and patency.
Follow-up Visits and Length of Follow-up	Clinical follow-up and diagnostic test evaluations were scheduled pre-discharge, at one month, six months, one year and annually thereafter through five years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	192 endovascular stent graft patients and 66 control patients
Actual Number of Sites Enrolled	15 sites
Patient Follow-up Rate	56% in the device group, 39% in the control group
Final Safety Findings	The overall implant success rate was 98% (188/192), with three patients requiring conversion to open surgical aneurysm repair. Of the 192 device patients, 108 (56.2%) patients were followed (107 had CT imaging follow-up), 43 (22.4%) patients had died, 4 (2.1%) had a conversion to open repair, and 37 (19.3%) withdrew or were lost to follow-up at 5 years. Of the 66 surgical controls 26 (39.4%) patients were followed, 15 (22.7%) patients had died, and 25 (38.9%) withdrew or were lost to follow-up at 5 years. There were four reported aneurysm related deaths in the device group. There were no deaths due to aneurysm rupture. The deaths occurred at 1-day, 9-days, 33-days, and 403-days. The late death occurred during a conversion to open repair. There does not appear to be a problem with a late failure rate in the device.
Study Strengths & Weaknesses	Weakness: Higher proportion of patients wtithdrew or were lost to follow-up in control group (39%) Therere 19% of patients who withdrew or were lost to follow-up in the device group.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P980003 / PAS001
Date Original Protocol Accepted	02/02/1999
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was a one-armed, observational, prospective cohort study, the purpose of which was to compare device safety and effectiveness with objective performance criteria.
Study Population	The study population was patients for whom the Chilli device is indicated, who had failed or were intolerant to drug therapy.
Sample Size	200 patients, 19 sites
Key Study Endpoints	Effectiveness Endpoints: ventricular tachycardia recurrence rate, defined as the percent of subjects with one or more episodes of ventricular tachycardia recurrence within six months following the index procedure. Safety Endpoints: Assessed as the occurrence rate of a procedure-related major adverse event within seven days of the index procedure.
Follow-up Visits and Length of Follow-up	Endpoints were assessed at 6-months post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	182 patients
Actual Number of Sites Enrolled	19 sites
Patient Follow-up Rate	88%
Final Safety Findings	The primary effectiveness goal was not met. The success criteria was a ventricular tachycardia recurrence rate of 54.2%, whereas the upper 95% confidence limit was 63.8%
Study Strengths & Weaknesses	Strength: Propensity analysis was conducted to control for confounding variables; Weakness: It is unclear whether to OPCs, on which the success criteria were based, were appropriate.
Recommendations for Labeling Changes	Labeling changes were made to reflect the failure to meet part of the success criteria.
General
Study Status	Completed
Application Number / Requirement Number	P000040 S014/ PAS001
Date Original Protocol Accepted	04/23/2012
Date Current Protocol Accepted	04/23/2012
Study Name	Genesys HTA Post Approval Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A Multi-center, Single-arm, Prospective Registry of the Genesys HTATM System for the Treatment of Menorrhagia will evaluate safety and technical performance of the device at time of treatment.
Study Population	All women treated with the Genesys HTATM System under the approved indications for use who agree to participate
Sample Size	1312 subjects at a maximum of 100 clinical sites
Key Study Endpoints	Rate of clinically significant burns (primary) Rate of technical complaints with the system (secondary) Assessment of serious adverse events (secondary)
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,014
Actual Number of Sites Enrolled	18
Patient Follow-up Rate	91.8% (931/1,014)
Final Safety Findings	There have been 4 burn events: 3 non-clinically significant burns and 1 clinically significant burn were reported. The rate of this clinically significant event was 0.1% (95% CI 0.0%, 0.6%). The primary hypothesis of the PAS is that the subject rate of clinically significant burns is not significantly greater than 1.0%. For the secondary endpoint, there has been one (1) Serious Adverse Device Effect. This was a superficial 2nd degree burn for a subject for a rate of 0.1% (95% CI: 0.0% ¿ 0.6%).
Final Effect Findings	There was no effectiveness endpoint per se. The secondary objective of the study was to obtain data on technical problems with the device. Fifty-three (53) technical complaints were reported for 44 subjects in the intent-to-treat population (N=992). Therefore, the rate of technical complaints per subject was 5.3% (53/992).
Study Strengths & Weaknesses	This study had an adequate sample size that was large enough to study key safety issues.
Recommendations for Labeling Changes	No labeling changes are recommended
General
Study Status	Completed
Application Number / Requirement Number	P080032 / PAS001
Date Original Protocol Accepted	07/27/2010
Date Current Protocol Accepted	07/27/2010
Study Name	AIR2 - Extended Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	190
Actual Number of Sites Enrolled	30
Patient Follow-up Rate	Follow-up rates were 95.2%, 87.4%, 85.3%, 83.7%, and 85.3% at years 1-5, respectively.
Final Safety Findings	There were six safety endpoints evaluated after the Alair treatment, and they were acceptable at 5 years follow-up. The Rates for Severe Exacerbation Event, for Respiratory Adverse Event (events/subject/year), for Emergency Room Visits for respiratory symptoms (events/subject/year), and for Hospitalizations for respiratory symptoms (events/subject/year) in each subsequent year (2 through 5) compared to year 1 post therapy (0.486, 2.0, 0.07, 0.039) were non- inferior and were sustained through year five. There was no increase in the above rates and Respiratory Serious Adverse Events over time. FEV1 did not deteriorate over 5 years. There were no structural changes in the airways based on the review of 93 High-resolution computed tomography (HRCT) pairs at Baseline and at Year 5.
Final Effect Findings	The proportions of subjects (expressed in percentages) experiencing one or more severe exacerbations in Years 1-5 after the Alair treatment were 30.9%, 23.6%, 34.0%, 36.5%, and 21.6%, respectively. The upper 95% confidence limit of the difference between the subsequent 12-month proportions (for Years 2, 3, 4, and 5) compared to the first 12-month proportion remained less than the pre-specified non-inferiority margin of 20%. Therefore, the proportions are not significantly worse, i.e. the primary endpoint for the study has been met. Treatment effectiveness is durable out to five years.
Study Strengths & Weaknesses	The study cohort was originally randomized and treated. However, during the 5-year follow-up, it became an open-label single-arm study, i.e. subjects became unblinded to treatment introducing a possible placebo effect. The subject population is predominately Caucasians (~80%), thus, the results may best represent the Caucasian population.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P080032 / PAS002
Date Original Protocol Accepted	04/27/2010
Date Current Protocol Accepted	09/14/2010
Study Name	New Patient Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, open-label, multi-center, single-arm study conducted in the United States and Canada
Study Population	Adults (18-65 years) with asthms
Sample Size	Enroll up to 300 adult subjects (a minimum of 250 subjects)
Key Study Endpoints	The primary endpoint is the proportion of subjects experiencing severe exacerbations during the subsequent 12-month periods (for Years 2, 3, 4, and 5) compared to the first 12-month proportion after the Alair treatment.
Follow-up Visits and Length of Follow-up	Up to 5 years from the end of last treatment. Every 6 months between annul visits, and annul visits at 1, 2, 3, 4, and 5 years from the end of last treatment.
Interim or Final Data Summary
Actual Number of Patients Enrolled	279
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	271 – Subjects Enrolled and received at least one treatment (97%) 262 – Subjects completed 1 year follow up (94%) 249 – Subjects completed 2 year follow up (89%) 244 – Subjects completed 3 year follow up (88%) 237 – Subjects completed 4 year follow up (85%) 227 – Subjects completed 5 year follow up (81%)
Final Safety Findings	There were six safety endpoints evaluated after the Alair treatment, and they were acceptable at 5 years follow-up. The Rates for Severe Exacerbation Event, for Respiratory Adverse Event (events/subject/year), for Emergency Room Visits for respiratory symptoms (events/subject/year), and for Hospitalizations for respiratory symptoms (events/subject/year) in each subsequent year (2 through 5) compared to year 1 post therapy were non-inferior and were sustained through year five. There was no increase in the above rates and Respiratory Serious Adverse Events over time. FEV1 did not deteriorate over 5 years.
Final Effect Findings	The proportions of subjects (expressed in percentages) experiencing one or more severe exacerbations in Years 1-5 after the Alair treatment were 50.4%, 46.6%, 47.1%, 44.7%, and 42.7%, respectively. The upper 95% confidence limit of the difference between the subsequent 12-month proportions (for Years 2, 3, 4, and 5) compared to the first 12-month proportion remained less than the pre-specified non-inferiority margin of 20%. Therefore, the proportions are not significantly worse, i.e. the primary endpoint for the study has been met. Treatment effectiveness is durable out to five years.
Study Strengths & Weaknesses	The study was open-label, single arm, which may introduce the placebo effect. The subject population is predominately Caucasians (~80%), thus, the results may best represent the Caucasian population.
Recommendations for Labeling Changes	Update the label with the respiratory-related serious adverse event rates.
General
Study Status	Completed
Application Number / Requirement Number	P040003 S015/ PAS001
Date Original Protocol Accepted	08/31/2015
Date Current Protocol Accepted	07/23/2025
Study Name	Post ExAblate Pregnancy Outcomes Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational [single cohort] global Post-ExAblate Pregnancy Outcome Registry-based Study. The objective is to collect safety information regarding patient pregnancy/outcomes following treatment of their symptomatic fibroid(s) with the ExAblate MR guided focused ultrasound system. All adverse events that are possibly related to pregnancies and pregnancy outcomes, including post-partum complications for both mother and infant, will be collected in consenting patients.
Study Population	All consented patients from participating sites who receive an ExAblate procedure or have previously undergone an ExAblate procedure for symptomatic uterine fibroids will be recruited for this registry. There is no control group.
Sample Size	The registry is open to all who would consent at participating sites, and will be open for enrollment for two years. The study aims to enroll up to 198 patients in total. A minimum of ten sites from around the world will participate, including a minimum of six sites from the U.S.
Key Study Endpoints	Main safety endpoint: Adverse events related to pregnancies, including but not limited to pregnancy outcome, and post-partum complications for the mother and infant. The nature of each adverse event, date and time (when appropriate) of onset, outcome, frequency, maximum intensity, action taken, expectedness, and causal relationship will be recorded.
Follow-up Visits and Length of Follow-up	Up to two years after ExAblate treatment, or until pregnancy completion. Sites should contact the subject 2 times a year (approximately every 6 months) for 2 years after the ExAblate procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	198 patients
Actual Number of Sites Enrolled	9 sites
Patient Follow-up Rate	Of the 198 total patients to enter the registry, 104 (53%) completed the study, and 94 exited the study. Of the 94 that exited the study, 36 subjects were exited from the study due to a center shutting down, 14 were lost to follow up, 8 due to Exablate treatment failure, 3 due to patient decision, 4 were not qualified, 4 were non-compliant, 4 withdrew consent, 2 completed child-bearing, 5 had myomectomies, 4 had hysterectomies, and 11 had others reason for exiting the study.
Final Safety Findings	There were 20 pregnancies, four miscarriages and 16 deliveries reported in the study cohort, resulting in a miscarriage rate of 20% (4/20). Five out of sixteen (31%) of deliveries were vaginal deliveries, with 11/16 (69%) of deliveries through C-section. Six adverse events were reported in the pregnancy cohort, which included events during pregnancy and post-partum. One reported pregnancy complication related to a conversion from vaginal delivery to Cesarean section was considered possibly related to the device.
Final Effect Findings	No effectiveness endpoints in this study
Study Strengths & Weaknesses	The strengths of the study are enrollment at multiple diverse sites. The weakness of the study includes high attrition due to site closures and loss to follow up, 91 out of 198 patients exited the study, which may increase bias in study results. Due to the observational structure of the study, study results are not inferential in nature, and definitive conclusions regarding relative rates of adverse events cannot be made.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P150003 / PAS001
Date Original Protocol Accepted	10/02/2015
Date Current Protocol Accepted	05/12/2017
Study Name	EVOLVE Short DAPT Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The EVOLVE Short DAPT clinical trial is a prospective, multicenter, single-arm study designed to assess the safety of 3-month dual antiplatelet therapy (DAPT) in subjects at high risk for bleeding undergoing percutaneous coronary intervention (PCI) with the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System (SYNERGY Stent System).
Study Population	Device: SYNGERGY Everolimus-Eluting Platinum Chromium Coronary Stent System Subject considered at high risk for bleeding, defined as meeting one or more of the following criteria at the time of enrollment: =75 years of age, current anticoagulation therapy, history of major bleeding, stroke, or renal insufficiency (creatinine =2.0 mg/dl) or renal failure (dialysis dependent). Control: Historical data collected from subjects at high risk for bleeding receiving 12 months of DAPT
Sample Size	2,250 subjects will be enrolled in up to 120 sites worldwide in the United States, Europe, Japan, and Brazil. Number of evaluable test subjects required in the propensity score model is 1,650 (1,500 *1.1) including additional 10% subjects accounting for model variability Expected drop out rate due to ineligibility for 3 month DAPT in 0 to 3 months = 15% Expected attrition rate in 3 to 15 months = 3%
Key Study Endpoints	Co-Primary Endpoints: The study has two co-primary endpoints which will be assessed: (1) rate of death and myocardial infarction between 3- and 15- months and (2) rate of Academic Research Consortium (ARC) definite/probable stent thrombosis (ST) involving SYNERGY between 3 and 15 months. Secondary Endpoint: Rate of bleeding, based upon the Bleeding Academic Research Consortium (BARC) classification (types 2, 3, and 5) between 3 and 15 months in subjects not taking chronic anticoagulation.
Follow-up Visits and Length of Follow-up	All enrolled subjects are to be followed through 15 months after the index procedure. The study will be considered complete with regard to the primary endpoint after all subjects have completed 15-months follow-up.
Interim or Final Data Summary
Actual Number of Patients Enrolled	2009
Actual Number of Sites Enrolled	110
Patient Follow-up Rate	1767/2009 (88.0%) available for 15-month follow-up
Final Safety Findings	Co-Primary Endpoint (1) death or MI: 5.58% Co-Primary Endpoint (2) Academic Research Consortium (ARC) definite/probable Stent Thrombosis: 0.2%
Study Strengths & Weaknesses	prospective, multicenter, single-arm study designed to assess and underserved patient population (high risk for bleeding)
Recommendations for Labeling Changes	Revisions to the labeling will be recommend that provide additional information and context regarding the clinical study that was performed.
General
Study Status	Completed
Application Number / Requirement Number	P040003 / PAS001
Date Original Protocol Accepted	10/22/2004
Date Current Protocol Accepted	10/22/2004
Study Name	Long Term Exablate Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was design to provide descriptive data on the long term performance (safety and effectiveness) of the device. This is an observational prospective study that includes the extended follow-up of the premarket cohorts and enrollment of a new cohort of African American women who were treated following the commercial treatment guidelines. The study does not include a comparison group. However, before and after treatment comparisons are made.
Study Population	Study population is as per device indication. This device is indicated for ablation of uterine fibroid tissue in pre- or peri-menopausal women with symptomatic uterine fibroids who desire a uterine sparing procedure. Patients must have a uterine size of less than 24 weeks and have completed child bearing.
Sample Size	269 from premarket cohorts; 75 African American women newly enrolled postmarket
Key Study Endpoints	The study is used a standardized quality of life questionnaire for uterine fibroids (Uterine Fibroid Symptoms-Quality of Life Questionnaire). The questionnaire is administered at baseline prior to treatment and then at the follow-up visits. There is also fibroid volume data collected by MRI
Follow-up Visits and Length of Follow-up	The study includes follow-up visits at 3, 6, 12, 24 and 36-months of follow-up.
Interim or Final Data Summary
Interim Results	Final Report accepted, sponsor was advised to submit labeling change supplement. Study will be marked as completed when the labeling change supplement is approved.
Actual Number of Patients Enrolled	169 from premarket cohort + 73 postmarket
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	68.6% follow-up rate. However, those with alternative treatments, second ExAblate treatments, and/or became pregnant were discontinued from follow-up as per protocol. Therefore, long term data is only available on 32.8%
Final Safety Findings	No new device related adverse events occurred during the postmarket follow-up of the study
Study Strengths & Weaknesses	Given that the study provides long-term data on 32.8% of study participants, the results are not generalizable to the overall patient population treated with ExAblate. The treatment guidelines limited to 50% of volume size. There are currently new treatment guidelines (100%). Results under new treatment guidelines may differ.
Recommendations for Labeling Changes	Final Report is accepted. Sponsor was advised to update labeling with a new section that includes summary of the post-approval study design, results (long-term data), and study strenghts and limitations. Study will be marked as completed when labeling changes are received. Sutdy will be marked as completed when the labeling change is approved.
General
Study Status	Completed
Application Number / Requirement Number	P040034 / PAS001
Date Original Protocol Accepted	04/07/2005
Date Current Protocol Accepted	04/07/2005
Study Name	Duraseal
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS is a prospective, randomized, single-blinded (patients), multi-center study to further characterize the DuraSeal Sealant as compared to "standard of care" in patients scheduled for cranial surgery that entails a dural incision.
Study Population	This device is indicated for use as an adjunct to sutured dural repair during cranial surgery to provide watertight closure.The study population includes subjects scheduled for clean, elective cranial surgery that entail dural incisions that are closed primarily with sutures with or without autologous duraplasty. To be eligible for the study, subjects had to be between 18 and 75 years of age, scheduled for an elective cranial procedure entailing a dural incision, and provided informed consent on an IRB approved consent form, and intra-operatively, there must have been evidence of non watertight closure after primary dural closure, either spontaneously or upon Valsalva maneuver, at 20 cm water for 5-10 seconds.
Sample Size	250 patients; approximately 25 centers
Key Study Endpoints	The primary outcome is the incidence of neurosurgical complications related to unplanned intervention (i.e., minimally invasive procedures) or return to the operating room. The secondary outcomes are 1) the incidence of post-operative surgical site infections within 30 days post-operation defined as (a) Superficial Incisional, (b) Deep Incisional, (c) Organ/Space; and 2) the presence or absence of CSF leaks within 30 days post-operation as determined from clinical diagnosis.
Follow-up Visits and Length of Follow-up	Patients are followed for 30 days after treatment, and are evaluated clinically at discharge and at 30 days post-procedure.
Interim or Final Data Summary
Interim Results	Study is completed. See Final Results
Actual Number of Patients Enrolled	237 patients
Actual Number of Sites Enrolled	17 centers
Patient Follow-up Rate	98.30%
Final Safety Findings	There were 18 primary endpoint complications in 16 subjects: 9 happened in 8 patients in the DuraSeal group of which 6 (66.7%) were procedure related, 1 treatment related (11.1%), 1 not related and 1 unable to determine. Nine happened in 8 patients in the standard of care group: 7 (77.7%) were procedure related and 2 were treatment related (22.2%). All reported neurosurgical complications for the DuraSeal Sealant group are anticipated and expected. The incidence and nature of the complications that have been reported are consistent with the type and complexity of the procedures performed.
Study Strengths & Weaknesses	High follow up rate. Randomized design.
Recommendations for Labeling Changes	The sponsor updated the labeling to reflect the post-approval study results prior to FDA completing review of the final report. The lableing changes were also reviewed by FDA and the labeling does reflect the study results.
General
Study Status	Completed
Application Number / Requirement Number	P040016 / PAS001
Date Original Protocol Accepted	04/12/2005
Date Current Protocol Accepted	04/12/2005
Study Name	Longterm Outcomes
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P000008 / PAS002
Date Original Protocol Accepted	06/05/2001
Date Current Protocol Accepted	03/28/2016
Study Name	HERO-002
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center study designed to evaluate the 5-year explant rate.
Study Population	Subjects must be at least 18 years old and meet one of the following obesity criteria: (a) BMI greater than or equal to 40 kg/m2; (b) BMI greater than or equal to 35 kg/m2 with at least one severe comorbid condition; or (c) 45.5 Kg/100 lbs above ideal body weight.
Sample Size	The primary analysis of the HERO-002 protocol involves 655 subjects enrolled across up to 17 US and 1 Canadian clinical sites. A sample of 426 subjects will provide 89% power to find a point estimate of 32.5% as statistically superior to the null hypothesis of 39.4%.
Key Study Endpoints	The primary endpoint is the explant rate over 5 years of follow-up. The secondary endpoint is the rate of device-related reoperations over 5 years.
Follow-up Visits and Length of Follow-up	5-years post-implant. Patients were followed for 5 years post LAP-BAND placement, with assessments occurring at baseline, 3 months, 6 months, and annually thereafter for 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	671 subjects
Actual Number of Sites Enrolled	17 sites
Patient Follow-up Rate	73.1% at 5 years
Final Safety Findings	The primary endpoint of the study was met, with a 5-year explant rate of 8.74% (95% CI 6.60%, 10.90%) in the Safety Population being significantly lower than a success criterion of 39.4%. The 5-year reoperation rate was 7.7%.
Final Effect Findings	The average %TBWL was -17% through the first year of follow-up and plateaued thereafter until the 5-year visit. Similarly, other anthropometric measures (weight, waist circumference, hip circumference, and BMI) demonstrated decreases during the first year and relatively little change thereafter.
Study Strengths & Weaknesses	Strengths of this study include a multi-center, prospective design of adequate sample size for long-term (5-year) evaluation of the safety and effectiveness endpoints. The main limitation is the limited generalizability of study results. Given the high attrition rate of 26.9% at 5 years, the main study findings may be an over-estimate of the true device performance. PAS data indicate that subjects who did not complete 5 years of follow-up were less successful, in terms of weight loss, compared to those who completed the 5-year study.
Recommendations for Labeling Changes	Labeling changes are recommended based on the long-term safety and effectiveness results of the PAS and inclusion of real world evidence (including literature and possibly other data sources)
General
Study Status	Terminated
Application Number / Requirement Number	P070014 S022/ PAS001
Date Original Protocol Accepted	09/16/2011
Date Current Protocol Accepted	07/11/2014
Study Name	LifeStent SOLO PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multicenter, single- arm, non-randomized study.
Study Population	Subjects with lifestyle-limiting claudication or ischemic rest pain attributable to lesion(s) in the infra-inguinal segment and/or proximal popliteal artery that are amenable to PTA and stenting. The control group is historical cohorts of RESILIENT PTA group
Sample Size	Subjects will be enrolled at 25 study sites within the USA A minimum of 234 subjects: at least 64 subjects with target lesion lengths < 160 mm; at least 64 subjects with target lesion lengths > 160 mm and < 240 mm and at least 64 subjects treated with the 200 mm LifeStent will be enrolled.
Key Study Endpoints	The Primary Safety endpoint is freedom from occurrence of death at 30-days and 12-months post-index procedure. The Primary Effectiveness is device success defined as freedom from acute delivery failure, and primary target lesion patency (TLP) at 12 months post index procedure. Freedom from Fracture (FFF)
Follow-up Visits and Length of Follow-up	Subjects will be followed for 36 months Subjects will undergo clinical assessments at 30 days, 12, 24- and 36-month post procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 173 subjects were enrolled as follows: 113 enrolled under P070014 (Target Lesion lengths less than or equal to 160 mm), 18 enrolled under subgroup P070014/S010 (Target Lesion lengths >160 - 240 mm) and 41 enrolled under subgroup P070014/S022 (Target Lesions treated with 200 mm LifeStent SOLO). 1 subject had target lesion length of 280 mm that is not included in the subgroup categories.
Actual Number of Sites Enrolled	A total of 30 sites received IRB approval and were enrolled.
Patient Follow-up Rate	Follow-up rates for the combined subgroups at 30 days, and 12, 24, and 36 months was 98.8% (163/165), 98.6% (142/144), 98.3% (115/117) and 97.7% (84/86), respectively.
Final Safety Findings	Primary safety was defined as freedom from occurrence of death at 30 days and 12-months post procedure. The freedom from primary safety event rate at 30 days and 12 months post index procedure was 99.4% (95% confidence interval [CI] 95.9%, 99.9%) and 95.1% (95% CI 90.4%, 97.5%) respectively.
Final Effect Findings	Primary effectiveness (Device Success) for the CONTINUUM study was defined as: freedom from device delivery failure and primary Target Lesion Patency (TLP) at 12-months post-index procedure measured by DUS. TLP was defined as the interval following the index procedure until a DUS assessment indicates that the target lesion(s) is no longer patent; that is, the treated segment has a peak systolic velocity ratio (PSVR) greater than or equal to 2.5. Primary effectiveness at 12 months by Kaplan Meier method was 72.7% (95% confidence interval [CI] 61.8 to 81.0%). Primary target lesion patency (TLP) at 12-Months post-index procedure by Kaplan Meier analysis for CONTINUUM LifeStent group was 75.3% (95% CI: 67.4%, 81.6%) compared to RESILIENT PTA 36.7% (95% CI: 25.1%, 48.4%). The hazard ratio for CONTINNUUM LifeStent over RESILIENT PTA (ITT) was 0.123, P <0.001. For non- inferiority comparison of the CONTINUUM Lifestent to RESILIENT LifeStent, the primary TLP at 12 months for CONTNUUM LifeStent was 81.1% versus RESILIENT LifeStent 73.2% using Cox’s regression model with regression covariates: treatment group, Rutherford Category, target lesion length, total treated segment length, age, and gender. The difference in primary TLP at 12 months between CONTINUUM LifeStent and RESILIENT LifeStent is 0.079 (7.9%). The lower bound of the 95% CI for the difference in TLP between CONTINNUUM LifeStent and RESILIENT LifeStent of -0.006 is greater than -0.075, the non-inferiority margin, indicating that the CONTINUUM arm is not inferior to the RESILENT arm. The Z-test statistic is equal to 2.99, p-value = 0.0014. Freedom from TLR and/or TVR at 12 months post index procedure for the CONTINUUM LifeStent group was 82.2% (95% CI 75.2%, 87.3%) compared to that of RESILIENT PTA (ITT) group 45.2% (95% CI: 33.4%, 56.3%) – (p-value <0.001). The percentage of subjects free from stent fracture at 12- and 24-months post-index procedure was 92.4% (110/119) and 67.6% (69/102) respectively.
Study Strengths & Weaknesses	Overall, approximately 74% (173/234) of required enrollment was achieved in the CONTNUUM study. The target enrollment of at least 64 subjects in each subgroup was not achieved in two subgroups. The two subgroups were: 1) Target Lesion Lengths > 160 mm and less than or equal to 240 mm, and 2) Target Lesions treated with the 200 mm LifeStent SOLO.
Recommendations for Labeling Changes	Labeling change is not recommended with the post approval study results as the study was not completed.
General
Study Status	Completed
Application Number / Requirement Number	P080006 S002/ PAS001
Date Original Protocol Accepted	04/01/2011
Date Current Protocol Accepted	04/01/2011
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	1140
Actual Number of Sites Enrolled	119
Patient Follow-up Rate	85.2%
Final Safety Findings	The primary safety endpoint is lead complication free rate >92.5% at 5 years. The most common event is lead dislodgement, followed by infection and stimulation issue. The complication free rate at 60 months is 96.33%. Dislodgements (2.36%) are known to be common for LV leads. Most of the returned leads were found to be ok with no anomalies found. None of the deaths were related to the lead.
Final Effect Findings	Electrical performance appears to be within adequate ranges.
Study Strengths & Weaknesses	Enrollment exceeded expectations and follow up rate was adequate. A common deviation was incomplete data collection during follow up visits, which may impact overall information available for assessments.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P040020 S049/ PAS001
Date Original Protocol Accepted	10/11/2018
Date Current Protocol Accepted	08/28/2020
Study Name	AcrySof IQ ReSTOR +3.0 Toric PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Phase A: This is a prospective, multicenter, post-approval active surveillance study to report the rate of post-surgical intraocular inflammation (based upon a specified case definition) reported within a 180-day post-surgical period following implantation of an ACRYSOF IQ RESTOR Toric IOL in the US. Phase B: This is a retrospective epidemiological study to estimate the historical background rate of post-surgical intraocular inflammation following implantation of an intraocular lens (IOL) in the United States. All cataract surgeries reported in 2011 through 2013 in the Medicare Limited Data Set (LDS) files will be reviewed to look at the frequency of post-surgical intraocular inflammation within 180 days of cataract surgery.
Study Population	Cohort 1: Adult subjects, 22 years of age or older, implanted from November 2018 through July 2020 with an ACRYSOF® IQ RESTOR® Multifocal Toric IOL (+3.0 D or +2.5 D). The study enrollment is complete for Cohort 1. Cohort 2: Adult subjects, 22 years of age or older, implanted after July 2020 with an ACRYSOF® IQ RESTOR® +3.0 D Multifocal Toric IOL or ACRYSOF® IQ RESTOR® +2.5 D Multifocal IOL. Phase B: Data from the Part B (Physician/Supplier) files from all beneficiaries with one or more claims for cataract surgery in 2011 to 2013 were considered. The Part B file encompasses service by the ophthalmologist in both inpatient and outpatient settings.
Sample Size	Cohort 1: 478 subjects were enrolled, 706 eyes were implanted, and 703 eyes completed the postoperative follow-up evaluation up to 180 days. Cohort 2: 3600 eyes will enroll to implant 3300 from 30 sites across the U.S. to ensure 3,000 eyes evaluable for up to postoperative 180 days.
Key Study Endpoints	There are no performance endpoints in this study. Safety Endpoints: The primary safety endpoint is the rate (per 1,000 IOL implants) of post-surgical intraocular inflammation (based upon the specified case definition) reported within a 180-day post-surgical period following attempted implantation of ACRYSOF® IQ RESTOR® Toric +3.0 D Multifocal IOL or ACRYSOF® IQ ReSTOR® +2.5 D Multifocal IOL (Cohort 2). The secondary safety endpoints are the rates (per 1,000) of Toxic Anterior Segment Syndrome (TASS), acute postoperative endophthalmitis, chronic postoperative endophthalmitis, and uncategorized cases of post-surgical intraocular inflammation (based upon the specified case definition), respectively, reported within a 180-day post-surgical period following implantation of ACRYSOF® IQ RESTOR® Toric IOLs or ACRYSOF® IQ ReSTOR® IOL (Cohort 2).
Follow-up Visits and Length of Follow-up	Within postoperative 180 days.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1972
Actual Number of Sites Enrolled	34
Patient Follow-up Rate	Subjects, n (%) 1747 (97.49) successfully implanted 45 (2.51) discontinued subjects include 30 (1.67) lost to follow up with the other 15 subjects discontinued due to death, adverse event(s), or withdrawal by subject.
Final Safety Findings	According to Section 4.4.1 of report, overall rate of postsurgical inflammation (any type) was 5.1 per 100 attempted implants (two-sided 95% CI 2.95, 8.10). It was similar for first and second eyes; none of the cases were assessed to be related to study device. Subgroup analysis by age showed a similar rate of postsurgical inflammation in subjects < 65 years (5.0 events per 1000) and subjects greater than or equal to 65 years (5.1 events per 1000). For comparison purposes, Cohort 1's rate was much higher 8.5 per 1000 implants (2-sided 95% CI 3.13, 18.41), and the rate reported in PAS Phase B Medicare study was also much higher at 10.31 per 1000 implants (95% CI 9.89, 10.74). Most eyes (14) had uncategorized inflammation, 2 eyes had TASS, and 1 eye had acute postoperative endophthalmitis. Ocular adverse events (AE) occurred in about 17% of eyes; AEs are consistent with known risks in cataract surgery. Ocular serious AE (SAE) rate was relatively rare at 1.22%. Individual SAEs n (%): Vitrectomy, 12 (0.36) Cataract Surgery Complication, 10 (0.3) Device dislocation, 6 (0.18) IOL repositioning, 11 (0.33) Lens extraction, 9 (0.27) Glare, 4 (0.12) Retinal detachment, 5 (0.15) cystoid macular edema, 4 (0.12) All other SAE rates were below 0.1%
Final Effect Findings	Study is focused only on device safety, so there are no effectiveness endpoints.
Study Strengths & Weaknesses	5 eye implanted with non study IOL; they were excluded from all analyses. There were no other protocol deviations since previous report
Recommendations for Labeling Changes	No labeling changes because Applicant has stopped manufacturing the subject device
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS004
Date Original Protocol Accepted	04/20/2010
Date Current Protocol Accepted	04/20/2010
Study Name	Kaiser Permanente Joint Registry
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry study
Sample Size	Kaiser has identified approximately 90 patients at multiple clinical sites in their total joint registry that have DURALOC Option ceramic on ceramic hip replacements.
Key Study Endpoints	Depuy will provide the following information as the data exists and is permitted by Kaiser Permanente: ¿ Femoral Stem types ¿ The years in which the surgeries were performed ¿ Patient demographic summaries (age, gender, diagnosis, height, weight, BMI) ¿ Patient listing of reasons for revisions ¿ Revision rate ¿ Death rate ¿ Kaplan-Meier survival estimates ¿ Harris Hip Score over time ¿ Adverse Events ¿ Radiographic results
Follow-up Visits and Length of Follow-up	The length of follow-up for this study is 5 years. Pending contract execution, Depuy will request that Kaiser recall these patients for annual follow-up visits.
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS005
Date Original Protocol Accepted	04/20/2010
Date Current Protocol Accepted	04/20/2010
Study Name	Natl Joint Registry for England and Wales
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry study
Sample Size	In data extracted in June 2009, there were approximately 400 hips reportedly implanted with a DURALOC Option Metal Outer Shell in combination with either an AML, Corail, or S-ROM femoral stem.
Key Study Endpoints	DePuy will provide the following information as the data exists and is permitted by the NJR-EW: ¿ Femoral Stem types ¿ The years in which the surgeries were performed ¿ Patient demographic summaries (age, gender, diagnosis, height, weight, BMI) ¿ Patient listing of reasons for revisions ¿ Revision rate ¿ Death rate ¿ Kaplan-Meier survival estimates
Follow-up Visits and Length of Follow-up	The length of follow-up for this study is 10 years. DePuy will request annual data extract reports from the NJR-EW and provide these reports to the FDA in annual progress reports.
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS006
Date Original Protocol Accepted	04/20/2010
Date Current Protocol Accepted	04/20/2010
Study Name	Australian Ortho Assc Natl Joint Registry
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry study
Sample Size	In the 2009 AOA-NJRR Annual Report there were 666 hips reportedly implanted with a DURALOC Option Metal Outer Shell in combination with an S-ROM femoral stem. DePuy does not yet have confirmation on the number of ceramic-on-ceramic articulations. However, based on internal data it is anticipated that approximately 450 hips will have ceramic on ceramic articulations.
Key Study Endpoints	DePuy will provide the following information as the data exists and is permitted by the AOA-NJRR: ¿ Femoral Stem types ¿ The years in which the surgeries were performed ¿ Patient demographic summaries (age, gender, diagnosis, height, weight, BMI) ¿ Patient listing of reasons for revisions ¿ Revision rate ¿ Death rate
Follow-up Visits and Length of Follow-up	The length of follow-up for this study is 10 years. DePuy will request annual ad-hoc reports from the AOA-NJRR and provide these reports to the FDA in annual progress reports.
General
Study Status	Completed
Application Number / Requirement Number	P860057 S018/ PAS001
Date Original Protocol Accepted	11/14/2003
Date Current Protocol Accepted
Study Name	Perimount Magna Pericardial Bioprosthesis
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Analysis Type	Descriptive
General
Study Status	Ongoing
Application Number / Requirement Number	P000025 S134/ PAS001
Date Original Protocol Accepted	01/23/2026
Date Current Protocol Accepted	01/23/2026
Study Name	MED-EL Cochlear Implant Pediatric PAS
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	Pediatric Expansion Post-Approval Study (PEPAS) in the MED-EL Cochlear Implant Population combines an extended follow-up study and a new, prospectively designed, retrospective study to assess long-term safety and effectiveness of cochlear implantation up to a minimum of 2 years post-implantation in children aged 7 months to 18 years.
Study Population	The target study population will include approximately 100 children implanted at ages greater than or equal to 7 months to < 18 years. Cohort 1 will include approximately 26 children prospectively implanted at ages greater than or equal to 7 to < 12 months in IDE G180269. Cohort 2 will include 30 new retrospective participants implanted at ages greater than or equal to 1 to < 6 years. Cohort 3 will include 50 new retrospective participants implanted at ages greater than or equal to 6 to < 18 years. Study participants will include children with bilateral SNHL who received a MED-EL cochlear implant before January 1, 2024, and meet the expanded indications approved in PMA Supplement P000025/S134.
Sample Size	Cohort 1 will consist of 26 subjects implanted at ages greater than or equal to 7 to < 12 months from pivotal study G180269. Cohort 2 will include 30 new subjects implanted at ages greater than or equal to 1 to < 6 years. Cohort 3 will include 50 new subjects implanted at ages greater than or equal to 6 to < 18 years.
Key Study Endpoints	Primary effectiveness endpoint: The primary effectiveness endpoint is to evaluate the performance of the cochlear implant on age-appropriate speech tests. Formal hypothesis tests are planned to establish superiority of the 24-month post-operative condition over the pre-operative condition. A within-subject analysis will be conducted on at least 75% of subjects who will demonstrate clinical success by 2 years post-activation on developmentally-appropriate measures of subjective benefit (e.g., improvement of greater than or equal to 25 percentage points on developmentally-appropriate parent questionnaires) or speech recognition (e.g., improvement of greater than or equal to 10 percentage points on the same developmentally-appropriate speech recognition test or non-zero score on a more difficult test in the speech recognition hierarchy) when compared to pre-implantation baseline or first available postoperative score. Secondary Effectiveness endpoint: 1. Mean postoperative audibility, defined by aided thresholds at 125-8000 Hz in the cochlear implant ear(s) alone through 2 years post-activation, including functional gain in subjects with preoperative thresholds available for comparison. 2. Mean improvement on available outcome measures in subjects with preoperative and postoperative scores on the same test. A descriptive analysis of change in audiometric thresholds and speech performance pre- to post-operatively will be conducted to demonstrate improving speech recognition. Primary safety endpoint: The primary safety endpoint will be summarized with the number and percentage of participants experiencing an adverse device effect (ADE) through 2 years.
Follow-up Visits and Length of Follow-up	2 years post-implantation for each subject.
General
Study Status	Ongoing
Application Number / Requirement Number	P200048 / PAS001
Date Original Protocol Accepted	11/28/2025
Date Current Protocol Accepted	11/28/2025
Study Name	IsoPSA Assay PAS
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-blind, multi-site post-approval study of the IsoPSA Assay in an African American population.
Study Population	African American population
Sample Size	At least 250 African American subjects resulting in at least 50 African American subjects with an IsoPSA Index less than or equal to 6.0.
Key Study Endpoints	Clinical performance measures of IsoPSA Assay with three outputs for Target Condition = (Grade Group greater than or equal to 2, Geason Score greater than or equal to 7) and an Assessment of the TC = prostate biopsy.
Follow-up Visits and Length of Follow-up	No follow-up
General
Study Status	Completed
Application Number / Requirement Number	P020031 / PAS001
Date Original Protocol Accepted	09/23/2003
Date Current Protocol Accepted	09/23/2003
Study Name	MEA PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continue to follow all subjects from the multi-center study for a period of three years from the time of treatment. The patient follow-up reports will be submitted annually as PMA reports. When a full three-year followup report is submitted, FDA was to determine if continued follow-up of these study subjects is required.
Study Population	Study population is as per device indication. This device is indicated for ablation of the endometrial lining of the uterus in pre-menopausal women with menorrhagia (excessive uterine bleeding) due to benign causes for whom childbearing is complete.
Sample Size	215 device group; 107 control
Key Study Endpoints	Data collected should include: need for hysterectomy or repeat ablation; assessment of patient's menstruation pattern; adverse events and/or complications; Quality of Life information; patient's pregnancy and contraception status; and diagnosis of malignancy of the uterus.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	141 device group; 74 control group
Actual Number of Sites Enrolled	Not mentioned
Patient Follow-up Rate	66% device group; 69% control group
Final Safety Findings	No significant difference in amenorrhea rates at 3 years between the microwave endometrial ablation and rollerball endometrial ablation groups was observed. Patient acceptance and satisfaction at 3 years were very high, in excess of 98%, for both treatment arms. No significant difference in the quality of life, based on SF-36 scores was observed between the two treatment arms. No pregnancies were reported among the study participants, an observation of note given that pregnancy has been reported in the literature among endometrial ablation recipients.
Study Strengths & Weaknesses	The pre-market study was a randomized clinical trial with the patients randomized to microwave endometrial ablation or rollerball endometrial ablation arms. However, the loss to follow-up was appreciable over the three year follow-up period; 33% among the microwave endometrial ablation arm and 31% among the rollerball endometrial ablation arm. Loss to follow-up can introduce bias and limit interpretation of study results.
Recommendations for Labeling Changes	As per PAS Closing letter: labeling should be revised to reflect the long-term safety and effectiveness data gathered on the MEA System
General
Study Status	Completed
Application Number / Requirement Number	P030054 S019/ PAS001
Date Original Protocol Accepted	03/14/2006
Date Current Protocol Accepted	03/14/2006
Study Name	Longterm
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P980049 S020/ PAS001
Date Original Protocol Accepted	04/28/2006
Date Current Protocol Accepted	04/28/2006
Study Name	Ovatio DR6550 Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 6-month, multi-center, single arm, prospective cohort study. All subjects in the study receive the device.
Study Population	Study Population: Patients with an accepted indication for an implantable cardioverter defibrillator implant. Indication: The device is indicated for use in patients who are at high risk for sudden death due to ventricular tachyarrhythmia who have experienced at least one episode of cardiac arrest due to tachyarrhythmia or who have recurrent poorly tolerated, sustained ventricular tachycardia.
Sample Size	60 subjects at 5 sites
Key Study Endpoints	Endpoints include incidence and nature of device related adverse events through 6 months follow-up (safety) and the percentage of patients with two successful reductions of ventricular fibrillation (VF) at 24Joules (10 Joules below maximum output) at implant (effectiveness).
Follow-up Visits and Length of Follow-up	Patients will be evaluated at implant, 3 months, 6 months, and at unscheduled visits as needed for adverse events and effectiveness of device therapy.
Interim or Final Data Summary
Interim Results	There were 62 adverse events have been seen in 43 patients including 3 deaths. The deaths were not deemed device-related by the sponsor and were due to aspiration pneumonia/sepsis, pancytopenia, and renal disfunction (end-stage renal disease).
Actual Number of Patients Enrolled	5
Actual Number of Sites Enrolled	77 successful implants (85 enrolled)
Patient Follow-up Rate	84.4% (65 patients completed study of 77 implanted)
Final Safety Findings	There were 12 applicable system complications in 8 patients for a 6-month system complication free rate of 89.6% (95% lower confidence bound: 85%). There were 4 deaths; none were device related. There were 12 serious, implant- or device-related events (complications) including: 2 pocket infections, 3 lead dislodgement/migrations, 1 non-conversion of ventricular tachycardia (VT) or ventricular fibrillation (VF), 3 lead losses of capture, 1 elevated pacing threshold, 1 pocket erosion, and 1 cardiac perforation. All were resolved within one day, except the 2 pocket infections which required explant of the device.
Final Effect Findings	Two successful reductions of VF occurred in 72 of the 77 implanted patients (93.5%; 95% CI 89-98%). Four patients received 7 shocks for spontaneous VT or VF in the six months following implant. All had successful reductions of VT or VF. The sensitivity for correctly detecting and shocking induced VT or VF was 99.5%. The sensitivity for spontaneous VF was 100%. The sensitivity for spontaneous VT was 100%. And, the specificity for (correctly detecting and not shocking) supraventricular tachycardia or sinus tachycardia was 99.1%.
Study Strengths & Weaknesses	The purpose of the study was to follow at least 60 patients for 6 months and to report on complications and successful shocks during that time. There was no stated hypothesis or specified maximum attrition rate. Thus, the results are descriptive and representative of the patients who completed the 6 month follow-up and not necessarily all patients who utilize this device.
Recommendations for Labeling Changes	Yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P040048 / PAS001
Date Original Protocol Accepted	06/28/2006
Date Current Protocol Accepted	06/28/2006
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a prospective, multi-center, uncontrolled cohort study of subjects in whom the device was implanted after FDA approval. The purpose of the post-approval study is to evaluate the safety and effectiveness of the Trilogy AB Acetabular System through long-term follow-up of 10 years. However, because of the lack of progress on the original PAS, FDA asked the sponsor to redesign the PAS. The PAS was revised per a FDA letter dated 7/14/09. The new protocol is not approved yet [Aug 13,2010]. The description presented here is for the old study
Study Population	Study population is as per device indication and it includes: age from 21 to 80 years, body mass index less than 30, willing and able to provide informed consent. The device is indicated for either cemented or noncemented use in skeletally mature individuals undergoing primary surgery for rehabilitating hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) such as osteoarthritis, avascular necrosis, congenital hip dysplasia, and traumatic arthritis.
Sample Size	250 patients
Key Study Endpoints	Endpoints not mentioned
Follow-up Visits and Length of Follow-up	During the first five years of the study clinical, radiographic, and subject self assessment information will be collected for each subject. Data will be collected pre-operatively, immediately post-operatively, at three months and annually up to five years. An independent radiographic review will be conducted at five years. For the sixth through the tenth postoperative years, patients will be asked to return an outcomes questionnaire designed to determine the status of their hip replacement. In addition, you have agreed to record and report each adverse event regarding full details of the nature of the complication, treatment and outcome on the appropriate Case Report Form. You will send in Interim Study Status Reports to the FDA every six months for the first two years of the study and annually thereafter until a Final Study Report has been submitted. The results of this long-term data must be reflected in the product labeling (via supplement) when the post-approval study is completed.
General
Study Status	Completed
Application Number / Requirement Number	P040025 / PAS001
Date Original Protocol Accepted	12/20/2006
Date Current Protocol Accepted	12/20/2006
Study Name	VON Registry
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective observational study, using the Vermont Oxford Network (VON) Registry, Burlington, Vermont: this is a non-profit voluntary collaboration of health care professionals dedicated to improving the quality and safety of medical care for newborn infants and their families, established in 1988. The sponsor will provide each hospital that purchases a Cool-Cap with information on the existing VON. This network maintains a dataset including information about the care and outcomes of high-risk newborn infants. The sponsor explains to the hospitals that purchases the device how to join the VON, who to contact, and an explanation of how their participation can help in monitoring the use of this new treatment. The VON is independently establishing a registry for infants with symptoms of hypoxic ischemic encephalopathy (HIE). Patients receiving the Cool-Cap for HIE will be included in this registry. VON will collect data for this registry through a software module added to the system currently used by their members to report data for their other registries.
Study Population	Study population is as per device indication. The device is indicated for use in fullterm infants with clinical evidence of moderate to severe hypoxic-ischemic encephalopathy (HIE)*. Cool-Cap provides selective head cooling with mild systemic hypothermia to prevent or reduce the severity of neurologic injury associated with HIE.
Sample Size	No sample size or power calculations are provided in the protocol.The sponsor expects that participation in the registry will be a subset of all Cool-Cap customers/patients. It is expected that a reasonable percentage of hospitals will already be a member of this registry and will participate.
Key Study Endpoints	Data to be collected on infants treated with the Cool-Cap will include the following information. Demographic and Admission data: sec, race / ethnicity, measurements at birth (weight, head circumference, length), gestational age, gestational category (AGA, LGA, SGA <10%), date of birth, time of birth, inborn or transfer, method of delivery, multiple births, delivery complications, NICU admit temperature, Apgar scores, CFM / aEEG Score, Sarnat Stage, cord pH, base deficit, assisted ventilation, cooling start date/time, cooling stop date/time, stop date/time, restart date/time, duration, and reason for any interruptions of cooling that exceed 30 minutes. Data that reports the occurrence of potential serious adverse events due to hypothermia as defined in the clinical trial protocol. This would include: - Major cardiac arrhythmia (such as ventricular tachycardia, ventricular fibrillation or acquired conduction block), - Major venous thrombosis not related to an infusion line,- Severe hypotension despite full inotrope support and volume correction,Data that reports the occurrence of adverse events encountered in the clinical trial. This would include:- Clinical seizures during rewarming,- Abnormal EKG (minor cardiac arrhythmia or prolonged QT interval),- Scalp edema,- Sclerema neonatorum,Data that will provide information on the infant's condition when discharged from the hospital would include:- Discharge Date,- Discharge Diagnosis or Cause of Death
Follow-up Visits and Length of Follow-up	The sponsor will discontinue participation in the registry, and reporting of data, after 5 years.
Interim or Final Data Summary
Interim Results	As of the 36-month PAS report, finalized tabulation of results for the year 2008, including infants for whom the 3-day treatment began January 1, 2008 through December 31, 2008. In addition to 76 infants in 2007, a total of 129 infants from 8 hospitals are included, a relevant increase from the 49 infants from 4 hospitals reported in the initial tabulation. The last report also provides initial tabulation of results for the year 2009: 69 infants were included from 7 hospitals for whom the 3-day treatment began January 1, 2009 through November 12, 2009. The overall number of infants included in the report is 274.
Actual Number of Patients Enrolled	551
Actual Number of Sites Enrolled	16
Patient Follow-up Rate	100%
Final Safety Findings	Infants in the current registry had higher rates of adverse events including minor cardiac arrhythmias, seizures, and scalp edema than those in the randomized clinical trial; this trend does not appear to change over time. The sponsor has provided explanations on the observed difference, which was mainly due to the longer observational period and different definitions of adverse events in PAS contrast to the PMA data
Final Effect Findings	Effectiveness findings were not reported.
Study Strengths & Weaknesses	Although important data was collected about patient characteristics and adverse events for these infants during their NICU hospitalization, the registry may not be able to provide any useful information in assessing device performance (safety and effectiveness) under actual conditions of use because of its following limitations: (1) lack of valid comparison group; (2) potential selection bias due to the lack of baseline information on infants who may receive the device but whose data were not entered in the registry; (3) no continued follow-up for premarket and continued access patients who have already received the device; (4) failure to obtain data on infants after discharge from the NICU; and (5) no long-term follow-up with neurodevelopmental assessments.
Recommendations for Labeling Changes	The sponsor was asked to update their labeling to reflect the changes in clinical practice of therapeutic hypothermia for neonatal HIE based on the final PAS report.
General
Study Status	Completed
Application Number / Requirement Number	P040024 / PAS001
Date Original Protocol Accepted	03/25/2005
Date Current Protocol Accepted	03/25/2005
Study Name	Restylane
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was a prospective, randomized, comparative, efficacy evaluator-blinded, design. Subjects meeting the enrollment criteria will have bilateral nasolabial folds and, if needed, oral commissures corrected with Restylane /Perlane to optimal correction using each product as intended. - One of the sides of the face will be randomly assigned to be corrected with Restylane and the opposite side will be treated with Perlane at Visit 1 and, potentially at Visit T, 2 weeks after for touch-up. - All patients should receive at least a one-grade improvement in WSRS. - The patients will be aware that they are receiving both treatments, but they will not be informed of which treatment is applied to which side of their face (see also paragraph 4.2 regarding Randomization and Blinding Procedure).
Study Population	This device is indicated for mid-to-deep dermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. The study population includes patients with Fitzpatrick Skin Types 5 or 6
Sample Size	150 patients from 10 or more centers
Key Study Endpoints	Assessments include pain, tenderness, redness, ecchymosis, swelling. itching, mass (nodule / cyst / abscess) formation, dermeal pignentation and keloid changes at the site of injection at each follow-up point post-optimal cosinesis. Safety endpoint assessments include: keloid formation at the site of injection at 12 and 24 weeks, 2) pigmentation changes at the site of injection compared to adjacent skin at 2 and 6 weeks, and 3) adverse experience assessment, 4) patient diary symptom profile. and 5) immunologic panel oUtcomc (to include at a mininmuim histamine release, W1BC diflberential, and anti-body titer).
Follow-up Visits and Length of Follow-up	Screen/Baseline, 72 hours, 2 weeks, 6 weeks, 12 weeks and 24 weeks
Interim or Final Data Summary
Interim Results	Study is completed. See Final Study Results
Actual Number of Patients Enrolled	150 subjects were randomized and treated. 148 subjects completed 24 weeks of follow-up and skin test.
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	98.70%
Final Safety Findings	Based on skin testing, antibody data and histopathology, neither Restylane nor Perlane are immunogenic. There were no deaths. Three intercurrent serious injuries were unrelated to test products. There were 45 true systemic events that were unrelated to test products or of unknown relationship. There were 36 true local unrelated/unknown events. There were 104 related local adverse experiences all of which were assigned to a specific treatment site. All local related events were expected in incidence, severity and duration. Local adverse experiences were largely limited to bruising, tenderness, edema, redness, itching, pain, and pigmentary changes. These listed events account for over 90% of local related events. No patient developed a keloid during the study. There was one hypertrophic scar reported that was most likely related to inflammatory acne at entry but that resolved spontaneously. There were 9 Perlane-treated patients and 14 Restylane-treated patients with pigmentation changes at the nasolabial fold or oral commissures. All were of mild or moderate severity. Most resolved within 6 weeks with 7/9 Perlane events resolving by 12 weeks. Unintended feel occurred in 3 patients. In one, there was spontaneous resolution. In thetwo others, a nodule developed into an abscess and treatment of the infectious process was successful. There were no delayed onset local related experiences that suggest, therefore, an absence of immune reactivity. There were 17 injection site experiences of pigmentation changes and 14 local related adverse experiences that lasted more than 2 weeks. Adverse experience assessment and analysis demonstrated that there was no difference between incidence or severity between Restylane and Perlane. The protocol-specified screening analysis of relationship of injection technique to adverse experience failed to identify a significant relationship except generation of a hypothesis that multiple puncture technique may increase pigmentary changes. Patient diary complaints demonstrated a 75% to 90% incidence of local events in the first two weeks of such complaints as bruising, redness, swelling, tenderness, and pain. Itching was less common. Most complaints were mild and predominantly in the initial days followed by resolution by end of the diary period.
Study Strengths & Weaknesses	One of the study strengths is the randomized study design, which allows for control of potential confounders. Another strength is the high follow-up rate.
Recommendations for Labeling Changes	Amend the label with a summary of the postapproval study and findings regarding assessing the likelihood of hypersensitivity reactions, the likelihood of keloid formation, changes in pigmentation and the development of clinically relevant antibodies to Restylane.
General
Study Status	Ongoing
Application Number / Requirement Number	P040033 / PAS001
Date Original Protocol Accepted	05/09/2006
Date Current Protocol Accepted	04/01/2011
Study Name	US Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is a multi-center, single arm, prospective cohort study.
Study Population	Study population is as per device indication. Patients who underwent Birmingham Hip Resurfacing (BHR) System, a metal on metal resurfacing artificial hip replacement system, surgically implanted to replace a hip joint. The BHR System is intended for patients who, due to their relatively youneger age or increased activity level may not be suitable for traditional total hip arthroplasty, due to an increased possibility of requiring future ipsilatcral hip joint revision.
Sample Size	The sample size is 350 patients.
Key Study Endpoints	Study endpoints include Harris Hip Score and device survival.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical and radiographic examinations for the first five years of follow-up with a final clinical and radiographic examination at 10 years. Subjects will receive annual questionnaire follow-up in years 6 through 9.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P040051 / PAS001
Date Original Protocol Accepted	05/12/2006
Date Current Protocol Accepted	05/12/2006
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is a prospective cohort. This 10-year postapproval study would be conducted to evaluate the longer-term safety and effectiveness of the Stelkast Surpass Acetabular System. The recruitment of patients, physicians and health care facilities in the post-approval study for this device has been inadequate.Due to enrollment problems. in a letter dated, July 14, 2009, FDA requested a revised post-approval study. The new protocol is not approved yet [Aug 13,2010]. The description presented here is for the old study
Study Population	Patients who have been implanted with Stelkast Surpass Acetabular System is a ceramic/ceramic acetabular bearing couple for a total hip prosthesis.
Sample Size	300 subjects enrolled
Key Study Endpoints	Study endpoints include device revision and Harris Hip Score during the first five years of follow-up.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical and radiographic examination for their first five ears of follow-up. During their last 5 years of follow-up patients will receive questionnaires regarding the status of their total hip replacements.
General
Study Status	Completed
Application Number / Requirement Number	P040033 / PAS002
Date Original Protocol Accepted	05/09/2006
Date Current Protocol Accepted	05/09/2006
Study Name	UK Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is a single arm, cohort study.
Study Population	Study population is as per device indication. Patients who underwent Birmingham Hip Resurfacing (BHR) System, a metal on metal resurfacing artificial hip replacement system, surgically implanted to replace a hip joint. The BHR System is intended for patients who, due to their relatively youneger age or increased activity level may not be suitable for traditional total hip arthroplasty, due to an increased possibility of requiring future ipsilatcral hip joint revision.
Sample Size	The sample size is 350 patients.
Key Study Endpoints	Study endpoints include OSHIP scores and device survival.
Follow-up Visits and Length of Follow-up	At the time of PMA submission, all subjects had passed their 5 year post-implantation anniversary. Subjects will be followed annually through the use of self-assessment questionnaires until they reach 10 years of follow-up. At the ten year interval, a final clinical and radiographic examination will occur in addition to the questionnaire.
Interim or Final Data Summary
Interim Results	A total of 22 deaths (27 hips) have occurred within the original 350 subject (400 hips) study population prior to completion of both 10 year study activities. No new deaths are reported in this report. Radiographic evaluations are done at the 10 year clinical evaluation. Radiographic information for patients seen at the 10 year interval is presented below. Of the 400 hips eligible for radiographic evaluation, 295 have data available.
Actual Number of Patients Enrolled	A total of 350 patients and 400 hips were enrolled in the study.
Actual Number of Sites Enrolled	Two study sites in the United Kingdom participated in the study.
Patient Follow-up Rate	The follow-up rate for clinical examination was 89.5% at 10 post-operative years.
Final Safety Findings	Heterotopic ossification of all grades was seen in 12.0% at 10 years; however, grade III and IV heterotopic ossification was found in only 1.3% hips.. According to the independent radiographic review of the acetabular cup area, 13/316 hips (4.1%) showed some degree of radiolucency at 10 year follow-up. No hips were defined as radiographic failures for the acetabular component, which would have been denoted by a score ranging from 7, 8, or 9. According to independent radiographic review, femoral radiolucencies were seen in 12/316 (3.8%) hips. Radiographic failure, represented by a score of 7-9 was found in 1/316 (0.32%) hips evaluated. A total of 19/400 revisions (4.8%) of the BHR System are included in the final disposition of the population at 10 years. Infection was a prominent contributor to revision accounting for 6/19 (31.6%) of revisions between the 2nd and 5th postoperative years. Collapsed femoral head was also a condition, which led to 4/19 (21.1%) of the revisions, and was especially prevalent around year 5 and after. Although not as prevalent, femoral neck fracture led to 3/19 (15.8%) revisions
Final Effect Findings	At the 10 year follow up, 281/319 (88.1%) had OSHIP (Oswestry-modified Harris Hip Scores) of 80 or above. Specifically, 228/319 (71.5%) were at least 90 or above and another 53/319 (16.6%) were above 80 at 10 years.
Study Strengths & Weaknesses	An important study strength is the 89.5% follow-up rate over 10 years. A weakness of the study was the fact that all patients were implanted by the design surgeon, limiting generalization of the results.
Recommendations for Labeling Changes	Yes. Ten-year device performance data can be updated
General
Study Status	Completed
Application Number / Requirement Number	P040038 / PAS002
Date Original Protocol Accepted	10/12/2005
Date Current Protocol Accepted	10/12/2005
Study Name	EXACT Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P040037 S060/ PAS001
Date Original Protocol Accepted	09/19/2014
Date Current Protocol Accepted	09/19/2014
Study Name	RELINE Extended F/U Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	100 (47 Viabhn and 53 POBA) 88 subjects (42 Viabahn and 46 POBA) were available at 1 year for the PAS
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	90.9% (80/88) at 2-year follow-up visit (based on the number of subjects available at 1 year for the PAS)
Final Safety Findings	A total of 178 Serious Adverse Events, 80 in the Viabahn treatment group and 98 in the POBA Control group were reported through 24 months.
Final Effect Findings	Primary Endpoint Primary patency at 24 months by Kaplan-Meier (KM) estimate for the Viabahn group was 59.6% versus 10% for the POBA Control group (log rank test p-value: p <0.001) Secondary Endpoints Primary assisted patency at 24 months (KM estimate) was 74.8% for the Viabahn group versus 47.9% for the and POBA Control group (log rank test p-value: p =0.008) Secondary patency at 24 months (KM estimate) was 90.6% for the Viabahn group and 69.5% for the control group at 24 month follow-up (log rank test p-value: p =0.010). Freedom from target lesion revascularization (KM estimate) for the Viabahn group was 68.1% versus 19.6% for the POBA control group (log rank test p-value: p<0.001). Clinical success was achieved by 88.9% (32/36) of Viabahn subjects and 90.2% (37/41) of Control subjects at 24 months (Fisher¿s Exact test, P = 1.0)
Study Strengths & Weaknesses	The post-approval study subjects were randomized subjects who were followed through 2 years post stent implant. As such the limitations associated with observational studies are expected to be reduced in this two-arm randomized study. The primary and secondary endpoints for the Viabahn group were evaluated against POBA Control group by formal statistics. Study Weaknesses No issues of significance were identified.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the 2-year long-term results from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow-up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P040037 S060/ PAS002
Date Original Protocol Accepted	04/03/2015
Date Current Protocol Accepted	04/03/2015
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objectives: to evaluate post-market safety and effectiveness of the GORE Viabahn endoprosthesis for treatment of ISR of the SFA. Study design: a prospective, non-randomized, multicenter, single-arm observational study involving a minimum of 108 newly enrolled subjects.
Study Population	Subjects presenting with symptomatic peripheral artery disease (Rutherford Category 2-5) with occlusive lesion(s) within and adjacent to previously implanted non-covered stent(s) located in the SFA.
Sample Size	A total of 108 subjects, comprising of a minimum of 81 subjects in the US and maximum of 27 OUS subjects will be enrolled from 15 US and 5 OUS sites. The study population will include a minimum of 20 subjects with ISR lesion length 230- 270mm. The sample size of 108 subjects is expected to yield an evaluable sample size of 86 subjects at 1-year after 20% lost to follow-up.
Key Study Endpoints	Primary Effectiveness Endpoint: Primary Patency at 12 months Primary Safety Endpoint: Device- and procedure-related SAEs within 30 days of the index procedure Secondary Endpoint: Acute Procedural Success Secondary endpoint to be evaluated at 30 days, 12, 24 and 36 months include: Primary Patency Primary Assisted Patency Secondary Patency Freedom from Target Lesion Revascularization (TLR) Freedom from Major Amputation Change in Ankle-Brachial Index from pre-procedure Change in Rutherford Category from pre-procedure Adverse Event Report Stent Fracture Assessment at 12, 24 and 36 months by the Core Lab
Follow-up Visits and Length of Follow-up	3 years 30 days, 1, 2 and 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	108
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	30 day visit: 101 out of 108 (93.5%) 12-month visit: 78 out of 95 (82.1%) 2-year follow-up visit: 61 out of 73 (83.6%) 3- year follow-up visit: 53 out of 61 (86.9%)
Final Safety Findings	SAE events were reported within 30 days: Three (2.8%; sepsis, retroperitoneal bleed, groin hematoma) Free from SAE within 30 days: 105 (97.2%)
Final Effect Findings	Primary patency at 12-months for the intent-to-treat subject cohort is 71.5% (Kaplan-Meier Estimates 95% Confidence Interval: 60.7%, 79.7%). Patency: 30 days: 99.0% 12 months: 71.5% 24 months: 56.1% 36 months: 44.9 %
Study Strengths & Weaknesses	The follow-up compliance and study deviations were within reasonable expectations.
Recommendations for Labeling Changes	Additional information is available from these results that supplements information already contained in the publicly available SSED and labeling. Therefore, labeling changes are recommended.
General
Study Status	Completed
Application Number / Requirement Number	P030011 / PAS001
Date Original Protocol Accepted	10/15/2004
Date Current Protocol Accepted	01/04/2011
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	.Enhanced surveillance of all device usage.
Study Population	No human subjects will be enrolled in this enhanced surveillance of the Companion 2 Driver System Study. The data for this study are being collected under an existing procedure for reporting and assessing Customer Experiences relating to all SynCardia devices being used globally.
Sample Size	This surveillance study will be conducted over one year commencing with the first use of the Companion 2 Driver System after study initiation and continued for one year with no specified sample size. It is anticipated that the Companion 2 Driver System will be used approximately 100 times in the United States during the one year duration of this study.
Key Study Endpoints	1. Number of times the Companion 2 Driver System is used to support a patient during the study period. (Each time a patient is transferred to a Companion 2 Driver System will count as one use.) 2. Number of Customer Experiences related to the Companion 2 Driver System or its accessories submitted during the study period. 3. Number of Customer Experiences related to the Companion 2 Driver system or its accessories that involved human factors submitted during the study period. 4. Types of identified human factors, severity of impact to patient care, and frequency of occurrence, will be calculated across all sites and by individual site.
Follow-up Visits and Length of Follow-up	Not applicable Not applicable
General
Study Status	Completed
Application Number / Requirement Number	P040047 / PAS001
Date Original Protocol Accepted	11/10/2005
Date Current Protocol Accepted	09/29/2008
Study Name	Coaptite
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	10% of patients have developed urge incontinence, which may be advisable to monitor.
Actual Number of Patients Enrolled	459 Patients
Actual Number of Sites Enrolled	23 Sites
Patient Follow-up Rate	91.3% (419/459) at 6 months, 88.2% (405/459) at 12 months, 81.5% (374/459) at 18 months, 78.9% (362/459) at 24 months, 73.4% (337/459) at 30 months, and 72.5% (333/459) at 36 months.
Final Safety Findings	Primary Safety Objective The primary safety objective of the study was to assess the long-term safety of Coaptite, specifically tissue erosion, dissection, and material migration. At 36 months, only one patient among the 459 enrolled patients developed this event for an incidence of 0.2% (95% confidence interval: 0.01%, 1.4%). The incidence in the initial 24-month follow-up IDE trial was 1.3% in the Coaptite group and 1.5% in the control group. The 36-month incidence in this study supports the hypothesis that tissue erosion occurred at a rate of < 5% of subjects, because the upper limit of the 95% confidence interval for the incidence is lower than 5%. One to two retreatments with the device were needed in 262 patients, two to three in 90, three to four in 26, four to five in 7, and five to six in 1 patient. Fifty-one subjects reported a variety of alternative treatments for the incontinence during the study. Other Adverse Events Of a total of 459 enrolled subjects, 68% of the subjects reported AEs; 10% of study subjects experienced a severe AE. A total of 20.5% and 47.7% of study subjects experienced device-related and not device-related AEs, respectively. The most frequent AE was UTI, observed among 29.6% (136/459) of the study subjects, followed by urge incontinence, and urinary retention. The most frequent treatment was antibiotics. Of the 136 subjects with urinary tract infection (29.6%), 13 were documented as related to treatment and 123 were documented as unrelated. Of the 109 subjects with urge incontinence (23.7%), 8 of them were documented as related to treatment and 101 were documented as unrelated. Of the 66 subjects with urinary retention (14.4%), 60 subjects were documented as related to treatment and 6 were documented as unrelated. Of the 29 subjects with micturition urgency (6.3%), 4 subjects were documented as related to treatment and 25 were documented as unrelated.
Final Effect Findings	Analysis of Stamey Grades (Primary Objective) The primary effectiveness endpoint was the percent of subjects who maintained at least 1-point improvement from baseline, at the following times, based on observed cases in which a 4-day voiding diary was available for evaluation: • 44.8% (171/382) of subjects with voiding diaries at 6- and 12-month follow-up • 46.9% (129/275) of subjects with voiding diaries at 3-year follow-up • 39.3% (42/107) of subjects who had device failure or were discontinued before 3 years A similar trend was observed when considering the “Baseline Observation Carried Forward” (BOCF) imputation, where 37.3%, 43.3% and 26.3% of subjects maintained at least 1-point improvement from baseline among the three disposition groups. Urge Incontinence Medication (UIM) Status Urge Incontinence Medication (UIM) Status went up from 15.2% during pre-treatment to 41.5% at the end of the 3-year follow-up. Incontinence Quality of Life (QoL) Scores The overall QoL scores were much higher for all time points post-baseline: Baseline QoL score was 39.5, while it was 69.6 at 6 months, 70.3 at 12, 70.4 at 18, 71.2 at 24, 73.5 at 30, and 72.7 at 36 months.
Study Strengths & Weaknesses	Strengths: Multi-center study, large sample size, long follow-up up to 3 years, while the premarket study followed subjects through 1 year. Weaknesses: No concomitant comparator, and 27.5% losses to follow-up.
Recommendations for Labeling Changes	The labeling should be updated to include results of the PAS
General
Study Status	Completed
Application Number / Requirement Number	P040021 / PAS001
Date Original Protocol Accepted	08/03/2006
Date Current Protocol Accepted	08/30/2012
Study Name	Biocor & Biocor Supra Valves
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort
Study Population	Subjects requiring an aortic valve replacement were implanted with either the Biocor aortic valve or the Biocor Supra aortic valve
Sample Size	A total of 800 patient- years of follow-up with a minimum of 100 patients followed for at least 5 years, enrolled across 25 sites.
Key Study Endpoints	NYHA, hemolysis, nonstructural dysfunction, paravalvular leak, structural deterioration/failure, bleeding events, embolism, endocarditis, valve thrombosis, reoperation, explant and death (all and valve-related).
Follow-up Visits and Length of Follow-up	>120 patients would be out 4 years or more, -50-70 patients will be out 6 years or more and of these 25-30 would be out 7 years. Annually out to 8 years
Interim or Final Data Summary
Interim Results	At one year the majority of subjects report none or trivial hemodynamic insufficiency. There were no mean gradients greater than 14.9 mmHg reported.
Actual Number of Patients Enrolled	300 (297 subjects met eligibility criteria)
Actual Number of Sites Enrolled	17
Patient Follow-up Rate	at 5 years (114 eligible subjects) - 94.7% (108/114) Overall cumulative follow-up - 959.4 late patient-years (average of 3.2± 1.9 years)
Final Safety Findings	Early adverse event rate (? 30 days post implant) based on 297 subjects: Bleeds 7.4% (7.1% major), Deaths 2.4% (0.3% valve-related), Embolism 0.7%, and 0.3% Paravalvular leak. Linearized late adverse event rate (number per 100 late patient year) based on 959.4 late patient years are as follows: Bleeds 4.48 (4.17 major), Deaths 3.86 (0.52 valve-related), Reoperation 1.36, Endocarditis 1.04, Embolism 0.83 (TIA 0.52, stroke 0.10), Nonstructural dysfunction 0.42, Structural deterioration 0.31, and Thrombosis 0.10. The rates of freedom from event at 5 years post implant by Kaplan Meier analysis are Structural valve deterioration - 97.7% Reoperation- 94.2% Valve-related mortality- 97.5% Bleeding Event ? 76.1% Embolism- 95.2% Endocarditis- 96.1%
Final Effect Findings	The proportion of subjects in NYHA class I or II at 5 years: all Biocor valve positions - 91.5% (97/106), Aortic position - 93.1% (41/44), Aortic Supra position - 90.9% (40/44) and Mitral position- 88.9% (16/18)
Study Strengths & Weaknesses	The study achieved a high follow-up rate of 94.7% at 5-year post implant, and an overall follow-up of 959.4 late patient years greater than the expected 800 late patient years. At least 100 patients were followed out to 5 years as required per protocol. Weaknesses This was a single arm study without a comparator. Thus, the study result was not evaluated by a formal statistical test.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow ?up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P040038 / PAS001
Date Original Protocol Accepted	02/05/2007
Date Current Protocol Accepted	02/05/2007
Study Name	PROTECT Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	There have been no unanticipated adverse device effects or rare events thus far in the trial. The sponsor demonstrates high procedural success rates with very low stroke number and no unanticipated adverse events. (Note: 6.89 % of the pre-market cohort experienced a stroke at 30 days. The data here show no concern about the safety and effectiveness of carotid artery stenting using the Xact stent at 2-years.
Actual Number of Patients Enrolled	A total of 322 patients have been enrolled into the study.
Actual Number of Sites Enrolled	There are a total of 38 study sites that enrolled patients.
Patient Follow-up Rate	Follow-up rate is 75.2% (242/322).
Final Safety Findings	1) A total of six clinically driven target revascularization (TLR) events were reported in five patients. The event free rate is 99.3% at one year, 98.2% at two years, and 98.2% at three years showing a higher (1.0~1.2%) event free percentage compared to the historical control group in the ARCHeR long term follow-up (LTFU) study. 2) Two point five percent (2.5%, 8/322) of patients experienced stoke and zero point nine percent (0.9%, 3/322) of patients experienced MI within 30 days post index procedure. Three point seven percent (3.7%, 12/322) of patients experienced stroke and four point seven percent of patients (4.7%, 15/322) experienced MI between 31 days and 3 years.
Final Effect Findings	The primary endpoint was a composite of DSMI at 30 days, plus ipsilateral stroke between days 31 and 365 and annually thereafter for 3 years. A total of 14 events were reported of which 11 events occurred within 30 days of procedure and 3 events occurred after 30 days during long-term follow-up. The overall composite event free rate is 96.6% at one year, 95.9% at two years, and 95.5% at three years showing a higher event free percentage at one-, two-, and three-year compared to the historical control group in the ARCHeR long term follow-up (LTFU) study.
Study Strengths & Weaknesses	Strength: The study provides long term follow-up of patients at high risk for adverse events from carotid endarterectomy implanted with the Xact stent in the treatment of atherosclerotic carotid artery disease. Weakness: 1) Low percentage of minority group participants restricts the generalization of the results. 2) Only descriptive analysis is available for this study. No statistical tests are being made for the comparison of event free rate between the study cohort and the historical control group in the ARCHeR long term follow-up (LTFU) study.
Recommendations for Labeling Changes	Yes, labeling will be updated with the 3-year data.
General
Study Status	Completed
Application Number / Requirement Number	P030025 / PAS001
Date Original Protocol Accepted	03/04/2004
Date Current Protocol Accepted	03/04/2004
Study Name	ARRIVE I
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ARRIVE Program consists of 2 safety surveillance registries which enrolled 7,601 patients at 103 United States (US) based sites. ARRIVE 1 is a peri-approval registry established to satisfy the Agency's conditions of approval and ARRIVE 2 is a sponsor-initiated postmarket registry. ARRIVE 1 and ARRIVE 2 were designed to study common physician usage patterns and safety outcomes with the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System (hereafter referred to as the TAXUS stent).
Study Population	This device is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries >2. 25 to <4. 0mm in diameter in lesions < 28mm in length. In there overall conclusions the sponsor states that through consecutive enrollment the ARRIVE 1 registry captured a full spectrum of patients and treatments, which were generally more complex than that seen in the controlled TAXUS stent clinical trials. In contrast to the TAXUS IV trial, for example, where the majority of patients received a single stent for a single lesion, approximately 65% of ARRIVE 1 patients were considered higher risk and underwent more complex procedures. These included patients with AMI and treatments for ISR, grafts, chronic total occlusions, bifurcation lesions, and LM disease. The demographic characteristics of the ARRIVE population are typical of most registries.
Sample Size	7,601 patients, 103 sites
Key Study Endpoints	The primary endpoint was the rate of protocol-defined TAXUS stent-related cardiac events at 1 year after the implant procedure as adjudicated by the Clinical Events Committee with 100% of cardiac adverse event data verified against source documents. Despite inclusion of high risk patients and lesions outside the approved indications, the sponsor believes that the observed outcomes from ARRIVE indicate a safety profile consistent with data from randomized controlled trials with the TAXUS stent.
Follow-up Visits and Length of Follow-up	The sponsor compares the patient populations as well as rates of cardiac events for ARRIVE 1 and ARRIVE 2 at 1 and 2 year intervals.
Interim or Final Data Summary
Actual Number of Patients Enrolled	7601 patients
Actual Number of Sites Enrolled	103 sites
Patient Follow-up Rate	93%
Final Safety Findings	The sponsor provides the final report for the ARRIVE 1 registry. The ARRIVE 1 TAXUS stent-related major cardiac event rate of 9.9% for the 2-year follow-up period is consistent with previous TAXUS programs. The 2-year follow-up of 93% was very good. The sponsor did note higher outcome rates in the target vessel revascularization patients, driven mainly by subsequent arget vessel revascularization , and this may reflect the higher-risk nature of this patient group.
Study Strengths & Weaknesses	Strengths: ARRIVE 1 was designed to minimize selection bias by requesting that each participating physician enroll patients in a consecutive manner. Weaknesses: There was no concurrently enrolled control in this study.
Recommendations for Labeling Changes	The label was updated to reflect ARRIVE 1 results.
General
Study Status	Terminated
Application Number / Requirement Number	P040040 / PAS001
Date Original Protocol Accepted	09/07/2007
Date Current Protocol Accepted	09/07/2007
Study Name	5 year long term (IDE)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will provide long-term follow-up of forty-three subjects from the premarket cohort that have been designated as High Risk.
Study Population	This device is indicated for use in patients with a complex VSD of significant size to warrant closure (large volume left to right shunt, pulmonary hypertension and/or clinical symptoms of congestive heart failure) who are considered to be at high risk for standard transatrial or transarterial surgical closure based on anatomical conditions and/or based on overall medical condition.
Sample Size	43 patients, 21 sites
Key Study Endpoints	Safety endpoints include adverse events.
Follow-up Visits and Length of Follow-up	Annual office visits were required out to 5 years.
Interim or Final Data Summary
Interim Results	The study was terminated early due a low follow-up rate
Actual Number of Patients Enrolled	43
Actual Number of Sites Enrolled	38
Patient Follow-up Rate	24%
Final Safety Findings	A total of 35 overall events were reported in 20 of 43 subjects (46.5%). The most frequently reported event was hypotension which was reported in 11.6% of subjects (5 reports in 5 of 43 subjects).
Study Strengths & Weaknesses	Strengths: Lessons learned on requesting for long term follow-up consent at tiem of IDE enrollment Weaknesses: Extremely low follow-up of the cohort.
Recommendations for Labeling Changes	No labeling changes were recommended.
General
Study Status	Completed
Application Number / Requirement Number	P030028 / PAS001
Date Original Protocol Accepted	09/10/2004
Date Current Protocol Accepted	11/10/2011
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Retrospective and Prospective Cohort Study
Study Population	704 subjects will be evaluated, additional subjects are needed to compensate the lost to follow-up patients
Sample Size	704 subjects. Participating sites will be determined by the number of patients available.
Key Study Endpoints	Primary endpoint: Retinal Detachment; Secondly: device related adverse events such as: 1. Retinal detachment 2. Cataract formation 3. Corneal decompensation 4. Chronic uveitis 5. Persistent (>3 months) elevated intraocular pressure requiring medication, and 6. Secondary surgical intervention (e.g., lens exchange and explants).
Follow-up Visits and Length of Follow-up	5 years Annually postoperative
Interim or Final Data Summary
Interim Results	The latest reports prior to study termination show the following advesres events: The highest rates at all visits were for glare/halos (approx 10 15 % at all visits), lens reposition (approx 1 2%), lens dislocation requiring reattachment (approx 0.5 - 1.5%), and "other eye disease" (approx 1 - 2 % at most visits). All other categories generally are reported in <1% of patients.
Actual Number of Patients Enrolled	383 subjects / 706 eyes
Actual Number of Sites Enrolled	A total of 37 doctors participated in the PAS
Patient Follow-up Rate	Most data (362 out of 383 subjects) were collected retrospectively. Among the 383 enrolled subjects, the proportion of patients who had clinical visits at one year, two years, three years, and four years post-operatively were 94.5%, 59.85%, 38.6%, and 32.6% respectively. All subjects (100%) had follow-up data at five years post-operative.
Final Safety Findings	The primary endpoint for this study is the rate of retinal detachment following lens implantation. This PAS study observed four events of retinal detachment out of 706 eyes. The event rate was 0.57%, which is less than the expected rate of retinal detachment of 2.4% based on a previous literature. Secondary Endpoints: Rates of corneal decompensation, chronic uvetitis, and persistent elevated intraocular pressure observed in the PAS were relatively consistent with the controlled clinical trial (PMA P030028). Rates of cataract formation (12.04% vs. 0.25%) and surgical intervention (6.80% vs. 2.37%) were higher in the PAS than in the controlled clinical trial (PMA P030028).
Final Effect Findings	N/A
Study Strengths & Weaknesses	Strengths: The study involved formal hypotheses testing and it met its primary endpoint at 60 months. Weaknesses: A majority of the study population (361 out of 383 subjects) was consented after 5 years post-operation. For these patients, the safety endpoints were collected retrospectively from medical records. Because of the retrospective nature, the study was subject to selection bias, misclassification bias, and confounding. Many patients had missing data at the two, three, and four year data points, and the rates of adverse events including retinal detachment may be underestimated. Moreover, the causes of the adverse events were often difficult to assess.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the 5-year long term results from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P040040 / PAS002
Date Original Protocol Accepted	09/07/2007
Date Current Protocol Accepted	03/18/2016
Study Name	Post Approval Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs, All Pediatric Patients: 0-21 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, non-randomized, multi-site clinical study. The primary safety objective is to evaluate the proportion of subjects experiencing a major (serious) adverse event within 12 months of the procedure. The effectiveness objective is to evaluate the proportion of subjects whom experience technical success, closure success, and acute procedure success.
Study Population	This device is indicated for use in patients with a complex VSD of significant size to warrant closure (large volume left to right shunt, pulmonary hypertension and or clinical symptoms of congestive heart failure) who are considered to be at high risk for standard transatrial or transarterial surgical closure based on anatomical conditions and or based on overall medical condition. Eligible patients can be enrolled retrospectively. The comparison group is the Historical Control.
Sample Size	One hundred (100) subjects will be enrolled at up to 50 U.S. sites and additional sites in Europe and Canada. If subject follow-up drops below 80%, additional subjects will be enrolled to ensure a final population of 80 subjects either meet a defined endpoint or are followed for five years.
Key Study Endpoints	Primary safety endpoint: Any major (serious) adverse event within 12 months of the procedure. A serious adverse event is defined as any untoward medical occurrence that: results in death; is a life-threatening adverse event; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a medically significant event. Primary effectiveness endpoints: Technical Success Acute Procedure Success Shunt Closure Success at 12 months
Follow-up Visits and Length of Follow-up	Each study subject receiving a device will be followed for 60 months post-procedure, unless the device is explanted. Follow-up assessments will be conducted at 30 days, 6 months , one year, and annually until the five-year visit is complete. If the delivery system enters the subject’s body in an attempt to place a device but no device is implanted during the initial procedure, the subject will be discontinued from the study after a 30-day adverse event collection period. If the device explant occurs before the 12-month visit and a SAE is associated with the device explant, the subject will be discontinued on the date the device is explanted. (In this case, the subject is considered a failure for all endpoints except Technical Success.) If a device explant is not associated with a SAE, the subject will continue to be followed through the 12-month visit. The subject will then be discontinued at the 12-month visit. If a subject has a device explanted after the 12-month visit, the subject will be discontinued on the date of the explant procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 92 subjects were enrolled into the study.
Actual Number of Sites Enrolled	28 sites in the United States and Canada.
Patient Follow-up Rate	All subjects have completed the 5-year follow-up visit. The percentage of subjects that covered each follow up visit are presented below: 1 year - 96.4% 2 year - 90.2% 3 year - 86.3% 4 year - 94.7% 5 year - 96.1
Final Safety Findings	The point estimate for the primary safety endpoint was, 52.2% (47/90), with a 97.5% upper confidence bound of 62.9%, which met the performance goal of 63.2%.
Final Effect Findings	The point estimate for Technical Success for prospectively enrolled subjects was 93.8%, with a 97.5% lower confidence bound of 86.0%, which exceeded the performance goal of 64.0%. Acute Procedure Success and Shunt Closure Success estimates were 78% and 94.4%, respectively. The 97.5% lower confidence bound for Acute Procedure Success was 68.1%, surpassing the performance goal of 61.3%. Shunt Closure Success had a 95% lower confidence bound of 87.7%, which exceeded the performance goal of 58.7%.
Study Strengths & Weaknesses	Study strengths: Long-term follow-up post 5-year implant. Weaknesses: This was a single arm non-randomized study.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and efficacy results from this study.
General
Study Status	Completed
Application Number / Requirement Number	P040043 S051/ PAS002
Date Original Protocol Accepted	11/20/2014
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The purpose of this surveillance project, using the Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) registry, will be to obtain data that can be used to refine the selection of and treatment strategy for patients with Type B aortic dissections managed through endovascular graft repair. Data will also be evaluated to identify any signals of device- specific safety or effectiveness issues. This project will be used to establish performance goals for future studies. Specifically, the project will evaluate the short- and long-term clinical performance of endovascular grafts for the treatment of Type B thoracic aortic dissection, following premarket approval.
Study Population	Inclusion criteria: Patients whose index procedure is on or after September 10, 2013 (date of first device approval) for treatment with an endovascular stent-graft used to repair Type B dissections in the descending thoracic aorta may be included in the 1-year or 5-year cohort. Patients diagnosed with classic “double-barrel” Type B thoracic aortic dissection in the descending thoracic aorta and an identifiable intimal flap, with visible contrast enhancement in the false lumen that are treated with endovascular grafts at centers participating in the VQI registry. For the 5-year cohort, subjects will be considered enrolled in the study after arterial cut- down and introduction of the endovascular graft. Data will be collected for unsuccessfully implanted patients through their in-hospital stay. Exclusion criteria: Medial disruption with formation of intramural hematoma/hemorrhage. Plaque rupture leading to aortic ulceration, penetrating aortic atherosclerotic ulcer with surrounding hematoma, usually subadventitial. Iatrogenic and traumatic dissection.
Sample Size	Two surveillance arms: a. Five (5)-year: Data will be captured on a minimum of 194 chronic and 200 acute patients with Device Technical Success, and treated at centers agreeing to participate in the Surveillance Project through the VQI registry. At least 60 patients treated with the final device design of a participating manufacturer will be enrolled in each surveillance arm (i.e., acute and chronic). If the total sample size of 200 or 194 patients has been reached for one arm (acute or chronic respectively) of the 5-year surveillance arm, but an individual device has not met the 60 patients minimum required for that arm, enrollment will only continue for that specific device. b. One (1)-year: All-comers until 200 patients have been surveilled to the VQI registry during the specified enrollment period.
Key Study Endpoints	The sponsor will report any significant observations from the surveillance described below of the use of the TAG device to repair Type B dissections in the descending thoracic aorta. Specifically, this surveillance should monitor: Primary Safety 5year arm: Freedom from dissection related mortality at 5 years 1year arm: Freedom from dissection related mortality through 1 year Primary Effectiveness 5 year arm: Device technical success at the time of the procedure (successful delivery, successful and accurate deployment, and successful withdrawal of the delivery system) Device procedural success at 30 days (device technical success with absence of the following at 30 days: major adverse events [MAE] subset, primary intimal tear false lumen perfusion [PIT FLP], retrograde extension of the dissection, and unintentional dissection septum rupture). 1 year arm: Device technical success at the time of the procedure (successful delivery, successful and accurate deployment, and successful withdrawal of the delivery system) Secondary endpoints 5 year arm: Elements of device technical and procedural success Additional endovascular and surgical dissection related interventions pre procedure, index procedure, and post index procedure (within 30 days, 1 year, yearly) The following endpoints at 30 days, 1 year, and yearly assessments: Dissection treatment success and its individual elements: -Aortic enlargement in the region encompassed by the initial dissection (1 year and yearly only) -Aortic rupture -Dissection-related mortality -Extension of the dissection (proximally or distally) with or without complications -False lumen perfusion (FLP): Primary intimal tear Proximal aorta Distal aorta Proximal branch Distal branch -Fistula formation (e.g., aorto-esophageal, aorto-tracheal) -MAEs subset -Unintentional dissection septum rupture Conservative estimate of dissection?related mortality All-cause mortality False lumen patency Endovascular device penetration of the aortic wall Loss of device integrity 1-year arm:Elements of device technical success The following endpoints at procedure and 1 year assessments: FLP (all elements) Aortic enlargement in the region encompassed by the initial dissection (1 year only) Aortic rupture Dissection-related mortality Conservative estimate of dissection?related mortality All-cause mortality MAEs subset Additional endovascular and surgical dissection-related interventions Major adverse events are pre-specified as: paraplegia*+ paraparesis*+ disabling stroke* non-preexisting and sustained contrast?induced renal failure requiring dialysis not due to malperfusion of the kidneys present at presentation* new ischemia (i.e., not evident at the time of the index procedure) due to branch vessel compromise (malperfusion of organ, upper limb, or lower limb)+ *Subset of MAEs for device procedural success ++Subset of MAEs for dissection treatment success and 1-year arm
Follow-up Visits and Length of Follow-up	5 year cohort: 30 days, 1 year, and annually through 5 years following the index procedure. 1 year cohort: 30 days and 1 year following the index procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	227 subjects enrolled total: 5-year Acute cohort: 85 subjects 5-year Chronic cohort: 65 subjects 1-year Acute cohort: 48 subjects 1-year Chronic cohort: 29 subjects
Actual Number of Sites Enrolled	37
Patient Follow-up Rate	Any data | Imaging data 5 Year Acute Cohort at 1 year: 82.7% (62/75) | 57.3% (43/75) 5 Year Acute Cohort at 5 years*: 81.1% (43/53) | 45.3% (24/53) 5 Year Chronic Cohort at 1 year: 87.1% (54/62) | 75.8% (47/62) 5 Year Chronic Cohort at 5 years**: 78.7% (37/47) | 51.1% (24/47) 1 Year Acute Cohort at 1 year: 82.1% (32/39) | 61.5% (24/39) 1 Year Chronic Cohort at 1 year: 88.9% (24/27) | 70.4% (19/27) *13 subjects in the 5 Year Acute cohort were lost to follow-up at 5 years (2 consecutive visits missed) **13 subjects in the 5 Year Chronic cohort were lost to follow-up at 5 years (2 consecutive visits missed)
Final Safety Findings	N/A - Data for the primary safety endpoints were collected for all study devices combined; device-specific safety data is not available for presentation.
Final Effect Findings	Primary Effectiveness: Device Technical Success during procedure: 5 Year Acute: 98.8% (84/85) 5 Year Chronic: 100% (65/65) 1 Year Acute: 91.7% (44/48) 1 Year Chronic: 100% (29/29) Device Procedural Success at 30 days: 5 Year Acute: 93.4% (71/76) 5 Year Chronic: 91.9% (57/62) Secondary Endpoints: Technical Success Elements (5 Year Acute | 5 Year Chronic) Successful device delivery: 98.8% | 100% Successful and accurate deployment: 98.8% | 100% Successful withdrawal of delivery system: 100% | 100% Procedural Success Elements (5 Year Acute | 5 Year Chronic) Freedom from retrograde extension of dissection: 96.8% | 100% Freedom from unintentional dissection septum rupture: 100% | 100% Freedom from PIT FLP: 96.5% | 88.1% Freedom from the subset of MAE: 98.7% | 100% KM estimate of freedom from dissection-related interventions (5 Year Acute | 5 Year Chronic) Through 1 year: 87.5% (SE=4.2%) | 87.2% (SE=4.8%) Through 5 years: 77.6% (SE=6.2%) | 83.4% (SE=5.8%) Dissection Treatment Success Elements (5 Year Acute | 5 Year Chronic) Freedom from aortic enlargement in the region encompassed by the treated section (range across all timepoints): 57.1-71.4% | 47.8-66.7% Freedom from aortic rupture: 100% | 100% KM estimate of freedom from dissection-related mortality: Through 1 year: 94.1% (SE=2.6%) | 98.5% (SE=1.5%) Through 5 years: 90.0% (SE=3.4%) | 98.5% (SE=1.5%) Freedom from extension of the dissection (range across all timepoints): 88.6-100% | 95-100% KM estimate of freedom from all-cause mortality: Through 1 year: 83.5% (SE=4.0%) | 95.4% (2.6%) Through 5 years: 71% (SE=5%) | 84.1% (SE=4.6%) Complete false lumen thrombosis within the treated segment (range across all timepoints): 68.8-81.8% | 58.6-93.3% Partial false lumen thrombosis within the treated segment (range across all timepoints): 9.1-19% | 5.6-20.7% Loss of device integrity (range across all timepoints): 0-3.7% | 0-4.2% 1 Year Cohort Endpoints (1 Year Acute | 1 Year Chronic) Aortic enlargement in the region encompassed by the initial dissection at 1 year: 21.7% | 15.8% Aortic rupture at discharge: 2.1% | 0% Aortic rupture at 1 year: 0% | 0% KM estimate of freedom from dissection-related mortality through 1 year: 93.7% (SE=3.5%) | 100% KM estimate of freedom from all-cause mortality through 1 year: 83.3% (SE=5.4%) | 89.3% (SE=5.8%) KM estimate of freedom from dissection-related interventions through 1 year: 85.7% (SE=5.4%) | 88.4% (SE=6.4%) MAE subset (1 Year Acute at discharge / at 1 year | 1 Year Chronic at discharge / at 1 year) Paraplegia: 4.2% / 0% | 0% / 0% Paraparesis: 0% / 0% | 3.4% / 0% Stroke or transient ischemic attack: 6.2% / 0% | 0% / 0% Spinal cord deficit: 4.2% / 0% | 6.9% / 0% Lower limb ischemia: 2.1% / 0% | 0% / 0% Mesenteric ischemia: 0% / 0% | 3.4% / 0%
Study Strengths & Weaknesses	Strengths: Study gathers and separately presents results on acute and chronic dissections through five years, represents geographically diverse health centers in the US, includes representation of some patients with connective tissue disorders, and maintains standard definitions and reporting among the manufacturers participating in the registry. The study compares patient baseline characteristics and outcomes between the VQI study sites and the all-comer VQI population. Weaknesses: The follow-up compliance, particularly for imaging data, is very low, which leads to uncertainty in the longer-term outcomes due to a large portion of missing data. Enrollment of subjects in the 5-year cohorts was non-consecutive, which may introduce selection bias. The study sample size is not powered to determine event rates for each device. The patient population treated was heavily represented by male (73.1%) and Caucasian (59.9%) patients, with reasonable representation from female (26.9%) and African American (29.5%) patients. Limited data was available for other races or ethnicities.
Recommendations for Labeling Changes	Labeling changes are recommended to present the long-term outcomes of this device while acknowledging the limitations of this post-market registry.
General
Study Status	Other
Application Number / Requirement Number	P110032 / PAS002
Date Original Protocol Accepted	06/06/2014
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Surveillance of Aorfix patients entered into the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI)
Study Population	Patients implanted with the Aorfix for its intended use
Sample Size	234 prospectively enrolled patients
Key Study Endpoints	Procedural information, including the number of devices used, procedural duration, blood loss, and postoperative leg or bowel ischemia. The surveillance should also monitor aneurysm-related mortality, device migration, fracture in the fixation zone, conversion to open surgery, change in aneurysm size, aneurysm rupture, graft patency, secondary interventions, change in renal function, and endoleaks (including Type)
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Clinically assessed patency at 3 and 4 years was 100% (24/24 and 15/15, respectively) for the main body and limbs. No device migration or fracture was observed. 7 patients demonstrated sac expansion by volume.
Actual Number of Patients Enrolled	42
Actual Number of Sites Enrolled	17
Patient Follow-up Rate	36/36 (100%) clinical follow-up and 11/35 (11%) CT follow-up at 3 years 24/33 (73%) clinical follow-up and 6/33 (18%) CT follow-up at 4 years
Study Strengths & Weaknesses	The device is no longer marketed in the U.S. The study is on hold and there is no continued enrollment. Enrollment is low and CT follow-up is limited, making it difficult to interpret results from minimal data. Patency is appropriate and no device migration or fracture was observed.
General
Study Status	Completed
Application Number / Requirement Number	P030002 S027/ PAS001
Date Original Protocol Accepted	05/20/2013
Date Current Protocol Accepted	02/09/2016
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval safety study is to evaluate the incidence of IOL vaulting (ie, position change such as clinically significant anterior vaulting, clinically significant tilt, and secondary surgical intervention related to such vaulting) of the Trulign Toric IOL following cataract surgery at up to three years post implantation. This is a prospective, multicenter, open-label, single arm, post approval study at a minimum of 30 and up to 50 clinical sites in the US.
Study Population	All subjects who meet eligibility criteria will be consecutively offered enrollment into the trial until a site meets the maximum number, or the study has fulfilled all enrollment requirements. If both eyes of a subject are eligible for enrollment, the first treated eye should be chosen at the discretion of the surgeon after consultation with the subject. All eyes will be treated in accordance with the Trulign Toric IOL labeled indications for use and the Physician Labeling Directions for Use (DFU).
Sample Size	The study will enroll up to approximately 686 eyes: A final sample size of 500 eyes is required. Given losses of 10% per year, after three years the remaining proportion would then be 0.93 or 0.729. Given these losses, if 500/0.729 = 686 eyes are enrolled then approximately 500 eyes will be available after three years.
Key Study Endpoints	The study endpoint is the incidence of clinically significant IOL vaulting (ie, position change such as clinically significant anterior vaulting, clinically significant tilt, and secondary surgical intervention related to such vaulting) up to three years post implant.
Follow-up Visits and Length of Follow-up	Study participants will be followed for 3 years postoperatively.
Interim or Final Data Summary
Actual Number of Patients Enrolled	442 (698 eyes)
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	Study schedule of subject follow-up: Preoperative Visit – Day -90 to 0 Operative Visit – Day 0 Postoperative Visit 1 – Day 1 - 2 Postoperative Visit 2 – Day 7 - 14 Postoperative Visit 3 – Day 30 - 60 Postoperative Visit 4 – Day 120 - 180 Postoperative Visit 5 – Day 330 - 420 Postoperative Visit 6 – Day 630 - 780 Postoperative Visit 7 – Day 990 – 1,140
Final Safety Findings	Two of 686 enrolled eyes had clinically significant IOL vault, for an incidence of 0.29% three years after implantation. In addition, 66 eyes underwent prophylactic neodymium: yttrium-aluminum-garnet (Nd:YAG) procedures to prevent capsular contraction syndrome or vaulting problems. No other safety measures were evaluated in this study.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The primary study endpoint was the incidence of clinically significant IOL vaulting (i.e., position change such as clinically significant anterior vaulting, clinically significant tilt, and secondary surgical intervention related to such vaulting) up to 3 years post implant. Strengths: The study addressed reports in the literature that suggested vault was a significant problem with this type of device, but rates were not well understood. This study provides a reasonable estimation of vault rate. Potential Weaknesses: The investigators did not always provide detailed reports of all suspected cases of vault, which may have led to underreporting.
Recommendations for Labeling Changes	Update the label to describe findings of the post-approval study and risk of vault
General
Study Status	Completed
Application Number / Requirement Number	P040046 / PAS002
Date Original Protocol Accepted	02/20/2013
Date Current Protocol Accepted
Study Name	Continued Access Study (Natrelle 410 CAS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multicenter, prospective, nonrandomized study to evaluate the safety and effectiveness of NATRELLE® 410 Highly Cohesive Anatomically Shaped Silicone-Filled Full and Moderate Height/Projection Breast Implants in women who have undergone breast implant augmentation, reconstruction, or revision surgery.
Study Population	Subjects signed informed consent documents and underwent implantation and some follow-up as part of the 410 Continued Access (CA) Clinical Study or 410 Continued Access Reconstruction/Revision Expansion (CARE) Clinical Study. Subjects who have not yet completed the 5-year timepoint and who are not lost to follow-up will be re-consented to participate in the 410CA-002 Clinical Study.
Sample Size	The sample size of approximately 3,500 subjects across approximately 110 sites is based on the number of subjects previously enrolled in the 410 CA Clinical Study or 410 CARE Clinical Study who were implanted with NATRELLE® 410 approved implant styles and who have not yet completed the 5-year timepoint nor have been lost to follow-up.
Key Study Endpoints	At all post-implantation visits, the Investigator will evaluate the occurrence of local complications that occurred between office visits and inquire whether the subject has received a magnetic resonance imaging (MRI) examination since the last scheduled visit to screen for implant rupture (including the dates of the MRIs), the subject will complete the Activities and Lifestyle questionnaire, the subject and Investigator will assess satisfaction with the implants, and subjects who have undergone breast augmentation or reconstruction surgery will complete the Quality of Life questionnaire. Breast photographs will be taken at Year 1. Additionally, a subset of subjects who were enrolled in the serial MRI cohort to evaluate the occurrence of asymptomatic rupture will undergo the final MRI at 5 years post-implantation. Subjects enrolled in the MRI cohort who have both original study implants removed will not attend any subsequent MRI. Complications, reoperations, explantations, cancer, connective tissue disease (CTD), and reproduction and lactation outcomes will be captured at each study visit, and at any time during the study, as reported.
Follow-up Visits and Length of Follow-up	Subjects will continue to be evaluated at their remaining follow-up visits 1, 2, and 5 years after primary implant surgery.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 7274 subjects were enrolled who reached the 5-year follow-up window: 3267 Augmentation, 1390 Revision-Augmentation, 1753 Reconstruction, and 864 Revision-Reconstruction. The serial MRI cohort consisted of 158 subjects: 76 Revision-Augmentation, 37 Reconstruction, and 45 Revision-Reconstruction. There were no Augmentation subjects in the serial MRI cohort.
Actual Number of Sites Enrolled	52
Patient Follow-up Rate	At year 5, the follow-up rates by cohort were: 62.3% Augmentation, 54.7% Revision-Augmentation, 48.3% Reconstruction, and 54.7% Revision-Reconstruction. Year 5 compliance for the MRI cohort was: 55.4% Revision-Augmentation, 55.9% Reconstruction, and 63.6% Revision-Reconstruction.
Final Safety Findings	Following are the observed Year 5 Kaplan-Meier rates with 95% confidence intervals for key complications at the subject level by cohort: Augmentation ¿ Reoperation 13.28% (12.06, 14.62); Implant removal with replacement 5.34% (4.55, 6.27); Implant removal without replacement 1.28% (0.93, 1.78); Implant rupture MRI cohort N/A; Implant rupture Non-MRI cohort 0.91% (0.59, 1.38); Capsular contracture, Baker Grade III/IV 3.88% (3.20, 4.70); Revision-Augmentation ¿ Reoperation 29.29% (26.69, 32.09); Implant removal with replacement 16.78% (14.63, 19.21); Implant removal without replacement 4.42% (3.34, 5.84); Implant rupture MRI cohort 4.75% (1.56, 14.05); Implant rupture Non-MRI cohort 1.73% (0.99, 2.99); Capsular contracture, Baker Grade III/IV 8.70% (7.09, 10.65); Reconstruction ¿ Reoperation 33.91% (31.38, 36.58); Implant removal with replacement 13.85% (12.04, 15.92); Implant removal without replacement 5.35% (4.24, 6.75); Implant rupture MRI cohort 3.45% (0.49, 22.05); Implant rupture Non-MRI cohort 1.19% (0.66, 2.14); Capsular contracture, Baker Grade III/IV 7.87% (6.42, 9.64); Revision-Reconstruction ¿ Reoperation 33.79% (30.25, 37.62); Implant removal with replacement 17.16% (14.37, 20.42); Implant removal without replacement 6.49% (4.78, 8.78); Implant rupture MRI cohort 0% (N/A); Implant rupture Non-MRI cohort 2.53% (1.45, 4.39); Capsular contracture, Baker Grade III/IV 8.89% (6.83, 11.54).
Final Effect Findings	n/a
Study Strengths & Weaknesses	The Continued Access Study (CAS) was initiated to allow for continued physician experience with the device before device approval and to collect additional safety data. The post-approval Continued Access Study was designed to evaluate 5-year device safety performance in subjects who underwent implantation and some follow-up as part of the 410 Continued Access (CA) Clinical Study or 410 Continued Access Reconstruction/Revision Expansion (CARE) Clinical Study. The overall patient follow-up rate was 52.8% at Year 5. This follow-up rate limits the interpretation of the available safety results.
Recommendations for Labeling Changes	No labeling change is recommended at this time. The labeling contains 3, 5, 7 and 10 year data from the extended pivotal cohort study (Core Post-Approval Study).
General
Study Status	Ongoing
Application Number / Requirement Number	P040046 / PAS003
Date Original Protocol Accepted	02/20/2013
Date Current Protocol Accepted	07/26/2021
Study Name	Natrelle and 410 Combined Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). This Combined Cohort study was designed as part of the re-design of the LARGE PAS. This is a smaller cohort study to primarily address safety outcomes (i.e., including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problems, effects on mammography, effects on patient satisfaction with breasts and psychosocial well-being, and silicone subject compliance with magnetic resonance imaging (MRI) recommendations. This re-structured PAS, once completed as designed, would satisfy the post-approval requirements for both the Natrelle® (P020056) and Natrelle® 410 (P040046) silicone breast implants. The Round Responsive and Style 410 implants will be compared with saline implants or national norms. In addition, information gained from the NBIR will help strengthen the general understanding of implantation rates and certain risks associated with breast implants.
Study Population	Study Population Subjects who have received Allergan silicone gel-filled breast implants or saline implants will be eligible to participate in the study. INCLUSION: Subjects must meet all of the following inclusion criteria at the time of surgery: 1) Female, age 18 years or older (age 22 or older for breast augmentation subjects) 2) Exhibit fluency and literacy in English or Spanish EXCLUSION: Subjects who meet any of the following criteria are not eligible for enrollment in the study: 1) Are transgender 2) If a saline implant subject, have a current or past unilateral or bilateral silicone gel-filled breast implant 3) Investigator decision that subject is not a suitable candidate for a long-term observational study CONTINUATION (BIFS ARM ONLY): Subjects are eligible to continue in the BIFS arm if they meet all of the following criteria: 1) Have complete baseline and years 1, 2, 3, and 4 follow-up questionnaires available (including the Satisfaction with Breasts and Psychosocial Well-Being modules of the BREAST-Q). Saline reconstruction and revision reconstruction do not need to have complete BREAST-Q questionnaires at baseline. 2) Meet all enrollment criteria, specifically the minimum age requirements for silicone implants (18 or older for reconstruction subjects and 22 or older for augmentation subjects), and were free of all target diseases at baseline 3) Are enrolled at a site that is selected in the cluster sampling to continue in the BIFS arm under Amendment 5.
Sample Size	2,000 subjects with Allergan Round Responsive silicone gel filled breast implants and 245 subjects with saline implants selected from the Breast Implant Follow-up Study (BIFS) cohorts, and 530 newly enrolled Style 410 highly cohesive silicone breast implants. The BIFS continuation arm will be targeted to include 20 saline revision augmentation, 11 saline reconstruction, and 11 saline revision-reconstruction subjects. If the cluster sampling results in insufficient subjects from these groups, additional subjects (who would otherwise not qualify for the BIFS arm) will be selected from continuing sites at random to meet the targets.
Key Study Endpoints	Adverse events (including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problem, effects on mammography, effects on satisfaction with breasts and psychosocial well�]being, and silicone subject compliance with MRI recommendations.
Follow-up Visits and Length of Follow-up	10 years. Subject questionnaire will be collected annually. Office visits at Year 1, 4 and 10 for participants enrolled in the device group.
General
Study Status	Terminated
Application Number / Requirement Number	P040046 / PAS004
Date Original Protocol Accepted	08/03/2012
Date Current Protocol Accepted
Study Name	Case Control Studies
General Study Protocol Parameters
Study Design	Case Control Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put on-hold while the systematic literature review was conducted. The systematic literature review showed insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value. The FDA continues to monitor for these rare adverse events using other postmarket surveillance tools and real-world data (e.g. MDRs, NBIR, PROFILE).
Study Population	Women in the UK with the studied rare diseases (i.e., rare CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma) as cases and women in the UK without any of the 5 studied rare diseases as controls.
Sample Size	For each of the 5 case-control studies, 1,500 cases of women diagnosed with each specific studied rare disease will be identified from the GPRD. A total of 4000 women identified from the GPRD without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
Key Study Endpoints	Patient data will be collected from three sources: the GPRD database, directly from the patient via a structured questionnaire, and if the patient had silicone breast implants, directly from the surgeon who performed the implantation procedure. The study data will be entered into an electronic data capture system (EDC) using an electronic case report form (eCRF). Available data will be abstracted from the GPRD database and entered into the eCRF. The de-identified completed patient questionnaires will also be entered into the EDC. For patients who had breast implants, the surgeon who performed the implantation procedure will be contacted directly to obtain the data on the manufacturer and style of silicone breast implant. Information obtained from both the cases and controls will include the following: ¿ Data collected from the GPRD database will include date of birth, date at diagnosis (all cases), date of identification from database (controls), socioeconomic status (census area-level based on post code), history of breast cancer, history of oral contraceptive use, tobacco use history, body mass index (BMI), number of live births, age at first pregnancy, age at first live birth ¿ Data collected from the patient will include ethnicity, for cases family history of the studied rare disease (cases), for controls family history of any of the five studied rare diseases, breast implant history (i.e., indication, type, shape, date of implantation, contact information of the surgeon), smoking history, alcohol use history, for controls sexual history ¿ Data collected from the surgeon (if patient had implants) will include date of implant, manufacturer of Implant, style of Implant Cases will be identified among the diagnoses starting 2004 to allow about 10 years of exposure to the silicone breast implants from the GPRD database.
Follow-up Visits and Length of Follow-up	There is no prospective follow-up for case-control studies
General
Study Status	Completed
Application Number / Requirement Number	P010012 S230/ PAS001
Date Original Protocol Accepted	09/16/2010
Date Current Protocol Accepted	01/18/2013
Study Name	MADIT-CRT ACC NCDR
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study
Study Population	Patients in the NCDR ICD Registry will be identified, who, at the time of device implant were diagnosed with one of the following:  NYHA functional class II with non-ischemic or ischemic cardiomyopathy OR  who are NYHA functional class I with ischemic cardiomyopathy AND  Have left ventricular dysfunction (EF ≤30%), prolonged intraventricular conduction (QRS ≥ 130 ms), and with a LBBB These Registry patients will be further split into the following patient cohorts for the purposes of analysis. CRT-D group: Patients implanted with a Boston Scientific CRT-D device after the MADIT-CRT indication approval date. ICD group: Patients implanted with a Boston Scientific ICD; either, (a) after the MADIT-CRT indication approval date, or, (b) before the MADIT CRT indication approval date.
Sample Size	A minimum of 1300 patients who meet the specified criteria; have been implanted with a Boston Scientific CRT-D device followed for a minimum of 5 years. A minimum of 1300 patients who meet the specified criteria; have been implanted with a Boston Scientific ICD device followed for a minimum of 5 years. A minimum of 500 Class I patients who meet the specified criteria, including a minimum of 225 who have been implanted with a with a Boston Scientific CRT-D device, have been identified and followed for a minimum of 5 years.
Key Study Endpoints	The primary endpoint for the study is to evaluate the /real-world/ effect of CRT-D, compared to ICD, on the time-to-all-cause mortality over a period of 5 years.
Follow-up Visits and Length of Follow-up	5-years post-implant. Progress reports will be generated every 12 months and will include: demographics, mortality, and procedural related adverse events.
Interim or Final Data Summary
Actual Number of Patients Enrolled	ICD Historical Cohort: 998 ICD Concurrent Cohort: 1359 CRT-D Cohort: 7617 (207 NYHA functional Class I)
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	Mean follow-up time for each cohort: 95 months for ICD historical cohort 54 months for ICD concurrent cohort 46 months for CRT-D cohort
Final Safety Findings	Primary Objective Outcome: Rate of 60-month mortality: ICD historical cohort = 31.6% ICD concurrent cohort = 26.9% CRT-D cohort = 15.2% The benefit of CRT-D is consistently observed in all three pre-specified subgroups (further stratified into seven subgroups). A statistically significant benefit of CRT-D vs. ICD was observed in six of seven subgroups: NYHA Class and ischemic status at implant (Ischemic Class I, Ischemic Class II, Non-Ischemic Class II), Gender (Female, Male), the presence (or absence) of a HF hospitalization prior to device implant (prior HF diagnosis, no prior HF diagnosis) The difference in mortality between CRT-D and ICD patients in the NYHA Class I Ischemic subgroup failed to achieve statistical significance (p = 0.285) due to smaller sample and effect sizes than those observed in the NYHA Class II patients. However, the effect size observed in Class I patients does trend toward significance.
Final Effect Findings	n/a
Study Strengths & Weaknesses	Strengths: MADIT-CRT PAS 1 is a real-world evidence study that showed long-term mortality benefits of CRT-D in a MADIT-CRT (LBBB) patient population compared to ICD. Weaknesses: Data collection was slow as the study relied on the NCDR ICD registry and National Death Index for data collection. The use of the NCDR ICD registry was originally mandated by CMS, but no longer required as of 2018.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P040050 / PAS001
Date Original Protocol Accepted	10/30/2006
Date Current Protocol Accepted	10/30/2006
Study Name	5 year registry - ROSE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Real-Time Observation of Safety and Effectiveness (ROSE) study is a non-randomized, prospective, multi-center, registry of Macroplastique safety and effectiveness.
Study Population	The study population consists of women at least 18 years of age diagnosed with stress urinary incontinence primarily due to intrinsic sphincter deficiency who are candidates for treatment with the device according to the approved labeling,. This device is indicated for transurethral injection in the treatment of adult women diagnosed with stress urinary incontinence primarily due to intrinsic sphincter deficiency.
Sample Size	275 enrolled patients and maximum of 20 sites
Key Study Endpoints	The primary endpoints are additional or alternative surgical treatment over a 5-year period and incidence of genitourinary and treatment-related adverse events. Other endpoints collected are: change in Incontinence Quality of Life questionnaire, change in Stamey grade, and change in number of incontinence episodes per day from baseline to 5 years as well as subject perception of treatment success.
Follow-up Visits and Length of Follow-up	Subjects are followed for 5 years following initial treatment with Macroplastique or until alternative treatment for stress urinary incontinence.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Two hundred and seventy-six (276)
Actual Number of Sites Enrolled	Twenty (20)
Patient Follow-up Rate	86% (148/172). This rate of follow-up is arrived at by excluding 93 patients who discontinued, 11 patients who died, 20 patients who were lost to follow-up and 4 patients who missed the 5 year follow-up visit.
Final Safety Findings	The primary safety objective was to describe the incidence of genitourinary and treatment related adverse events, including transient symptoms associated with the injection procedure. No formal hypothesis testing was conducted. A total of 343 genitourinary adverse events (AEs) occurred in 276 study subjects. The highest rate of reported non-serious AEs is Urinary Tract Infection (UTI) at 59.8%. The highest rate of related non-serious AEs is Urinary Retention occurring in 6.2% subjects and is a known side effect of the treatment. Other related reported treatment events are Post Procedure Catheterization (2.9%), Hematuria (2.2%). Incomplete Bladder Emptying (1.8%), Pain at Implantation Site (1.4%), and Hesitance (1.1%). The adverse event of Erosion has been reported five (5) times in the study,, three (3) urethral (1.09%) and one (1) vaginal (0.36%) were deemed related to the device and one (1) urethral (0.36%) was assessed to be unrelated. The event of worsening of urgency/frequency symptoms was noted 3 times of which one was assessed to be related to the procedure. Additionally, device protrusion, device migration, vaginal mass, and an incidence of a benign neoplasm were observed which were reported as “other” urogenital adverse events. The protocol specified that subjects exiting the study prior to five (5) years of follow-up (e.g., lost to follow-up, withdrawals other than to seek other treatment, death) with no additional treatment reported during follow-up will be censored at the time of study exit or at the last documented follow-up visit where the endpoint is known. Therefore, the reported rates only reflect best case imputation and do not reflect the observed and worst case imputation.
Final Effect Findings	The primary effectiveness objective was to describe the incidence of additional or alternative treatment for stress urinary incontinence (SUI) primarily due to intrinsic sphincteric deficiency (ISD) following up to two Macroplastique treatments in order to evaluate the durability of the treatment effect over a 5-year period. No formal hypothesis testing was conducted. A Kaplan Meier analyses showed the percentage of patients seeking alternate treatment decreased during the 5-years at 12-month interval measuring points. The rates were 7% in the first year (93% event free),6.5% in the second (86.4% event free), 4.2% in third 82.2% event free), 3.2% in the fourth (79.0% event free), and 2.5% in the fifth year after initial treatment (76.5% event free). The protocol specified that subjects exiting the study prior to five (5) years of follow-up (e.g., lost to follow-up, withdrawals other than to seek other treatment, death) with no additional treatment reported during follow-up will be censored at the time of study exit or at the last documented follow-up visit where the endpoint is known. Therefore, the reported rates above show the percentage of patients seeking alternate treatment where subjects are censored and excluded from the denominators in the calculation. A total of 143 subjects were censored at 60 months. The observation proportion of patients seeking alternative treatments, based on the available data at 60 months, was 60/207 (29.0%) and the estimated proportion based on the ITT population was 129/276 (46.7%) when subjects with missing data were treated as failures, constituting a worst-case scenario. The combined total volume of Macroplastique injected from the first and second treatment (if needed) is correlated with failure, with higher volumes more likely to experience failure.
Study Strengths & Weaknesses	Some study limitations include the single arm design of the study, no pre-specified formal hypothesis, no clearly defined method of outcome evaluation, no adjudication of adverse events, and too many subjects with missing data. The high rate of follow up is because of excluding 93 patients who discontinued, 11 patients who died, 20 patients who were lost to follow-up and 4 patients who missed the 5 year follow-up visit. This type of censoring, i.e., patients who counted as failures vs. patients who discontinued for reasons other than seeking alternative treatments, was stated in the protocol. Additionally, due to the missing numbers at follow up, some emerging AEs like urethral/vaginal erosion were not adequately evaluated.
Recommendations for Labeling Changes	Recommend update to the labeling to reflect safety and effectiveness results from the study. Specifically, the labeling should address the following: 1. The revised labeling should adequately reflect the observed adverse events (AEs) based on the safety findings of the study including, but not limited to, urinary tract infection (UTI), urinary retention, device protrusion, device migration, vaginal mass, and benign neoplasm. 2. Based on the final results of the PAS, there is a risk of vaginal/urethral erosion with use of the device, which is not adequately reflected in the labeling. The revised labeling should adequately reflect the risk of erosion, including a reporting of the erosion rate, the required treatment (e.g., methods of surgical resection) that was observed in the study, and information regarding potential symptoms related to possible erosion and surgical resection instructions. 3. The revised labeling should include the primary effectiveness endpoint results based on the observation proportion based on the available data at 60 months and the estimated proportion based on the intent-to-treat (ITT) population to adequately report the durability and long term effectiveness of the subject device.
General
Study Status	Completed
Application Number / Requirement Number	P040012 S034/ PAS001
Date Original Protocol Accepted	05/06/2011
Date Current Protocol Accepted	03/04/2016
Study Name	CANOPY Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, multi-center, non-randomized, single arm.
Study Population	Patients with neurological symptoms and > 70% stenosis of the common or internal carotid artery by ultrasound or > 50% stenosis of the common or internal carotid artery by angiogram OR patients without neurological symptoms and > 70% stenosis of the common or internal carotid artery by ultrasound or > 60% stenosis of the common or internal carotid artery by angiogram.
Sample Size	The trial will enroll a minimum of 1,200 subjects (336 symptomatic and 864 asymptomatic subjects) at up to 350 sites in the United Sates. The overall trial sample size was determined based on the secondary endpoint of peri- procedural DS by symptomatic status and its comparison with the respective PG (Symptomatic subjects: n= 336, accounting for 22 subject lost to follow-up; Asymptomatic subjects: n= 864 subjects, accounting for 58 subject lost to follow-up).
Key Study Endpoints	Primary Endpoint: A composite rate of peri-procedural (within 30 days of the procedure) DS, plus ipsilateral stroke between day 31 and 1 year (365 days) Secondary Endpoints 1. Composite of peri-procedural DS by symptomatic status 2. Ipsilateral stroke at 2 years 3. Composite of peri-procedural DS plus ipsilateral stroke at 1 and 2 years for octogenarians 4. Annual rate of clinically driven target lesion revascularization (TLR) through 2 years
Follow-up Visits and Length of Follow-up	2 years Follow-up for all subjects will be performed at 24 hours post-procedure, 30 days, 1 year, and annually for a total of 2 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1203 Full Analysis Set population: 1196 subjects
Actual Number of Sites Enrolled	97
Patient Follow-up Rate	85.9 % at 2 years (based on the Full Analysis Set population)
Final Safety Findings	Primary Endpoint The study met the 12 month primary endpoint. The primary endpoint was the composite of death and Stroke (DS) within 30 days after the index procedure plus Ipsilateral Stroke rate between 31 days and 365 days. The primary endpoint rate for the overall patient population by Kaplan Meier (KM) analysis was 4.2% with upper one-sided 95% confidence interval (CI) of 5.15% which is less than the 8.4% performance goal (PG, p< 0.0001). The freedom from death and stroke within 30 days and ipsilateral stroke between 31 days through 3 years in the overall population was 96.8% at 30 days, and 95.8%, 95.4% and 95.2% at 1, 2 and 3 years respectively. Secondary Endpoints Ipsilateral Stroke Rates The freedom from ipsilateral stroke through 3 years by KM analysis was 97.5% at 30 days, 96.5% at 1 year, 96.1% at 2 years and 95.8% at 3 years. Majority of the ipsilateral strokes (63.8%, 30/47) occurred during the first 30 days and only 6 (12.8%) strokes occurred after 1 year. Composite of Death and Stroke by Symptomatic Status The composite of death and stroke rate at 30 days in the symptomatic group was 5.5% with upper one- sided 95% CI of 7.5% which is significantly less the 10.3% PG (p<0.0001). For the Asymptomatic group DS at 30 days was 2.3% with upper one-sided 95% CI of 3.19 % which is significantly less the 5.2 % PG (p<0.0001). The freedom from death and stroke at 30 days and ipsilateral stroke at 1, 2 and 3 years was 92.9%, 92.6% and 91.9% respectively in the Symptomatic group and 96.9%, 96.5% and 96.4% respectively in the Asymptomatic group [Log Rank test p= 0.0020]. Composite of Death and Stroke by age The death and stroke rate within 30 days for octogenarians (subjects = 80 years) was 3.4% and non- octogenarians (subjects < 80 years) was 3.2% [95% CI for the rate difference of -0.23 was -5.40% to 2.21%]. The freedom from death and stroke within 30 days plus ipsilateral stroke was 93.8% at 1, 2, and 3 years in octogenarians and 96.0%, 95.6%, and 95.3% at 1, 2 and 3 years respectively in non- octogenarian subjects [Log rank test, p =0.4486]. Clinically-driven target lesion revascularization (CD-TLR) The freedom from clinically driven target lesion revascularization was 99.9% at 30 days, 99.3% at 1 year, 98.1% at 2 years and 97.5% at 3 years.
Study Strengths & Weaknesses	The study met the primary endpoint and provided 2- year long term as well as available 3-year data. The 2 year follow-up compliance rate was adequate. This was a single-arm non randomized study that may not have the advantages of a randomized control trial. There were several protocol deviations reported and corrective actions were implemented where necessary.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow–up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P020056 / PAS006
Date Original Protocol Accepted	10/17/2006
Date Current Protocol Accepted	10/17/2006
Study Name	Informed Decision Process
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Interim Results	There is no interim device safety Information from this study
Actual Number of Patients Enrolled	The Informed Decision Process consisted of yearly surveys. Each year a different sample was selected for the survey. These are the results for 2011 annual report. 84 surveys were returned. Per the condition of approval, the sponsor did administer the survey to a random selection of 50 physicians.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	The majority (85.7%) of all respondents are satisfied with the Patient Planner, with 55.9% rating it Very Good and 29.8% rating it Good.
Study Strengths & Weaknesses	The sample of physicians was chosen randomly, which is a strength of the study. However, the observational, cross-sectional design of the study does not allow for any hypothesis testing. The results are descriptional only.
Recommendations for Labeling Changes	Allergan is not currently proposing labeling changes based upon the survey results.
General
Study Status	Completed
Application Number / Requirement Number	P050006 S060/ PAS001
Date Original Protocol Accepted	03/30/2018
Date Current Protocol Accepted
Study Name	Continued f/u of IDE Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The REDUCE study is a prospective, randomized (2:1), open-label, multi-center clinical study. The current post approval study is a continued follow-up of the premarket cohorts out to 5 years.
Study Population	Enrollment in the REDUCE study was limited to patients who met the following key inclusion criteria: Patient greater than or equal to 18 years and <60 years of age Cryptogenic, ischemic stroke of presumed embolic etiology, verified by a neurologist within 180 days prior to randomization, meeting either criteria: Ischemic stroke clinical symptoms persisting =24 hours; or Clinical symptoms persisting <24 hours and MRI evidence of infarction. For MRI-incompatible patients (i.e., patients that are claustrophobic and/or have implants that are contraindicated for MR), CT scan accepted PFO, confirmed by TEE with bubble study demonstrating spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver Absence of an identifiable source of thromboembolism in the systemic arterial circulation. Vascular imaging that rules out other potential sources of cerebral thromboembolism (e.g., dissection of the aorta or neck vessels, carotid stenosis >50% and/or presence of ulcerated plaques, or intracranial stenosis >50%) No evidence of hypercoagulable state, which requires anticoagulation therapy, based on the evaluation of, at a minimum: Platelet count, Prothrombin Time (PT) or INR, aPTT, and antiphospholipid antibodies. A history of thromboembolic events in first degree family members obtained for all patients. For patients who had a first-degree family member with such an event prior to age 55, or whose family history is unknown, the following additional tests were required and must be interpreted as normal: Factor V Leiden mutation, Prothrombin Gene G20210A mutation, protein C, protein S, and Antithrombin III. Testing for prothrombotic disorders may be performed at the discretion of the treating physicians but was not required. Patients were randomized 2:1 to the test or the control group. Device group subjects were treated with antiplatelet medical management and PFO closure with the GORE® CARDIOFORM Septal Occluder or GORE® HELEX® Septal Occluder (prior device generation approved under P050006). Control group subjects were treated with antiplatelet medical management alone. Subjects at each site were treated with the same antiplatelet therapy regardless of study arm. Investigators chose one of the following options: aspirin alone (75-325 mg once daily), combination aspirin (50-100 mg) and dipyridamole (225-400 mg), or clopidogrel (75 mg once daily). Other combinations or the use of anticoagulants was not permitted.
Sample Size	In the PMA study, 664 patients enrolled. There were 441 subjects randomized to the test group and 223 subjects randomized to the control group. The current post approval study is a continued follow-up of the premarket cohorts out to 5 years.
Key Study Endpoints	Effectiveness Endpoints With regards to effectiveness, there were two co-primary endpoints for the study. The first was freedom from recurrent clinical ischemic stroke through at least 24 months. A recurrent ischemic stroke event was defined as the first occurrence of one of the following: • Clinical finding of ischemic stroke that may be associated with MRI evidence of a new relevant brain infarction. An ischemic stroke was defined as a neurological deficit, presumed due to ischemia, persisting longer than 24 hours or until death. • Transient neurological deficit, presumed due to ischemia, persisting less than 24 hours that also had MRI evidence of a new relevant brain infarction. The second co-primary endpoint was the incidence of subjects with new brain infarction or clinical findings of ischemic stroke from screening through 24 months or last follow-up visit, whichever occurred first. New brain infarction was defined as the composite of clinical ischemic stroke (defined above) or radiographically-detected but clinically covert brain infarct. Any subject with at least one new T2 hyperintense MRI lesion with diameter = 3 mm between the screening MRI and the 24-month MRI, or clinical findings of ischemic stroke through 24 months, and confirmed by the blinded MRI Core Lab or CEC, was classified as having a new brain infarction. Secondary effectiveness endpoints consisted of an assessment of PFO closure in the device group subjects by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). With regards to safety, endpoints included the proportion of subjects who experienced adverse events (AEs) that are determined to be related to device, procedure, and/or antiplatelet medical management. The safety assessment included specific adverse events and groups of adverse events such as all-cause adverse events, device-related events, procedure-related events, antiplatelet medical therapy-related events, and any serious adverse events.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	664 subjects were enrolled in this study at investigational sites in the United States, Canada and Europe with no persite subject limit. 223 subjects were randomized to the Control Arm and 441 subjects were randomized to the Test Arm. 331 subjects were enrolled at US sites with 216 randomized to the Test Arm and 115 randomized to the Control Arm.
Actual Number of Sites Enrolled	A total of 63 investigational sites in the US, Canada and Europe enrolled subjects with 44 sites in just the US.
Patient Follow-up Rate	87.3% (385/441) of subjects in the Test Arm completed the 5 year follow up visit. 78.9% (176/223) of subjects in the Control Arm completed the 5 year follow up visit.
Final Safety Findings	The safety endpoint included the proportion of subjects who experienced adverse events (AEs) that are determined to be related to device, procedure, and/or antiplatelet medical management. The safety assessment included specific adverse events and groups of adverse events such as all-cause adverse events, device-related events, procedure-related events, antiplatelet medical therapy-related events, and any serious adverse events. Overall, 28.6% (126/441) of subjects in the Test Arm and 30.9% (69/223) of subjects in the Control Arm had one or more serious adverse events.
Final Effect Findings	There were two co-primary endpoints for the study. The first was freedom from recurrent clinical ischemic stroke through at least 24 months. A recurrent ischemic stroke event was defined as the first occurrence of one of the following: • Clinical finding of ischemic stroke that may be associated with MRI evidence of a new relevant brain infarction. An ischemic stroke was defined as a neurological deficit, presumed due to ischemia, persisting longer than 24 hours or until death. • Transient neurological deficit, presumed due to ischemia, persisting less than 24 hours that also had MRI evidence of a new relevant brain infarction. Freedom from recurrent ischemic stroke or imaging confirmed TIA through 24 months was observed in 98.8% of the Test Arm subjects and 95.2% of the Control Arm subjects. At 60 months post-procedure, freedom from recurrent strokes was observed in 98.1% of the Rest Arm subjects and 94.1% of the Control Arm subjects. The second co-primary endpoint was the incidence of subjects with new brain infarction or clinical findings of ischemic stroke from screening through 24 months or last follow-up visit, whichever occurred first. New brain infarction was defined as the composite of clinical ischemic stroke (defined above) or radiographically-detected but clinically covert brain infarct. Any subject with at least one new T2 hyperintense MRI lesion with diameter = 3 mm between the screening MRI and the 24-month MRI, or clinical findings of ischemic stroke through 24 months, and confirmed by the blinded MRI Core Lab or CEC, was classified as having a new brain infarction. Composite new brain infarction occurred in 23 subjects (6.0%) in the Test Arm and 20 subjects (11.3%) in the Control Arm at 2 years.
Study Strengths & Weaknesses	A strength of the study was that it provided results on the long-term (5 years) safety and efficacy of the device. A weakness of study was that there was no pre-specified, quantitative safety endpoint.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and efficacy results from the Post Approval Study cohort.
General
Study Status	Ongoing
Application Number / Requirement Number	P050006 S060/ PAS002
Date Original Protocol Accepted	12/07/2018
Date Current Protocol Accepted	07/06/2022
Study Name	GORE CARDIOFORM New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm, prospective, new enrollment, multi-center study. The objective is to assess and confirm the safety and effectiveness of the Gore Septal Occluder (GSO) device. This device was evaluated in the REDUCE pivotal IDE study. This study is to evaluate the quality of perator education and training, and transferability of trail experience to a post-market setting.
Study Population	18-70 years of age with a Patent Foramen Ovale (PFO) who have experienced an embolic stroke of undetermined source in the past year.
Sample Size	At least 636 patients with a limit of 10% (~63) patients will be allowed to be 61-70 years of age at the time of enrollment. Currently 40 eligible sites in the US.
Key Study Endpoints	Primary Effectiveness Endpoint: The proportion of subjects with ischemic stroke at 2 years in subjects with the study device implanted. This will be compared to a performance goal (PG) of 3.8%. Primary Safety Endpoint: The cumulative incidence of device- or procedure-related serious adverse events through 30 days. This will be compared to a PG of 6.4%. Secondary Effectiveness Endpoint: Effective PFO Closure – Proportion of subjects with complete PFO closure or a trivial or small residual shunt, at 1 year. The secondary endpoints for this study include: • Clinically Significant New Atrial Arrhythmia • Clinically Significant New Atrial Arrhythmia by Age • Technical Success • Residual Shunt Characterization • Procedural Success
Follow-up Visits and Length of Follow-up	Follow ups at 1, 6, 12 and 24 months. Over the phone follow up out to 60 months.
Interim or Final Data Summary
Interim Results	Safety Results There have been 4 site-reported serious adverse events (SAE) related to the device and 9 site-reported SAE related to the procedure. Device and procedure-related SAE included atrial fibrillation, other abnormal heart rhythms (sinus tachycardia, supraventricular tachycardia, ventricular tachycardia), pericardial effusion, cardiac tamponade, encephalopathy, presyncope, and incision site hematoma. Effectiveness Results 99.4% (310/312) attempted implants were successful; of these, 93.6% (292/310) had an estimated shunt grade post-implant of Grade 0. There are not yet results available regarding the effectiveness endpoint of the study (ischemic stroke at 2 years).
Actual Number of Patients Enrolled	312
Actual Number of Sites Enrolled	35
Patient Follow-up Rate	Subject follow-up is ongoing. The reported follow-up rate is currently 92.6% at the 1-month study visit, 81.5% at the 6-month study visit, 77.1% at the 12-month study visit, 66% at the 24-month visit, and 34.1% at the 36-month visit
General
Study Status	Ongoing
Application Number / Requirement Number	P030031 S100/ PAS001
Date Original Protocol Accepted	03/26/2021
Date Current Protocol Accepted	05/13/2021
Study Name	Real-World Experience of Catheter Ablation of PsAF
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm, retrospective analysis of prospectively collected EHR, observational cohort study to demonstrate the long-term and continued safety and effectiveness of ablation for persistent atrial fibrillation with the THERMOCOOL SMARTTOUCH SF catheter in the real-world setting. Primary Objective: To demonstrate the long-term effectiveness and safety of ablation for persistent atrial fibrillation (PsAF) with the THERMOCOOL SMARTTOUCH SF catheter in the real-world setting among patients followed for up to 36 months Secondary Objective: To identify predictors of clinical outcomes of ablation among patients with PsAF in the real-world setting.
Study Population	PsAF patients aged 18 years or older and who underwent first time catheter ablation with the THERMOCOOL SMARTTOUCH SF Catheter.
Sample Size	A total of 350 consecutive eligible PsAF patients.
Key Study Endpoints	Primary Safety Endpoint: A composite of primary adverse events (PAEs) that occurred within 7 days* following ablation procedure: • Atrio-esophageal fistula* • Cardiac tamponade/perforation* • Death* • Acute myocardial infarction • Acute stroke/cerebrovascular accident • Thromboembolism • Transient ischemic attack (TIA) • Diaphragmatic paralysis • Pneumothorax • Heart block • Pulmonary vein stenosis* • Pulmonary edema • Pericarditis • Major vascular access complications/bleeding requiring transfusion *Death, pulmonary vein stenosis and atrio-esophageal fistula that occurred greater than one week (7 days) post-procedure up to 3 months, and cardiac tamponade/perforation that occurred greater than one week (7 days) post-procedure up to 30 days will be considered and analyzed as PAEs. Primary Effectiveness Endpoint: A composite of direct current cardioversion for atrial arrhythmia (AF/atrial tachycardia [AT]/atrial flutter [AFL]*), repeat ablation for AF/AT/AFL*, or hospitalization for AF/AT/AFL* at 12-month follow-up (with a 3-month blanking period) * including atypical atrial flutter Secondary Endpoints • Procedural data (procedure time, fluoroscopy time) • Repeat ablations through 1-year, 2-year, and 3-year • All-cause hospitalization through 1-year, 2-year, and 3-year • Cardiovascular (including heart failure related) hospitalization through 1-year, 2-year, and 3-year • Direct current cardioversions through 1-year, 2-year, and 3-year • Composite effectiveness endpoint without blanking period at 1-year follow-up • Composite effectiveness endpoint through 2-year and 3-year • Complications at 1-year, 2-year, and 3-year
Follow-up Visits and Length of Follow-up	Follow-up data are extracted from the EHR. Length of Follow-up: 3 years. Frequency of Follow-up: Per standard of care.
Interim or Final Data Summary
Interim Results	Safety Findings 0.56% primary safety event rate Effectiveness Findings 82.49% of subjects free from primary effectiveness event
Actual Number of Patients Enrolled	354 (eligible for two-year analysis)
Actual Number of Sites Enrolled	Multiple sites w/n single EHR
Patient Follow-up Rate	95.8% for greater than or equal to 720 days post-procedure
Study Strengths & Weaknesses	N/A
General
Study Status	Completed
Application Number / Requirement Number	P030047 / PAS001
Date Original Protocol Accepted	09/22/2006
Date Current Protocol Accepted	09/22/2006
Study Name	Longterm & CASES Studies
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was a multi-center, prospective, single arm, open-label study to assess safety and efficacy outcomes of stenting with distal protection in the treatment of obstructive carotid artery disease during peri-approval/initial commercialization phase of Cordis' carotid program in relation to the outcomes of the SAPPHIRE clinical trial.
Study Population	This device is indicated for use in conjunction with the ANGIOGUARD XP Emboli Capture Guidewire for the treatment of patients at high risk for adverse events from carotid endarterectomy (defined in the IFU) who require carotid revascularization and meet the criteria outlined: 1) Patients with neurological symptoms and >50% stenosis of the common or internal carotid artery by ultrasound or angiogram OR patients without neurological symptoms and >80% stenosis of the common or internal carotid artery by ultrasound or angiogram, AND 2) Patients must have a vessel diameter of 4-9mm at the target lesion. The vessel distal to the target lesion must be within the range of 3mm and 7.5mm to allow for placement of the ANGIOGUARD XP Emboli Capture Guidewire. The study population was designed to be comprised of up to 1500 patients with de novo atherosclerotic or post-endarterectomy restenotic obstructive lesions in native carotid arteries.
Sample Size	1500 patients, 112 sites
Key Study Endpoints	This study was a non-inferiority trial designed to test the primary endpoint, major adverse events at 30 days, against an established performance criteria (9.3%).
Follow-up Visits and Length of Follow-up	Clinical follow-up was conducted at 30 days and conducted via telephone contact at 1-year post-procedure. The assessment at 30 days included a neurological examination and an evaluation of any adverse events. At 1-year post-procedure an evaluation of any adverse events was performed.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	1472 patients
Actual Number of Sites Enrolled	80 sites
Patient Follow-up Rate	84%
Final Safety Findings	The rate of the primary endpoint, major adverse events, at 30 days post-procedure is 5.0% (74/1492) with a 95% confidence interval (CI) 3.9%, 6.2%. The rate of major adverse events at 360 days post-procedure is 11.6% (173/1492) with 95% CI [10.0%, 13.3%] for all intent-to-treat patients. The 30 day rate of 5.0% is below the SAPPHIRE rate of 6.3% and the OPC rate of 9.3%.
Study Strengths & Weaknesses	Strengths: The sponsor utilized the peri-approval approach to rapidly start up this study. Weaknesses: The sponsor does not provide a context within which to interpret the 360 day rate, therefore it is difficult to assess whether the device is safe at 360 days post-implant.
Recommendations for Labeling Changes	Updated labeling requested from sponsor to reflect 30 day major adverse event rates.
General
Study Status	Completed
Application Number / Requirement Number	P050025 / PAS001
Date Original Protocol Accepted	10/12/2006
Date Current Protocol Accepted	10/12/2006
Study Name	CABERNET Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study was to determine whether morbidity and mortality for high-risk surgical patients treated with the NexStent Over the Wire in conjunction with the FilterWire EXIEZ System Distal Protection Device will be less than an Objective Performance Criterion derived from historic controls undergoing surgical intervention with carotid endarterectomy.
Study Population	The NexStent Carotid Stent System used in conjunction with the FilterWire EZ System, is indicated for treatment of patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the criteria outlined below 1) Patients with neurological systems associated with >50% stenosis of the common or internal carotid artery OR patients without neurological symptoms and >80% stenosis of the common or internal carotid artery by ultrasound or angiogram AND 2) Patients must have a reference vessel diameter within the range of 4 mm and 9 mm at the target lesion and a stenosis less than 30 mm in length. The subject population being studied included subjects indicated for NexStent Carotid Stent System placement.
Sample Size	488 patients including 454 registry patients and 34 Roll-In patients, 21 sites
Key Study Endpoints	Primary safety endpoints include: 1) Major clinical events at one-year defined as any death, stroke or myocardial infarction, and 2) 30 day event rate defined as any death, stroke or myocardial infarction at 30 days post-procedure. 12 month event rate defined as the 30 day event rate plus any ipsilateral stroke and/or death as a result of an ipsilateral stroke.
Follow-up Visits and Length of Follow-up	Follow-up at 30 days and one year post procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	488 patients
Actual Number of Sites Enrolled	21 sites
Patient Follow-up Rate	86%
Final Safety Findings	On June 6, 2008, BSC initiated a voluntary recall of all units of the NexStent Carotid Stent System due to reported complaints involving detachment of the tip from the stent delivery System.
Study Strengths & Weaknesses	Strengths: The post-approval study was able to detect an early problem involving detachment of the tip from the stent delivery system. Weaknesses: There was no predetermined hypothesis for postapproval analysis.
Recommendations for Labeling Changes	Nexstent carotid stent was taken off the market due to adverse events that have occurred as part of the SONOMA post-approval study. Labeling changes were not recommended since the device is no longer marketed.
General
Study Status	Completed
Application Number / Requirement Number	P050006 / PAS001
Date Original Protocol Accepted	08/11/2006
Date Current Protocol Accepted	12/13/2006
Study Name	GORE HELEX
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is prospective cohort study. The study population consists of two different cohorts: 1) Continued Access Study of the GORE HELEX Septal Occluder and 2) Post-Approval Study of the GORE HELEX Septal Occluder (CA-PAS Subjects HLX 06-04).
Study Population	The GORE HELEX Septal Occluder is a permanently implanted prosthesis indicated for the percutaneous, transcatheter closure of ostium secundum atrial septal defects. This study will enroll approximately 200 subjects, including subjects from the Icontinued Access Study, who have been successfully implanted.
Sample Size	200 patients, 19 sites
Key Study Endpoints	Composite Clinical Success is evaluated at 12 months and is defined as a subject with the targeted defect assessed by TTE as being either completely occluded or the residual shunt is clinically insignificant, with an absence of repeat procedure to the target ASD, and absence of any major complication.
Follow-up Visits and Length of Follow-up	The safety endpoints defined above will be evaluated annually through 5 years post procedure. The efficacy endpoints defined above will be evaluated at year 1, 3, and 5 post-procedure.During Year 2 and Year 4 of long-term follow-up, the site will contact the subject (or legal guardian if subject is a minor) by telephone to evaluate their status. During Year 3 and Year 5 of long-term follow-up, the site will schedule subject for a follow-up visit. Follow-up visit will include physical examination, ECG, and echocardiogram. A fluoroscopy exam without contrast will be conducted at Year 5.
Interim or Final Data Summary
Interim Results	No unanticipated adverse events have been reported to date. There have been no new Major Adverse Events reported during this reporting period. Clinically successful defect closure (Complete Occlusion or Clinically Insignificant Leak) was observed in 97.8% (43/44) of subjects evaluated at 12 months post procedure by the Echocardiographic Core Lab. Of the echo core lab reviews available for the 16 subjects at 36 months post procedure, clinically successful defect closure was observed in 100.0%. Of the 17 echo core lab reviews available for the 17 subjects at 60 months post procedure, clinically successful defect closure also was observed in 100.0%. Clinical Success was achieved in 85.0% (17/20) of subjects evaluated at 60 month post procedure. Three subjects were considered clinical failures. These are the same three (3) subjects identified at the 12 month post procedure interval. Clinical Success has been determined in 20 (40.0%) of the 50 evaluable subjects at the 60 month follow-up interval. Of the 30 subjects not evaluated, 15 were lost to follow-up and 15 have not completed Echo Core Lab evaluations of residual defect status (pending or missing).
Actual Number of Patients Enrolled	Continued Access Study: 50 PAS: 215
Actual Number of Sites Enrolled	Continued Access Study: 13 Post-approval Study (PAS): 21 sites
Patient Follow-up Rate	Continued Access Study: 70% PAS: 76%
Final Safety Findings	Continued Access Study: Major adverse events were reported in 6.0% (3/50) of subjects. These included 2 device embolizations in the first 24 hours post-procedure and 1 wire frame fracture. All of these major adverse events were device-related and occurred within 12 months. PAS: Major adverse events (MAEs) were reported in 4.7% (10/215) of subjects through the 60-month follow- up. Out of 8 device-related MAEs, there were 2 device embolizations within the first 30 days post- procedure and 5 device removals (4 due to fracture and 1 due to device malposition).
Final Effect Findings	Continued Access Study: Clinically successful defect closure was observed in 91.5% (43/47), 84.2% (16/19), and 87.5% (21/24) of subjects evaluated at 12, 36, and 60 months post-procedure, respectively. PAS: Clinically successful defect closure was observed in 95.0% (171/180), 92.5% (123/133), and 94.1% (143/152) of subjects evaluated at 12, 36, and 60 months post-procedure, respectively.
Study Strengths & Weaknesses	Continued Access Study: The 50 subjects in this study provided safety and efficacy data in support of the PMA approval for the Gore Helex septal occluder. Subjects in this study had to be re-consented for longer-term follow-up. Many of the subjects missed the 36-month follow-up and consequently, this information was not available for analysis. This also impacted the overall study follow-up. Analysis presented showed no evidence of selection bias introduced in the study due to loss-to-follow-up. This study shows the initial results of the long-term performance of this device. PAS: The results of this study provide long-term safety and effectiveness data for the Gore Helex septal occluder. Although patient follow-up was 76%, only 4% shy of the protocol defined expectations, a sensitivity analysis showed no evidence of selection bias. Further, the data demonstrated that over 90% of the patients implanted with the investigational device maintained composite clinical success through 60 months.
Recommendations for Labeling Changes	It is not recommended because W.L. Gore & Associates, Inc. ceased the production of the GORE HELEX Septal Occluder.
General
Study Status	Completed
Application Number / Requirement Number	P050010 / PAS001
Date Original Protocol Accepted	08/14/2006
Date Current Protocol Accepted	08/14/2006
Study Name	PRODISC-L Long Term Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is continuation of the IDE study, which was a multi-center, prospective, randomized, controlled clinical trial. The objective of PAS is to evaluate the long-term safety and effectiveness of Prodisc -L Total Disc Replacement to spinal fusion surgery in the treatment of discogenic pain associated with Degenerative Disc Disease in the lumbosacral spine.
Study Population	Study population is as per device indication. The study population consists of all patients from IDE study who were enrolled and treated without major protocol violation. This device is indicated for spinal arthroplasty in skeletally mature patients with degenerative disc disease (DDD) at one levelfrom L3-Sl. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient history and radiographic studies. These DDD patients should have no more than Grade I spondylolisthesis at the involved level. Patients receiving the PRODISC -L Total Disc Replacement should have failed at least six months of conservative treatment prior to implantation of the PRODISC Total Disc Replacement.
Sample Size	A total of 286 patients (161 randomized investigational subjects, 75 randomized control subjects, and 50 non-randomized investigational subjects) enrolled in the PAS
Key Study Endpoints	The outcome measures in the PAS include patient self-assessment on Oswestry score, SF-36, Pain and satisfaction; physical & neurological examination and radiographic evaluation of the implanted level and adjacent segments. The composite overall success is defined as: - Oswestry score improves by at least 15% over baseline value;- SF-36 score will be improved; - Maintained or improved neurological parameters, i.e., motor, sensory, reflexes and straight leg raise tests; - No re-operations were required to modify or remove the implant (Prodisc -L group); no re-operations were required to modify the fusion site or correct a complication with an implant (Fusion group). - Radiological success as assessed by independent radiographic review.
Follow-up Visits and Length of Follow-up	The subjects were followed at 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months post-operation in the PMA study. They will be followed annually after 24 month, up to 60 month post-operation in PAS.
Interim or Final Data Summary
Actual Number of Patients Enrolled	161 randomized investigational subjects, 50 training investigational subjects, and 75 control subjects. Overall 286 patients continued participation from the IDE study.
Actual Number of Sites Enrolled	17 sites were enrolled for the Post-Approval Study.
Patient Follow-up Rate	60.2%, 60.1% and 82.5% were the overall follow up rates at 36, 48, and 60 months, respectively.
Final Safety Findings	During the 3 years of the PAS, there were several AEs with higher occurrence in the ProDisc randomized group compared to the fusion randomized group: infection/other non wound (4 vs. 1); back pain (18 vs. 4), pain ¿ back and lower extremities (10 vs. 5), surgery other (16 vs. 7). All AEs involving pain considered together look definitely higher in the ProDisc randomized group.
Final Effect Findings	At month 60 non-inferiority was demonstrated for Overall Success (p=0.0099) and Overall Success (Secondary Analyses) (p=0.0101).
Study Strengths & Weaknesses	The main strength of the study is the randomized design. The main weakness of the study is the relatively low follow up rate, especially during follow up visits before the final visit; this may partially hamper the validity of the randomized comparison, since loss to follow up may not be independent of randomization group as well as patients outcomes.
Recommendations for Labeling Changes	Yes.
General
Study Status	Completed
Application Number / Requirement Number	P050023 / PAS001
Date Original Protocol Accepted	08/10/2006
Date Current Protocol Accepted	08/10/2006
Study Name	COROX LEAD (COSMO)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	In this study patients are enrolled 1-30 days after successful implantation of the Corox OTW Steroid LV lead connected to a BIOTRONIK CRT-D device. Successful implantation is defined as when the pacing threshold of the Corox OTW Steroid LV lead is less than one-half of the maximum programmed output of the BIOTRONIK CRT-D at 0.5 ms without phrenic nerve stimulation.
Study Population	Study Population: Patients implanted with the Corox OTW Steriod LV lead.
Sample Size	250 subjects, at up to 100 sites
Key Study Endpoints	The evaluation of safety is based on the analysis of Corox over-the-wire Steroid lead related adverse events that are classified into two types: observations and complications. Additionally, left ventricular lead pacing parameters (acute and chronic pacing thresholds and impedance values) will be evaluated. The study data will also be used to determine the ability of the Corox over-the-wire steroid lead to deliver chronic cardiac resynchronization pacing.
Follow-up Visits and Length of Follow-up	The patients will be followed for a period of three years. The specific visits that are part of this registry are at enrollment, 3-months, 6-months, 1-year, and routine follow-ups (every subsequent 6 months). It is required that patients are seen at 3, 6, 12, 18, 24, 30, and 36 months post enrollment within ± 1-month at the first (3month) follow-up and at ± 45 days for all subsequent routine follow-ups thereafter.
Interim or Final Data Summary
Actual Number of Patients Enrolled	221
Actual Number of Sites Enrolled	34
Patient Follow-up Rate	59% through three years
Final Safety Findings	Observations. A total of 23 (10.4%) of the enrolled patients have reported a Corox OTW Steroid Unipolar lead related observation. The rate of Corox OTW Steroid Unipolar lead related observations per patient-year is 0.056. Ten observations were due to high LV lead threshold, 14 were from phrenic nerve stimulation, and one was from intermittent loss of capture. Complications. A total of 9 (4.1%) of the enrolled patients experienced a Corox OTW Steroid Unipolar lead related complication. The rate of Corox OTW Steroid Unipolar lead related complications per patient-year is 0.019. The eight complications were: LV lead dislodgement (3), phrenic nerve stimulation (1), infection (2), high LV lead threshold (2), and lead integrity compromise (1).
Final Effect Findings	At all scheduled follow-up intervals and interim visits, the CRT system provided appropriate biventricular pacing with capture in 91.9% to 97.8% of subjects. The average overall LV lead impedance was 709 ± 176 ohms. When measured at 0.5 ms pulse width, the average LV lead threshold was 1.3 ± 0.9 ms at enrollment and for all follow-ups was 1.3 ± 1.1 V. In total 1200 subject visits had been reported in 221 subjects.
Study Strengths & Weaknesses	The study results they provide little long term follow-up of the lead. Overall the lead appears to cause few complications although the data collection is weak and adverse events might have occurred but not been reported.
Recommendations for Labeling Changes	Updated to include the long-term post-approval study data and findings.
General
Study Status	Completed
Application Number / Requirement Number	P910023 S088/ PAS001
Date Original Protocol Accepted	03/14/2006
Date Current Protocol Accepted	03/14/2006
Study Name	EPIC Notifiers
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P050019 / PAS002
Date Original Protocol Accepted	10/23/2008
Date Current Protocol Accepted	10/23/2008
Study Name	BEACH STUDY
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The BEACH Trial was a prospective, single-arm, multi-center trial intended to evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) Carotid WALLSTENT Endoprosthesis in conjunction with the FilterWire EX/EZ System in selected high-risk surgical patients with stenosis of the carotid artery. Success of this trial was assessed by comparison to an OPC representative of similar patients treated with CEA. A maximum of six hundred eighty (680) patients with carotid stenosis at high risk for complications associated with CEA who met specific enrollment criteria were to be evaluated in the Pivotal portion of the trial and a maximum of 96 for the Bilateral Registry. Clinical follow-up for all patients was planned to occur at 1 month, 6 month, and 12 months and annually thereafter up to 60 months post index procedure. Preliminary examinations included angiography, ultrasound, and computed tomography (CT) or magnetic resonance imaging (MRI). The procedural evaluation included baseline angiography. Follow-up examinations included carotid duplex ultrasound imaging. If for any reason carotid ultrasound was not possible, an angiographic examination was required. A complete lab study was performed after the patient qualified for entry into the clinical trial.
Study Population	The Carotid WALLSTENT Monorail Endoprosthesis, used in conjunction with the Boston Scientific embolic protection system, is indicated for the treatment of patients at high risk for adverse events from carotid endarterectomy due to either anatomic or co-morbid conditions who require carotid revascularization in the treatment of ipsilateral or bilateral carotid artery disease.
Sample Size	747 patients, 47 sites
Key Study Endpoints	The primary endpoint (defined as the composite of Non Q-wave myocardial infarction within the 24 hours following carotid stenting; death, stroke and Q-wave myocardial infarction within 30 days; and ipsilateral stroke or death due to neurological events from 31 days to one year) was compared to the weighted performance criteria.
Follow-up Visits and Length of Follow-up	Patients will be assessed at 30 days, and annually to 3 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	747 patients
Actual Number of Sites Enrolled	47 sites
Patient Follow-up Rate	90%
Final Safety Findings	The 3 year death, stroke and myocsrdial infarction rates were 5.6%, 2.3%, and 0.3%. These rates declined from their peaks which were seen at one year: 7.7%, 8.3%, and 2.6% respectively.
Study Strengths & Weaknesses	Strengths: The sponsor did complete this study within a reasonable period of time (2 years after device approval), eventhough there was not a study timeline. Weaknesses: The sponsor notes that 315 of the 480 patients were evaluable at 3 years. There were 84 deaths in the study. If the deaths are not included in the lost-to-follow-up rate than the 3 year follow-up was 83% (399/480). This is lower than would be expected for an IDE study however, it is an acceptable rate.
Recommendations for Labeling Changes	Labeling changes were not recommended.
General
Study Status	Completed
Application Number / Requirement Number	P050023 S087/ PAS001
Date Original Protocol Accepted	06/16/2016
Date Current Protocol Accepted	07/21/2017
Study Name	ProMRI ICD Post-Approval Study
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	All subjects implanted with a ProMRI ICD system enabled with Home Monitoring® in the United States will be retrospectively assessed for VF episodes detected by the ICD following MRI exposure.
Study Population	All subjects implanted with ProMRI ICD system and enabled with Home Monitoring® in the United States will be retrospectively assessed through a de-identified Home Monitoring database.
Sample Size	25 subjects with a post-MRI VF episode have been identified or the 5-years post-approval time point has been reached, whichever comes first.
Key Study Endpoints	The primary endpoint is the freedom of VF detection delays, as determined by an independent Clinical Events Committee, in the ProMRI ICD system following MRI exposure. The secondary endpoint is the analysis of user compliance to the requirement to restore the tachycardia detection and ICD therapy device settings after the MRI scan.
Follow-up Visits and Length of Follow-up	25 subjects with a post-MRI VF episode have been identified or the 5-years post-approval time point has been reached, whichever comes first. Constantly followed by home monitoring system
Interim or Final Data Summary
Actual Number of Patients Enrolled	The number of enrolled patients was defined as the number of patients implanted with a device that was required to be part of the post approval study and that was also registered on Home Monitoring. The total number of patients satisfying both conditions was 24,249. A subgroup of patients undergoing at least one MRI (1,208) was monitored for changes (pre vs. post MR) in LV pacing capture threshold and as well as potential MRI induced delays in VF Detection. Post MRI VF episodes occurred in 110 subjects.
Actual Number of Sites Enrolled	No study sites were enrolled since the study was designed to be an enhance surveillance study that monitored periodic device transmissions via the firm’s Home Monitoring System. Transmissions of all patients were filtered based on pre-defined events.
Patient Follow-up Rate	Patient follow up was not required. In fact, the patient data were de-identified and follow up was only required if the observed change in LV pacing capture threshold or delay in post MR VF therapy exceeded predefined thresholds. Since no such events occurred, follow up was not required.
Final Safety Findings	The first endpoint was the proportion of subjects with a greater than or equal to 5.0 second delay in post- MRI VF detection attributable to the MRI scan as adjudicated by the CEC. For subjects with more than one VF episode post-MRI, only the first VF episode post-MR exposure classified as VF by the CEC contributed to the primary objective. The following hypothese was tested: H0: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post-MRI is > 1. HA: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post- MRI is less than or equal to 1. A rejection of the null hypothesis would demonstrate that there is evidence that there is not more than 1 subject with delayed post-MRI VF detection. A total of 45 unique ProMRI ICD/CRT-D subjects (40 ICD, 5 CRT-D) experiencing at least one post-MRI VF episode adjudicated as True VF contributed to the 106 total episodes, satisfying the objective criteria of evaluating a minimum of 25 ICD subjects. Analysis of the Primary Objective 1 results indicate rejection of the null hypothesis and acceptance of the alternative hypothesis as a post-MRI VF episode detection delay of greater than or equal to 5.0 seconds was not observed in the 45 evaluable subjects (0/45, 0%). Therefore, Primary Objective 1 is met and demonstrated no evidence of delay in VF episode detection following an MRI. The second endpoint evaluated the proportion of LV pacing leads with a LV pacing threshold increase between Pre-MRI and One-Month (30 days) post-MRI. The threshold behavior of the LV lead was defined as a success if the increase is not larger than 1.0 V. For a clear and concise definition of “success” the following abbreviations was used: PTA = LV pacing threshold at Pre-MRI PTB = LV pacing threshold at 30 days post-MRI Success was defined as: PTB – PTA less than or equal to 1.0 V The proportion (pPT) of pacing threshold successes was calculated by dividing the number of LV leads without a ventricular pacing threshold increase as defined above by the total number of all LV leads. H0: The success rate pPT for LV leads is smaller than or equal to 95%: pPT less than or equal to 95%. HA: The success rate pPT for LV leads is greater than 95%: pPT > 95%. A rejection of the null hypothesis would demonstrate that there is evidence that pPT is greater than 95%. Left ventricular pacing threshold differences between one-month post-MRI and pre-MRI were available for 92 subjects. The proportion of pacing threshold success is 100% with none of the 92 subjects demonstrating a pacing threshold increase of greater than 1.0V between the pre-MRI measurement and one month post-MRI measurement. An average change in LV pacing capture threshold of 0.03 (min: -0.2, max: 1.0) with a standard deviation of 0.154 was observed.
Final Effect Findings	The primary effectiveness endpoint was defined as the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy post-MRI. Home Monitoring alerts for tachycardia detection/ICD therapy disabled within 24 hours following MR exposure were observed during the study to monitor for non-compliance to the post-MRI workflow. If there was a Home Monitoring transmission gap within the first 24 hours post-MRI, the next successful Home Monitoring transmission was utilized for this analysis. It was expected that the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy would be greater than or equal to 90%. Of the 1,208 subjects undergoing an MRI with an MRI mode activated 227 subjects have undergone more than one MRI with an MRI mode activated for a total of 1,512 MRI procedures. Tachycardia detection and ICD therapy was restored in 1,202 of 1,208 (99.5%) subjects and after a total of 1,506 of 1,512 (99.6%) MRI Procedures; showing good compliance to the workflow. The secondary effectiveness endpoint was defined as the proportion of subjects who experience LV sensing amplitude attenuation. LV R-wave amplitude attenuation was defined as an LV R-wave amplitude decrease (between pre-MRI follow-up and 30 days post-MRI) exceeding 50%. The proportion (pRsensing) was calculated by dividing the number of subjects with LV R-wave Sensing Attenuation by the total number of subjects. Left ventricular R-wave sensing amplitude differences between one-month post-MRI and pre-MRI were available for 121 subjects. The proportion of LV R-wave amplitude attenuation between pre- and one-month post-MRI measurements is 0.8% (mean 0.14 mV, Stdev 2.39 mV, min -15 mV, median 0 mV, max 8.4 mV) Only one subject reported an LV R-wave attenuation exceeding 50% of measured pre-MRI values.
Study Strengths & Weaknesses	The study design allowed the capture of rare events in a post market setting by monitoring > 24,000 patient in a de-identified data base. The event rate of post MRI VF was <0.19%, not observable in a traditional pre-market study design.
Recommendations for Labeling Changes	Labeling update not required.
General
Study Status	Completed
Application Number / Requirement Number	P050023 S094/ PAS001
Date Original Protocol Accepted	08/01/2016
Date Current Protocol Accepted	07/21/2017
Study Name	ProMRI ICD/CRT-D System Home Monitorin
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	All subjects implanted with a ProMRI ICD/CRT-D system enabled with Home Monitoring® in the United States will be retrospectively assessed for VF episodes detected by the ICD/CRT-D following MRI exposure.
Study Population	All subjects implanted with ProMRI ICD/CRT-D system and enabled with Home Monitoring® in the United States will be retrospectively assessed through a de-identified Home Monitoring database.
Sample Size	25 subjects with a post-MRI VF episode have been identified or the 5-years post-approval time point has been reached, whichever comes first.
Key Study Endpoints	Primary Endpoint 1: Characterize VF Detection Following MR Exposure Primary Endpoint 2: Left Ventricular Pacing Threshold Secondary Endpoint 1: Characterize Workflow Compliance Following MR Exposure Secondary Endpoint 2: Left Ventricular Sensing Attenuation
Follow-up Visits and Length of Follow-up	25 subjects with a post-MRI VF episode have been identified or the 5-years post-approval time point has been reached, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	The number of enrolled patients was defined as the number of patients implanted with a device that was required to be part of the post approval study and that was also registered on Home Monitoring. The total number of patients satisfying both conditions was 24,249. A subgroup of patients undergoing at least one MRI (1,208) was monitored for changes (pre vs. post MR) in LV pacing capture threshold and as well as potential MRI induced delays in VF Detection. Post MRI VF episodes occurred in 110 subjects.
Actual Number of Sites Enrolled	No study sites were enrolled since the study was designed to be an enhance surveillance study that monitored periodic device transmissions via the firm’s Home Monitoring System. Transmissions of all patients were filtered based on pre-defined events.
Patient Follow-up Rate	Patient follow up was not required. In fact, the patient data were de-identified and follow up was only required if the observed change in LV pacing capture threshold or delay in post MR VF therapy exceeded predefined thresholds. Since no such events occurred, follow up was not required.
Final Safety Findings	The first endpoint was the proportion of subjects with a greater than or equal to 5.0 second delay in post- MRI VF detection attributable to the MRI scan as adjudicated by the CEC. For subjects with more than one VF episode post-MRI, only the first VF episode post-MR exposure classified as VF by the CEC contributed to the primary objective. The following hypothese was tested: H0: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post-MRI is > 1. HA: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post- MRI is less than or equal to 1. A rejection of the null hypothesis would demonstrate that there is evidence that there is not more than 1 subject with delayed post-MRI VF detection. A total of 45 unique ProMRI ICD/CRT-D subjects (40 ICD, 5 CRT-D) experiencing at least one post-MRI VF episode adjudicated as True VF contributed to the 106 total episodes, satisfying the objective criteria of evaluating a minimum of 25 ICD subjects. Analysis of the Primary Objective 1 results indicate rejection of the null hypothesis and acceptance of the alternative hypothesis as a post-MRI VF episode detection delay of greater than or equal to 5.0 seconds was not observed in the 45 evaluable subjects (0/45, 0%). Therefore, Primary Objective 1 is met and demonstrated no evidence of delay in VF episode detection following an MRI. The second endpoint evaluated the proportion of LV pacing leads with a LV pacing threshold increase between Pre-MRI and One-Month (30 days) post-MRI. The threshold behavior of the LV lead was defined as a success if the increase is not larger than 1.0 V. For a clear and concise definition of “success” the following abbreviations was used: PTA = LV pacing threshold at Pre-MRI PTB = LV pacing threshold at 30 days post-MRI Success was defined as: PTB – PTA less than or equal to 1.0 V The proportion (pPT) of pacing threshold successes was calculated by dividing the number of LV leads without a ventricular pacing threshold increase as defined above by the total number of all LV leads. H0: The success rate pPT for LV leads is smaller than or equal to 95%: pPT less than or equal to 95%. HA: The success rate pPT for LV leads is greater than 95%: pPT > 95%. A rejection of the null hypothesis would demonstrate that there is evidence that pPT is greater than 95%. Left ventricular pacing threshold differences between one-month post-MRI and pre-MRI were available for 92 subjects. The proportion of pacing threshold success is 100% with none of the 92 subjects demonstrating a pacing threshold increase of greater than 1.0V between the pre-MRI measurement and one month post-MRI measurement. An average change in LV pacing capture threshold of 0.03 (min: -0.2, max: 1.0) with a standard deviation of 0.154 was observed.
Final Effect Findings	The primary effectiveness endpoint was defined as the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy post-MRI. Home Monitoring alerts for tachycardia detection/ICD therapy disabled within 24 hours following MR exposure were observed during the study to monitor for non-compliance to the post-MRI workflow. If there was a Home Monitoring transmission gap within the first 24 hours post-MRI, the next successful Home Monitoring transmission was utilized for this analysis. It was expected that the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy would be greater than or equal to 90%. Of the 1,208 subjects undergoing an MRI with an MRI mode activated 227 subjects have undergone more than one MRI with an MRI mode activated for a total of 1,512 MRI procedures. Tachycardia detection and ICD therapy was restored in 1,202 of 1,208 (99.5%) subjects and after a total of 1,506 of 1,512 (99.6%) MRI Procedures; showing good compliance to the workflow. The secondary effectiveness endpoint was defined as the proportion of subjects who experience LV sensing amplitude attenuation. LV R-wave amplitude attenuation was defined as an LV R-wave amplitude decrease (between pre-MRI follow-up and 30 days post-MRI) exceeding 50%. The proportion (pRsensing) was calculated by dividing the number of subjects with LV R-wave Sensing Attenuation by the total number of subjects. Left ventricular R-wave sensing amplitude differences between one-month post-MRI and pre-MRI were available for 121 subjects. The proportion of LV R-wave amplitude attenuation between pre- and one-month post-MRI measurements is 0.8% (mean 0.14 mV, Stdev 2.39 mV, min -15 mV, median 0 mV, max 8.4 mV) Only one subject reported an LV R-wave attenuation exceeding 50% of measured pre-MRI values.
Study Strengths & Weaknesses	The study design allowed the capture of rare events in a post market setting by monitoring > 24,000 patient in a de-identified data base. The event rate of post MRI VF was <0.19%, not observable in a traditional pre-market study design.
Recommendations for Labeling Changes	Labeling update not required.
General
Study Status	Completed
Application Number / Requirement Number	P050023 S101/ PAS001
Date Original Protocol Accepted	07/21/2017
Date Current Protocol Accepted
Study Name	ProMRI ICD/CRT-D System
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Retrospective, observational, post-approval study. To gather additional data to assess VF episode detection following MRI exposure as a condition of FDA approval. Secondarily, this post-approval study will provide additional data on the MRI mode programming following the MRI and LV pacing threshold changes between pre-MRI and one-month post-MRI.
Study Population	All subjects implanted with a ProMRI ICD/CRT-D system and enabled with Home Monitoring® in the United States
Sample Size	Primary Objective 1: An estimated 75% of US ICD implants are registered for Home Monitoring® and approximately 75% of those subjects regularly transmit device data. Applying these Home Monitoring® registration and transmission rate to the estimated US sales of the ProMRI ICD system, approximately 8437 ProMRI ICD subjects will be actively monitored by Home Monitoring® within 3 years of product approval. With an estimated annual MRI scan rate of 10%, approximately 1702 will have at least one MRI scan within 4 years post product approval. Annual true VF episode rate is approximately 2%. Applying the estimated 2% to the expected annual implant and MRI rates, results in approximately 16-34 subjects with a true VF episode occurring after an MRI scan within 5 years post-approval. Primary Objective 2: With a = 0.025, 1 - ß = 80%, an anticipated pacing threshold success rate of 99%, a performance goal of 95% and a one-sided exact binomial test, a sample size of n = 145 evaluable subjects with LV leads is required.
Key Study Endpoints	Primary Objective: Characterize VF detection following MRI exposure, as determined by an independent Clinical Events Committee, to ensure there is no delay in VF detection attributable to the MRI scan. MRI induced Left Ventricular pacing threshold changes between Pre-MRI and One-Month post-MRI. Secondary Objectives: Characterize appropriate tachycardia detection and ICD therapy programming following MRI exposure. Characterize changes in LV sensing and pacing impedance between pre-MRI and one-month post-MRI.
Follow-up Visits and Length of Follow-up	When 50 patients implanted with the ProMRI ICD system with a documented post-MRI VF episode have been identified or 5-years post-approval, which ever comes first
Interim or Final Data Summary
Actual Number of Patients Enrolled	The number of enrolled patients was defined as the number of patients implanted with a device that was required to be part of the post approval study and that was also registered on Home Monitoring. The total number of patients satisfying both conditions was 24,249. A subgroup of patients undergoing at least one MRI (1,208) was monitored for changes (pre vs. post MR) in LV pacing capture threshold and as well as potential MRI induced delays in VF Detection. Post MRI VF episodes occurred in 110 subjects.
Actual Number of Sites Enrolled	No study sites were enrolled since the study was designed to be an enhance surveillance study that monitored periodic device transmissions via the firm’s Home Monitoring System. Transmissions of all patients were filtered based on pre-defined events.
Patient Follow-up Rate	Patient follow up was not required. In fact, the patient data were de-identified and follow up was only required if the observed change in LV pacing capture threshold or delay in post MR VF therapy exceeded predefined thresholds. Since no such events occurred, follow up was not required.
Final Safety Findings	The first endpoint was the proportion of subjects with a greater than or equal to 5.0 second delay in post- MRI VF detection attributable to the MRI scan as adjudicated by the CEC. For subjects with more than one VF episode post-MRI, only the first VF episode post-MR exposure classified as VF by the CEC contributed to the primary objective. The following hypothese was tested: H0: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post-MRI is > 1. HA: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post- MRI is less than or equal to 1. A rejection of the null hypothesis would demonstrate that there is evidence that there is not more than 1 subject with delayed post-MRI VF detection. A total of 45 unique ProMRI ICD/CRT-D subjects (40 ICD, 5 CRT-D) experiencing at least one post-MRI VF episode adjudicated as True VF contributed to the 106 total episodes, satisfying the objective criteria of evaluating a minimum of 25 ICD subjects. Analysis of the Primary Objective 1 results indicate rejection of the null hypothesis and acceptance of the alternative hypothesis as a post-MRI VF episode detection delay of greater than or equal to 5.0 seconds was not observed in the 45 evaluable subjects (0/45, 0%). Therefore, Primary Objective 1 is met and demonstrated no evidence of delay in VF episode detection following an MRI. The second endpoint evaluated the proportion of LV pacing leads with a LV pacing threshold increase between Pre-MRI and One-Month (30 days) post-MRI. The threshold behavior of the LV lead was defined as a success if the increase is not larger than 1.0 V. For a clear and concise definition of “success” the following abbreviations was used: PTA = LV pacing threshold at Pre-MRI PTB = LV pacing threshold at 30 days post-MRI Success was defined as: PTB – PTA less than or equal to 1.0 V The proportion (pPT) of pacing threshold successes was calculated by dividing the number of LV leads without a ventricular pacing threshold increase as defined above by the total number of all LV leads. H0: The success rate pPT for LV leads is smaller than or equal to 95%: pPT less than or equal to 95%. HA: The success rate pPT for LV leads is greater than 95%: pPT > 95%. A rejection of the null hypothesis would demonstrate that there is evidence that pPT is greater than 95%. Left ventricular pacing threshold differences between one-month post-MRI and pre-MRI were available for 92 subjects. The proportion of pacing threshold success is 100% with none of the 92 subjects demonstrating a pacing threshold increase of greater than 1.0V between the pre-MRI measurement and one month post-MRI measurement. An average change in LV pacing capture threshold of 0.03 (min: -0.2, max: 1.0) with a standard deviation of 0.154 was observed.
Final Effect Findings	The primary effectiveness endpoint was defined as the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy post-MRI. Home Monitoring alerts for tachycardia detection/ICD therapy disabled within 24 hours following MR exposure were observed during the study to monitor for non-compliance to the post-MRI workflow. If there was a Home Monitoring transmission gap within the first 24 hours post-MRI, the next successful Home Monitoring transmission was utilized for this analysis. It was expected that the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy would be greater than or equal to 90%. Of the 1,208 subjects undergoing an MRI with an MRI mode activated 227 subjects have undergone more than one MRI with an MRI mode activated for a total of 1,512 MRI procedures. Tachycardia detection and ICD therapy was restored in 1,202 of 1,208 (99.5%) subjects and after a total of 1,506 of 1,512 (99.6%) MRI Procedures; showing good compliance to the workflow. The secondary effectiveness endpoint was defined as the proportion of subjects who experience LV sensing amplitude attenuation. LV R-wave amplitude attenuation was defined as an LV R-wave amplitude decrease (between pre-MRI follow-up and 30 days post-MRI) exceeding 50%. The proportion (pRsensing) was calculated by dividing the number of subjects with LV R-wave Sensing Attenuation by the total number of subjects. Left ventricular R-wave sensing amplitude differences between one-month post-MRI and pre-MRI were available for 121 subjects. The proportion of LV R-wave amplitude attenuation between pre- and one-month post-MRI measurements is 0.8% (mean 0.14 mV, Stdev 2.39 mV, min -15 mV, median 0 mV, max 8.4 mV) Only one subject reported an LV R-wave attenuation exceeding 50% of measured pre-MRI values.
Study Strengths & Weaknesses	The study design allowed the capture of rare events in a post market setting by monitoring > 24,000 patient in a de-identified data base. The event rate of post MRI VF was <0.19%, not observable in a traditional pre-market study design.
Recommendations for Labeling Changes	Labeling update not required
General
Study Status	Completed
Application Number / Requirement Number	P050023 S107/ PAS001
Date Original Protocol Accepted	05/06/2017
Date Current Protocol Accepted
Study Name	MPP QP-ExCELs Sub-Study PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Confirm long-term safety of the Biotronik Sentus OTW QP left ventricular pacing leads. The evaluation of safety will be freedom from Sentus QP related complications at 5 years post-implant.
Study Population	CRT-eligible Heart Failure patients
Sample Size	Postmarket Sample Size Required: 979 Postmarket Sample Size Required including attrition = 1754
Key Study Endpoints	Primary Endpoint: The purpose is to evaluate the long-term Sentus related complication-free rate through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Number of study sites enrolled 8 Sites Number of subjects enrolled 12 Subjects Follow-up rate Two (2) out of the 12 enrolled subjects reached the 3-month follow-up window and completed the 3-month follow-up visit. Therefore, 100% follow-up rate at 3 months. None of the 12 subjects reached the 6-month follow-up window. Summary of Interim Results No study data are available for testing the primary hypothesis and estimating the defined metrics for the secondary endpoints. Strengths and Weaknesses Study strengths and weaknesses cannot be assessed with this report given the study duration and little study data available.
Actual Number of Patients Enrolled	A total of 53 subjects were enrolled.
Actual Number of Sites Enrolled	A total of 26 study sites were enrolled.
Patient Follow-up Rate	The overall follow-up compliance was 97.16%.
Final Safety Findings	There were 4 events reported by the site which were classified as attributable to the MPP feature. All four events were due to extracardiac stimulation, and resolved with device programming. At the time of this report, there have been 3 subject deaths adjudicated by the CEC. All death events have been adjudicated as cardiovascular death events. In total, 7 subjects had a total of 11 adjudicated adverse events. There were 9 events adjudicated as cardiovascular hospitalization and two events were collected and adjudicated to be non system related/non protocol defined events.
Final Effect Findings	When comparing the improvement rate (35.6%) to the goal (3%), it was determined that there was a statistically significant difference (p-value <.0001) compared to the adjusted alpha of 0.0026 for the interim analysis. This result indicates the MPP Sub-Study had a superior responder improvement rate compared to the performance goal. Overall, there were no subjects reported with an MPP system related adverse event requiring additional invasive intervention to resolve. AE-free rate was 100%.
Study Strengths & Weaknesses	Overall, the results of the MultiPole Pacing Clinical Study indicate that the MPP feature is effective at converting a percentage of CRT non-responders to responders (35.6%) over 6-months of follow-up. Due to the non-randomized study design and small sample size of the MPP Sub-Study, these results should be interpreted with caution. Since delayed responders to CRT are not controlled for in this study, it is difficult to distinguish between true responders to MPP therapy and subjects who responded to an additional 6 months of bi-ventricular pacing.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P040052 / PAS002
Date Original Protocol Accepted	10/18/2007
Date Current Protocol Accepted	10/18/2007
Study Name	SURE Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was designed to have the 295 pairs (590 individual slides) of slides. Each subject was represented by a pair of slides: a Pap Smear slide and a MonoPrep Pap test slide. The MonoPrep Pap test slide was prepared from the Pap Smear slide residuum. Both sets of slides were assessed for specimen adequacy by the participating laboratories, and the slides were labeled as 'satisfactory' or 'unsatisfactory' accordingly. The adequacy determination (satisfactory/unsatisfactory status) and the underlying reason for an unsatisfactory status according to the TBS2001 criteria. For slides with adequacy determination of satisfactory, a diagnosis was assigned to the slide according to the TBS2001 criteria.
Study Population	Study Poluation: Women 18 years or older who receive cervical cancer screening. Indication: The MonoGen Pap Test is intended for use in collecting and preparing cervical-vaginal cytology specimens for Pap stain-based screening for cervical cancer, its precursor lesions, and other cytologic categories and conditions defined by the 2001 Bethesda System for Reporting Results of Cervical Cytology.
Sample Size	295 patients, 85 sites
Key Study Endpoints	The goal of the study was to evaluate cytology slides for adequacy determination and the underlying reason for unsatisfactory status. Data collection consisted of obtaining cervical cytology specimens.
Follow-up Visits and Length of Follow-up	Follow-up was not required for this study.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	295
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	Follow-up was not required for this study.
Final Safety Findings	The performance of MonoGen Pap Test and Pap Smear methods with regard to "miscall of unsatisfactory slides" are the same.
Study Strengths & Weaknesses	A weakness of the study was that each slide evaluated by only one pathologist and not a panel of pathologists.
Recommendations for Labeling Changes	The sponsor submitted a labeling change. The revisions submitted by the sponsor were not approved.
General
Study Status	Completed
Application Number / Requirement Number	P060018 / PAS002
Date Original Protocol Accepted	07/16/2007
Date Current Protocol Accepted	07/16/2007
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an enhanced surveillance system to collect the patietns demographic, clinical and device information for all complaints and adverse events (both MDR and non-MDR) possibly related to the PRESTIGE device up to 5 years after device approval
Study Population	Study includes all patients who received Prestige Cervical Disc after device approval as per device indication. This device is indicated indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy. Intractable radiculopathy and/or myelopathy should present with at least one of the following items producing symptomatic nerve root and/or spinal cord compression which is documented by patient history (e.g., pain [neck and/or arm pain], functional deficit, and/or neurological deficit), and radiographic studies (e.g., CT, MRI, x-rays, etc.): 1) herniated disc, and/or 2) osteophyte formation. The PRESTIGE 9 device is implanted via an open anterior approach.
Sample Size	N/A
Key Study Endpoints	Complaints and Adverse events
Follow-up Visits and Length of Follow-up	up to 5-year after device approval
Interim or Final Data Summary
Interim Results	During the period of December 11, 2008 through June 15, 2009, the Sponsor has received 8 complaints related to the device and 5 resulted in the filing of MDRs.
Actual Number of Patients Enrolled	n/a
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	Since the PMA approval date of July 16, 2007 through May 13, 2012, a cumulative total of implants have been sold in the U.S., a cumulative total of MDRs have been reported for implants sold in the U.S., and a cumulative total of MDRs have been reported for instruments sold in the U.S. A Kaplan-Meier analysis was conducted on adverse events and second surgeries reported from PMA approval on July 16, 2007 through May 13, 2012. events were included in the time-to-adverse event analysis, with cumulative event rates of 0.413% at months, 0.479% months, 0.479% months, and 0.598%. events were included in the time-to-second surgery analysis, with cumulative event rates of 0.124% at months, 0.190% at months, 0.190% at months, and 0.309% at months and beyond following surgery
Final Effect Findings	n/a
Study Strengths & Weaknesses	The study duration was for 5 years after PMA approval, allowing time to monitor adverse events and complaints received by the company for the device in the postmarket setting. There may be under-reporting of adverse events and complaints to the company. Therefore, the true number of adverse events and complaints during the 5-year study period is unknown. In addition, the total number of implants sold may be an overestimate of the number of devices actually implanted. Therefore, the true number of devices implanted during the 5-year study period is unknown.
Recommendations for Labeling Changes	A labeling change based on the results from this study is not recommended because the study was designed as a surveillance study.
General
Study Status	Completed
Application Number / Requirement Number	P050023 / PAS002
Date Original Protocol Accepted	08/10/2006
Date Current Protocol Accepted	08/10/2006
Study Name	TUPOS LV
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-site post-approval study involving previously implanted Tupos LV/ATx patients who participated in the OPTION CRT/ATx Clinical Investigation. The purpose of this post-approval study is to collect long term survival and long term left ventricular (LV) lead data on patients previously implanted with the Tupos LV/ATx ICD and enrolled into the OPTION CRT/ATx (Cardiac Resynchronization Therapy and Atrial Therapy) clinical investigation.
Study Population	The study population consists of previously implanted Tupos LV/ATx patients who participated in the OPTION CRT/ATx Clinical Investigation. These are patients receiving optimized and stable congestive heart failure (CHF) drug therapy, symptomatic CHF (NYHA class III/IV and LVEF <= 35%), intraventricular conduction delay (QRS 130 ms).
Sample Size	The post-approval study required following the existing OPTION Tupos LV/ATx patient cohort and did not require enrollment of any new patients with Tupos LV/ATx CRT-D devices. Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients still remained actively followed in the OPTION CRT/ATx study when FDA granted approval of the Tupos LV/ATx CRT-D device (P050023) on August 10, 2006. Therefore, since no new enrollment was planned, time to close enrollment is not applicable for this study as enrollment was closed as soon as all 49 active patients were approached and provided consent.
Key Study Endpoints	The post-approval study will report patient mortality, left ventricular (LV) lead capture thresholds and specific left ventricular lead related complications, such as diaphragmatic stimulation and loss of left ventricular capture. In addition, data regarding the Tupos LV/ATx system status, the percentage of patients receiving CRT, and left ventricular lead adverse events will be collected.
Follow-up Visits and Length of Follow-up	The patients are followed every 3-months for a period of three years. The patient's follow-up schedule is a continuation of the OPTION CRT/ATx follow-up schedule. The follow-up visits coincide with their routine ICD care.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients remained active for follow-up in the OPTION CRT/ATx study.
Actual Number of Sites Enrolled	19 sites
Patient Follow-up Rate	Of the original 129 OPTION CRT/ATx patients successfully implanted with a Tupos LV/ATx, 49 patients remained active for follow-up (every 3-months for a period of three years) in the OPTION CRT/ATx study. Of the 49 patients enrolled in the post approval study, 10 withdrew consent, 4 died, and 35 had the device explanted.
Final Safety Findings	A total of 119 measurements in 47 patients were performed at routine and interim follow-ups. The average left ventricular lead threshold at 0.5 ms pulse width was 1.7 V with a standard deviation of 1.1 V and a range of 0.5 to 6.0 V. Thirty-three percent of the patients had average thresholds 2.0V or more and 20% of the patients averaged 3.0 V or more. There were many explants due to the end of service life, accounting for 32 of the 34 reported complications. There is quite a bit of variability in the left ventricular lead threshold regardless of the variability associated with the small sample size. However, 80% of the final thresholds were < 3V, and 96% were < 4V.
Study Strengths & Weaknesses	Weakness: Of the 49 patients enrolled in the post-approval study, 10 withdrew consent, 4 died, and 35 had the device explanted.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P030025 / PAS002
Date Original Protocol Accepted	03/04/2004
Date Current Protocol Accepted
Study Name	TAXUS (IDE)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a follow-up of the pre-market cohort.
Study Population	This device is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries >2. 25 to <4. 0mm in diameter in lesions < 28mm in length. The study population consisted of individuals in the original IDE study population.
Sample Size	TAXUS IV 662 patients, TAXUS V 556, 76 sites
Key Study Endpoints	No endpoints were specified.
Follow-up Visits and Length of Follow-up	Annually to five years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1218 patients
Actual Number of Sites Enrolled	76 sites
Patient Follow-up Rate	95%
Final Safety Findings	The major adverse cardiac event rates over time were significantly lower for TAXUS treatment group as compared with the Control arm. Through 5 years, the event rate was 24.0% in the TAXUS group compared with 32.8% for the Control group, for a relative percent change of 26.9%.
Study Strengths & Weaknesses	Strengths: The sponsor had excellent patient follow-up at 95%. Weaknesses: There was no postapproval followup protocol.
Recommendations for Labeling Changes	There were no recommendations for changes to the labeling based on the results of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P060001 / PAS002
Date Original Protocol Accepted	08/02/2007
Date Current Protocol Accepted	08/02/2007
Study Name	CREATE (IDE)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P060033 / PAS002
Date Original Protocol Accepted	02/01/2008
Date Current Protocol Accepted	09/16/2008
Study Name	Registry PROTECT CA
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This post-approval study (PAS) uses the pooled data from the PROTECT and PROTECT Continued Access (CA) studies in on-label patients to evaluate the annual rates of stent thrombosis (ST) and cardiac death (CD) plus myocardial infarction (MI) for all Endeavor on-label patients. The PROTECT study is a prospective, multi-center, randomized, two-arm, open-label study. The primary objective is to compare the overall stent thrombosis rate of the Endeavor Zotarolimus-Eluting Coronary Stent System versus the Cypher Sirolimus-Eluting Coronary Stent System in a patient population requiring stent implantation. The PROTECT CA study is a prospective, multi-center, non-randomized, single-arm, open label study. The primary objective is to evaluate the overall stent thrombosis rate of the Endeavor Zotarolimus-Eluting Coronary Stent System in a patient population requiring stent implantation.
Study Population	The PROTECT and PROTECT CA patient populations include consecutive patients eligible for drug-eluting stent implantation in one or more target lesions. Patients with lesions in native coronary arteries who met all eligibility criteria were enrolled.
Sample Size	A minimum of 1,000 Endeavor patients will be enrolled in the US, including: a. US patients enrolled in the PROTECT study and randomized to ¿Endeavor¿; and b. US patients enrolled in a single arm fashion in PROTECT CA. Sites: 60 to 100 US sites
Key Study Endpoints	Primary Endpoint ST rate defined as definite and probable stent thrombosis, according to the ARC definition. Secondary Endpoint CD/MI composite endpoint. CD defined as any death due to immediate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia). MI per Medtronic historical definition (Q wave or non-Q wave MI).
Follow-up Visits and Length of Follow-up	Length of follow-up: 5 years Follow up at: 1, 6 , 12, 18, 24, 30, 36, 48, and 60 months
Interim or Final Data Summary
Interim Results	None reported for this portion of study.
Actual Number of Patients Enrolled	The PAS analyses included 1,769 on-label patients.
Actual Number of Sites Enrolled	64 sites
Patient Follow-up Rate	At five years the follow-up rate was 94.6% (1673/1769).
Final Safety Findings	The annual rate of ARC-defined definite and probable stent thrombosis at 5 years for on-label patients in PROTECT and PROTECT CA studies was 0.06% (1/1673, upper 95% CI: 0.28%, p<0.001).
Final Effect Findings	The 5-year cumulative rate of cardiac death or myocardial infarction for on-label patients in PROTECT and PROTECT CA studies was 6.40% (107/1673). This rate is below the performance goal of 8.4% (p<0.001)
Study Strengths & Weaknesses	The study had a low rate of attrition, thus minimizing selection bias. The study met its performance goals and had a large sample size showing a long-term outcome of the stent
Recommendations for Labeling Changes	A labeling change is not needed because Medtronic Vascular has ceased manufacturing and distribution of the Endeavor Spring OTW and RX devices.
General
Study Status	Completed
Application Number / Requirement Number	P050031 / PAS001
Date Original Protocol Accepted	06/06/2007
Date Current Protocol Accepted	06/06/2007
Study Name	Paragon PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a retrospective study design where a randomly selected, stratified sample of 200 practitioners will be identified to determine their patients fit with duration of lens wear, and establish the presence or absence of a history of microbial keratitis. For practitioners who ordered less than 25 pairs of the lenses in 2004 and 2005, all patients will contribute to the analysis and those who ordered 25 or more, no more than 50 patients will contribute to the analysis. This post-approval study condition of approval is being fulfilled by a 522 study that was already proposed when this device was approved.
Study Population	Study population is as per approved device indication: The lenses are indicated for use in the reduction of myopic refractive error in non-diseased eyes. The lenses are indicated for overnight wear in a Contact Lens Corneal Refractive Therapy fitting program for the temporary reduction of myopia up to 6.00 diopters in eyes with astigmatism up to 1.75 diopters. The lenses may be disinfected using only a chemical disinfection system. Practitioners were surveyed and asked if they had observed microbial keratitis cases among the patients who received the device.
Sample Size	Approximately 1,000 pediatrics and 1,000 Adults. A total of 2,000 patient-years had to be accrued
Key Study Endpoints	Cases of microbial keratitis (MK)
Follow-up Visits and Length of Follow-up	On average each subject was to be followed for 1 year
Interim or Final Data Summary
Interim Results	Final Report submitted, currently under FDA review.
Actual Number of Patients Enrolled	1317
Actual Number of Sites Enrolled	86
Patient Follow-up Rate	84.8%
Final Safety Findings	Incidence of microbial keratitis was the main study endpoint. A total of 2,599 patient-years of lens wear for 1,317 patients were included in the analysis. At the original fitting date the mean age of the pediatric group was 12.2_+ 2.5 years and for adults was 38.0 + 11.1 years. The mean follow-up for the pediatric group was 2.1+0.8 years, with 620 (92%) having at least 12 months of follow-up, for adults the mean follow-up was 1.8+10 years, with 497 (78%) having at least 12 months of follow-up. The outcome Assessment Panel identified two cases of microbial keratitis within 2,599 patient years of overnight corneal reshaping lens wear. Both cases of microbial keratitis occurred at least one year after fitting and neither resulted in any documented long-term loss of best corrected visual acuity. The overall estimated incidence of microbial keratitis is 0.00077 per patient-year including the estimated incidence of 0.00139 per patient-year for the pediatric group, and 0.0 per patient-year for adults. The two-sided 95% confidence interval for difference in risk between the two age groups was -0.00139 to 0.00509. A conservative analysis of 685 patients who began wear of overnight corneal reshaping lenses after January 2005 and had at least one year of document lens wear shows a total of 1,415 patient-years of lens wear (794 pediatric and 621 adult). The two-sided 95% confidence interval for difference in risk between the two age groups was -0.00341 to 0.00927.
Final Effect Findings	Not applicable
Study Strengths & Weaknesses	Due to the nature of retrospective study design, the study was conducted in relatively short period of time, achieving the required number of patient years, as per protocol. However, there are certain study limitations: loss of follow-up of patients with the event of interest, who could seek medical care elsewhere, may introduce bias that could result in no difference between the comparison groups. Additionally, there was low participation rate among the practitioners who were asked to participate in the study, only 86 out of 200 participated.
Recommendations for Labeling Changes	Yes. The recommended labeling change includes a summary of the 522 study including: introduction, study objective, study design, results, conclusions and strengths and limitations.
General
Study Status	Terminated
Application Number / Requirement Number	P040048 / PAS002
Date Original Protocol Accepted	06/04/2010
Date Current Protocol Accepted	06/04/2010
Study Name	Trilogy PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Mixed retrospective and prospective cohort
Study Population	Trilogy AB Acetabular System hip implant recipients -- All patients eligible to receive a primary Zimmer trilogy AB acetabular shell, BIOLOX forte ceramic liner, and a BIOLOX forte ceramic head
Sample Size	250 patients
Key Study Endpoints	1) Harris Hip Score 2) Device survivorship 3) Radiographic parameters (e.g. cup migration)
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Completed
Application Number / Requirement Number	P050034 / PAS002
Date Original Protocol Accepted	10/13/2010
Date Current Protocol Accepted	10/13/2010
Study Name	Premarket Cohort IMT-002-LTME
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ¿LTME¿ Study is designed to further evaluate the safety of the participants of IMT-002 at 84 and 96 months post-implantation of the IMT. The IMT-002 was the pivotal clinical trial that provided 24-month safety and efficacy data for patients with bilateral moderate to severe central vision impairment due to age-related macular degeneration treated with the telescope implant. A number of patients enrolled in Protocol IMT-002 have been followed through 60 months. The proposed post-approval study is to follow these patients through 8 years post-surgery. The planned study is a prospective, observational cohort, open label, single group study of patients who participated in the IMT-002 and the IMT-002-LTM trials regardless of successful telescope implantation. These subjects will be re-contacted and asked to participate in this study.
Study Population	Patients who participated in the IMT-002 trial will be contacted and asked to participate in this study provided they are able to understand and comply with the clinical study and provide informed consent. Inclusion criteria for patients participating in the IMT-002 trial were: Patients with bilateral, stable, untreatable central vision disorders (untreatable AMD or Stargardt¿s macular dystrophy) as determined by fluorescein angiography, and cataract. Patients must have distance BCVA between 20/80 and 20/800, and adequate peripheral vision in one eye (the non-implanted eye) to allow navigation. Patients must achieve at least a five letter improvement on the ETDRS chart in the eye scheduled for surgery, with the external telescope. The planned operative eye must have an anterior chamber depth of at least 2.5mm. Patients must be available for the study duration of approximately 24 months and be willing to attend all visits for training and evaluation. Patients must be alert, mentally competent, and able to understand and comply with the requirements of the clinical trial, and be personally motivated to abide by the requirements and restrictions of the clinical trial. Patients must be able to provide voluntary informed consent. Patients must be at least 55 years of age. Patients must sign and be given a copy of the written Informed Consent form.
Sample Size	The sponsors anticipate a cohort of approximately 70 IMT-002 subjects enrolling at approximately 20 participating sites in this protocol.
Key Study Endpoints	The clinical parameters to be evaluated at study visits in both eyes are: Best spectacle-corrected distance visual acuity (BSDVA) with ETDRS chart Slit lamp examination Fundus examination by indirect ophthalmoscopy Intraocular pressure Adverse events Corneal endothelial cell density in the intraocular telescope operated eye
Follow-up Visits and Length of Follow-up	Subjects will be examined at the time of entry into the study, and then will return for evaluation on the 84-month and 96-month anniversaries dated from the original surgery performed in the IMT-002 study. This schedule of visits is as follows: Enrollment Required only if patient presents more than 3 months before or after the 84-month visit 84 Months (+/- 3 months) 96 Months (+/- 3 months) Up to 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	51
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	94%
Final Safety Findings	The cohort that went to the LTME study and the cohort without going to the LTME study showed similar result in terms of ECD change and adverse events. Mean ECD was somewhat lower at the last available visit prior to LTME enrollment for subjects participating in study LTME, 1575 cells/mm2, compared to subjects not participating in LTME, 1719 cells/mm2 With respect to ocular adverse events of interest, there were no reports of persistent vision impairing corneal edema, no reports of corneal transplantation, no reports of retinal detachment, no reports of device explant, and no reports of device malfunction in LTME subjects during the period of the LTME study. Decrease in BCDVA greater than 2 lines from IMT-002 pre-surgery baseline in the telescope- implanted eye was observed in 7 subjects (14%); 2 (4%) were reported as severe, 2 (4%) as moderate, and 3 (6%) as mild. Decrease in BCDVA was reported as related to the device in 3 of the subjects (6%), unlikely to be related in 3 (6%) and not related in 1 (2%). It is noteworthy that a decrease in BCDVA greater than 2 lines from the IMT-002 baseline was reported in 14 non- implanted eyes of the LTME subjects (29%). Thus, a loss of BCDVA >2 lines occurred in twice as many fellow eyes as in telescope implanted eyes. Ocular hypertension was reported in 1 subject (2%); severity was rated as mild and was reported to be device related. There was no report of telescope dislocation, choroidal neovascularization, endophthalmitis, or retinal vascular occlusion during the LTME study in intraocular telescope implanted eyes. One (1) subject (2%) was hit in the telescope implanted eye by a tree branch while tilling his garden; the event was rated as severe and was related to the device.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The study was an extended follow-up study of the IDE study cohort. The final follow-up rate was 96% (49/51). Due to the advanced age of the patients, the delay in approval of the PAS protocol and the associated time constraints, and the fact that many sites chose not to participate, the PAS study had only a small number (i.e., 49 patients in the device group) of the subjects who completed the LTME study and data were almost exclusively from a single study visit. This may present a limitation of the data in terms of the generalizability of the study results.
Recommendations for Labeling Changes	Yes, update label with 5-years post-op data .
General
Study Status	Completed
Application Number / Requirement Number	P050037 / PAS001
Date Original Protocol Accepted	12/22/2006
Date Current Protocol Accepted	12/22/2006
Study Name	Radiesse
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort study desgined to extend the follow-up patients enrolled in the premarket study. Patients will be followed for 18-months.
Study Population	This device is indicated for subdermal implantation for restoration and/or correction of the signs of facial fat loss (lipoatrophy) in people with human immunodeficiency virus (HIV). The study population includes patients with facial lipoatrophy due to antiretroviral therapy for human immunodeficiency virus.
Sample Size	98 patients, 3 sites
Key Study Endpoints	At the 18-month visit, subjects had a Global Aesthetic Improvement Scale assessment, photograph, skin thickness measurement, patient satisfaction assessment, CD4+ cell count and viral load test, and recording of adverse events and medications.
Follow-up Visits and Length of Follow-up	The study required 18 month follow-up. As a part of the post-market requirement, study participants had one additonal visits at 18 months.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	92 patients
Actual Number of Sites Enrolled	3 sites
Patient Follow-up Rate	92%
Final Safety Findings	Adverse events including allergic reaction, ecchymosis, edema, embolization, erosion, erythema, extrusion, granuloma, hematoma, infection, necrosis, needle jam, nodule, pain, and pruritis were noted. Most of these adverse events coincided with the device injection time.
Study Strengths & Weaknesses	The weakness of the study was that there was no control group.
Recommendations for Labeling Changes	Labeling change were submitted by the manufacturer. The revisions submitted by the sponsor were not approved.
General
Study Status	Completed
Application Number / Requirement Number	P050052 / PAS001
Date Original Protocol Accepted	12/22/2006
Date Current Protocol Accepted	12/22/2006
Study Name	Long Term (Nasolabial Folds)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is desgined to extend the follow-up patients enrolled in the premarket study. Patients will be followed for 3 years after the date of their first Radiesse study injection in the premarket study.
Study Population	This device is indicated for subdermal implantation for the correction of moderate to severe facial wrinkles and folds such as nasolabial folds. Thr study population includes premarket study population.
Sample Size	100 subjects, 4 sites
Key Study Endpoints	There were no primary effectiveness endpoints defined. Patients were assessed for the late onset of Radiesse adverse reactions experienced since their last visit. Late onset adverse reactions included nodule, granuloma, necrosis, erosion, or infection.
Follow-up Visits and Length of Follow-up	The study required 3 year follow-up. As a part of the post-market requirement, study participants had one or two additonal visits to meet the 3 year follow-up requirement.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	102 of the 117 patients who participated in premarket study enrolled 99 of the 102 subjects compltede 2 study visits and 3 years of follow-up
Actual Number of Sites Enrolled	4 sites
Patient Follow-up Rate	97%
Final Safety Findings	No adverse events were reported by the study although its purpose was to collect long-term safety information on the use of the device and to assess the effect of multiple injections. Expected immediate post-injection site adverse events were not collected either.
Study Strengths & Weaknesses	The weakness of the study was that there was no control group. Study weaknesses inlcude the the following: The safety assessment is confounded by the use of other dermal fillers or Botulinum Toxin. The PAS did not collect information about the exact date of Radiesse injections; only approximate date is provided. This report does not provide the volume of Radiesse injection either.
Recommendations for Labeling Changes	Update labeling to reflect the results of the PAS taking into account study limitations
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P050039 / PAS001
Date Original Protocol Accepted	07/05/2007
Date Current Protocol Accepted	12/09/2010
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, open label clinical study. Up to ten (10) centers around the United States will participate in this study. However, because of the lack of progress on the original PAS, FDA asked the sponsor to redesign the PAS. The PAS was revised per a FDA letter dated 7/14/09. The new protocol is not approved yet [Aug 13, 2010]. The description presented here is for the old study.
Study Population	The study population is comprised of patients implanted in the United States and potentially outside the United States in Greece and/or France. Sample size and power calculations are not provided in the protocol. Patients who receive the Novation Ceramic Articulation System for Non-inflammatory Degenerative Joint Disease
Sample Size	prospective and retrospective cohort, active surveillance, up to 10 clinical sites in prospective and retrospective cohort, and 7 sites in active surveillance
Key Study Endpoints	The first phase of the study extending through 5 years of patient follow-up, will consist of clinical examination, including the determination of a Harris Hip Score, radiographic examination and the collection of subject self-assessment data. These data will be obtained pre-operatively, immediately post-operatively, at three months, and annually up to five years. An independent radiographic review will be conducted at five years In the second phase, during postoperative years 6-10, an outcomes questionnaire will be mailed to subjects to determine the status of their hip replacement. No clinical and/or radiographic examinations are proposed for this time period. The study endpoints are as follows: Efficacy Endpoints 1) Survivorship of the Novation Ceramic AHS system at 2, 5, and 10 years. 2) Patient success defined as: - Absence of revision - Harris Hip Score greater than or equal to 70 - No complete radiolucencies The following endpoints will also be evaluated at the 2-year follow-up: - Harris Hip Score - Radiographic assessment - SF-12 Safety endpoints will encompass complication rates, including incidence, severity and the relationship to the device.
Follow-up Visits and Length of Follow-up	The length of patient follow-up is 10 years. Follow-up visits will occur pre-operatively, immediately post-operatively, at six weeks, six months, and annually up to five years. Study subjects will receive annual questionnaires from postoperative years 6 through 10.
General
Study Status	Ongoing
Application Number / Requirement Number	P030053 S069/ PAS001
Date Original Protocol Accepted	01/17/2025
Date Current Protocol Accepted	05/11/2026
Study Name	Athena PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Demonstrate safety and effectiveness of Mentor’s larger size Ultra High Profile (UHP-L) smooth and textured breast implants in women who are undergoing post-mastectomy primary reconstruction or revision reconstruction.
Study Population	The study planned to enroll a minimum of 280 (maximum 400) patients. The actual enrollment was completed in January 2019 with 400 patients. Enrollment numbers by indication: • Primary Reconstruction in women at least 18 years old with surgically absent breast tissue (post-mastectomy, requiring a two-stage breast reconstruction): the study planned to enroll a minimum of 180 patients; the actual enrollment was 225 patients. • Revision Reconstruction in women at least 18 years old with surgically absent breast tissue: the study planned to enroll a minimum 100 patients; the actual enrollment was 175 patients.
Sample Size	The study enrolled 225 primary reconstruction subjects and 175 revision reconstruction subjects. The calculation of the minimum number of subjects required in the primary reconstruction cohort is based on the precision of estimates for the complication rates at 2 years. Consideration is also given to the precision of estimated complication rates at 3 and 5 years for the cohort as well as to the precision of estimates within the ADM subsets at the subject level, using 2-sided 95% confidence intervals. The calculation of the minimum number of subjects required in the revision reconstruction cohort is based upon the minimally detectable complication rate of 3.3% within the Revision Reconstruction cohort without ADM use. Enrollment of at least 20 subjects per implant size will be targeted and achieved. Implant sizes 750-800cc may be pooled together to reach a reasonable number of subjects for the smallest pooled implant size. Implant sizes of 1340-1445cc may be pooled together to reach a reasonable number of subjects per the largest pooled implant sizes. Enrollment of subjects in each size will be monitored and no plans to cap enrollment in any specific size are being made at this time so as to reflect real world demand and usage. Total number of sites: the study planned to enroll patients in up to 35 (Each PI/site may have multiple facilities and/or multiple surgeons for performing surgery, located in the United States.); the actual enrollment occurred in 31 sites.
Key Study Endpoints	The following safety endpoints are being evaluated to assess the safety of the device: • The incidence, timing and resolution of all complications. • The incidence, timing and nature of difficulties with pregnancy. • The incidence, timing, and cause of subject deaths. • The incidence, timing, and type of any new breast cancer diagnosis for the subject post-implantation. Effectiveness is being assessed during the study based on subject-reported outcomes for self-esteem, body image, and general health. Subject satisfaction and investigator satisfaction will also be assessed.
Follow-up Visits and Length of Follow-up	Subject visits have been planned at baseline, operative visit, 10 weeks post implant, and annually up to 10 years. MRIs or ultrasound were scheduled at year 3, 5, 7, 9 and 10.
General
Study Status	Ongoing
Application Number / Requirement Number	H230007 / PAS001
Date Original Protocol Accepted	12/04/2024
Date Current Protocol Accepted
Study Name	Continued Follow-up of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, non-blinded, single-arm, multicenter interventional study to assess continued follow-up of IDE subjects. To assess the safety and effectiveness of AMDS to treat patients with acute DeBakey type I dissection with evidence of radiographic and/or clinical malperfusion, through open surgical repair.
Study Population	Patients with acute DeBakey Type I aortic dissection presenting with radiographic and/or clinical evidence of organ malperfusion, who meet all of the selection criteria.
Sample Size	93 patients in the pivotal study cohort
Key Study Endpoints	The co-primary endpoints for the primary cohort are the following event rates at 30-days: 1. Patients experiencing at least one of the following MAEs: • All-cause mortality (ACM) • New disabling stroke • New onset renal failure requiring dialysis • Myocardial infarction (MI) 2. Patients with DANE documented by the independent Core Lab on a post-operative CTA Key secondary endpoints: • Mortality • Additional Aortic Procedures • Device Related Events • Major Adverse Events • Remodeling in the treated aortic segmented
Follow-up Visits and Length of Follow-up	60 months
General
Study Status	Completed
Application Number / Requirement Number	P050050 / PAS001
Date Original Protocol Accepted	05/27/2009
Date Current Protocol Accepted	05/09/2014
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The specific objective of this long-term study is to obtain information on the revision and removal rate for the STAR Ankle over time in order to establish the device¿s survivorship. The post approval study is a prospective, multi-center, single-arm study at up to the 10 primary sites that participated in the pivotal and continued access studies. The study is continued follow-up of the premarket cohort and continued access cohort.The long-term results of Ankle Arthrodesis summarized from literature review by meta-analysis will be used as historical fusion control.
Study Population	The study population consists of all living subjects who participated in the continued access study. Device Group: subjects implanted with the STAR Ankle Comparison Group: Historical Fusion Control (i.e., the long-term results of Ankle Arthrodesis summarized from literature review by meta-analysis) Fusion results reported by Haddad, et al. (2007)7 will serve as the control group for the STAR Continued Access subjects. [Haddad SL, Coetzee JC, Estok R, Fahrbach K, Banel D, Nalysnyk L. Intermediate and long-term outcomes of total ankle arthroplasty and ankle arthrodesis. A systematic review of the literature. J Bone Joint Surg Am. 2007 Sep;89(9):1899-905.]
Sample Size	minimum 125 patients (STAR Ankle recipients) The comparison of the STAR ankle is to a literature control, in Haddad et al. [2007], with a survivorship rate of 86.3%. An informal calculation indicates how many successes are needed in the STAR ankle group to claim non-inferiority. Sponsor assumed that the observed success rate for the fusion control was 94/109 = 86.3%, where the 109 is the effective sample size. Then, from StatXact-8 software, 40/47 = 85.1% is the smallest observed success rate so that a lower 90% confidence bound for the difference of success probabilities is no less than ¿15%. Note: This calculation uses two observed proportions, and is not a power-based calculation of detectable effect size. Using PASS2005 sample size software, the sponsor performed a two-sample, exact non-inferiority calculation to compare the STAR ankle to a historical control with 109 subjects, a true success rate of 86.3%, and using a one-sided test with 5% Type 1 error rate, 80% power, and a 15% non-inferiority margin. The necessary sample size to show non-inferiority is 47 subjects in the STAR ankle study arm. However, SBi¿s intention is to enroll at minimum 125 patients and follow all who continue to participate. The meta-analysis performed by Haddad et al. [2007] had a sample size of 1262 subjects who received an arthrodesis. However, for purposes of the sample size calculation, the effective sample size in Haddad et al. [2007] is only 109, far less than the 1262 subjects in the articles that were included in Haddad¿s meta-analysis. A technical justification for this reduced number of control subjects appears in protocol Section 6.1.3.1
Key Study Endpoints	Primary Effectiveness Endpoint Device Survivorship (Revision and Removal) at 8 years after implantation Note: The information collected at these post-operative intervals will be added to the previously collected follow-up data (e.g., demographic, baseline, post-operative through 24-months). Other Effectiveness Endpoints Total Buechel-Pappas Scale score (100-point scale consisting of subscales for pain (40 points), function (40 points), range of motion (15 points), and deformity (5 points)) Pain Visual Analog Scale (VAS) (100mm scale) Quality of Life (SF-36) AOFAS Radiographic endpoints (assessed by Anterior-posterior and lateral x-ray images of the treated ankle) Radiolucency Migration Safety Endpoints All adverse events, including information concerning the nature, onset, duration, severity, and relationship to the device and operative procedure
Follow-up Visits and Length of Follow-up	96 months 48 months (± 8 weeks) , 72 months (± 8 weeks), and 96 months (-8 weeks and any time after 96 Months) post-operatively. Baseline, 6 week, 12 month, and 24 month data will be used as collected for the study in which they originally participated.
Interim or Final Data Summary
Actual Number of Patients Enrolled	95
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	91% (87/95)
Final Safety Findings	There were 82 device-related AEs in 37 subjects. Based on 87 subjects with 96-month follow-up, at least 12 (13.8%) were for polyethylene fracture, all requiring revision. 18 (20.7%) of the device-related adverse events were for formation of cysts, 16 of which required surgical treatment. 21 of 95 (22%) subjects had to undergo one or more secondary procedures related to revision or removal of the device.
Final Effect Findings	The overall Kaplan-Meier survivorship estimate for the cumulative surviving proportion based on the first removal/revision at 96 Months is 75.5% (std. error: ±3.9%). This was found to be not worse than the predefined arthrodesis control.
Study Strengths & Weaknesses	Long-term (8 year) follow-up are available in 91% of the enrolled study subjects, a study strength. Study weaknesses include: the study enrolled only 76% of the subjects from the continued access study from the IDE study and only 5 of 10 of the IDE study sites. Though some similarities among study participants and non-participants were demonstrated, selection bias remains a study limitation. Also, the study population may not be representative of real-world use.
Recommendations for Labeling Changes	A labeling change is recommended to include the long-term follow-up data generated in this Post-Approval study, including revision rates and device-related adverse event rates. The risk related to polyethylene fracture should be identified.
General
Study Status	Ongoing
Application Number / Requirement Number	P000037 S030/ PAS001
Date Original Protocol Accepted	06/19/2015
Date Current Protocol Accepted	08/15/2019
Study Name	Newly Enrolled On-X PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To assess the occurrence of bleeding, valve related thromboembolism and valve thrombosis with the On-X Aortic Prosthetic Heart Valve when targeted at an International Normalized Ratio (INR) level of 1.8 (1.5-2.0 range) during a 5-year follow-up period. The study is a prospective, multicenter, observational single arm study of newly enrolled patients treated with the On-X Aortic Prosthetic Heart Valve.
Study Population	1. Adult patients (age 18 years or older) who have an isolated On-X aortic prosthetic heart valve implant and agreed to participate in the registry. 2. Life expectancy of at least 5 years. 3. Patients whose operation occurred within the year prior to recruitment. The following are criteria for exclusion of patients from this study: 1. Patients having any other type of prosthetic valve implant (isolated or in combination with another valve(s)) or any On- X mitral valve; i.e. no mitral or multiple valve implants. 2. Patients with a prior history of arterial thromboembolic events, or who have such events prior to recruitment. 3. Death prior to discharge or recruitment. 4. Patients whose surgery predates enrollment by more than 1 year. Comparison groups shall be the control groups, individually or together, as appropriate for AVR in the prior IDE trial.
Sample Size	510 The sample size for the registry was calculated with the following assumptions: Incidence of composite outcome estimated via Poisson regression 1-sided test comparing the composite outcome to the reference value 5% significance level 90% power Expected overall composite proportion from the IDE high risk treatment group (pT) = 0.0457/patient-year (ptyr) Reference value (p95, upper 95% confidence bound from PROACT study) =0.0693/ptyr 800 patient-years of follow-up Anticipated 5 years of follow-up per subject Loss to follow-up over 5 years of 20%
Key Study Endpoints	The primary safety endpoint is the composite of major bleeding, total TE and valve thrombosis. Composite outcome incidence rate in: Clinic monitored high-risk patients Clinic monitored low-risk patients Home monitored low-risk patients Home monitored high-risk patients Events are to be considered individually including subsets of bleeding and TE as secondary endpoints. Death, reoperation and explant when associated with a primary endpoint event shall be reported. Sudden death will also be recorded as a secondary endpoint. Asditional Endpoints: Peripheral TE Minor bleeding All bleeding (major and minor) Ischemic stroke TIA Hemorrhagic stroke Reoperation, explant, and death (associated with valve-related TE, VT, or bleeding)
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P140003 / PAS001
Date Original Protocol Accepted	11/13/2015
Date Current Protocol Accepted
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: to evaluate the safety and effectiveness of the IMPELLA 2.5 System compared to a predefined Performance Goal (PG) based on the PROTECT II 90 days Major Adverse Events (MAE) rates. Design: a multicenter, prospective single arm study. This is a new enrollment study.
Study Population	High risk subjects indicated for nonemergent percutaneous treatment after heart team evaluation including a cardiac surgeon of at least one de novo or restenotic lesion in a native coronary vessel or bypass graft. The high risk subjects are defined by the combination of anatomical and left ventricular function criteria: a) Ejection Fraction =< 35% AND ¿ Intervention on the last patent coronary conduit at least one of the following criteria: ¿ Intervention on an unprotected left main coronary artery Or, b) Ejection Fraction =< 30% and intervention on patient presenting with triple vessel disease. Three-vessel or triple vessel disease is defined as at least one significant stenosis* in all three major epicardial territories: Left Anterior Descending Artery (LAD) and/or side branch, left circumflex artery (LCX) and/or side branch, Right Coronary Artery (RCA) and or side branch. *Significant stenosis is defined as at least 50% diameter stenosis by visual estimate or any total occlusion. In the case of left coronary artery dominance, a lesion in the LAD and the proximal LCX qualifies as three-vessel disease. No comparator group.
Sample Size	A total of up to 70 sites will be enrolled. At least 20 or more sites will be non-IDE sites and will enroll 25-35% of the patients. No study center (site) is allowed to have more than 20% of all subjects. Assuming the true proportion of 90 day MAE is 0.45, a total of 335 evaluable subjects will provide 90% power to reject the null hypothesis with one-side alpha error of 5%. Assuming 10% loss to follow-up to 90 days, 369 subjects will be enrolled in the study.
Key Study Endpoints	Main Safety Endpoints: A composite rate of the following 10 intra-procedural and post- procedural major adverse events (MAE) at 90 days post index procedure. 1) Death 2) Myocardial infarction 3) Stroke/TIA 4) Repeat revascularization 5) Need for cardiac operation or thoracic or abdominal vascular operation or vascular operation for limb ischemia 6) Acute renal dysfunction 7) Increase in aortic insufficiency by more than one grade 8) Severe hypotension defined as systolic blood pressure <90 mmHg for >=5 min requiring inotropic/pressor medications or IV fluid 9) Cardiopulmonary resuscitation or Ventricular arrhythmia requiring cardioversion 10) Failure to achieve angiographic success defined as residual stenosis <30% after stent implantation Secondary Safety/Effectiveness Endpoints: ¿ Improved baseline hemodynamics post support initiation as measured by maximal increase in Mean Arterial Pressure within 30 min of support initiation. ¿ Improvement in Left Ventricular Ejection Fraction (LVEF) at 90 days as compared to baseline ¿ Improvement in NYHA class at 90 days as compared to baseline Additional Exploratory Endpoints: 1.Rate for each of the individual components of the composite primary endpoint at 90 days; 2.Procedural safety endpoint: composite endpoint at 30 days post index procedure including: - Death - Stroke or TIA - Need for vascular operation - Peri-procedural myocardial infarction - Transfusion of 2 units of PRBCs - Increase in aortic insufficiency by more than one grade - Acute renal dysfunction 3. Procedure effectiveness endpoint: composite at 30 days post index procedure, i.e. alive at 30 days with none of the following: - Procedural hypotension requiring treatment - Failure to achieve angiographic success - Intra-procedural cardiopulmonary respiration or cardioversion. 3. Long term assessment (composite at 90 day and 1 year): Proportion of patients alive and none of the following: spontaneous myocardial infarction, repeat re-hospitalization for heart failure or repeat revascularization (PCI or CABG). 4. Composite endpoint at 90 days and 1 year post index procedure: Major Adverse Cardiac and Cerebrovascular Events (MACCE), including death, stroke, myocardial infarction, repeat revascularization
Follow-up Visits and Length of Follow-up	1 year Pre- and during the PCI procedure, immediately following the PCI procedure or device explant, in the ICU or the floor where the patient will spend the remainder of his or her hospital stay, at hospital discharge, 30 days, 90 days, and 1 year post PCI.
General
Study Status	Completed
Application Number / Requirement Number	P050052 S049/ PAS002
Date Original Protocol Accepted	11/23/2015
Date Current Protocol Accepted	09/18/2017
Study Name	Radiesse New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a 2-year, prospective, open-label, new enrollment study in 250 subjects enrolled at up to 12 sites to evaluate the safety and effectiveness of Radiesse implantation for very severe volume loss in the dorsum of the hands in MHGS 4 subjects. The primary objective is to compare the rate of device/injection- related severe adverse events (AEs) in the Merz Hand Grading Scale (MHGS) 4 group (Group A) versus the MHGS 2/3 group (Group B). A secondary objective is to assess the effectiveness of Radiesse for very severe volume loss in the dorsum of the hands. Another secondary objective is to assess the safety of multiple retreatments with Radiesse in the dorsum of the hand.
Study Population	The study population will consist of subjects who are at least 22 years old with hands rated as MHGS 2, 3, or 4. Additional inclusion and exclusion criteria are specified in the protocol. All subjects will receive an initial treatment with Radiesse and have an opportunity to receive up to 3 additional treatments over the course of this study.
Sample Size	A maximum of 250 subjects will be enrolled at a minimum of 5 sites and a maximum of 12 sites in the US. At 6-months, 244 subjects are expected to provide approximately 80% power to test the hypothesis. With a 5% attrition rate per year, a minimum of 225 evaluable subjects are required to provide 2-year follow-up data.
Key Study Endpoints	The primary safety endpoint is the 6-month rate of devices/injection-related severe AEs. The secondary endpoints of the study are: -The rate of device/injection-related severe adverse events at 24 months -MHGS at 3-months after initial treatment -MHGS at 3-months following retreatment for those receiving retreatment -Global Aesthetic Improvement Scale (GAIS) at 3-months after initial treatment -GAIS at 3-months following retreatment for those receiving retreatment -Hand function testing at baseline, study exit, and other collected time points o Inter-rater correlation of hand function testing results for each site o Differences between sites in hand function testing results Other endpoints of the study are: -MHGS at 1-, 6-, 12-, 18-, and 24-months after initial treatment -MHGS at 1-, 6-, 12- and 18-months follow retreatment for those receiving retreatment -GAIS at 1-, 6-, 12-, 18-, and 24-months after initial treatment -GAIS at 1-, 6-, 12- and 18-months follow retreatment for those receiving retreatment -Michigan Hand Outcomes Questionnaire (MHQ) at baseline, study exit, and other collected time points -Incidence of all adverse events over the course of the study
Follow-up Visits and Length of Follow-up	Subjects will be followed for 24 months. After screening/enrollment, subjects will be followed at 2 weeks, 1, 3, 6, 7, 12, 13, 18, 19, and 24 months. (The 7 and 19 month visits are only to document serious or medically concerning AEs).
Interim or Final Data Summary
Actual Number of Patients Enrolled	256
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	94%
Final Safety Findings	Adverse events include swelling, pain, redness, bruising, difficulty performing activities, itching, loss of sensation, bumps/lumps, and hematoma. Two (2) device/injection-related severe treatment emergent adverse events (swelling) were reported during the study
Final Effect Findings	Majority of subjects in both groups showed at least one point in the Global Aesthetic Improvement Scale (GAIS) when compared to baseline. Re-treatment showed less pronounced GAIS improvement.
General
Study Status	Completed
Application Number / Requirement Number	P060001 / PAS001
Date Original Protocol Accepted	08/02/2007
Date Current Protocol Accepted	08/02/2007
Study Name	CREATE PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-site, non-randomized study in which consecutive qualifying subjects undergoing carotid interventional procedures are enrolled. No formal statistical hypothesis testing will be conducted, except for the sequential monitoring against a predefined criteria for rate of events, which will be carried out by the Clinical Events Committee.
Study Population	The PROTÉGÉ Stent will be implanted in stenoses in the common and/or internal carotid artery in subjects with a high risk for complications during carotid endarterectomy. The interventional procedure will be performed with the SpiderFX Device that is intended to reduce the risk of distal embolization during percutaneous carotid interventions.
Sample Size	A total of xx subjects in two cohorts will be enrolled into the study. The first 500 subjects will be enrolled in the one-year cohort and will be followed for one year post-study procedure. The next 1000 subjects will be enrolled in the 30-day cohort and will be followed for 30 days post-study procedure. Up to 150 sites.
Key Study Endpoints	One-year Cohort: Subjects will be evaluated for the combined incidence of Major Adverse Cardiac and Cerebrovascular Events defined as myocardial infarction ipsilateral cerebrovascular accident, procedure-related contralateral cerebrovascular accident, or death, within 30 days of implantation; and ipsilateral cerebrovascular accident from 31 days to one year post-implantation. 30-day Cohort: Subjects will be evaluated for the combined incidence of Major Adverse Cardiac and Cerebrovascular Events defined as myocardial infarction, ipsilateral cerebrovascular accident, procedure related contralateral cerebrovascular accident, or death, within 30 days of implantation.
Follow-up Visits and Length of Follow-up	Folllow-up for the One-year Cohort includes a pre-discharge visit, 30-day and one year clinic visits and a telephone contact at six months post study procedure. Follow-up for the 30-day Cohort includes a pre-discharge visit, 30-day clinic visit post study procedure. Length of follow-up: One year
Interim or Final Data Summary
Interim Results	The primary analysis of the one-year cohort is an assessment of Major Adverse Cardiac and Cerebrovascular Events, defined as the combined incidence of death, myocardial infarction, ipsilateral cerebrovascular accident and procedure-related contralateral cerebrovascular accident through 30 days post implantation. It also includes an assessment of ipsilateral cerebrovascular accident from 31 days to one year post-implantation when subjects have reached that stage of follow-up. The secondary analysis includes a presentation on the primary analysis stratified by the implanting physician's experience level. The death rate for the 1-year cohort at 30 days was 3%. The MI rates for the 1-year cohort at 30 day was 1.2%. The procedure-related contralateral cerebrovascular accident rate for the 1-year cohort was 0% and the ipsilateral cerebrovascular accident at 1-year was 0.4%.
Actual Number of Patients Enrolled	1,500
Actual Number of Sites Enrolled	57
Patient Follow-up Rate	93% (1,400/1,500)
Final Safety Findings	In the total cohort, the death rate was ... The one-year serious adverse event rate was ... in the one-year PAS cohort.
Final Effect Findings	The primary analysis of the one-year cohort is an assessment of Major Adverse Cardiac and Cerebrovascular Events (MACCE), defined as the combined incidence of death, myocardial infarction (MI), ipsilateral cerebrovascular accident (CVA) and procedure-related contralateral CVA through 30 days post-implantation. The rates found in the CREATE PAS for both the one-year and 30-day follow-up are both well below the % OPC used for the IDE study.
Study Strengths & Weaknesses	The sponsor attained over ... follow-up for the entire study. The study was not powered to detect rare adverse events. The sponsor was also asked in the approval order to enroll patients from high, moderate and low volume centers and treated by physicians that represent Category 1, 2, and 3 training. The sponsor has done this; however the overwhelming majority of subjects were treated by physicians with level 1 experience. The low number of level 2 and level 3 operators makes it difficult to make any conclusions on the training program.
Recommendations for Labeling Changes	yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P970004 S022/ PAS001
Date Original Protocol Accepted	09/24/2002
Date Current Protocol Accepted	10/23/2007
Study Name	Urgency Frequency (UF 1635)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P060006 / PAS001
Date Original Protocol Accepted	12/11/2008
Date Current Protocol Accepted	12/11/2008
Study Name	BSC Express PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Renaissance study is a prospective, multi-center, single-arm study for use of the Express Renal stent in the treatment of ostial atherosclerotic lesions of the renal artery Single, de novo or restenotic from prior PTRA lesions were to be included in the clinical trial. The primary objective of the study was to demonstrate a superior 9-month binary restenosis rate of the Express Renal Premounted Stent System as compared to an Objective Performance Criterion representative of PTRA, for atherosclerotic lesions in the aortorenal ostium.
Study Population	The Boston Scientific Express SD Renal Monorail Premounted Stent System is indicated as an adjunct to percutaneous transluminal renal angioplasty of a single de novo or restenotic atherosclerotic lesion (< 15 mm in length) of the renal artery, located within 5 mm of the opacified aortic lumen, with a reference vessel diameter of 4.0-7.0 mm to assist in the maintenance of vessel patency. The study population consists of the existing cohort of patients from the RENAISSANCE trial.
Sample Size	100 subjects with 117 lesions, the number of sites not reported
Key Study Endpoints	The primary endpoint is binary in-stent restenosis rate of the Express Renal Stent at nine months, defined as the proportion of lesions with >50% diameter stenosis as determined by quantitative angiography.
Follow-up Visits and Length of Follow-up	All subjects will be evaluated at 30 days, 4 months, 9 months, and annually for five years following the index procedure. The 30-day and 9-month visits must be office visits; the 4-month assessment is accomplished over the telephone. All subjects will undergo duplex ultrasound at 9 months and at 2 years after the index procedure. Office visits are required for the 1 -year and 2-year follow-ups. For the 3-, 4-, and 5-year annual follow-ups, office visits are strongly recommended; however, phone follow-ups at a minimum are required.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	100 patients
Actual Number of Sites Enrolled	Not reported
Patient Follow-up Rate	82%
Final Safety Findings	No serious, device-related events that were unanticipated in nature, frequency or severity occurred during the study. Furthermore, no new major adverse events occurred between the 4- and 5-year time points. Rates of target lesion revascularization, target vessel revascularization, and major adverse events have remained stable through 5 years of long-term follow-up with no unanticipated adverse device related events. No device- or procedure-related deaths or stent thromboses have been reported. No subjects progressed to require dialysis through 5 years of follow-up. The results from the study suggest that the Express SD Renal Stent System poses no serious concerns in terms of safety and effectiveness out to 5 year follow-up. As of October 23, 2009, no new revascularizations or significant embolic events have been reported between the 4-year and 5-year visits in any subject; 66 subjects completed the 5-year follow-up visit. Twenty-seven of 100 subjects (27%) had suffered a total of 49 reports of renal artery stenosis categorized as an SAE. The number of site-reported renal artery stenosis events requiring revascularization was 44; 26 of these 44 events in 16 subjects were adjudicated as target lesion revascularization. There have been a total of 19 reported deaths as of October 23, 2009. No deaths were adjudicated as either device- or index procedure-related. Based on the distribution of baseline co-morbidities, (e.g., congestive heart failure (CHF) rates, coronary artery disease (CAD) rates and the mean baseline age of the subjects enrolled in the RENAISSANCE study,) the sponsor concludes that the number of deaths through 5 years of follow-up is at an expected rate.
Study Strengths & Weaknesses	Strengths: Overall follow-up was 81.5% of eligible subjects returning for 5-year follow-up. Weaknesses: There was no post approval hypotheses studied.
Recommendations for Labeling Changes	There were no recommendations for changes to the labeling based on the results of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P060033 / PAS004
Date Original Protocol Accepted	02/01/2008
Date Current Protocol Accepted	02/01/2008
Study Name	Product Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an implementation of updated final product testing methodologies.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	This is an implementation of updated final product testing methodologies.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A This is a bench testing study.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P030050 S002/ PAS001
Date Original Protocol Accepted	09/09/2010
Date Current Protocol Accepted	09/09/2010
Study Name	Pre Clinical PAS
General Study Protocol Parameters
Study Design	Animal Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is an animal study designed to determine the potential visibility of device by various imaging technologies including X-ray computed tomography, radiography, magnetic resonance imaging, and ultrasound imaging at 1 and 90 days after subcutaneous injection to rats. Additionally, injection sites will be microscopically evaluated. all animals will receive the same treatment (subcutenous injection, once on day 1 and once on Day 90 with an Injection volume of 0.2 ml/injection). Injections will be administered to two distinct locations on the dorsal surface of the rat.
Study Population	8-9 weeks old male rats [Crl:CD (SD), Charles River, US Raleigh, NC USA]
Sample Size	The study includes 10 rats.
Key Study Endpoints	Bioimaging procedures will be taken on Day 91, approximately 24 hours after 2nd injection.All animals will be anesthetized for the ultrasound imaging and subsequently euthanized for MRI and X-ray CT/radiography procedures. Imaging procedures will be conducted on the two injection sites and one untreated reference site. Images will be evaluated and categorized. A necropsy will be performed on Day 91 to examine the injection and the untreated reference sites by a pathologist.
Follow-up Visits and Length of Follow-up	The rats will be followed for approximately 91 days.
Interim or Final Data Summary
Interim Results	N/A This is a rat study.
Actual Number of Patients Enrolled	10 male rats
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	100%
Final Safety Findings	Not applicable
Final Effect Findings	Not applicable
Study Strengths & Weaknesses	Strengths: (1) Phantom studies were conducted for each imaging modality to estimate the possible visualization of the injection sites, (2) Results of the in vivo rat studies are consistent with the results of the phantom studies. Weaknesses: (1) the absence of objective criteria for determining the adequacy of visualization (2) the results of the imaging studies in this animal model may not predict the outcomes of bioimaging in humans.
Recommendations for Labeling Changes	The labeling will be changed to report the objectives, methods and results of the preclinical study; conclusions; and possible implications for clinical practice. The conclusions will state that the sponsor has provided adequate and reasonable data exploring the appearance of Sculptra Aesthetic implants as a function of time and imaging modality. Based on the composition of the device, the visualization of the implant shortly after injection by ultrasound and magnetic resonance imaging (MRI), but not computed tomography (CT) and radiography seems consistent with the poly-lactic acid microparticle / aqueous solution composition. Similarly, the decreased incidence of device visualization at 90 days after implant is consistent with the resorbable nature of the implant. Implications for Clinical Practice: The study has met its objective of determining the potential visibility of reconstituted Sculptra® Aesthetic with various imaging technologies. The results of the imaging studies in this animal model may not predict the outcomes of bioimaging in humans. An analysis of the material composing Sculptra® Aesthetic revealed that the material is entirely organic and that it does not appear to contain any metallic or iodine material that would create radiographic contrast to tissue. For this reason conventional radiography is unlikely to visualize the presence of Sculptra Aesthetic in the facial area. Second, PET or other nuclear medicine imaging will not visualize the device because Sculptra Aesthetic¿s components are not radioactive.
General
Study Status	Completed
Application Number / Requirement Number	P050019 / PAS001
Date Original Protocol Accepted	10/23/2008
Date Current Protocol Accepted	10/23/2008
Study Name	CABANA REGISTRY
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The CABANA study is a multi-center surveillance registry. The objectives of the registry are to: 1) to compile early clinical outcomes data for the Carotid WALLSTENT Endoprosthesis and FilterWire EZ System in routine clinical practice, 2) to evaluate clinical outcomes using the death, stroke, and myocardial infarction rate at 30 days or less, in total and by center experience tier, and 3) to assess the adequacy of the Boston Scientific Corporation Carotid Stenting Training Program.
Study Population	The Carotid WALLSTENT Monorail Endoprosthesis, used in conjunction with the Boston Scientific embolic protection system, is indicated for the treatment of patients at high risk for adverse events from carotid endarterectomy due to either anatomic or co-morbid conditions who require carotid revascularization in the treatment of ipsilateral or bilateral carotid artery disease. This includes patients with neurological symptoms and > 50% stenosis of the common, internal carotid artery and/or the bifurcation by ultrasound or angiogram, or patients without neurological symptoms and > 80% stenosis of the common, internal carotid artery and/or the bifurcation by ultrasound or angiogram and patients with a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.
Sample Size	1,500 patients, 150 sites
Key Study Endpoints	The endpoint for the 1,000 newly enrolled patients will be a 30-day composite death, stroke and myocardial infarction
Follow-up Visits and Length of Follow-up	Patients will be followed at 30 days and annually through 3 years.
Interim or Final Data Summary
Interim Results	The 30 day myocardial infarction rate in the BEACH trial was 1.0% while it is 0.5% in the CABANA trial. Death (0.7% in CABANA vs. 1.5% in BEACH) and stroke rates (2.5% in CABANA vs. 4.2% in BEACH) are lower in the CABANA trial than they were in the BEACH pre-market study. The rates of center-reported serious adverse events and non-serious adverse events were 20.1 % (111/553 subjects) and 32.7% (181/553 subjects), respectively. No serious, device-related events that were unanticipated have occurred.
Actual Number of Patients Enrolled	1097
Actual Number of Sites Enrolled	99
Patient Follow-up Rate	95%
Final Safety Findings	Of the 1,025 subjects evaluable for 30-day postprocedure MAE, 0.5% (5/1,025) had MIs, 3.3% (34/1,025) had strokes, and 1.3% (13/1,025) had CEC-adjudicated deaths, contributing to an overall CEC-adjudicated MAE rate of 4.6% (47/1,025). Out of the 34 subjects who had strokes within 30 days postprocedure, the majority (58.8%; 20/34) had strokes that were classified as ¿major,¿ while the rest (41.2%; 14/34 ) had strokes classified as ¿minor.¿ In almost all of the 34 subjects with stroke, the stroke was on the ipsilateral side (88.2%; 30/34) and in most cases the stroke was considered ischemic (85.3%; 29/34).
Final Effect Findings	The sponsor reports that system technical success was achieved in 97.1% of evaluable subjects.
Study Strengths & Weaknesses	The sponsor reports good follow-up of study subjects. However, the study may not have been adequately powered to detect rare adverse events.
Recommendations for Labeling Changes	Yes
General
Study Status	Other
Application Number / Requirement Number	P060025 / PAS001
Date Original Protocol Accepted	10/30/2008
Date Current Protocol Accepted	10/13/2015
Study Name	ATS 3f
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, non-randomized trial, registry study designed to follow at least 101 patients for 6 years (obtaining at least 606 patient years). The study will evaluate if there an increased incidence and risk of aortic regurgitation in a patient population 70 years of age or younger implanted with the ATS Medical, Inc., ATS 3f Aortic bioprosthesis, Model 1000 (Equine Pericardial bioprosthesis) undergoing isolated aortic valve replacement of his / her native aortic valve, or replacement of a failed prosthesis.
Study Population	For patients undergoing isolated aortic valve replacement of his / her native aortic valve, or replacement of a failed prosthesis who are 70 years of age or younger at implant.
Sample Size	101 patients 70 years of age or less across 8 sites
Key Study Endpoints	Hemodynamic performance, specifically the proportion of regurgitation, will be used to evaluate the safety of the valve. Hemodynamic performance will be evaluated with doppler echocardiographic studies at 3-6 months, 11-14 months and annually up to the 6 year postoperative evaluation. Values of mean gradient, peak gradient, EOA, EOA index (EOA/body surface area), performance index (EOA/pre-implant internal orifice area), CO, CO index, and valvular regurgitation will be presented.
Follow-up Visits and Length of Follow-up	Patients will be enrolled and followed preoperative, operative, at discharge (or postoperatively at less than 30 days, whichever comes last), 3-6 months, 11-14 months and annually (plus/minus 2 months) thereafter until they reach the six years follow-up visit. Doppler echocardiography is required at 3-6 months, 11-14 months and annually up to the 6 year postoperative evaluation.
Interim or Final Data Summary
Interim Results	A total of 5 patients have been enrolled and implanted with the study device. Three (3) incidences of regurgitation were reported: 2 perivalvular leaks and 1 nonstructural valve dysfunction - valve bioprosthesis mismatch.
Actual Number of Patients Enrolled	34; There were 26 eligible subjects implanted with the Model 1000 valve including 14 prospectively enrolled subjects and 12 retrospectively enrolled subjects.
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	90.9% at 4 years, 85.7% at 5 years
Final Safety Findings	Adjudicated Events Non Structural dysfunction 3, major perivalvular leak 3, Structural valve deterioration 2, Thromboembolism 5, bleeding event 1, severe respiratory sepsis with hypovolemic shock 1 Explants 6, Other Events: Reoperation 3
Final Effect Findings	Six (6) of 26 (23.1%) study subjects, experienced aortic regurgitation (AR) of moderate or greater severity. Among these 6 subjects, the moderate or greater regurgitation was transvalvular in 5 subjects and perivalvular in 1 subject, and these regurgitations required valve explant in 5 subjects.
Study Strengths & Weaknesses	The study experienced difficulty with recruiting eligible subjects
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P060008 / PAS002
Date Original Protocol Accepted	10/10/2008
Date Current Protocol Accepted	09/29/2014
Study Name	TAXUS Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center study designed to observe clinical outcomes in patients receiving the TAXUS Liberte-Paclitaxel-Eluting Coronary Stent and prasugrel as part of a dual antiplatelet therapy drug regimen. This is a consecutively-enrolled study with follow-up through 5 years. This study will also contribute patient data to an FDA-requested and industry-sponsored research study that will evaluate the optimal duration of dual antiplatelet therapy study.
Study Population	Patients with ischemic heart disease due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing percutaneous coronary intervention (PCI) with TAXUS Liberté stent placement and no contraindications to prolonged DAPT.
Sample Size	Approximately 4,200 consecutive, eligible patients will be enrolled at up to 100 U.S. sites. Primary Endpoint Given the non-inferiority margin of 1.6% and a one-sided 5% significance level, 2,363 on-label TAXUS Liberté patients would be required to provide 80% power to test the hypothesis for the primary endpoint. Secondary Endpoints A total of 2,100 on-label patients treated with the TAXUS Liberté stent and followed through 3 years post stent index procedure is required. To allow for approximately 3.5% attrition per year, 2,546 on-label patients will be required to provide at least 2,100 on-label patients through 3-year follow-up. This will include 871 patients enrolled in the TAXUS ATLAS Workhorse protocol and 1,675 on-label patients enrolled into the TAXUS Liberté Post Approval Study.
Key Study Endpoints	The rate of Cardiac Death or Myocardial Infarction (MI) among all on-label patients through 12 months or survive free of Cardiac Death or MI for at least 335 days (Day 365 minus 30 days). Secondary Endpoints 1. Stent thrombosis (ST) rate, using the historical TAXUS definition in the following populations: overall patient population, TAXUS Liberté on-label population, TAXUS Liberté off-label population. 2. ST rate using Academic Research Consortium (ARC) definition (definite/probable with no censoring for Target Lesion Revascularization) in the following populations; overall patientpopulation, TAXUS Liberté on-label patient population and off-label patient population. 3. Overall and TAXUS-related MACCE rates (cardiac death, myocardial infarction, target vessel revascularization, stroke). 4. Overall and TAXUS-related cardiac death, MI or stroke rates. 5. Overall and TAXUS-related MACE rates (cardiac death, myocardial infarction, target vessel revascularization). 6. Overall and TAXUS-related cardiac death or MI rates. 7. Overall and TAXUS-related target vessel failure (TVF) rates. 8. Overall and TAXUS-related target vessel revascularization (TVR) rates. 9. Overall and TAXUS-related MI rates. 10. Overall and TAXUS-related cardiac death rates. 11. All cause death rate. 12. Non-cardiac death rate. 13. All death or MI rate. 14. All stroke rate. 15. Rate of bleeding complication will be studied separately for GUSTO classifications severe and moderate as well as for major bleeding (the composite of GUSTO severe + moderate bleeding).
Follow-up Visits and Length of Follow-up	Patients will be consecutively-enrolled and followed up through a minimum of three years. Length of Follow-up All patients will be followed for a minimum of three years. For patients who are unblinded at 30 months, determined to have been randomized to prasugrel (blinded), and subsequently provided with additional prasugrel: the 36-month follow-up visit should be conducted as an office visit. In addition, a 42-month follow-up visit is required for this subset of patients by telephone or office visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Overall: 4, 199 subjects On-label: 1,592 subjects
Actual Number of Sites Enrolled	82 sites
Patient Follow-up Rate	Overall: At three years: 85.8% (3579/4173) On-label: At three years: 86.3% (1370/1588)
Final Safety Findings	Safety/Effectiveness Findings: The primary endpoint (12-month Cardiac Death or myocardial infarction) was met as the difference of -0.9%, with a 1-sided 95% upper confidence limit of -0.2%, was less (P<0.001) than the pre-specified non-inferiority margin of 1.6%. The annualized stent thrombosis rate on on-label subjects met the pre-specified performance goal. It was 0.56% between 1 and 2 years (upper 1-sided 95% confidence limit (95% UCL): 0.82%) which was below the 1.0% performance goal (P=0.0025). Between 2 and 3 years, it was 0.51% (1-sided 95% UCL: 0.76%, p<0.001). The secondary endpoint related to on-label subjects with diabetes also met its performance goal. The 12-month target vessel failure rate of 5.1% (1-sided 95% UCL 6.8%) was less (P<0.001) than the pre-specified non-inferiority performance goal of 12.6%.
Study Strengths & Weaknesses	This study provides longer term (3 years) safety and effectiveness results of the TAXUS Liberté paclitaxel-eluting coronary stent system. This post-approval study contributed subjects to the Dual Antiplatelet Therapy (DAPT) trial, an industry/academic research organization/FDA collaboration with the Harvard Clinical Research Institute. This study supports the safety and effectiveness results of the premarket data on the TAXUS Liberté paclitaxel-eluting coronary stent system.
Recommendations for Labeling Changes	Labeling changes are not recommended since this device is no longer on the market.
General
Study Status	Completed
Application Number / Requirement Number	P060008 / PAS003
Date Original Protocol Accepted	06/28/2010
Date Current Protocol Accepted	01/21/2014
Study Name	Dual Antiplatelet Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the Dual Antiplatlet Study is to evaluate multiple durations of DAPT following DES implantation to determine the optimal duration. The patients will be randomized to either their DAPT or placebo and followed from 12 months to 30 months post index procedure
Study Population	This device is indicated for improving luminal diameter for the treatment of de novo lesions < 28 mm in length in native coronary arteries > 2.5 mm to < 4.0 mm in diameter. Study patients with ischemic heart disease due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing percutaneous coronary intervention with TAXUS Liberté stent placement and no contraindications to prolonged dual antiplatlet therapy are eligible to be enrolled in this study. Patients randomized to the control group will receive placebo.
Sample Size	Up to 4200 patients will be randomized for participation in DAPT. The sample size is estimated based on the expected follow-up rate.
Key Study Endpoints	No endpoints are specified for the descriptive analyses of the DAPT study. Secondary Endpoints: Stent thrombosis, cardiac death, myocardial infarction, target vessel revascularization, stroke, target vessel failure, and bleeding complication.
Follow-up Visits and Length of Follow-up	60 months post index procedure
Interim or Final Data Summary
Interim Results	No results can be shared since this study is being conducted under an IDE.
Actual Number of Patients Enrolled	Overall: 4, 199 subjects On-label: 1,592 subjects
Actual Number of Sites Enrolled	82 sites
Patient Follow-up Rate	Overall: At three years: 85.8% (3579/4173) On-label: At three years: 86.3% (1370/1588)
Final Safety Findings	The primary endpoint (12-month Cardiac Death or myocardial infarction) was met as the difference of -0.9%, with a 1-sided 95% upper confidence limit of -0.2%, was less (P<0.001) than the pre-specified non-inferiority margin of 1.6%. The annualized stent thrombosis rate on on-label subjects met the pre-specified performance goal. It was 0.56% between 1 and 2 years (upper 1-sided 95% confidence limit (95% UCL): 0.82%) which was below the 1.0% performance goal (P=0.0025). Between 2 and 3 years, it was 0.51% (1-sided 95% UCL: 0.76%, p<0.001). The secondary endpoint related to on-label subjects with diabetes also met its performance goal. The 12-month target vessel failure rate of 5.1% (1-sided 95% UCL 6.8%) was less (P<0.001) than the pre-specified non-inferiority performance goal of 12.6%.
Study Strengths & Weaknesses	This study provides longer term (3 years) safety and effectiveness results of the TAXUS Liberté paclitaxel-eluting coronary stent system. This post-approval study contributed subjects to the Dual Antiplatelet Therapy (DAPT) trial, an industry/academic research organization/FDA collaboration with the Harvard Clinical Research Institute. This study supports the safety and effectiveness results of the premarket data on the TAXUS Liberté paclitaxel-eluting coronary stent system.
Recommendations for Labeling Changes	Labeling changes are not recommended since this device is no longer on the market.
General
Study Status	Progress Adequate
Application Number / Requirement Number	P060008 / PAS004
Date Original Protocol Accepted	10/10/2008
Date Current Protocol Accepted	10/10/2008
Study Name	Fatigue & Stability Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P060002 / PAS001
Date Original Protocol Accepted	03/13/2008
Date Current Protocol Accepted	03/13/2008
Study Name	FLAIR Endovascular Grafts
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective randomized study. One arm will receive balloon angioplasty of the target lesion only, and the other arm will receive balloon angioplasty plus the FLAIR Endovascular Stent Graft (referred to as the FLAIR group).
Study Population	Patients with hemodynamically significant stenosis (>50%) with clinical evidence of graft dysfunction (without thrombotic occlusion) at the synthetic arteriovenous access graft anastomosis, who have a life expectancy of at least 25 months at enrollment, who meet administrative requirements for participation in the study, are at least 18 years old, whose target lesion meets appropriate anatomic criteria, and who are not characterized by any of the study's exclusion criteria.
Sample Size	270 subjects, 30 sites
Key Study Endpoints	Primary endpoints includ: 1) access Circuit Primary Patency (ACPP - defined as the interval following the index procedure until the next access thrombosis or reintervention; it ends with a reintervention anywhere within the access circuit.); 2) Patency Function (IPF - defined as the time from the index study procedure to complete graft abandonment divided by the number of visits for a reintervention performed on the AV access circuit in order to maintain vascular access for hemodialysis at 12 months follow-up); 3) number of device and/or procedure related adverse events; Secondary endpoints include:: 1) Number of reinterventions until graft abandonment or through 12 months post-index procedure, 2) Postintervention Assisted Primary Patency, 3) Postintervention Secondary Patency, 4) Procedure Success, and 5) Incidence of major device-related adverse events through 30 days post index procedure.
Follow-up Visits and Length of Follow-up	Subject follow-up will occur at 30 days and 6, 12 and 24 months. Follow-up will occur by telephone at 30 days, 6 months and 24 months. It will occur by office visit/review of dialysis records at 12 months. The following will be assessed at follow-up: arteriovenous graft status, repeat interventions to the access circuit and treatment area, and device and/or procedure related adverse events.
Interim or Final Data Summary
Actual Number of Patients Enrolled	270
Actual Number of Sites Enrolled	35
Patient Follow-up Rate	98%
Final Safety Findings	Subjects with device- or procedure-related AEs at 12 months: Control group ¡V 6%; FLAIR group ¡V 27% Subjects with device- or procedure-related AEs at 24 months: Control group ¡V 6%; FLAIR group ¡V 33%
Final Effect Findings	Primary endpoint # 1: Access Circuit Primary Patency (ACPP) Time period ACPP for PTA ACPP for FLAIR 12 months 0.110 [95% CI = 0.05-0.17] 0.240 [95% CI = 0.17-0.32] 24 months 0.055 [95% CI = 0.01-0.10] 0.095 [95% CI =0.03-0.16] p value = .007 (comparison of PTA with FLAIR), showing superiority of FLAIR at 12 months Primary endpoint # 2: Index of Patency Function (IPF) Time period IPF for PTA IPF for FLAIR (months per intervention) (months per intervention) 12 months 4.4 +/- 3.5 5.2 +/- 4.1 24 months 5.3 +/- 5.2 7.1 +/- 7.0 p value for comparison of PTA with FLAIR at 12 months is .009, showing non-inferiority (7 days) for FLAIR compared with PTA.
Study Strengths & Weaknesses	Strengths: ¿Þ Excellent follow-up (98%) ¿Þ Prospective cohort study ¿Þ Randomization to control vs. subject group Weakness: ¿Þ Some measures of safety were found to be inferior in the subject compared with the control group. A post-hoc analysis was required in order to cast some doubt on the significance of those findings.
Recommendations for Labeling Changes	Yes: Update label with primary safety and effectiveness endpoints
General
Study Status	Completed
Application Number / Requirement Number	P040013 S009/ PAS001
Date Original Protocol Accepted	08/25/2008
Date Current Protocol Accepted	08/25/2008
Study Name	Working Standard for Biomatrix
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Development of a new working standard for use in analytical testing of the rhPDGF-BB component of GEM 21S Growth-factor Enhanced Matrix.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	N/A
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	The proposed specification is acceptable given the constraints of the assay and equipment precision.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P060018 / PAS001
Date Original Protocol Accepted	07/16/2007
Date Current Protocol Accepted	07/16/2007
Study Name	Long-Term Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort to continue follow-up of the subjects who participated in (1) the IDE premarket study and (2) the continued access arm and metal ion study.
Study Population	The study include IDE, CAS and metal ion study subjects. This device is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy. Intractable radiculopathy and/or myelopathy should present with at least one of the following items producing symptomatic nerve root and/or spinal cord compression which is documented by patient history (e.g., pain [neck and/or arm pain], functional deficit, and/or neurological deficit), and radiographic studies (e.g., CT, MRI, x-rays, etc.): 1) herniated disc, and/or 2) osteophyte formation. The PRESTIGE 9 device is implanted via an open anterior approach.
Sample Size	A minimum of 200 patients (minimum of 100 patients each from control and PRESTIGE groups) at 7-year follow-up
Key Study Endpoints	A patient will be considered an overall success if all of the following conditions are met: 1. Postoperative Neck Disability Index score improvement of at least a 15-point increase from preoperative; 2. Maintenance or improvement in neurological status from preoperative; 3. Functional spinal unit height success; 4. No serious adverse event classified as implant associated or implant/surgical procedure associated; and 5. No additional surgical procedure classified as a "failure".
Follow-up Visits and Length of Follow-up	Postoperative data will be collected at 3, 5, and 7 years
Interim or Final Data Summary
Interim Results	Between initial surgery and the 60 months visit, there were 1098 adverse events (AEs) reported in 249 investigational patients (90.2%) and 932 AEs reported in 227 control patients (85.7%). Among SAEs (serious adverse events) in the investigational group there were a total of 256 SAEs reported in 127 patients (46.0%) and there were a total of 185 SAEs in 110 control patients (41.5%).
Actual Number of Patients Enrolled	600 (100%)
Actual Number of Sites Enrolled	31 (100%)
Patient Follow-up Rate	The sponsor was expected to follow a minimum of 200 patients (minimum of 100 patients each from control and PRESTIGE groups) through 7-year follow-up, at 31 study sites. The sponsor has followed-up 228 (84.8%) investigational and 199 (80.9%) control patients through year 7. However, the follow-up is lower, when availability of data on Functional Spinal Unit (FSU) if taken into account, n=168 (62.5%) and n=135 (54.9%) for the investigational and control patients, respectively. There were 59 continued access patients with investigational device (34 subjects participating in a metal ion study and 25 subjects who did not participate in the metal ion study). The follow-up on these patients was 77% and 96%, respectively.
Final Safety Findings	In terms of cumulative adverse events n=259 (97.7%) of investigational patients had an adverse event during the study as compared to n= 232 (94.5%) of control patients (pWilcoxon=0.722). For neck the time-to-event analysis, the cumulative rate is 70.2% and 64.7% for the investigational and control groups, respectively, with pWilcoxon = 0.070. Further, no adverse local tissue reactions (ALTR) were observed in 6 explanted investigational devices. However, four (n=4) explanted devices showed greater than anticipated wear rate (derived from bench studies). In the metal ion group of the investigational device patients (n=34), the Chromium levels were higher than pre-operative levels, but about 41 fold less than undesired level (7 ng/ml)
Final Effect Findings	The primary end-point for the study was overall success-a composite of safety and effectiveness. Hundred twenty two (n=122) out of 168 or 72.6% of investigational patients have reached overall success. In comparison, 81 (60%) out of 135 control patients have reached overall success, p (non- inferiority)<0.001. Please refer to the table below for additional information.
Study Strengths & Weaknesses	This study provided much needed information on the Prestige long term (7-years) performance. However, the findings and interpretation of this study are limited due to the observed high loss to the follow-up. A total of 108 study subjects in the investigational group and 130 in the control group have missing data on the overall success with FSU at 84 months. Additionally, 64 study subjects in the investigational group and 83 in the control group have missing data for overall success without FSU at 84-month. Furthermore, 48 study subjects in the investigational group and 66 in the control group have no 84-month data. The high proportion of loss to follow-up can introduce bias in the rate estimates, possibly due to differences in loss to follow-up between patients with different overall success at 24- months. For example, study subjects who completed the PAS in Prestige group were more likely to have achieved overall success at 24-month; whereas, study subjects in the control group who did not achieve overall success at 24-month were more likely to complete the PAS. This suggests differential loss to the follow-up between treatment groups, which limits the interpretation of the study results. Trends for several of the other study outcomes were similar.
Recommendations for Labeling Changes	Yes: Long term data on the device safety and effectiveness is available and the labeling should include additional information on the long term device performance; (2) Higher than predicted wear during bench testing was observed in the explanted devices after long-term use.
General
Study Status	Hold
Application Number / Requirement Number	P060017 / PAS002
Date Original Protocol Accepted	10/29/2007
Date Current Protocol Accepted	10/29/2007
Study Name	TS Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is designed to address the following objectives: 1) to determine, under clinical use conditions, the assay turn-around-time from the time of node removal to the report of the assay result to the surgeon, 2) to determine, under clinical use conditions, whether the assay result was or was not received in time to make an intra-operative decision, and 3) to collect data in relation to other surgical procedures during the sentinel lymph node dissection/breast surgery to determine if the assay turn arround time resulted in longer surgery time than would have occurred if the assay had not been used.
Study Population	Study Population: Breast cancer patients. Indication: The device is indicated as an in vitro diagnostic test for the rapid detection of greater than 0.2 mm metastases in nodul tissue removed from the sentinel lymph nodes biopsies of breast cancer patients.
Sample Size	320 patients, 4 sites
Key Study Endpoints	Assay turn-around-time data was collected on each eligible patient from the time the sentinel lymph node(s) were excised from the patient until the patient assay result was reported back to the surgeon. The relationship to other surgical procedures during the sentinel lymph node dissection/breast surgery will be collected to determine if the assay turn-around-time resulted in longer surgery time than would have occurred if the assay had not been used.
Follow-up Visits and Length of Follow-up	Follow-up was not required for this study.
General
Study Status	Completed
Application Number / Requirement Number	P060008 S008/ PAS001
Date Original Protocol Accepted	07/23/2009
Date Current Protocol Accepted	07/23/2009
Study Name	TAXUS ATLAS Small Vessel
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center study designed to observe clinical outcomes in patients receiving the TAXUS Liberte-Paclitaxel-Eluting Coronary Stent and prasugrel as part of a dual antiplatelet therapy drug regimen. This is a consecutively-enrolled study with follow-up through 5 years. This study will also contribute patient data to an FDA-requested and industry-sponsored research study that will evaluate the optimal duration of dual antiplatelet therapy.
Study Population	The TAXUS Liberté Atom (2.25 mm) Paclitaxel-Eluting Coronary Stent is an expandable, mesh-like stainless steel tube with a drug (paclitaxel) contained within a thin polymer coating on its surface. The stent is mounted over a deflated balloon attached to the end of a long thin flexible tube called a stent delivery catheter. The stent is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries > 2.25 mm to < 4.00 mm in diameter in lesions < 28 mm in length.
Sample Size	168 subjects, 100 sites
Key Study Endpoints	Data will be collected on the rate of cardiac death or myocardial infarction through 12 months. This will be compared with the cardiac death or myocardial infarction rates observed through 12 months in control arm of the TAXUS ATLAS Workhorse Clinical Trial and the ARRIVE 1 and 2 registries.
Follow-up Visits and Length of Follow-up	Patient follow up will occur at months 6, 12, 15, 18, 24, 30, 33, 36, 48 and 60 post index procedure, for all enrolled patients. Follow-up for months 15, 33, 36, 48 and 60 may be conducted via telephone. Follow-up for months 6, 12, 18, 24 and 30 must be conducted during a clinical visit for the purposes of study drug dispensing and accountability. The 18-month office visit is intended to serve the purposes of drug dispensing and accountability only.
Interim or Final Data Summary
Actual Number of Patients Enrolled	261 TAXUS ATLAS patients, 75 DES control, 155 BMS control
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	91.3% TAXUS ATLAS, 90.4% DES Control, 85.5% BMS Control. These percentages include patients who died in both the numerator and denominator.
Final Safety Findings	MACE (cardiac death, MI, and TVR): The rate at 5 years was 26.3 in the TAXUS ATLAS Group and 36.9% in the DES Control group and 44.4% in the BMS Control group.
Final Effect Findings	TVR, TLR and TVF rates at 5 years were 20.1%, 13.4% and 25.6%, respectively, for the TAXUS ATLAS Group. The rates for the DES Control Group were 30.8% (TVR), 23.1% (TLR) and 35.4% (TVF). The rates for the BMS Control Group were: 38.3% (TVR), 32.3% (TLR), and 42.9% (TVF).
Study Strengths & Weaknesses	The sponsor present a well designed study with a control group with good follow-up at 5 years.
Recommendations for Labeling Changes	Updated to include the long-term post-approval study data and findings.
General
Study Status	Completed
Application Number / Requirement Number	P060023 / PAS001
Date Original Protocol Accepted	05/12/2009
Date Current Protocol Accepted	05/12/2009
Study Name	Long-Term Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort study that involves continued follow-up of the premarket cohort. The goal of this post-approval study is to assess longer-term performance of the BRYAN Cervical Disc in the treatment of patients with cervical degenerative disc disease. The primary consideration of longer-term performance will be overall success, a composite variable comprised of key safety and effectiveness parameters. The overall success rate for the BRYAN disc treatment will be compared to that of a concurrent fusion control group. Study success will be based on showing non-inferiority for the BRYAN device group overall success rate at ten years following surgery. The secondary objective of the study is to assess superiority, if non-inferiority can be established.
Study Population	Study population is as per device indication. This device is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy. The BRYAN device is implanted via an open anterior approach.
Sample Size	Postoperative data will be collected at 5, 7, and 10 years on a minimum of 200 eligible patients (minimum of 100 patients each from control and BRYAN groups)
Key Study Endpoints	The primary outcome variable, overall success, is defined below. A patient will be considered an overall success if all of the following conditions are met:
Follow-up Visits and Length of Follow-up	Data will be collected at 60 months (5 years), 84 months (7 years), and 120 months (10 years) postoperative to determine the long-term safety and effectiveness of the device.
Interim or Final Data Summary
Interim Results	As of the latest 12-month PAS interim report, 356 IDE subjects have been enrolled into PAS. Of them, 83% (160/193) Bryan Disc patients and 75% (119/159) control achieved success at 60-month follow-up.
Actual Number of Patients Enrolled	463 randomized subjects were enrolled in the IDE. The number of subjects participating in the PAS (60 months) was 206 investigational subjects and 167 control subjects.
Actual Number of Sites Enrolled	17
Patient Follow-up Rate	63.1% (130/206) Investigational group; 62.3% (104/167) Control group.
Final Safety Findings	The cumulative rate of subjects who reported any Grade 3 or 4 adverse event up to 120 months was 68.6% in the investigational group and 73.0% in the control group. At 120 months, the rate of implant- or implant/surgical procedure-associated adverse events was 19.1% in the investigational group and 7.3% in the control group. The rate of implant- or implant/ surgical procedure-associated Grade 3 or 4 adverse events was 4.1% in the investigational group and 4.9% in the control group. In all categories of spinal events (overall, procedure-related, device-related), events were numerically greater in the investigational group than the control group, deemed clinically significant (though not statistically significant). Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and should be interpreted accordingly. The rate of secondary surgeries at the index level was 6.7% in the investigational group and 11.5% in the control group (not statistically significant).
Final Effect Findings	Based on the data available, the study met its primary objective d with non-inferiority of the investigational treatment over the control treatment in overall success rate for the primary composite endpoint at 120 months (81.3% investigational vs 66.3% control.) The study also met its secondary objective of superiority of the Bryan device over the control for the primary endpoint. Non-inferiority of the investigational treatment compared to the control was also reported in secondary effectiveness endpoints, including NDI success, neck pain success, arm pain success, SF-36 PCS and MCS success, and gait success status at 120 months following surgery. NDI success rate in the investigational group was superior to that in the control group. At 120 months following surgery, the radiographic success rate in the investigational group was 80.0%, while the fusion success rate in the control group was 97.2%. In the investigational group, 80.0% of subjects had angular motion maintained (more than 4°). The Functional Spinal Unit (FSU) success and subsidence success rates at all postoperative follow-up time points were 100.0% for both investigational and control groups, indicating there were no subjects having a surgical intervention due to FSU height loss or subsidence in either group. At 120 months, 7.4% (9/122) investigational subjects had Grade III HO, and 6.6% (8/122) had Grade IV HO. The incidence of HO increased and worsened over time with resultant loss of motion. Bryan implant migration was observed in two investigational subjects (one at 60 months and another at 120 months).
Study Strengths & Weaknesses	This long term (10-year) extended follow-up study was able to meet the study objectives, demonstrating both non-inferiority and superiority in the primary success outcome (a composite endpoint of safety and effectiveness) for the Bryan device compared to anterior cervical discectomy and fusion (ACDF). However, the study is limited to IDE study subjects, though patients, physicians, and clinical sites who utilize the device in the postmarket environment may differ significantly from the relatively select patients, physicians, and clinical sites that participated in the premarket trial; therefore, the study may not be representative of real-world use. Though there were no significant differences in AE rates between the groups, categorization of Adverse events is suboptimal in that all systemic AEs were considered non-device or non-procedure related, which may or may not be the case, and should be interpreted accordingly. Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and should be interpreted accordingly. Further, because fusion outcomes on subjects undergoing removal SSSI were not captured, the study does not permit a conclusion regarding possible deleterious effect of fusion after device removal (i.e., the possibility of incomplete or delayed fusion is not known). Overall, though missing data imputed in worst case sensitivity analyses withheld the claim of non-inferiority, there is a selection bias concern due to the high percentage of patients lost to follow-up and the ongoing (through 10 year) consent process. Accordingly, the final risk to benefit conclusions should be interpreted with caution.
Recommendations for Labeling Changes	The labeling should be updated to include the long-term follow-up data generated in this Post-Approval study.
General
Study Status	Completed
Application Number / Requirement Number	P060023 / PAS002
Date Original Protocol Accepted	05/12/2009
Date Current Protocol Accepted	05/12/2009
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Sponsor collects the information for any adverse events and complaints, including those which are not associated with any adverse clinical effect, received by the company for the BRYAN device following PMA approval.
Study Population	Study population is as per device indication.This device is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy.
Sample Size	NA
Key Study Endpoints	The primary outcome variable, overall success, is defined below. A patient will be considered an overall success if all of the following conditions are met: - Postoperative Neck Disability Index score improvement of at least 15-points from preoperative (score decrease signifies improvement); - Maintenance or improvement in neurological status from preoperative; - No serious adverse event classified as implant associated or implant/surgical procedure associated; and - No additional surgical procedure classified as a "failure". Second surgery "failures" are additional surgeries that occur after the treatment surgery that affect the original device configuration.
Follow-up Visits and Length of Follow-up	There is no follow-up of subjects. The study reporting occurs at six-month intervals for the first two years of approval and then continues on an annual basis until five years after PMA approval.
Interim or Final Data Summary
Interim Results	This ESS report covers the period from October 16, 2009 to April 12, 2010. No complaints and adverse events were reported for the BRYAN Cervical Disc or the instruments used with the implants in the US during the covered period. A total of 4 devices have been sold during this time period. There were 7 outside of the US complaints and adverse events recorded for the BRYAN Cervical Disc implants during the time period from October 16, 2009 to April 12, 2010. Two events were related to a revision surgery due to postoperative pain. one evet was related to a revision surgery following osteolysis and a low grade infection. One event was related to a revision surgery following formation of posterior osteophytes. Two events related to the device, which were reported that the Bryan Disc made a cracking noise when a surgeon moved the implants between his thumb and index finger. These two devices were not used to treat the 2 patients and no complications were reported. The last patient had been reported by the surgeon that there were bubbles coming from the Bryan Disc before implanting into the patient due to the torn sheath. Another implant was used to treat patient and no complications were reported.
Actual Number of Patients Enrolled	N/A - enhanced surveillance stud N/A - enhanced surveillance study
Actual Number of Sites Enrolled	N/A - enhanced surveillance study
Patient Follow-up Rate	Not applicable enhanced surveillance study The study duration was 5 years.
Final Safety Findings	A cumulative total of 1950* implants have been sold in the U.S. since the PMA approval date of May 12, 2009 to March 11, 2014. A cumulative total of twenty five MDRs have been reported for implants sold in the U.S. since the approval date to March 11, 2014. A cumulative total of twenty MDRs have been reported for instruments sold in the U.S. since the approval date. A cumulative total of 7769 implants have been sold outside of the U.S. since the PMA approval date of May 12, 2009 to March 11, 2014. A cumulative total of 86 MDRs have been reported for implants sold outside of the U.S. since the approval date to March 11, 2014.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study permitted monitoring of the AEs occurrence in the broader population of the device users. Due to the study design it is impossible to meaningfully evaluate the AEs rates. Further, due to study design and lack of clinical information reported to the company it is difficult to find any particular trends in occurrence of heterotopic ossification and osteolysis.
Recommendations for Labeling Changes	Yes Bryan Cervical Disc implantation associated with higher level of surrounding tissue dissection than other artificial disc systems currently on the market. This in turn leads to higher incidents of HO. The HO incidents were observed in the ESS study.
General
Study Status	Completed
Application Number / Requirement Number	P060028 / PAS001
Date Original Protocol Accepted	06/14/2013
Date Current Protocol Accepted	06/14/2013
Study Name	Post-Approval PMA Cohort Study (PACS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The MemoryShape Core Study is a post-approval cohort study to assess safety and effectiveness in augmentation, reconstruction, and revision (augmentation and reconstruction) patients. As part of the PMA conditions of approval, MemoryShape Core Study subjects will be expected to complete annual follow-up visits for safety and effectiveness through 10 years as well as MRI scans for all subjects at year 10.
Study Population	Women with Mentor¿s MemoryShape Breast Implants as indicated for primary augmentation, revision augmentation, primary reconstruction, and revision reconstruction of the female breast.
Sample Size	A total of 955 subjects have been enrolled in MemoryShape Core Study. The protocol does not specify the number of clinical sites.
Key Study Endpoints	During the 10-year follow-up period, long-term safety of the Implants will continue to be measured by collecting the incidence, severity, method of resolution and duration for all complications (including device failures and adverse device effects) on a per-implant and per- patient basis. MRI scans to detect silent rupture of the implant for a subset of patients are at 1, 2, 4, 6, 8, and 10 years. Additionally, all patients are scheduled to receive MRI scans at year 6, 8 and 10. Safety assessments include complication rates, reasons for reoperation, and reasons for implant removal. Effectiveness assessments include bra cup size change (augmentation patients only), circumferential chest size change, measures of patients¿ satisfaction, and assessments of body image, self-esteem, and health related quality of life.
Follow-up Visits and Length of Follow-up	Subjects will be seen by the investigator in the investigator's office once a year until all subjects have reached 10-years post-implantation. In addition, all subjects in the study are scheduled to receive MRI scan at 10 years post-implantation.
Interim or Final Data Summary
Actual Number of Patients Enrolled	In total, 955 female subjects, including 572 primary augmentation, 124 revision-augmentation, 190 primary reconstruction, and 69 revision-reconstruction subjects, were enrolled. Enrollment in the MRI Substudy included 252 primary augmentation, 56 revision-augmentation, 73 primary reconstruction, and 38 revision-reconstruction subjects.
Actual Number of Sites Enrolled	43
Patient Follow-up Rate	The follow-up rate at 10 years ranged from 60% to 74% across cohorts, with an overall follow-up rate of 63%. The cohort specific follow-up rates were as follows: 60% primary augmentation, 63% revision- augmentation, 67% primary reconstruction, and 74% revision-reconstruction. The follow-up rates at 10 years for the MRI subset of subjects ranged from 42% to 57% across cohorts, with an overall follow-up rate of 45%. The cohort specific MRI Substudy follow-up rates were as follows: 44% primary augmentation, 44% revision-augmentation, 42% primary reconstruction, and 57% revision- reconstruction.
Final Safety Findings	The Kaplan-Meier estimated cumulative incidence rates at the subject level for the complications of any reoperation, explantation with or without replacement, explantation with replacement with study device, Baker III/IV capsular contracture, and infection are presented by cohort. For the primary augmentation cohort, the KM estimated 10-year cumulative incidence rates were as follows: Baker Grade III/IV capsular contracture, 3.6%; infection, 0.7%; explantation with or without replacement, 9.2%; explantation with replacement with study device, 4.0%; and any reoperation, 22.3%. For the revision-augmentation cohort, the KM estimated 10-year cumulative incidence rates were as follows: Baker Grade III/IV capsular contracture, 15.5%; infection, 1.9%; explantation with or without replacement, 25.9%; explantation with replacement with study device, 10.8%; and any reoperation, 35.0%. For the primary reconstruction cohort, the KM estimated 10-year cumulative incidence rates were as follows: Baker Grade III/IV capsular contracture, 14.3%; infection, 1.6%; explantation with or without replacement, 34.1%; explantation with replacement with study device, 16.7%; and any reoperation, 52.7%. For the revision-reconstruction cohort, the KM estimated 10-year cumulative incidence rates were as follows: Baker Grade III/IV capsular contracture, 16.4%; infection, 2.9%; explantation with or without replacement, 49.0%; explantation with replacement with study device, 27.9%; and any reoperation, 59.7%. The Kaplan-Meier estimated cumulative incidence rates for rupture through 10 years for the MRI substudy subjects by cohort were: 6.6% primary augmentation, 9.6% revision- augmentation, 18.9% primary reconstruction, and 0% revision-reconstruction.
Final Effect Findings	For the primary augmentation cohort, the overall mean change in circumferential chest size through 10 years was 2.1 inches and statistically significant (p<0.0001), and the overall mean bra cup size increase from baseline across all follow-up visits was 2.2 cup sizes and statistically significant (p<0.0001). The primary effectiveness analysis was for the primary augmentation cohort only. The percentage of subjects who answered the Global Subject Satisfaction question indicating they would make the same decision to have breast implant surgery was 96.9% at the Year 10 follow-up visit. The results were similar for the four subject cohorts: 96.6%, 95.5%, 100.0%, and 94.1% for the primary augmentation, revision-augmentation, primary reconstruction, and revision-reconstruction cohorts, respectively.
Study Strengths & Weaknesses	One study strength is the 10-year prospective multi-center design to assess the long-term safety and effectiveness of the device. The weaknesses of the study were the lack of a comparison group, and lack of statistical power to detect rare events due to the sample size.
Recommendations for Labeling Changes	Yes, the labeling will be updated based on the post-approval study results to provide patients and physicians with 10-year descriptive data on device performance.
General
Study Status	Completed
Application Number / Requirement Number	P060028 / PAS002
Date Original Protocol Accepted	06/14/2013
Date Current Protocol Accepted	06/14/2013
Study Name	Post-Approval Cont Access Study (PACAS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Continued Access Study (CAS) was initiated to allow for continued physician experience with the device and to collect additional safety data. The PACAS is a post-approval continued access study designed to evaluate the safety of Mentor¿s MemoryShape Medium Height, Moderate Profile (CPG Style 321) Breast Implants in subjects previously enrolled in Mentor¿s CAS. Upon device approval, CPG CA study subject enrollment will be closed and the study will be converted to a post approval study for this style, i.e., CPG Style 321. The PACAS is to continue clinical follow-up of these patients with CPG Style 321 until each patient reaches her 5th year post-implantation. Subjects enrolled in the CA study with other CPG style breast implants will be followed under a new IDE protocol and study.
Study Population	Women with Mentor¿s MemoryShape Medium Height, Moderate Profile (CPG Style 321) Breast Implants as indicated for primary augmentation and revision augmentation of the female breast who were enrolled in the CAS but have not yet completed their 5-year follow-up.
Sample Size	A total of approximately 350 subjects who were enrolled in Mentor¿s Continued Access Study and implanted with MemoryShape Medium Height, Moderate Profile (CPG Style 321) for augmentation and reconstruction of the female breast and have not yet completed the 5-year study visit
Key Study Endpoints	During the 5-year follow-up period, safety of the implants will continue to be measured by collecting the incidence, severity, method of resolution and duration for all complications (including device failures and adverse device effects) on a per-implant and per-patient basis. Rheumatic Disease questionnaire will be employed at years 1, 2, 4 and 5. All PACAS subjects will be advised to see their surgeon if they believe they have a ruptured implant, and these subjects will undergo a Magnetic Resonance Imaging (MRI) scan.
Follow-up Visits and Length of Follow-up	Subjects will be seen by the investigator in the investigator's office once a year until all subjects have reached 5-years post-implantation. Follow-up study visits will take place at 10 weeks and then annually through 5 years after surgery.
Interim or Final Data Summary
Actual Number of Patients Enrolled	2,003
Actual Number of Sites Enrolled	62
Patient Follow-up Rate	62% at Year 5
Final Safety Findings	For the primary augmentation cohort, the KM estimated 5�year cumulative incidence rates for the key complications at the subject level were: Baker Grade III/IV capsular contracture, 0.7%; infection, 0.6%; explantation with or without replacement, 4.2%; explantation with replacement with study device, 1.1%; and any reoperation, 9.4%. For the revision�augmentation cohort, the KM estimated 5�year cumulative incidence rates for the key complications at the subject level were: Baker Grade III/IV capsular contracture, 0.6%; infection, 1.4%; explantation with or without replacement, 8.7%; explantation with replacement with study device, 2.5%; and any reoperation, 17.9%. For the primary reconstruction cohort, the KM estimated 5�year cumulative incidence rates for the key complications at the subject level were: Baker Grade III/IV capsular contracture, 5.3%; infection, 0.6%; explantation with or without replacement, 13.0%; explantation with replacement with study device, 7.6%; and any reoperation, 24.6%. For the revision�reconstruction cohort, the KM estimated 5�year cumulative incidence rates for the key complications at the subject level were: Baker Grade III/IV capsular contracture, 9.8%; infection, 3.2%; explantation with or without replacement, 16.6%; explantation with replacement with study device, 6.0%; and any reoperation, 25.1%. A total of 10 ruptures were reported, of which 9 were silent rupture.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The Continued Access Study (CAS) was initiated to allow for continued physician experience with the device before device approval and to collect additional safety data. The Post�]approval Continued Access Study (PACAS) was designed to evaluate the safety of MemoryShape Medium Height, Moderate Profile (CPG Style 321) Breast Implants in subjects previously enrolled in the CAS. The overall patient follow�]up rate of the PACAS was 62% at Year 5. This follow�]up rate limited the interpretation of the available safety results.
Recommendations for Labeling Changes	No labeling change recommended at this time. The labeling has already contained 3�and 6�year data from the premarket cohort study and will be updated based on the 10�year clinical data from the Post�approval PMA Cohort Study for the same device.
General
Study Status	Ongoing
Application Number / Requirement Number	P060028 / PAS003
Date Original Protocol Accepted	06/14/2013
Date Current Protocol Accepted	07/21/2026
Study Name	MemoryGel and Shape Glow Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The MemoryGel and Shape Glow Study was designed as part of the re-design of the Large PAS. This is a smaller cohort study (10 years follow-up) designed to address safety outcomes (i.e., including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problems, effects on mammography, effects on patient satisfaction with breasts and psychosocial wellbeing, and silicone subject compliance with magnetic resonance imaging (MRI) recommendations. This restructured PAS, once completed as designed, would satisfy the post-approval requirements for both the MemoryGel® (P030053) and Memory Shape (P060028) silicone breast implants. In addition, information gained from the NBIR will help strengthen the general understanding of implantation rates and certain risks associated with breast implants.
Study Population	Women who receive Mentor?s MemoryGel and MemoryShape breast implants for the purpose of primary or revisional breast augmentation and primary or revisional breast construction. Additionally, women who undergo aesthetic surgery (for example liposuction, rhinoplasty, brow lift, autoplasty, rhytidectomy, mentoplasty/genioplasty, otoplasty, or blepharoplasty) will be enrolled as concurrent controls.
Sample Size	The study will enroll 3,500 women who received MemoryGel or MemoryShape Breast Implants, with a minimum of 750 subjects enrolled in each device family, and a concurrent control group of 300 women undergoing an aesthetic surgery other than breast implant surgery. The study was designed to have 80% power to be able to detect as statistically significant a relative risk of 2.0 for adverse events that occur, without implants, with a frequency of 5.0 per 10,000 person-years, based on a one-sided test conducted at level of significance of 0.05. Based on these specifications, it was determined that approximately 20,328 person-years would be required. Patients are to be followed for 10 years. For purposes of sample size calculation, assuming a follow-up rate of 65% at 10 years and a linear loss to follow-up, there would be an average of 8.075 person-years per patient. Thus, in order to obtain the 20,328 person-years, a total of at least 2,518 breast implant patients would be required.
Key Study Endpoints	Data on all study patients will be collected on the following safety endpoints: local complications, connective tissue disease (CTD), rheumatologic and neurologic signs and symptoms, cancer, suicide, and lactation complications. Magnetic resonance imaging (MRI) compliance and results will also be evaluated. Effectiveness will be assessed in a subset of breast implant patients by responses to questions addressing their perceived quality-of-life and satisfaction with their breast implants. Data for the concurrent control group patients will be collected for rheumatological and neurological signs and symptoms.
Follow-up Visits and Length of Follow-up	Prospective patients are considered enrolled in the study after completing the Informed Consent Form, baseline questionnaire, and surgery. Enrollment in the MemoryShape group will include women who enroll prospectively, before undergoing their implant surgery, and women who enroll retrospectively, after having undergone their implant surgery. At Years 1 to 10, online questionnaires are to be completed off-site by the breast implant patients. At Years 1, 5, and 10, the online BREAST-Q will be completed off-site by a subset of patients. Retrospectively enrolled patients will be required to complete follow-up questionnaires annually through the 10-year anniversary of the index surgery. All study patients will be seen by the investigator at any standard-of-care office visits and relevant adverse events will be captured in the study database. At Years 1 to 10, online questionnaires are to be completed off-site by the concurrent control group patients. Patients will be followed for 10 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	3,611
Actual Number of Sites Enrolled	62
Patient Follow-up Rate	The 2 year follow-up rates are: 82.6% - MemoryGel cohort 90.6% - MemoryShape Prospective cohort 83.3% - MemoryShape Retrospective cohort 76.6% - Control cohort
General
Study Status	Terminated
Application Number / Requirement Number	P060028 / PAS004
Date Original Protocol Accepted	06/14/2013
Date Current Protocol Accepted	06/14/2013
Study Name	Breast Implant Case-Control Studies
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put on-hold while the systematic literature review was conducted. The systematic literature review showed insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value. The FDA continues to monitor for these rare adverse events using other postmarket surveillance tools and real-world data (e.g. MDRs, NBIR, PROFILE).
Study Population	Women in Denmark, Germany, and the United Kingdom with the studied rare diseases (i.e., rare CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma) as cases and women without any of the 5 studied rare diseases from the same countries as cases. Inclusion criteria for cases: ¿Alive at the time of enrollment ¿Between 22 and 60 years of age at the time of enrollment ¿Identified with one of the ICD10 codes included in the protocol for the 5 studied diseases ¿Valid histological or staging information (for cases with brain cancer, cervical/vulvar cancer and lymphoma Exclusion criteria for cases: ¿Women with a history of malignancy, connective tissue disease or neurological disease at the time of diagnosis Women who either refuse to give permission to use their registry information, or do not live in the respective country or do not speak English, Danish or German, respectively Inclusion criteria for the controls: ¿Between 22 and 60 years of age at the time of enrollment ¿Willing to provide the necessary information on their medical history (including the exposure to breast implants) and potential confounders Exclusion criteria for cases: ¿Women who either refuse to give permission to use their registry information, or do not live in the respective country or do not speak English, Danish or German, respectively ¿Women with a history of any condition studied in the array of five case-control studies. ¿Women who provide unclear information that cannot be clarified by the interviewers
Sample Size	For each of the 5 case-control studies, 1,150 cases of women diagnosed with studied rare disease identified from the specialized medical centers and cancer registries in Denmark, Germany and the UK will be enrolled. A total of 5,000 females identified from the same neighborhood as cases without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
Key Study Endpoints	Data will be collected by using questionnaires as well as electronic information provided by the cancer registries/tumor centers. The same questionnaires will be used for cases and controls. The participating women will fill in the questionnaires on potential confounders (e.g., life-style related covariates) and exposure to breast implants. Similar questionnaires have been successfully used in previous case-control studies with self-administered questionnaires. The documented information will include: -Country code -Study site number -Case/control ID number -Date of birth -Age at menarche -History of pregnancies -Regular menstrual bleeding -Start of menopause -History of breast implant -Reason for breast implant (cosmetic, reconstruction, other) -Names, types, and dates for breast implants -Reasons for switch or stop of breast implant -History of hormonal contraception -History of hormone replacement therapy -History of infection with HIV, Helicobacter pylori, or EBV -Frequency of routine medical check-up in the decade before diagnosis of rare disease studied -Number of lifetime x-rays, including computerized tomography -Staging and histological information on lymphoma -Date of lymphoma diagnosis -History of other cancer -History of other severe diseases -History of treatment with immunosuppressive drugs -Family history lymphoma -Marital status -Educational level achieved -Professional exposure to radiation -Postal code as proxy for size of town or city -Body height -Body weight -Smoking status -Alcohol consumption -Level of physical exercise -Date of completion of questionnaire
Follow-up Visits and Length of Follow-up	There is no follow-up for case-control studies.
General
Study Status	Completed
Application Number / Requirement Number	P060028 / PAS005
Date Original Protocol Accepted	06/14/2013
Date Current Protocol Accepted	06/14/2013
Study Name	Focus Group Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The purpose of the Focus Group Study is to evaluate the patient informed decision brochure and ensure that the consumer information for Memory Shape Breast Implant meets patients and FDA¿s requirements. The focus group will be conducted in person, rather than on the telephone with a moderator in the room.
Study Population	Women who have had breast reconstruction or breast augmentation or currently considering breast implant revision. At least 20% of participants should be non-Caucasian. For augmentation groups, at least 50% of participants must be between ages 25 to 35 years old.
Sample Size	Five in-person focus groups will be conducted (minimum eight respondents per conference): Augmentation ¿1 conference with women who have had breast augmentation ¿1 conference with women who have considered or are considering breast augmentation Reconstruction ¿1 conference with women who have had breast reconstruction ¿1 conference with women who have considered or are considering breast reconstruction Revision ¿1 conference with women who currently have breast implants and are considering or may have considered revision surgery to replace one or both of their implants
Key Study Endpoints	The study will employ two methods of data collection, focus groups and a self-administered survey, to capture both group-level and individual-level data. A moderator will lead each group using discussion guide. Throughout the discussion, the moderator will pay attention to any unintended effects of the materials¿ content, particularly if respondents have any perceptions or beliefs that are inconsistent with the facts included in the patient educational material. Additionally, the moderator will probe for reactions to the sequencing of information, layout and format, and the effectiveness and clarity of data displays and other visual aids. Respondents will also complete a self-administered survey designed to yield individual-level data on a number of critical questions. The survey will be designed to measure how well respondents¿ comprehended key information from the patient educational material, specifically what was learned in terms of the risks and benefits of receiving breast implants.
Follow-up Visits and Length of Follow-up	There is no follow-up in the Focus Group Study
Interim or Final Data Summary
Actual Number of Patients Enrolled	33 (18 in the augmentation group and 15 in the reconstruction group)
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	N/A
Final Safety Findings	Overall reactions to the patient educational materials are generally positive. Respondents in both the augmentation and reconstruction groups agree that the Patient Educational Brochure is relevant and clear. The study participants also offered suggestions for improving the materials.
Study Strengths & Weaknesses	The focus group study is quick, usually inexpensive, and useful in exploring ideas and concepts through group interaction. However, the analysis is qualitative, it is difficult to generalize results if small, unrepresentative samples of participants are used, and data analysis can be time consuming due to the open]ended nature of questions proposed for the focus group discussion.
Recommendations for Labeling Changes	No labeling change is recommended. The Focus Group Study was conducted to evaluate Patient Educational Brochures. No safety/effectiveness data of the sponsorfs approved device was collected in the study.
General
Study Status	Completed
Application Number / Requirement Number	P060033 / PAS003
Date Original Protocol Accepted	02/01/2008
Date Current Protocol Accepted	02/01/2008
Study Name	Dual Antiplatelet Therapy EDUCATE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center study designe to further understand Endeavor stent treatment patterns and clinical outcomes in broad, unselected patient populations in North America, and to understand North American physician prescription patterns of dual antiplatelet therapy and implications of compliance with dual antiplatelet therapy.
Study Population	This device is indicated for improving coronary luminal diameter in patients with ischemic heart disease due to de novo lesions of length < 27mm in native coronary arteries with reference vessel diameters of > 2.5mm to < 3.5 mm. Study subjects with ischemic heart disease due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing percutaneous coronary intervention with stent placement are eligible to be enrolled in this study. Subjects may have multi-vessel treatment. Patients eligible for randomization into the CPI should not have contraindications to prolonged dual antiplatelet therapy noted at the time of randomization.
Sample Size	A minimum of 2,000 patients and a maximum of 4,000 patients, 100-150 sites
Key Study Endpoints	Endpoints that will be analyzed include: 1) definite and probable stent thrombosis at one year; 2) Combined rate of cardiac death and MI at one year; 3) Composite of death, target vessel MI, stroke, and major bleeding (severe or moderate per GUSTO classification) at one year; and 4) dual antiplatlet therapy compliance rates at each follow up interval to one year.
Follow-up Visits and Length of Follow-up	Patients will be followed at 3 , 6, 9, 12, 15, 18, 24, 30, and 33 months. The 12 month and 30 month follow-up include a clincal visit, 6, 9, 15, 18, 24, and 33 month follow-up involves telephone follow-up.
Interim or Final Data Summary
Interim Results	No results can be shared since this study is being conducted under an IDE.
Actual Number of Patients Enrolled	2262 patients were enrolled and followed from baseline. Of those enrolled, 1,440 patients were considered 12 months clear, (defined as thienopyridine compliant with no event prior to the 12 month time point) and from those, 811 provided consent to be randomized into the Critical Path Initiative (CPI) portion of the study and followed through 33 months.
Actual Number of Sites Enrolled	A total of 92 sites were included in this study.
Patient Follow-up Rate	At 12 months, the follow-up rate was 87.9%. For the non-randomized group at 24 months, the follow- up rate was 99.6%. Finally, the CPI follow-up rate at 33 months was 99.7%.
Final Safety Findings	At one year, the Academic Research Consortium (ARC)-defined definite/probable stent thrombosis rate was 1.3%. The combined rate of cardiac death and myocardial infarction (MI) at one year was 3.8%. The rate of the composite endpoint, including death, target vessel MI, stroke, and major bleeding (severe or moderate per GUSTO classification) at one year was 7.4%. The rates for all key endpoints including ARC definite/probable stent thrombosis, cardiac death/MI, and the composite endpoint (death, target vessel MI, stroke, and major bleeding) were consistently low (below 10%) across all groups except for the rate of the composite endpoint among the non- randomized subjects followed to 24 months. Results of this composite endpoint for all groups beyond 12 months are as follows: Non-Randomized at 24 months: 16.9%, CPI Intent-to-Treat (ITT) 12 months Dual Antiplatelet Therapy (DAPT): 5.9%, CPI ITT 30 months DAPT: 5.9%, CPI on-treatment (OT) 12 months DAPT: 1.7%, and CPI OT 30 months DAPT: 4.8%. The rates of cardiac death/MI and thrombosis were similar between the 12 month DAPT group and the 30 month DAPT group at 33 months. Although not tested for significance, patients considered ¿complex¿ had higher rates of ARC definite/probable stent thrombosis, cardiac death/MI and the composite endpoint in comparison to non-complex patients.
Final Effect Findings	Rates of DAPT usage and compliance were as expected and per protocol, indicating use of placebo or thienopyridine in the randomized (CPI) portion of the study. DAPT compliance rates were 88.3% on the day of procedure, 98.1% at 30 days, 96.2% at 180 days, and 93.5% at one year. The increased rate of DAPT use in the CPI ITT 12 month DAPT group (5.85%) and the decreased rate of DAPT use in the CPI ITT 30 month DAPT group (80.7%) may represent the management of events that occurred during this phase as well as subject medication use. On-treatment rates were as expected, however, with only 1.3% using DAPT among the 12 months DAPT group at 30 months, and 99.6% among the 30 month DAPT group at 30 months.
Study Strengths & Weaknesses	The study observed clinical outcomes in a broad unselected patient population during one year, and up to 33 months in randomized subjects following PCI treatment to help define optimal duration of DAPT therapy. It also provides a background for future studies and analyses that will better and more definitively define optimal duration of DAPT therapy. Limitations to this study may include the omission of subjects who had an event prior to one year, as they are at most risk for subsequent complications from infarction or bleeding; as few, if any, studies are adequately powered to identify optimal DAPT duration, the omission is reasonable. This study was not powered to determine a treatment effect on clinical outcomes of different durations of DAPT treatment
Recommendations for Labeling Changes	A labeling update is not needed because Medtronic Vascular has ceased manufacturing and distribution of the Endeavor Spring OTW and RX devices.
General
Study Status	Completed
Application Number / Requirement Number	P030035 / PAS001
Date Original Protocol Accepted	05/13/2004
Date Current Protocol Accepted
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was designed to collect, characterize and report on the performance of the device system through three years post-implant.
Study Population	The study included patients rolled over from the pre-market study and newly enrolled post-approval study patients.
Sample Size	1,121 patients, 46 sites
Key Study Endpoints	Endpoints include all-cause mortality for patients implanted with CRT-D or CRT-P systems; Freedom from left ventricular lead or left ventricular lead implant procedure related adverse events; Electrical performance of the left ventricular leads
Follow-up Visits and Length of Follow-up	Patients will be followed every six months for 3 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	1127 patients
Actual Number of Sites Enrolled	46 sites
Patient Follow-up Rate	73%
Final Safety Findings	The freedom from all-cause mortality for patients implanted with CRT-D systems is 80% at 3 years. The freedom from LV lead or procedure-related complications is 94% at 3 years. The freedom from system-related complications is 89% at 3 years. The reviews by the lead reviewer and clinical reviewer show that these rates are consistent with expectations and that the 20% mortality is not unexpected given the high proportion of class III and IV heart failure patients.
Study Strengths & Weaknesses	Strength: Large sample size which allows for the examination of rarer events Limitation: Allowance for inclusion of IDE study participants. There was a substantial difference in the major outcomes (death, HF events, etc) between the subjects who were rolled in from the IDE and the newly enrolled PAS subjects (who faired notably worse). This substantial difference seems to be independent of the covariates that were looked at and so it may be concerning. One likely explanation for the difference is of selection bias. The subjects rolled in from the IDE had already been free of death and presumably major events before they enrolled in the PAS and so may have been overall less likely to have events compared to the newly enrolled subjects. But even if selection bias explains the difference, it seems to me that the results for the newly enrolled subjects is a better representation of real world outcomes.
Recommendations for Labeling Changes	None
General
Study Status	Terminated
Application Number / Requirement Number	P040006 / PAS001
Date Original Protocol Accepted	10/26/2004
Date Current Protocol Accepted	10/26/2004
Study Name	Charite Artificial Disc
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort to continue follow-up of subjects enrolled in IDE study comparing CHARITÉ Artificial Disc to the BAK cage fusion
Study Population	Study populationis as per device indications. This device is indicated for spinal arthroplasty in skeletally mature patients with degenerative disc disease (DDD) at one level from L4-S 1. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient history and radiographic studies. These DDD patients should have no more than 3)mm of spondylolisthesis at the involved level. Study included subjects enrolled in the IDE study who meet the following inclusion criteria:- Participated in either the training or randomized arm of the CHARITÉ Artificial Disc IDE study. - Still have the original implant they received in their index surgery. - Ability and willingness to comply with follow-up regimen.- Voluntarily signed the approved subject informed consent form.
Sample Size	maximum of 268 CHARITÉ subjects (67 Training and 201 Randomized), and 98 BAK cage fusion subjects.
Key Study Endpoints	Study endpoints include - Quality of Life (SF-36) - Oswestry Disability Index (ODI) - Subject Satisfaction - Visual Analog Scale (VAS) for Pain - Clinical Assessment: work status, medication use, neurological status, and adverse events since the subject was last seen.- Radiographic assessment of Anterior / Posterior x-ray, Lateral x-ray, Flexion / Extension x-ray. The primary endpoint of this study is Overall Success, which is defined as: - improvement of at least 15 points in the ODI compared with the score at baseline- no device failures requiring revision, re operation, or removal, - absence of major complications, defined as major vessel injury or major neurological deterioration (e.g., nerve root injury) , and- maintenance or improvement in neurological status vs. baseline, with no permanent neurological deficits compared to baseline status.
Follow-up Visits and Length of Follow-up	Study subjects are to be seen annually (i.e., 36-, 48- and 60-month post-operation) until they complete the 60-month evaluation.
General
Study Status	Completed
Application Number / Requirement Number	P060037 / PAS001
Date Original Protocol Accepted	11/06/2008
Date Current Protocol Accepted	11/16/2016
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: to assess the long-term safety and effectiveness of the NexGen® LPS-Flex Mobile Bearing Knee in the treatment of patients with severe knee pain or degenerative knee disease, in comparison with the LPS-Flex Fixed Bearing Knee. Design: a prospective, multi-center, parallel group, controlled post-approval study comparing the clinical performance of the LPS-Flex Mobile Bearing Knee with the LPS-Flex Fixed Bearing Knee. The study includes both continued follow-up of premarket IDE cohorts through the 10th post-operative year and new enrollment and follow-up of patients through their 5th post- operative year.
Study Population	Study population is as per device indication. This device is indicated for patients with severe knee pain and disability due to: - Rheumatoid arthritis (RA), osteoarthritis (OA), primary and secondary traumatic arthritis, polyarthritis. - Collagen disorders, and/or avascular necrosis of the femoral condyle or pseudo-gout - Post-traumatic loss of joint configuration, particularly when there is patellofemoral erosion, dysfunction or prior patellectomy.- Moderate valgus, varus, or flexion deformities. Group 1 consists of patients who received either the LPS-Flex Fixed Bearing Knee or the LPS-Flex Mobile Bearing Knee during the active IDE, completed the IDE study and have given written consent to participate in the post-approval study. Group 2 patients will be enrolled into a single-arm, historically controlled, mid-term study (5 years) and this group will consist of 100 patients who undergo Total Knee Replacement with the LPS-Flex Mobile Bearing Knee after the device approval.
Sample Size	The sample size is 400 patients. Group 1 approximately 300 patients already implanted during the IDE study with either the LPS-Flex Fixed Bearing Knee (control population, N=150) or the LPS-Flex Mobile Bearing Knee device (N=150) at one of approximately 10 sites. Group 2 100 patients who are eligible for a total knee replacement, have chosen to receive the LPS-Flex Mobile Bearing Knee, and meet the PAS eligibility criteria.
Key Study Endpoints	A composite clinical success, defined by the following criteria, will be used as the primary outcome: - Knee Society assessment score greater than/equal to 70 points- Knee Society function score greater than/equal to 70 points - No intended, actual, or planned removal of any component of the knee system - Absence of severe knee-related complications - An absence of subsidence of greater than or equal to 2 millimeters and an absence of both osteolysis and radiolucencies greater than or equal to 2 millimeters as determined by independent radiographic reviewer. Safety endpoints: revision, removal and device-related adverse Secondary endpoint: Quality of Life
Follow-up Visits and Length of Follow-up	Group 1: 10 years post-operation Group 2: 5 years post-operation Group 1: Postoperatively at 4 years (if applicable), 5 years (if applicable), 6 years, 8 years and 10 years. Group 2: Postoperatively at 6 weeks, 6 months, and at 1, 2, 3, 4 and 5 years post-operation. The patients will be followed at 6 weeks, 6 months and at annual increments up to 5 years post-operation for Group 2/And followed at 5, 6, 8/And 10 years post-operation for Group 1.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A subset of 146 subjs were enrolled into group 1 from the original IDE study for continued f/u to 10 yrs. Of these 146 subjs, 69 subjs received LPS-Flex Mobile-Bearing Knees which includes 66 unilateral knees and 3 bilateral knees in the investigational arm. A total of 77 subjs received unilateral LPS-Flex Fixed- Bearing Knees and were enrolled into the control arm. Based on the sponsor’s analysis of the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), 7,686 subjs received NexGen LPS-Flex Mobile tibial knees and 427,770 subjs received other tibial knees. Group 2: 133 subjs were enrolled. Of these, 120 pts received LPS-Flex Mobile-Bearing Knees (106 subjs received unilateral knees and 14 subjs received bilateral knees), and 13 subjs received other implants and were later terminated.
Actual Number of Sites Enrolled	Group 1: 10 Group 2: 3
Patient Follow-up Rate	Group 1: Complete Data: 61.5% (40/65) of subjs w/mobile-bearing knees and 68.0% (51/75) of subjs w/fixed- bearing knees had Complete Data at 10 yrs. Any Data: 64.6% (42/65) of subjs w/mobile-bearing knees and 73.3% (55/75) of subjs w/fixed-bearing knees had Any Data at 10 yrs. Group 2: Complete Data: 67.0% (71/106) of subjs had Complete Data at 5 yrs. Any Data: 69.8% (74/106) of subjs had Any Data at 5 yrs.
Final Safety Findings	Group 1 Device Revision Rates For PAS Group 1 at 10 yrs, there were 2.9% (2/69) revisions in mobile-bearing knees compared to 1.3% (1/77) in fixed-bearing knees. The sponsor analyzed the AOANJRR and found that at 10 yrs, there were 4.3% [95% CI (Confidence Interval): 3.7%, 4.9%] revisions in mobile tibial knees compared to 5.5% (95% CI: 5.4%, 5.6%) in other tibial knees. Additional analysis showed that subjects receiving NexGen LPS-Flex Mobile tibial knees showed survivorship of 98.7% (95% CI: 98.3%, 99.0%) at 2 yrs, 97.5% (95% CI: 96.9%, 97.9%) at 5 yrs, and 96.2% (95% CI: 95.4%, 96.8%) at 10 yrs. Device Removals At 10 yrs, 4.3% (3/69) of mobile-bearing knees and 1.3% (1/77) of fixed-bearing knees in IDE group 1 subjs had device removal. Adverse Events At 10 yrs, 56.5% (39/69) of subjs w/mobile-bearing knees reported an adverse event compared to 64.9% (50/77) of subjs w/fixed-bearing knees. Among those events, 4.4% (4/90) of adverse events were device-related for mobile-bearing knees and 0% (0/126) were device-related for fixed-bearing knees. At 10 yrs, 4.3% (3/69) of subjs w/mobile-bearing knees experienced severe knee-related complications compared to 2.6% (2/77) of subjs w/fixed-bearing knees. Group 2 Device Revisions Overall, there were 5.8% (7/120) revisions and 1.7% (2/120) re-revisions in PAS Group 2 patients who received mobile-bearing knees at 5 years, compared to 2.9% (2/69) revisions in mobile-bearing knees and 1.3% (1/77) revisions observed in fixed-bearing knees from IDE Group 1 patients at 10 years. Device Removals There were 5.0% (6/120) device removals/ reoperations in PAS group 2 patients at 5 years compared to 4.3% (3/69) in subjects with mobile- bearing knees and 1.3% (1/77) in subjects with fixed-bearing knees in IDE group 1 at 10 years. Adverse Events In PAS Group 2, 72.5% (87/120) of subjects with mobile-bearing knees reported an adverse event compared to 56.5% (39/69) of PAS Group 1 subjects with mobile-bearing knees and 64.9% (50/77) of PAS Group 1 subjects with fixed-bearing knees at 5 years. There was no device- related adverse events reported at 5 years for PAS Group 2 patients compared to 4.4% (4/90) in PAS Group 1 subjects with mobile-bearing knees and 0% (0/126) of PAS Group 1 subjects with fixed-bearing knees at 10 years. In PAS Group 2, 9.2% (11/120) of subjects with mobile-bearing knees experienced severe knee -related complications at 5 years compared to 4.3% (3/69) of PAS Group 1 subjects with mobile-bearing knees and 2.6% (2/77) of PAS Group 1 subjects with fixed-bearing knees at 10 years.
Final Effect Findings	Composite Clinical Success Data was not available for composite clinical success at 10 years because of increased rates of loss to follow-up in the long-term IDE cohort. The composite clinical success was also not available from the AOANJRR. Knee Society Score Assessment (KSSA) Clinical Outcome At 10 years, 92.1% (35/38) of Group 1 subjects with mobile-bearing knees and 95.9% (47/49) of subjects with fixed-bearing knees were above 70 points for the KSSA outcome. Knee Society Score Function (KSSF) Clinical Outcome At 10 years, 76.9% (30/39) of Group 1 subjects with mobile-bearing knees and 70.0% (35/50) of subjects with fixed-bearing knees were above 70 points for the KSSF outcome. Radiographic Clinical Outcome (Osteolysis and Radiolucency) At 10 years, radiographically, 9.1% (7/77) of Group 1 subjects with fixed-bearing knees and 1.4% (1/69) of subjects with mobile-bearing knees had significant radiolucencies greater than or equal to 2 mm. Quality of Life Evaluation (SF-12) Mental Health: SF-12 Mental Health Score for Group 1 subjects with fixed-bearing knees improved slightly from 4 years (50.5%) to 10 years (54.2%). Subjects with mobile-bearing knees improved as well from 55.4% at 4 years to 56.5% at 10 years. Physical Health: SF-12 Physical Health scores for Group 1 subjects with fixed-bearing knees changed slightly from 4 years (45.7%) to 10 years (45.2%). For subjects with mobile-bearing knees at 4 years the score was 52.1% and at 10 years 48.6%.
Study Strengths & Weaknesses	Strengths: The Group 1 PAS is a long-term f/u up of a subset of IDE study subjs for 10 yrs post-surgery. An analysis performed by the sponsor revealed a large sample of pts in real-world setting (n=7,686) from the AOANJRR that was used to supplement existing data. The sponsor was able to extrapolate safety and effectiveness from the registry data by comparing variables such as reasons for revision, sex distribution and primary diagnosis between the subjects in the registry and PAS Group 1. Weaknesses: The study failed to meet the enrollment target of 300 subjs. Only 61.5% (40/65) of subjs w/mobile-bearing knees had complete data at 10 yrs. The missing data may lead to a potential for selection bias. The sponsor was not able to provide a composite clinical success at 10 yrs because of high rates of loss to f/u in the long-term cohort. A one-to-one comparison of registry data to PAS study results could not be performed due to limited demographic data (e.g., primary diagnosis, gender, and reason for revision). Data from AOANJRR were only presented for revision rates and the sponsor was not able to report other study endpoints such as composite clinical success, data on pain, function, range of motion, deformity, radiographic parameters, health status, and detailed information on adverse events. Therefore, data collected from the registry was not adequate to supplement the original PAS.
Recommendations for Labeling Changes	It is recommended that the labeling be updated to reflect the final study results. A final labeling supplement was submitted and approved.
General
Study Status	Completed
Application Number / Requirement Number	P050023 S076/ PAS001
Date Original Protocol Accepted	07/03/2014
Date Current Protocol Accepted	04/15/2019
Study Name	Protego DF4 Post Approval Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is designed to gather safety data on BIOTRONIK’s lead using active monitoring of Medicare fee-for-service (FFS) claims data. The design is a prospective, single-arm, non-randomized, observational cohort study utilizing real world data.
Study Population	Patients who are implanted with the lead and are in the beneficiary match population for the claims data are included in the patient population.
Sample Size	750 minimum evaluable sample required to demonstrate superiority to a complication-free rate of 92.5%.
Key Study Endpoints	The purpose of primary endpoint 1 is to evaluate the overall incidence of complications attributable to the lead through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Interim Results	Th
Actual Number of Patients Enrolled	A total of 2,702 patients implanted with 2,721 Protego leads met all study inclusion and no study exclusion criteria and are included in the Protego claims cohort for this final report. Overall, 37.10% (2,702/7,283) of patients implanted with a Protego lead during the PAS enrollment period were matched as unique beneficiaries in the CMS database and had both FFS Medicare coverage during the month of the Protego lead implant and a Medicare claim during the analysis period.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	56 complications were identified to meet the primary endpoint. The estimated freedom from complications at 1,802 days is 97.18%, meeting 5 year rate >92.5%. There were no DF4 header connector malfunctions.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study successfully enrolled and matched patients to Administrative Claims data, permitting larger enrollments than traditional post approval study clinical follow up. Since event rates were rare, the CMS cell suppression policy does not permit additional granular information to be included.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P980023 S057/ PAS001
Date Original Protocol Accepted	07/03/2014
Date Current Protocol Accepted	04/15/2019
Study Name	Protego DF4 Post Approval Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This study is designed to gather safety data on BIOTRONIK’s lead using active monitoring of Medicare fee-for-service (FFS) claims data. The design is a prospective, single-arm, non-randomized, observational cohort study utilizing real world data.
Study Population	Patients who are implanted with the lead and are in the beneficiary match population for the claims data are included in the patient population.
Sample Size	750 minimum evaluable sample required to demonstrate superiority to a complication-free rate of 92.5%.
Key Study Endpoints	The purpose of primary endpoint 1 is to evaluate the overall incidence of complications attributable to the lead through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 year's post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 2,702 patients implanted with 2,721 Protego leads met all study inclusion and no study exclusion criteria and are included in the Protego claims cohort for this final report. Overall, 37.10% (2,702/7,283) of patients implanted with a Protego lead during the PAS enrollment period were matched as unique beneficiaries in the CMS database and had both FFS Medicare coverage during the month of the Protego lead implant and a Medicare claim during the analysis period.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	56 complications were identified to meet the primary endpoint. The estimated freedom from complications at 1,802 days is 97.18%, meeting 5 year rate >92.5%. There were no DF4 header connector malfunctions.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study successfully enrolled and matched patients to Administrative Claims data, permitting larger enrollments than traditional post approval study clinical follow up. Since event rates were rare, the CMS cell suppression policy does not permit additional granular information to be included.
Recommendations for Labeling Changes	Yes
General
Study Status	Terminated
Application Number / Requirement Number	P060038 S017/ PAS001
Date Original Protocol Accepted	07/15/2014
Date Current Protocol Accepted	11/25/2014
Study Name	NEMO PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, non-randomized, multicenter post-approval study (PAS) Primary effectiveness: *To evaluate the hemodynamic performance of the Mitroflow DL valve as compared to other stented aortic bioprostheses in the current literature; and *To evaluate the overall improvements in patient condition by comparison of pre- operative and post-operative New York Heart Association (NYHA) functional classification. Secondary safety objective: *To determine early (day 1-30) and late (>30 days) valve-related adverse event rates (including valve thrombosis, thromboembolism, paravalvular leak (all and major), bleeding (all and major) and endocarditis for Mitroflow DL are comparable to appropriate historical controls manifested as Objective Performance Criteria (OPC) in the FDA¿s Heart Valve Guidance4 and the ISO 5840 guidelines. * Additional safety endpoints to be included are rates of the following adverse events: hemolysis, non-structural dysfunction, valve-related embolism, reoperation, explant, and death (all- cause and valve-related).
Study Population	Patients who were implanted with Mitroflow, Model DL, implantation according to the Instructions for Use (IFU). Historical controls specified as objective performance criteria (OPCs) in the FDA Draft Replacement Heart Valve Guidance (where applicable).
Sample Size	Assuming a 32% mortality and 20% attrition rate into account, the PAS will include a minimum of 15 U.S. sites and 185 patients implanted with the Mitroflow DL valve in a commercial environment. A minimum of one hundred (100) patients followed for at least eight (8) years will be necessary to comply with the 800 patient/year requirement outlined in the FDA Heart Valve Guidance.
Key Study Endpoints	Occurrence of early and late structural valve deterioration (SVD) and valve-related complications (early and late), including valve thrombosis, thromboembolism, bleeding, anticoagulation-related bleeding, paravalvular leak, endocarditis, clinically significant hemolysis, non-structural dysfunction, reoperation, explant and death. The primary hemodynamic effectiveness endpoints for hemodynamic performance of the valve to be evaluated are trans-valvular peak and mean pressure gradients, effective orifice area (EOA) and EOA index (EOAI), performance index (PI), cardiac output (CO), cardiac index (CI), the location and severity of regurgitation, and LV mass regression.
Follow-up Visits and Length of Follow-up	8 years • Pre-implant • Implant • Post-operative (within 30 days of implant) • Annual clinical and echocardiographic follow-up
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 186 patients were enrolled in the study and implanted with a valve.
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	Follow-up was conducted for n=184 patients with a cumulative 469.65 patient-years of follow-up overall. A mean follow-up of 2.52 years was achieved before the study was terminated early on November 21, 2019, and no further follow-up was conducted after December 2019. • Year 1 Follow-Up Rate: 91.7% • Year 2 Follow-Up Rate: 85.1% • Year 3 Follow-Up Rate: 82.8% • Year 4 Follow-Up Rate: 16.8% (low follow-up primarily due to early termination of study and patient withdrawal prior to 4Y follow-up visit)
Final Safety Findings	The safety endpoints were evaluated based on events reported by sites per the Valve Academic Research Consortium-2 (VARC-2) definitions, and were stratified by early (less than or equal to 30 days) and late (>30 days) post-operative events for 186 patients with 455.24 late patient-years. A total of 33 deaths (17.7%) were observed during the follow-up period. • Early period (less than or equal to 30 days) safety findings: o All-cause death: 6 (3.2%) o Cardiovascular Mortality: 4 (2.2%) o Non-Cardiovascular Mortality: 2 (1.1%) o Reintervention: 3 (1.6%) o Valve Thrombosis: 1 (0.6%) o Bleeding Events: 5 (2.7%), and 1 case (0.6%) of arterial hemorrhage o Non-structural Valve Dysfunction: 1 (0.6%) o Not observed: Structural valve deterioration, hemolysis, clinically significant paravalvular leak • Late period (>30 days) safety findings: o All-cause death: 27 (14.7%; linearized-rate on 455.2 pts-year (LR) of 5.9%) o Cardiovascular Mortality: 11 (6.0%; LR of 2.4%) o Non-Cardiovascular Mortality: 16 (8.7%; LR of 3.3%) o Stroke and/or Transient Ischemic Attack: 5 (2.7%; LR of 1.1%) o Reintervention: 4 (2.2%) o Structural Valve Deterioration: 3 (1.6%; LR of 0.7%) and 1 (0.6%, LR of 0.2%) additional case of structural valve deterioration requiring intervention. o Peripheral Thromboembolic Events: 3 (1.6%; LR of 0.7%), which included pulmonary embolism, thrombectomy, and deep vein thrombosis. o Endocarditis: 1 (0.5%; LR of 0.2%) o Non-structural Valve Dysfunction: 2 (1.1%; LR of 0.4%) o Paravalvular Leak: 1 (0.5%: LR of 0.2%) o Cerebral Hemorrhage: 2 (1.1%; LR of 0.4%) o Not observed: Hemolysis, valve thrombosis o 52 (28.3%) subjects reported 125 serious adverse events
Final Effect Findings	As very few patients were included at the 4-Year Follow-Up due to study termination, 3-Year Follow-Up findings are presented. • NYHA Classification: There was improvement in NYHA classification that was sustained to 3Y o Baseline (n=186): patients were primarily NYHA Class II (n=68, 41.4%) and Class III (n=31, 31.2%) o 1 Year (n=155): Patients were primarily Class I (n=104, 69.7%) and Class II (n=29, 18.7%), with no Class IV classification. o 3 Year (n=125): Patients were primarily Class I (n=100, 80%) and Class II (n=15, 12%) • Mean Pressure Gradient (MPG): There was improvement in MPG that was sustained to 3Y o Baseline (n=147): 42.6 ± 16.5 mm Hg. o Discharge (n=165): 12.1 ± 5.0 mmHg o 1 Year (n=147): 12.1 ± 5.0 mmHg o 3 Year (n=52): 13.5 ± 5.7 mmHg • Effective Orifice Area (EOA): There was improvement in EOA that was sustained to 3Y o Baseline (n=84): 0.8 ± 0.3 cm2 o Discharge (n=150): 1.7 ± 0.4 cm2 o 1 Year (n=141): 1.5 ± 0.4 cm2 o 3 Year (n=51): 1.4 ± 0.4 cm2 • Regurgitation o Discharge (n=172 patients/echoes performed): 114 patients had no aortic regurgitation (66.3%) and 58 patients exhibited regurgitation. Of the 58 patients that did have regurgitation, 36 had central regurgitation, 9 had paravalvular regurgitation, and 2 had both forms of regurgitation. The severity of regurgitation was trace (n=31), mild (n=26), or moderate (n=1). o 1 Year (n=149): 105 patients had no aortic regurgitation (70.5%), and of the 44 patients that did have regurgitation, 36 had central regurgitation, and 6 had paravalvular regurgitation (2 patients were not evaluable). The severity of regurgitation was trace (n=27) or mild (n=17). o 2 Year (n=129): 91 patients had no aortic regurgitation (70.5%) and of the 38 patients that did have regurgitation, 22 had central regurgitation and 10 had perivalvular regurgitation (6 patients were not evaluable). The severity of the regurgitation was trace (n=20), mild (n=17), or moderate (n=1). o 3 Year (n=54): 38 patients had no aortic regurgitation (70.4%), and of the 16 patients that did have regurgitation, 12 patients had central regurgitation, and 4 had paravalvular regurgitation. The severity of regurgitation was trace (n=13) or mild (n=3).
Study Strengths & Weaknesses	This study was terminated early due to discontinued marketing of the device in the US; thus, the study did not meet the target 800 patient years follow-up, and instead only achieved a cumulative follow-up of 469.65 patient-years with <16.8% of subjects completing their 4-year follow-up visit. Due to study termination and significant missing data/echo measurements for the intended outcomes, the conclusions that can be derived from this study are limited.
Recommendations for Labeling Changes	No labeling change is recommended as the device has been discontinued.
General
Study Status	Completed
Application Number / Requirement Number	P010031 S104/ PAS001
Date Original Protocol Accepted	08/28/2008
Date Current Protocol Accepted	08/28/2008
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a prospective, non-randomized, combined cohort of subjects followed in two other studies. Data from the combined cohort are used prospectively to assess performance of the algorithm.
Study Population	Study population same as approved product. This device is a software algorithm designed to identify potential RV-Tip to RV-Ring pace/sense electrode issues earlier than contemporary out-of-range impedance criteria. The RVLIA algorithm uses two different criteria to determine potential lead noise. It uses data from the ventricular sensing integrity counter (SIC) and non-sustained VT episodes (NST) to determine potential noise and also looks at the RV pacing lead impedance values.
Sample Size	3873 subjects from multiple centers in 2 cohorts
Key Study Endpoints	Data are collected via review of the databases using the device algorithm. Triggers associated with the algorithm are reviewed. Lead fractures are confirmed.
Follow-up Visits and Length of Follow-up	The cohort is followed for two years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1779
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	n/a
Final Effect Findings	Of 41 events, 39 were detected by LIA algorithm, giving an estimated sensitivity of 95.1% (95% IC 83.5%-99.4). The inappropriate shock rate was 21%. Of 47 LIA triggers, there were eight false-positive alerts increase without lead modification as indicated in the Device Registration System. . The false-positives included two gradually increasing impedance, two T-wave oversensing cases, and one each caused by a header-connector problem, hypothermic ventricular fibrillation during cardiac arrest at cardiac surgery, ventricular fibrillation storm, and one case adjudicated as unknown with abrupt impedance. The estimated number of false positive LIA triggers based on the retrospective analysis was 0.00269 per patient-year.
Study Strengths & Weaknesses	Not all products were returned for the Return Product Analysis. Of 47 LIA triggers, 21 (47%) of the products were not analyzed, where 15 were not returned and 6 were listed as ¿no record¿.
Recommendations for Labeling Changes	Labeling changes should be accomplished in accordance with the findings of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S135/ PAS001
Date Original Protocol Accepted	08/28/2008
Date Current Protocol Accepted	08/28/2008
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a prospective, non-randomized, combined cohort of subjects followed in two other studies. Data from the combined cohort are used prospectively to assess performance of the algorithm.
Study Population	Study population same as approved product. This population consists of patients who require an implantable cardioverter defibrillator and could benefit from this software algorithm designed to identify potential RV-Tip to RV-Ring pace/sense electrode issues earlier than contemporary out-of-range impedance criteria. The RVLIA algorithm uses two different criteria to determine potential lead noise. It uses data from the ventricular sensing integrity counter and non-sustained ventricular tachycardia episodes (NST) to determine potential noise and also looks at the right venticular pacing lead impedance values.
Sample Size	3873 subjects from multiple centers in 2 cohorts
Key Study Endpoints	Data are collected via review of the databases using the device algorithm. Triggers associated with the algorithm are reviewed. Lead fractures are confirmed.
Follow-up Visits and Length of Follow-up	The cohort is followed for two years.
Interim or Final Data Summary
Interim Results	No adverse events or death information are collected for this study.
Actual Number of Patients Enrolled	1779
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	n/a
Final Effect Findings	Of 41 events, 39 were detected by LIA algorithm, giving an estimated sensitivity of 95.1% (95% IC 83.5%-99.4). The inappropriate shock rate was 21%. Of 47 LIA triggers, there were eight false-positive alerts increase without lead modification as indicated in the Device Registration System. . The false-positives included two gradually increasing impedance, two T-wave oversensing cases, and one each caused by a header-connector problem, hypothermic ventricular fibrillation during cardiac arrest at cardiac surgery, ventricular fibrillation storm, and one case adjudicated as unknown with abrupt impedance. The estimated number of false positive LIA triggers based on the retrospective analysis was 0.00269 per patient-year.
Study Strengths & Weaknesses	Not all products were returned for the Return Product Analysis. Of 47 LIA triggers, 21 (47%) of the products were not analyzed, where 15 were not returned and 6 were listed as ¿no record¿.
Recommendations for Labeling Changes	Labeling changes should be accomplished in accordance with the findings of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P030025 S028/ PAS001
Date Original Protocol Accepted	09/24/2008
Date Current Protocol Accepted	09/24/2008
Study Name	5 year Clinical Outcomes
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, randomized, controlled, multicenter, double-blind safety and efficacy study. Patients were randomized in a 1:1 ratio to receive either the TAXUS Express Slow-Release paclitaxel-eluting stent system or an uncoated Express control stent. Randomization included stratification by clinical site, target lesion length (<18 mm versus >18 mm), and the presence or absence of medically treated diabetes mellitus. The primary objective of this study was to further evaluate the safety and effectiveness of the TAXUS Express Paclitaxel-Eluting Coronary Stent System in long lesion lengths, small and large vessel diameters and with multiple overlapping stents in the treatment of de novo coronary artery lesions.
Study Population	The device is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries >=2. 25 to <=4. 00 mm in diameter in lesions <=28 mm in length, and within bare metal stent restenotic lesions >=2. 25 to <=3. 75 mm in diameter and <=28 mm in length.
Sample Size	1172 patients (86 in the TAXUS group and 586 in the Control group), 66 sites
Key Study Endpoints	The primary endpoint is the rate of ischemia-driven target vessel revascularization at 9 months after the index procedure. The 5 year safety data will be reported for 1) Major Adverse Cardiac Events, 2) Myocardial infarction (Q-wave and non-Q-wave), 3) All-cause death and cardiac death, 4) Serious adverse events, and 5) Stent thrombosis.
Follow-up Visits and Length of Follow-up	Patients will be follow for 5 years post procedure. A subset of patients will have a follow-up intravascular ultrasound at the 9-month follow-up evaluation.
Interim or Final Data Summary
Interim Results	The major cardiac eventrate at 4 years was significantly lower for TAXUS compared to Brachy (28.4% versus 41.6%; P=0.0054), a relative reduction of 31.7%. The decrease in the major cardiac event rate was largely driven by a significant reduction in target vessel revascularization in TAXUS patients (23.8%), as compared to Brachy patients (39.3%). Myocardial infarction rates through 4 years were comparable between the TAXUS (5.2%) and Brachy groups (9.3%). Cardiac death rates through 4 years were comparable between TAXUS (4.5%) and Brachy (3.4%).
Actual Number of Patients Enrolled	421
Actual Number of Sites Enrolled	37
Patient Follow-up Rate	86.3%
Final Safety Findings	Through 5 years of follow-up, the safety profile of the TAXUS group demonstrated better MACE outcomes compared to Brachytherapy. The MACE benefit observed for TAXUS at 1 year persisted through 5 years and was driven predominantly by a significantly lower TVR rate. There were no significant differences in the individual rates of cardiac death, MI, and target vessel thrombosis between the TAXUS and Brachytherapy groups at 5 years. The rate of stent thrombosis remained low in the TAXUS group with no new events after 4 years.
Final Effect Findings	Between 4 and 5 years, the rates of TVR (6.7% Brachytherapy, 5.5% TAXUS; P=0.6267) and TLR (5.5% Brachytherapy, 4.4% TAXUS; P=0.6296) were similar between treatment groups
Study Strengths & Weaknesses	Sponsor demonstrated adequate follow-up out to 5 years. The results do not raise any safety concerns. The strength of the clinical evidence of the TAXUS V-ISR results is enhanced by the RCT design and relatively large sample size (421 patients with ISR from 37 centers).
Recommendations for Labeling Changes	Updated labeling to include ISR 5 year study results.
General
Study Status	Completed
Application Number / Requirement Number	P060039 / PAS002
Date Original Protocol Accepted	06/13/2008
Date Current Protocol Accepted	11/19/2013
Study Name	Chronic Performance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a non-randomized, multi-site, clinical study of implanted commercially available Model 4195 leads. Data will be collected prospectively; however, retrospective study enrollment will be allowed to include leads implanted through the Attain StarFix Model 4195 LV Lead pre-market study. All enrolled subjects have been implanted with a Model 4195 LV Lead. This study is designed to monitor long term performance of the Model 4195 lead and to identify individual failure modes.The objective of the study is to demonstrate that the Model 4195 lead-related complication-free probability is greater than 92.5% at five years post-implant.
Study Population	The Attain StarFix Model 4195 steroid eluting, transvenous lead with deployable lobe fixation is intended for chronic pacing and sensing of the left ventricle via the cardiac vein, when used in conjunction with a compatible implantable pulse generator or implantable cardiac defibrillator.
Sample Size	1,016 patients will be enrolled to achieve an evaluable sample size of 600 for 5-year follow-up for an interim analysis. 120 active centers enrolled in this study.
Key Study Endpoints	The primary objective of the study is to demonstrate that the Model 4195 lead-related complication-free probability is greater than 92.5% at five years post-implant. Primary objective analysis will include all complications related to lead hardware or design failure. The complication free proportion will be estimated based on the chronic (> 30 days post implant) clinical adverse events including: 1) - Failure to capture, 2) Failure to sense / Undersensing, 3) Threshold rise, 4) Oversensing, 5) Abnormal pacing impedance, 6) Lead insulation breach, 7) Lead conductor fracture, 8) Extracardiac stimulation, 9) Cardiac perforation, 10) Lead dislodgement, and 11) Structural Lead Failure,
Follow-up Visits and Length of Follow-up	The follow-up schedule for this study is based on utilizing routine, scheduled office/clinic visits and unscheduled office/clinic visits prompted by symptoms or complaints. Follow-up office/clinic visits post-enrollment are to occur at a minimum of every 6 months, no longer than 210 days apart.
Interim or Final Data Summary
Interim Results	The sponsor reports four adverse events (two complications, two observations not adjudicated by the cut-off date), six total study exits (including 2 deaths) and no deviations from the study plan. As of the data cut-off date, two deaths have been reported in this study. These deaths have not been reviewed by the Event Adjudication Committee and tabled as additional information was required from the center. Updated information regarding these deaths will be provided in the next report. There is limited information in this report upon which to make conclusions on the safety of this device.
Actual Number of Patients Enrolled	1322 subjects
Actual Number of Sites Enrolled	98 sites
Patient Follow-up Rate	61.27%
Final Safety Findings	The Attain StarFix Model 4195 Lead related complication free-rate at 60months is 97.3%, and the lower bound of one-sided 95% confidence interval for the complication-free rate is 95.96%. This results are well above the acceptance boundary of 92.5%.
Final Effect Findings	During this study duration, a total of 147 elevated thresholds were reported with occurrence rate decreasing from 6.97% at impant to 2.10% at 60 months. In addition, a total of 10 out-of-range pacing impedance events were reported with occurrence rate varying from 0% to 0.35% at different time points from implant to 60 months. A total of 56 returned leads (4.22%) were reported during the study period.
Study Strengths & Weaknesses	Study Strength: Excellent device safety: high five-year complication free rate 97.3% ( 95%CI: 95.96%, 98.2%) Excellent device effectiveness: low five-year occurrence rates of elevated thresholds (2.10%) and out-of-range pacing impedance events (0.26%) at 60 months Study Weakness: High attrition rates excluding deaths (38.73%) and including deaths (64.99%) Lower number of subjects (446) who reached 5-year follow-up post implant than the minimum required 598 subjects
Recommendations for Labeling Changes	Yes
General
Study Status	Terminated
Application Number / Requirement Number	P070013 / PAS001
Date Original Protocol Accepted	09/15/2008
Date Current Protocol Accepted	09/15/2008
Study Name	EVOLENCE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is an open-label, multi-center, prospective study designed to assess the safety of EVOLENCE in subjects with Fitzpatrick skin types IV, V, and VI seeking correction of facial wrinkles.
Study Population	The study population is as per device indication. The device is indicated for [add here] The Study Population includes patients 18 years or older with Fitzpatrick skin types IV, V and VI who have clinical evidence of moderate to deep bilateral wrinkles in the nasolabial area corresponding to a rating of at least 2 on the validated MFWS. Indication: injection into the mid to deep dermis for the correction of moderate to deep facial wrinkles and folds;
Sample Size	165 patients, 10 sites
Key Study Endpoints	The effectiveness endpoint is the change in Modified Fitzpatrick Wrinkle Scale at six months. The safety endpoint is a composite measure of keloid formation and pigmentation change at 6 months post optimal cosmetic results visit.
Follow-up Visits and Length of Follow-up	The study required 6 month follow-up. Data collection at office visits included adverse events, Modified Fitzpatrick Wrinkle Scale. Visits were scheduled at 4 days, 1, 3, 6 months after the last injection.
General
Study Status	Completed
Application Number / Requirement Number	P040003 S006/ PAS001
Date Original Protocol Accepted	04/19/2010
Date Current Protocol Accepted	04/19/2010
Study Name	Exablate 2100 Type 1.0
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary goal of the study is to evaluate the incidence of post-procedure significant leg pain for the ExAblate treatment of uterine fibroids using enhanced sonication. Leg pain analysis will test non-inferiority of the ExAblate test group versus an incidence reference of 7%, allowing for a non-inferiority delta of 10%.
Study Population	Pre or peri-menopausal women who are not pregnant or breastfeeding, ages 18 and over, are seeking treatment for fibroid symptoms will be evaluated and invited to participate in the study.
Sample Size	A total of one hundred and fifteen (115) patients will be enrolled and treated. This study analysis of post-procedure significant leg pain will be based on the incidence of 7 percent suggested by FDA. Per FDA suggested sample calculation based on the non-inferiority one-sided alpha of 0.025, the sample estimate based on assumptions of type I error (alpha) = 0.025, type II error (beta (power)) = 0.86, an incidence of 7%, a non-inferiority delta of 0.10 resulted in a required sample size of 96. Allowing for a dropout rate of 20% results in a sample size of N = 115¿
Key Study Endpoints	Safety data will be collected, including the type, frequency, and severity of adverse events (see Attachment A for more details).
Follow-up Visits and Length of Follow-up	Patients will be followed at one week and one month.
Interim or Final Data Summary
Interim Results	Final Report accepted, sponsor was advised to submit labeling change supplement. Study will be marked as completed when the labeling change supplement is approved.
Actual Number of Patients Enrolled	115 subjects enrolled and treated
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	94% at 1-month
Final Safety Findings	There was a substantially higher occurrence of pain in the post-approval study (PAS) compared to the pivotal study. In the pivotal study the most common adverse events were as follows: abdominal pain (38.5%); Other pain (12.8%); and positional back pain (10.1%). Sonication-related pain in the leg and back were relatively less common (7.3% and 3.7%, respectively). Pain was also a common adverse event in the post-approval study and occurred more frequently than in the pivotal trial. The most commonly occurring types of pain in the PAS were as follows: sonication-related abdomen pain (52.1%); sonication-related leg pain (28.9%); and sonication-related back pain (14.9%). The most common adverse events were back/buttock/leg pain, abdominal pain, and skin pain (all sonication-related). Of the 366 adverse events, 306 (84%) were mild or moderate and 60 (16%) were severe. The most common severe adverse events were Pain Abdomen Sonication-related, Pain Back/Buttock/Leg ¿ Sonication-related, and Skin Pain Sonication-related. Seventy-six percent of all adverse events resolved on the day of treatment, and 88% of all events resolved within 10 days of treatment.
Final Effect Findings	No effectiveness endpoints in this study
Study Strengths & Weaknesses	High follow-up rate of 94%. Multi-center design increases representativeness of the study sample. Limitations The high screen failure rate limits the generalizeability of the PAS findings to women with uterine fibroids at large. Short follow-up period of 1 month.
Recommendations for Labeling Changes	Yes
General
Study Status	Terminated
Application Number / Requirement Number	P070027 S011/ PAS001
Date Original Protocol Accepted	02/04/2010
Date Current Protocol Accepted	07/16/2014
Study Name	Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multi-center, prospective, non-randomized, single arm post-market surveillance clinical registry study.
Study Population	Patients of 18 years of age and older who require secondary endovascular intervention for the prevention of AAA rupture
Sample Size	20
Key Study Endpoints	Endovascular treatment success, failure mode, adverse events, AAA-related mortality, all cause mortality, conversions to open surgery, secondary procedures, aneurysm growth, stent graft migration, integrity, and patency, endoleaks.
Follow-up Visits and Length of Follow-up	No specified - to be determined by standard of care. 5 years.
General
Study Status	Completed
Application Number / Requirement Number	P090018 / PAS001
Date Original Protocol Accepted	03/17/2010
Date Current Protocol Accepted	08/16/2010
Study Name	Extended Follow-up of PMA study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	51
Actual Number of Sites Enrolled	3
Patient Follow-up Rate	98% at 4 months, 98% at 10 months, 65% at 2 years, 73% at 3 years, 86% at 4 years, 100% at 5 years
Final Safety Findings	A total of three (3) SADEs in three (3) subjects have been reported during the PAS, in the second through fifth year of post-implant follow-up. These included a sore behind the implant ear caused by glasses requiring surgical intervention; once incision breakdown after battery replacement procedure; and one involved progression of external auditory canal abscess to transcanal infection, requiring explantation of the device.
Final Effect Findings	Overall mean Speech Reception Threshold (SRT) scores show significant improvement with Esteem compared with pre-implant baseline aided condition through the 4-year follow-up. Through 4-year follow-up, the 95% LCB for the mean difference relative to baseline aided condition ranges from +6.3 dB to +10.9 dB, greater than the +5 dB criteria for superiority. At the 5-year follow-up, the 95% LCB for the mean difference relative to baseline aided condition is +0.8 dB, greater than the -5 dB criteria for non- inferiority. Through the 4-year follow-up, the Esteem improves Word Recognition Scores (WRS) in a majority of subjects (ranging from 64% to 79%) compared to the pre-implant aided condition. At the 5-year follow- up, the Esteem improves word recognition scores in 49% of subjects, and scores the same in 41% of subjects compared to the pre-implant aided condition.
Study Strengths & Weaknesses	This is a single arm study with no comparator; however, the subjects served as their own control. It is a long term study (up to 5 years post-implantation) with high follow-up rate.
Recommendations for Labeling Changes	Yes. A labeling update is recommended regarding the lifetime of the battery, long term device effectiveness and a newly identified device failure ¿fluid ingress due to header abrasion¿ is of consideration.
General
Study Status	Completed
Application Number / Requirement Number	P040043 / PAS002
Date Original Protocol Accepted	08/31/2005
Date Current Protocol Accepted	08/31/2005
Study Name	Training Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational, multi-site, one armed prospective cohort study of patients with aneurysms treated with the TAG device.
Study Population	The study will enroll subjects diagnosed with aneurysm of the DTA who meet all inclusion/exclusion criteria. Patients previously treated with the commercially approved TAG device by a physician who has completed the GORE TAG Physician Training program may be retrospectively screened for enrollment into this study.
Sample Size	150 patients from 25 sites
Key Study Endpoints	The incidence of major adverse events at 30 days post-implant. Major Adverse Event are defined as those requiring therapy and short hospitalization (24-48 hours), major therapy, unplanned increase in level of care, prolonged hospitalization, permanent adverse sequelae, or death.
Follow-up Visits and Length of Follow-up	Patients are evaluated at 30 days post-implant.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	150 patients
Actual Number of Sites Enrolled	25 sites
Patient Follow-up Rate	100%
Final Safety Findings	All success criteria were met
Study Strengths & Weaknesses	Strength: Very good patient follow-up; Data collection was complete
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P960009 / PAS001
Date Original Protocol Accepted	04/16/2010
Date Current Protocol Accepted	04/16/2010
Study Name	Neurotoxicity/Carcinogenicity
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a lab study with the following objectives: (1) to extract Pellethane 80A and Elasthane 80A devices under aqueous conditions (phosphate buffered saline containing bovine serum albumin) and quantify 4, 4' methylene dianiline (MDA) in the extracts at particular timed intervals. Other target compounds will include ethylenediamine, butanediol, and tin. Target analytes will be quantified against standard curves of each analyte. (2) to determine extractable levels of 4, 4' methylene dianiline (MDA) by weight in Pellethane 80A used in the Model 3387 and 3389 DBS tremor lead. The testing is performed on Pellethane 80A as prepared for intended device use. The test is an exhaustive extraction. Two extraction media, isopropyl alcohol (IPA) and acetonitrile (ACN), are used.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	See study description
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P040050 / PAS002
Date Original Protocol Accepted	10/30/2006
Date Current Protocol Accepted	10/30/2006
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Enhanced surveillance to rapidly assess potential adverse events related to the use of Macroplastique following its launch in the U.S. marketplace. It involved the active solicitation of information on adverse events associated with Macroplastique from all U.S. physician customers on a quarterly basis for two years following PMA approval.
Study Population	All patients receiving the device. The device is indicated for women who have stress urinary incontinence due to poorly functioning urethral sphincter muscles.
Sample Size	N/A
Key Study Endpoints	Information on patient characteristics, treatment and retreatment, and onset, severity, and resolution of the event are to be obtained only if the customers have reportable events.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	87%
Final Safety Findings	No serious adverse events were identified by the Enhanced Surveillance Program since device was launched to market in the U.S through March 2008. The data for enhanced surveillance was collected for 2 years as per approval order.
Study Strengths & Weaknesses	Enhanced surveillance system with high response rate from participating physicians.
Recommendations for Labeling Changes	Update labeling to reflect the results of the Post-Approval Study
General
Study Status	Completed
Application Number / Requirement Number	P060040 / PAS001
Date Original Protocol Accepted	04/21/2008
Date Current Protocol Accepted	04/21/2008
Study Name	INTERMACS Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The proposed study is a prospective non-randomized observational study, with subjects obtained from the INTERMACS Registry, which included at least 84 sites with IRB approval as of December 31, 2007. The sponsor proposes to use the first 169 patients implanted with HeartMate II and the first 169 controls. If less than 169 control patients have entered the study by the time that 169 HeartMate patients have entered the study, consecutive controls will be chosen retrospectively.
Study Population	All patients who are identified pre-implant in the INTERMACS database as "Bridge to Transplant (patient currently listed for transplant)" or "Possible Bridge to Transplant - Likely to be eligible" will be enrolled in the post market study. Patients implanted with the Heartmate II will comprise the study group and patients implanted with any other LVAD will comprise a concurrent comparator group. In addition, all other patients implanted with a HeartMate II during the post market study, who are not part of an IDE, and not "Bridge to Transplant (patient currently listed for transplant)" nor "Possible Bridge to Transplant - Likely to be eligible" will be analyzed as a separate group to help assess how the device is used in the community.
Sample Size	169 HeartMate patients and 169 controls from the INTERMACS Registry
Key Study Endpoints	Endpoints include: 1) procedural success, 2) incidence of adverse events. Bleeding adverse events will include information on date and site of bleeding, anticoagulation use, and amount of blood transfusion, 3) Device malfunctions and failures, 4) Quality of Life as measured by EuroQOL (at 3 and 6 months), 4) Neurocognitive function (Trailmaking B), assessed in a subset of sites, detailed in a separate protocol, and 5) One year post explant survival.
Follow-up Visits and Length of Follow-up	All subjects and controls will be assessed at one week, one month, 3 months, 6 months, and one year post explant. Patients will be followed until one year post explant.
Interim or Final Data Summary
Interim Results	Most adverse events occur with similar frequencies in the HeartMate II and the control groups. Hypertension is more frequent in the control group.
Actual Number of Patients Enrolled	338
Actual Number of Sites Enrolled	77
Patient Follow-up Rate	99
Final Safety Findings	The most common adverse events overall were bleeding, infection, cardiac arrhythmia, and respiratory failure. Compared to the Comparison group, HMII patients had significantly lower risk for adverse events including device malfunctions. The most common type of device malfunction was ¿external control system failure, 21 cases reported.
Final Effect Findings	Success was defined as LVAS support for at least 180 days or to transplant, or to explant due to myocardial recovery and survival for at least 60 days post explant. Ninety-percent (90%) of the HMII patients achieved success compared to 79% of the Comparison patients (Fishers exact P=0.0064).
Study Strengths & Weaknesses	Strengths: Follow-up rate was very high (99%); all subjects were prospectively followed; a concurrent control group was available for comparison; all data was collected and evaluated through a registry that utilized standardized methods for data collection and evaluation. Weakness: Potential confounding variables were not controlled for in comparing subjects with controls ¿ however, baseline data was similar in the two groups.
Recommendations for Labeling Changes	Labeling changes should be accomplished in accordance with the findings of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P070001 / PAS001
Date Original Protocol Accepted	12/17/2007
Date Current Protocol Accepted	08/12/2008
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective cohort to continue follow-up of the subjects who participated in (1) the IDE premarket study and (2) the continued access study.
Study Population	The study population is as per device indication. The study includes IDE and CAS subjects. This device is indicated for skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable symptomatic cervical disc disease (SCDD). Symptomatic cervical disc disease is defined as neck or arm (radicular) pain and/or a functional/neurological deficit with at least one of the following conditions confirmed by imaging (CT, MRI, or X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or loss of disc height. The ProDiscTM-C Total Disc Replacement is implanted via an open anterior approach. Patients receiving the ProDiscTM-C Total Disc Replacement should have failed at least six weeks of non-operative treatment prior to implantation of the ProDiscTM-C Total Disc Replacement.
Sample Size	239 ProDiscTM -C (103 Randomized and 136 Continued Access) and 106 ACDF patients for a total of 345 patients
Key Study Endpoints	A patient will be considered an overall success if all of the following conditions are met: The patient's NDI score improves by at least 20% over preoperative baseline value; The patient's neurologic parameters, i.e. motor sensory, and reflexes are maintained or improved as compared to preoperative baseline value No removals, revisions, re-operations or additional fixation were required to modify any implant No adverse events occur which are related to the treatment.
Follow-up Visits and Length of Follow-up	Data will be collected at 36, 48, 60, 72 and 84 months postoperative
Interim or Final Data Summary
Interim Results	So far, since the approval of the device (December 17, 2007), a total of 86 Adverse Events (AEs) from 40 ProDisc-C patients (39% of 103) and 98 AEs from 47 ACDF control patients (44% of 106) have been reported in the post-approval period follow-up of the IDE cohort as of November 23, 2009. During the same period, 188 AEs from 74 ProDisc-C patients (54% of 136) reported in the CAS cohort. For implant-related AEs, the CAS cohort had 2 cases (1 upper extremity pain and one index level surgery); and ACDF patients in the IDE cohort had 1 implant-related surgery.
Actual Number of Patients Enrolled	PDC: 103 ACDF: 106 PDC-CA: 135 Total: 345
Actual Number of Sites Enrolled	Clinical sites: 14
Patient Follow-up Rate	At 84-month: PDC: 93.9% ACDF: 92.8% PDC-CA: 83%
Final Safety Findings	Death: There were 12 instances of death for enrolled subjects though 10 deaths (10/345, 2.9%) occurred within the study window. There are 3 deaths in the PDC cohort (3/103, 2.9%), which is not significantly different from the control group Adverse events: PRODISC C is not statistically different from ACDF when categorizing the data by the number of AEs. In the PDC group, there are 47 mild AEs (47/103, 45.6%), 38 moderate AEs (38/103, 36.9%), and 38 severe AEs (38/103, 36.9%). Device Underwent Surgical Intervention: 6 PDC subjects (6/103, 5.8%), 6 PDC-CA (6/135, 4.4%) subjects and 18 ACDF (18/106, 17.0%) subjects underwent subsequent surgical interventions at the index level.
Final Effect Findings	The results of Overall Success analyses indicate that the PRODISC C maintains non-inferiority to the ACDF control group in 7-year follow-up in both the primary analysis (Sponsor’s definition) and the additional analysis (FDA’s definition) of Overall Success.
Study Strengths & Weaknesses	This is a clinical study with a control group as the comparator which increased the internal validity in clinical interpretation. This study has a long range of follow-up (7 years) with a decent follow-up rate for a large sample size (345 patients).
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow–up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P980006 S004/ PAS001
Date Original Protocol Accepted	11/20/2001
Date Current Protocol Accepted
Study Name	Long Term
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	An open-label post-market surveillance study designed to assess the occurrence of serious adverse events with the Bausch and Lomb PureVision Contact Lens when worn on a 30-day continuous wear basis. A serious adverse event (for this study) was considered to be any case of microbial keratitis or a loss of more than two lines of best corrected (spherocylindrical refractive) visual acuity. The study was divided into two phases: Phase 1 represented the first 12 months of lens wear; Phase 2 was optional and represented the duration of wear time for each subject following completion of Phase 1. The maximum length of Phase 2 was three years. In both phases, each subject wore PureVision Contact Lenses on each eye on a 30-day continuous wear basis. Lenses were worn overnight without removal for 22-29 consecutive nights, and were removed and replaced with new lenses on the morning of the 30th day.
Study Population	This device is indicated for daily or extended wear from 1 to 7 days between removals, for cleaning and disinfection or disposal of the lens, as recommended by the eye care practitioner. The lens is indicated for the correction of refractive ametropia (myopia and hyperopia) in aphakic and/or not-aphakic persons with non-diseased eyes, exhibiting astigmatism of 2.00 diopters or less, that does not interfere with visual acuity. The study population is as per indication.
Sample Size	6500, minimal 100 sites
Key Study Endpoints	Development of microbial keratitis, and reduction in best corrected VA of more than two lines
Follow-up Visits and Length of Follow-up	The study was divided into two phases: Phase 1 lasted for approximately 12 months; Phase 2 was considered optional and consisted of the duration of time a subject was in PureVision lenses following completion of Phase 1. The maximum length of Phase 2 was 3 years. [Note: An amendment was approved by the US FDA approximately two years after study initiation. This amendment divided the study into 2 phases, allowing for continued follow-up (in Phase 2) of enrolled subjects beyond the original 12 month study period (after completion of Phase 1).] Date first subject enrolled: 22 Mar 2002; Date last subject exited: 14 Dec 2006
General
Study Status	Completed
Application Number / Requirement Number	P020018 S040/ PAS001
Date Original Protocol Accepted	04/04/2012
Date Current Protocol Accepted	12/12/2012
Study Name	Long Term F/U Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Observational, single-arm, multi-center, prospective cohort study
Study Population	Subjects from the pivotal trial plus at least 20 new subjects
Sample Size	88
Key Study Endpoints	Primary endpoint: 5-year aneurysm-related mortality rate; Secondary endpoints: Aneurysm rupture, conversion to open surgery, device integrity, device patency, change in aneurysm size, endoleak, device migration, secondary interventions, and morbidity index, defined as the percent of patients who have one or more specified adverse events.
Follow-up Visits and Length of Follow-up	5 years 30 days, 1 year, and annually thereafter for 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total on 88 patients (67 pre-approval patients and 21 post approval patients
Actual Number of Sites Enrolled	A total 21 sites were enrolled (15 pre-approval sites and 6 post-approval sites)
Patient Follow-up Rate	94.4% (51/54) and 88.9% (48/54) of patients completed clinical and CT follow -up at 5 years respectively; 63.0% (34/54) of patients had KUB X-ray imaging at 5 years.
Final Safety Findings	Aneurysm related mortality rate based on the numerate (n=2 deaths) and a denominator that included patients that had 5-year follow-up visit or death (per approved protocol) is 3.08% (2/65) [Upper confidence limit of 10.68%] compared to PG of 18% (P-value < 0.01). Kaplan Meier estimates for freedom from aneurysm related mortality using a z statistics was 97.5% [95% CI: 94.0%, 100%] versus PG of 82%. Thus the study met the performance goal. Tipping Point Analysis A total of 23 patients had missing 5-year vital status data for the primary endpoint analysis. Per the sponsor’s tipping point analysis, in addition to the 2 deaths already counted as AAA-related, it would require at least 22% (n=5) of the 23 cases with missing vital status data to also experience AAA-related death for the primary endpoint to fail the hypothesis. This is unlikely given that only 1 treated patient showed aneurysm growth due to Type II endoleak (> 5 mm increase in diameter) at last follow-up which resolved with reintervention while all remaining patients had favorable outcomes i.e., a stable or shrinking aneurysm at last follow-up (1 patient did not receive the study device).
Final Effect Findings	The percentage of patients with patency loss based on Core Lab analysis or as reported by site was 0% (0/66) at 2 years, 1.8% (1/56) at 3 years, 0% (0/49) at 4 years and 0% (0/44) at 5 years. No conversions to open repair were reported through 5 years. There were 30 secondary interventions in 25 unique patients. One (1) patient experienced component separation and aneurysm rupture at 5-year time point. One patient (2.1%, 1/48) experienced Type I distal endoleak at 3 years and one patient (3.0%, 1/33) experienced Type III at 5 years. Type II endoleak rate at 5 years was 9.1% (3/33). Ten patients experienced aneurysm growth at one or more follow-up time points. At 5 years 72.7% (32/44) of patients had aneurysm shrinkage, 15.9% (7/44) had no change in aneurysm size and 11.4% (5/44) had aneurysm expansion. Two cases of stent migration involving caudal movement of proximal components occurred in two patients, one at 2 years and the other at 5 years. Stent graft barb separation and component separation were the most frequently reported device integrity problems 2.2% (1/46) each at 5 years. For fenestration stent, fracture rate and separation rate was 0% (0/44) each at 5 years.
Study Strengths & Weaknesses	The study primary endpoint met the performance goal with aneurysm related mortality rate of 2.27% (2/88) compared to PG of 18% (p<0.0001) at 5 years. The impact of missing data on the primary endpoint result was evaluated. The absolute numbers for patients completing clinical follow-up and imaging assessment at 5 years were low: clinical follow-up (51), CT follow -up (48) and KUB X-ray (34).
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post approval study. The labeling change should include a new section in the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P020018 S040/ PAS002
Date Original Protocol Accepted	04/04/2012
Date Current Protocol Accepted	04/02/2014
Study Name	Training Program
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multicenter single-arm registry study
Study Population	Patients undergoing treatment for AAA with the Zenith fenestrated AAA endovascular graft who completed training program; no control group
Sample Size	82 subjects; no controls
Key Study Endpoints	Technical success of implant
Follow-up Visits and Length of Follow-up	None None
Interim or Final Data Summary
Actual Number of Patients Enrolled	82
Actual Number of Sites Enrolled	47
Patient Follow-up Rate	100%
Final Safety Findings	No safety endpoints in this study
Final Effect Findings	Technical success rate if implantation = 91.5%
Study Strengths & Weaknesses	There was 100% follow�]up of study subjects, and endpoint was fully assessed in all subjects. The primary endpoint was met by a wide margin. There were no significant weaknesses in this study.
Recommendations for Labeling Changes	No labeling change is recommended because there is no new information that is thought to be of sufficient value to justify a labeling change.
General
Study Status	Completed
Application Number / Requirement Number	P070004 / PAS002
Date Original Protocol Accepted	05/29/2012
Date Current Protocol Accepted	05/29/2012
Study Name	Post-Approval Cont Access Study (PACAS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Continued Access Study (CAS) was initiated under an FDA-approved investigational device exemption to provide supplemental data to the Core Clinical Study. The PACAS is to continue clinical follow-up of the primary augmentation and revision augmentation subjects previously enrolled in Sientra¿s CAS until each subject reaches her 5th year post-implantation.
Study Population	Women who received Sientra¿s silicone breast implants and were enrolled in the premarket augmentation cohorts of the Continued Access Study. The data obtained at baseline on each subject will be used as the control data for physical status, cancer history and status, rheumatologic history and status, medical history and status, and CTD history and status.
Sample Size	A total of 2,497 subjects have been enrolled in Sientra¿s PACAS at 33 sites throughout the United States.
Key Study Endpoints	The safety endpoints include local complications, implant rupture, connective tissue diseases (CTDs), CTD signs and symptoms, lactation complications, cancer and suicide. Effectiveness will be assessed based on quality of life (QOL) assessments and subject satisfaction.
Follow-up Visits and Length of Follow-up	5 years Annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	2,524
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	48.5% for both primary and revision augmentation cohorts at Year 5
Final Safety Findings	The Kaplan�]Meier risk rate of any complication at Year 5 was 34.8% in the primary augmentation cohort and 46.0% in the revision�]augmentation cohort. The most commonly reported complications in the primary augmentation cohort were Baker Grade III/IV capsular contracture and nipple sensation changes (10.0% and 4.6%, respectively). In the revision�] augmentation cohort, the most commonly reported complications were Baker Grade III/ IV capsular contracture, implant malposition and nipple sensation changes (13.3%, 5.7% and 5.7% respectively). The Kaplan�]Meier risk rate of reoperation was 20.2% in the primary augmentation cohort and 31.1% in the revision�]augmentation cohort. The Kaplan�]Meier risk rate of implant explantation was 10.4% in the primary augmentation cohort and 16.3% in the revision�]augmentation cohort. In the primary augmentation cohort there were four devices confirmed ruptured via explant and one device unconfirmed for a total of five reported ruptures through 5 years. In the revision�]augmentation cohort there was one device confirmed ruptured via explant and three devices with unconfirmed ruptures for a total of four reported ruptures through 5 years. There were no unanticipated adverse device events among the study subjects.
Final Effect Findings	In the primary augmentation cohort, 88.8% of patients increased their bra cup size by at least one cup, 79.2% increased by one to two cup sizes, while 9.5% increased by more than two cup sizes. Only 6.6% of the primary augmentation subjects achieved less than a one�]cup size increase.
Study Strengths & Weaknesses	The Continued Access Study (CAS) was designed to provide supplemental safety and effectiveness data for the premarket clinical study and to address the public health needs before device approval. It was conducted under the same protocol as the premarket clinical study. The subjects from the primary and revision reconstruction cohorts of the CAS were added to the premarket clinical study to support device approval and are now part of the Post�]approval PMA Cohort Study that will be followed for 10 years post�]implantation. The Post�]approval Continued Access Study (PACAS) only includes subjects from primary and revision�]augmentation cohorts of the CAS. The overall patient follow�]up rate of the PACAS was only 48.5% at Year 5. The low patient compliance significantly limited meaningful interpretation of the available safety results.
Recommendations for Labeling Changes	No labeling change recommended at this time. The labeling will be updated based on the 5�]year clinical data from the Post�]approval PMA Cohort Study for the same device.
General
Study Status	Completed
Application Number / Requirement Number	P070004 / PAS003
Date Original Protocol Accepted	03/09/2012
Date Current Protocol Accepted	05/26/2023
Study Name	US Post-Approval Study (US-PAS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The US-PAS is a 10-year post-approval cohort study to examine local complications and common diseases recommended by FDA for inclusion in the PAS. Common diseases were defined as conditions with incidence rates greater than 10/100,000. For evaluation of common diseases; reproductive outcomes, and suicide/attempted suicide, external comparisons will be made between the breast implant group and population-based disease rates derived from reliable data sources, from disease rate estimates available from other registries or epidemiologic studies, or from preoperative data. Internal comparisons will be made to baseline observations for quality of life endpoints. For the analysis of rheumatologic and neurologic signs and symptoms, the internal comparison group will be participants undergoing other aesthetic surgery. The study will enroll women who receive Sientra Silicone Gel Breast Implants for augmentation, revision augmentation, reconstruction, and revision reconstruction (these patients are referred to as “Gel participants”) in the naturally occurring proportions of these procedures at participating study sites. Participants will be followed over a 10-year period following breast implant surgery for common outcomes and all local complications. Gel participants will be evaluated by the Investigator at baseline and years 1, 5, and 9 and will complete questionnaires at baseline and years 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. A concurrent control group of women undergoing other aesthetic surgery (these patients are referred to as Control participants) will also be enrolled and will complete questionnaires at baseline and years 2, 4, 6, and 8.
Study Population	The device group will be women who received Sientras silicone breast implants as indicated for primary augmentation, revision augmentation, primary reconstruction, and revision reconstruction of the female breast. The control group will be women undergoing other aesthetic surgery.
Sample Size	The study will enroll 4,782 women receiving Sientras silicone breast implants and 300 women undergoing other aesthetic surgery as the comparison group.
Key Study Endpoints	The following safety outcomes will be evaluated: connective tissue diseases (CTDs), rheumatologic and neurologic signs and symptoms, cancer (lung and breast, including the potential of breast implant interference with mammography and delay of breast cancer detection), suicide/attempted suicide, local complications, reoperation and implant removal, reproductive and lactation complications. Effectiveness will be assessed based on quality of life (QOL) assessments and subject satisfaction.
Follow-up Visits and Length of Follow-up	10 years Investigator evaluations of breast implant participants will occur at baseline and years 1, 5, and 9. Additional study data will be obtained via questionnaires completed by the breast implant and Control participants. Breast implant participants will complete a baseline questionnaire, a condensed follow-up questionnaire at years 1, 5, and 9, and a standard follow-up questionnaire at years 3, 7 and 10. At years 2, 4, 6, and 8 they will complete a QOL and Signs/Symptoms questionnaire regarding QOL, suicide/attempted suicide, participant satisfaction, rheumatologic and neurologic signs and symptoms. Control participants will complete a baseline questionnaire. At years 2, 4, 6, and 8 they will complete a Signs/Symptoms questionnaire that will collect information on rheumatologic and neurologic signs and symptoms. The subgroup of 1,000 breast implant participants will receive additional reproductive outcome questions at years 1, 3, 5, 7, 9 and 10.
Interim or Final Data Summary
Actual Number of Patients Enrolled	5,498
Actual Number of Sites Enrolled	118
Patient Follow-up Rate	65%
Final Safety Findings	Local complications The most common complication was rupture in augmentation cohorts (27.9% and 39% by implant in primary and revision, respectively) and capsular contracture in reconstruction cohorts (18% and 13.3% in primary and revision, respectively). Reoperation Investigators reported 16.5% reoperation risk by implant, with 13.4% resulting in implant removal. Reoperation risk was lowest in primary augmentation (13.7%, 11% implant removal) and highest in revision reconstruction (41%, 37.8% implant removal). Common reasons included capsular contracture, patient request, style/size change, and malposition. Systemic complications The most reported systemic events were breast cancer (0.7%) and rheumatoid arthritis (0.6%). Fibromyalgia (0.7%) was most common systemic event in primary augmentation and breast cancer (1.4%) in revision augmentation cohorts. MH analysis showed participants had 3.36 times higher risk of rheumatoid arthritis (95% CI 2.240, 5.045) versus reference population (Doran et al., 2022). Signs and symptoms Gel and control participants reported similar rates of rheumatologic (34.1% vs. 32.7% reported at least 1) and neurologic (37.9% vs. 34% reported at least 1) signs/symptoms. The most common rheumatologic symptom was daily joint pain/swelling/tenderness (16.6% vs. 15.7%). The most common neurologic symptom was chronic fatigue in gel participants (15.2%) and difficulty concentrating/memory in controls (14.2%). Reproductive outcomes Across the 445 pregnancies, the most common complications were miscarriage (113 events), inadequate milk production (99 events), and Child was not satisfied/not gaining enough weight with breast milk (34 events). MH analysis showed 1.29 times higher miscarriage risk (95% CI 1.10, 1.51) versus reference population (Rossen et al., 2018). Suicide There were 19 attempted suicide events (0.4% KM risk) and 64 considered/planned events (1.5% KM risk). MH analysis indicated decreased risk versus reference populations. Deaths There were 42 deaths: 39 during the study, 1 after 10 years, and 2 post-explantation. One death was suicide related. Risk factor analysis In augmentation cohorts, lower adverse event risks were associated with younger age, smooth devices, submuscular placement, and inframammary incisions across multiple outcomes. Additional factors included white race and shaped style for capsular contracture; transaxillary incisions and <400cc for infection; round style and <400cc for rupture; and no Ecklund technique for reoperation.
Final Effect Findings	Quality of life (QOL)/BreastQ modules (at Year 8) Augmentation cohorts reported a 5-point decline from baseline in Physical well-being (chest) module scores but increase in psychosocial well-being (+20.5) and satisfaction with breast (+38.9) modules. Reconstruction cohorts reported increased scores from baseline for all three BreastQ modules. Participant satisfaction (at Year 8) Overall, 81.8% of gel participants were happy/satisfied and 12.1% were unhappy. In augmentation cohorts, 86.2% were satisfied and 13.8% dissatisfied. In reconstruction cohorts, 72.5% were satisfied and 27.5% dissatisfied. Compliance with MRI recommendations (at Year 9) Compliance was 1.5%, 2.8%, 5.6%, and 7.2% in augmentation, revision augmentation, reconstruction, and revision reconstruction cohorts, respectively.
Study Strengths & Weaknesses	The US-PAS study assessed women receiving Sientra silicone gel breast implants for augmentation, revision augmentation, reconstruction, and revision reconstruction, followed annually for 10 years to evaluate long-term safety and effectiveness. Data collection was staggered: office visits and condensed questionnaires at years 1, 5, and 9; standard questionnaires at years 3, 7, and 10; rheumatologic/neurologic signs/symptoms, satisfaction, and QOL questionnaires at years 2, 4, 6, and 8. The study faced significant retention challenges from external factors (COVID-19, Chapter 11 bankruptcy, asset acquisition by Tiger Aesthetics). Although the 10-year target follow-up rate of 65% was achieved, certain years had substantially lower follow-up, disproportionately impacting specific data types. For example, office visit years (1, 5, 9) had follow-up of 36%, 12%, and 8%, respectively. Caution is warranted when interpreting results due to uncertainty from low retention and missing data. While bias analysis found baseline characteristics do not predict differential outcomes, this makes indirect inferences using baseline characteristics rather than directly measuring outcomes in patients with incomplete data. Therefore, it does not fully address uncertainty from 35% missing data at year 10 and higher rates in other years. True rates could differ if non-compliant participants experienced systematically different outcomes.
Recommendations for Labeling Changes	Labeling update is recommended to reflect the long-term safety and effectiveness results
General
Study Status	Terminated
Application Number / Requirement Number	P070004 / PAS004
Date Original Protocol Accepted	03/09/2012
Date Current Protocol Accepted	03/09/2012
Study Name	Post-Approval Case-Control Studies(PACCS)
General Study Protocol Parameters
Study Design	Case Control Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75). The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put on-hold while the systematic literature review was conducted. The systematic literature review showed insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value. The FDA continues to monitor for these rare adverse events using other postmarket surveillance tools and real-world data (e.g. MDRs, NBIR, PROFILE).
Study Population	The case-control studies will be conducted in metropolitan urban areas of Southern Brazil. Sientra¿s Silicone Gel Breast Implants have been widely used in Brazil for more than a decade, providing the opportunity to evaluate rare disease outcomes, and its potential association in women with Sientra¿s Implants. Inclusion criteria for cases: ¿ Between 24 and 70 years of age at the time of enrollment ¿ The rare disease outcomes were identified and/or treated at a clinic collaborating in Sientra¿s post-approval study Exclusion criteria for cases: ¿ Deceased since diagnosis ¿ Diagnosis prior to March 1997 Inclusion criteria for the controls: ¿ Female ¿ Between 24 and 70 years of age at the time of enrollment ¿ Free from any of the diseases that will be evaluated as part of Sientra¿s post-approval study (i.e., rheumatic disease, neurological diseases, cancers of the cervix or brain, or lymphomas) ¿ Within selected age range of case definitions (frequency matched in 5-year age ranges) ¿ Within the general geographic region from which cases are recruited ¿ Currently a patient at one of the hospitals or clinics that provided cases for the studies. Exclusion criteria for the controls: ¿ Previous diagnosis of one or more of the conditions of interest (i.e., rheumatic disease, neurological diseases, cancers of the cervix or brain, or lymphomas)
Sample Size	For each of the 5 case-control studies, 1,280 cases of women diagnosed with studied rare disease at medical centers and hospitals in metropolitan urban areas of Southern Brazil will be enrolled. A total of 3,800 female hospital or clinic patients without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
Key Study Endpoints	During enrollment, each study participant will complete a self-administered questionnaire. Information obtained from both the cases and controls will include the following: ¿ Standard demographic data (e.g., name, mailing address, date of birth, race/ethnicity, marital status, educational attainment, occupation, family income, name of hospital/clinic of enrollment) ¿ Personal characteristics (e.g., menopausal status, smoking status, alcohol consumption, medical/surgical history, hours per day in the sun, sexual history) ¿ Disease/medication history (e.g., previously diagnosed with scleroderma, systemic lupus erythematosus (SLE), Sjogren¿s syndrome, multiple sclerosis, dermatomyositis/polymyositis, brain cancer, cervical/vulvar cancer, or lymphoma, family history of those diseases, previous treatment for any type of cancer with chemotherapy, oral contraceptive use, and previous diagnosis with Epstein-Barr virus, inflammatory bowel disease, HIV/AIDS, hepatitis B, hepatitis C, Helicobacter pylori, Chlamydia, or HPV ¿ Reproductive history (i.e., number of pregnancies, ages of children, maternal age at first birth) The medical records of each study participant will be reviewed by designated study personnel. The following information will be abstracted from the records of both the cases and controls: ¿ Use of specific prescription medications (specific list to be developed) ¿ Type, date, and results of radiology or imaging ¿ Date of last pap smear ¿ Date of any diagnoses of scleroderma, SLE, Sjogren¿s syndrome, multiple sclerosis, dermatomyositis/polymyositis, brain cancer, cervical/vulvar cancer, or lymphoma ¿ Date of breast implantation, any revisions made to the breast implant, manufacturer and type of breast implant
Follow-up Visits and Length of Follow-up	There is no follow-up for case-control studies
General
Study Status	Completed
Application Number / Requirement Number	P070004 / PAS005
Date Original Protocol Accepted	06/07/2012
Date Current Protocol Accepted	06/07/2012
Study Name	Focus Group Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Focus Group Study
Study Population	Women interested in breast augmentation or reconstruction with Sientra Silicone Gel Breast Implants.
Sample Size	Four focus groups with 8-10 participants in each group in Los Angeles, CA and Dallas, TX.
Key Study Endpoints	Participants¿ answers to the questions regarding the effectiveness of patient labeling in communicating the risks and benefits of breast implant surgery.
Follow-up Visits and Length of Follow-up	N/A N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	37 (18 in the augmentation group and 19 in the reconstruction group)
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	n/a
Final Safety Findings	In general, feedback from the four groups was positive and most participants found the Brochures to be helpful and beneficial in making an informed decision about breast implant surgery. Sientra is proposing revisions to the current Patient Educational Brochures based on comments from the participants. Information will be added to the brochures to guide patients to appropriate resources. In addition, the clinical study results will be updated and data presentation will be restructured with the 5-year follow-up data from the Post-approval PMA Cohort Study for Sientra¿s Silicone Gel Breast Implants.
Study Strengths & Weaknesses	The focus group study is quick, usually inexpensive, and useful in exploring ideas and concepts through group interaction. However, the analysis is qualitative, it is difficult to generalize results if small, unrepresentative samples of participants are used, and data analysis can be time consuming due to the open-ended nature of questions proposed for the focus group discussion.
Recommendations for Labeling Changes	No labeling change is recommended. The Focus Group Study was conducted to evaluate Patient Educational Brochures. No safety/effectiveness data of the sponsor¿s approved device was collected in the study.
General
Study Status	Completed
Application Number / Requirement Number	P110023 / PAS001
Date Original Protocol Accepted	03/07/2012
Date Current Protocol Accepted	11/23/2016
Study Name	Durability PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	The PAS is a prospective, multi‐center, non‐randomized, single arm study with sequential enrollment of all qualified subjects undergoing treatment of atherosclerotic lesions in the native superficial femoral artery or the superficial femoral and proximal popliteal arteries. All eligible subjects who provide informed consent will undergo PTA and stenting using the EverFlex device. Follow‐up will take place at pre‐ discharge, 30 days, 1 year, 2 years and 3 years.
Study Population	Adult patients with lesions no greater than 180 mm in length in the native superficial femoral artery or the superficial femoral and proximal popliteal arteries, who do not meet any of the exclusion criteria for this device.
Sample Size	The sample size of 108 is driven by the need for the above noted precision confidence interval for stent fracture rate. This sample size will ensure precision of the stent fracture rate at 1 year with a 95% confidence interval upper bound of 6.6%, assuming a proportion of 1 year fracture rate of 3.0%, and a 10% attrition at 1 year. Also, assuming that the true 36 month composite primary endpoint rate is 55% (with a performance goal of greater than 35%) and 30% attrition at 36 months, the resulting 108 evaluable subjects are greater than the 89 required to power the primary endpoint. Twenty (20) to 30 sites will be used in the study.
Key Study Endpoints	Primary endpoints A composite endpoint defined as freedom from acute death, freedom from 36‐month amputation, and freedom from 36‐month clinically‐ driven target lesion revascularization Secondary endpoints  Freedom from stent fracture at 1, 2, and 3 years  Freedom from 36‐month amputation at 1, 2, and 3 years  Freedom from 36‐month clinically driven target lesion revascularization at 1, 2, and 3 yrs  Freedom from acute death (within 30 days of the procedure)  Device success ¿ ability to employ the device as intended  Improvement in Rutherford clinical category at one year  Improvement in ankle‐brachial index at one year  Walking improvement at one year  Adverse events, including all cause mortality
Follow-up Visits and Length of Follow-up	Follow‐up visits will occur pre‐discharge, at one month, at one year, and annually thereafter, up to three years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	One hundred and eight (108) subjects were enrolled in the study.
Actual Number of Sites Enrolled	Twenty-three (23) sites were enrolled in the United States.
Patient Follow-up Rate	Follow-up rate at 1 year was 90.7% (98/108), at 2 years was 83.3% (90/108), and at 3 years was 76.9% (83/108).
Final Safety Findings	The primary safety endpoint is a composite endpoint of freedom from acute death (death within 30 days post procedure), freedom from 36- month amputation, and freedom from 36- month clinically driven target lesion revascularization (CD-TLR). The 36-month freedom from the primary safety composite event was 77.1% with 97.5% lower confidence bound of 67.8%, that is greater than the prespecified performance goal of 35% (p<0.001). Therefore, the study met the primary safety composite endpoint.
Final Effect Findings	Freedom from Stent Fracture at 1-year (365 days) was 100%, 98.9% at 2 years (730 days) and 96.5% at 3-years (1095 days) post procedure. Freedom from acute death, freedom from amputation and freedom from CD-TLR rate at 1-year post procedure was 86.0%, and at 2 years post procedure was 78.2%. Freedom from Amputation was 100% at 1 year and 99.0% at 2- and 3 years post-procedure. Freedom from Clinically Driven TLR was 86.0% at 1-year post-procedure, 79.2% at 2 year post procedure and 78.1% at 3 years post-procedure. Acute death rate at 30 days was 0%. Freedom from all-cause mortality rate at 1 year was 100%, at 2 years was 97.1%, and at 3 years was 91.6%. There were 118 stents implanted in 108 enrolled subjects. Device success rate was 100% (118/118). Improvement in Rutherford Clinical Category at 1 year compared to baseline was observed in 92.6% (88/95) of the Subjects. The mean Ankle-Brachial Index (ABI) at 1- year post-procedure improved by 0.26 (+/- 0.20) compared to baseline. The proportion of subjects with improvement was 87.3% (62/71).
Study Strengths & Weaknesses	Strength: The study met its primary safety composite endpoint compared to the pre-specified performance goal, (lower bound 67.8% vs 35% PG, p<0.001). Follow-up was achieved in approximately 80% of subjects at 3 years. Study was conducted on US subjects only. Weakness: This was a single- arm observational study and therefore did not have the inherent advantages of a randomized control trial.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the post- approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow-up visits etc.), final results, strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P110023 / PAS002
Date Original Protocol Accepted	03/07/2012
Date Current Protocol Accepted	03/07/2012
Study Name	Cont FU of Premarket Cohort-Durability II PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Interim or Final Data Summary
Actual Number of Patients Enrolled	287
Actual Number of Sites Enrolled	51
Patient Follow-up Rate	86%
Final Safety Findings	Stent fracture rate at 3 years:0.9% (Other key safety endpoints are subsumed in primary effectiveness endpoint (See below).
Final Effect Findings	CDTLR at 3 years: 30% Major amputation rate at 3 years: 0.8% Death rate at 30 days: 0%
Study Strengths & Weaknesses	The main study limitations derive from the fact that the study population consisted of subjects from the premarket cohort. Premarket studies are typically characterized by providers who are exceptionally skilled, and are therefore likely to provide relatively good results. However, this study is just one component of a two-component PAS requirement. The other component, which is not yet completed, utilizes newly enrolled patients obtained from different sites, which are more likely to be typical of the general population of providers.
Recommendations for Labeling Changes	yes
General
Study Status	Other
Application Number / Requirement Number	P070005 / PAS001
Date Original Protocol Accepted	03/06/2009
Date Current Protocol Accepted	03/06/2009
Study Name	REPEL CV
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, comparative, randomized study of REPEL-CV in pediatric patients (<21 years of age) undergoing cardiac procedures via sternotomy. The patient will be randomized to either treatment with REPEL-CV or no adhesion barrier.
Study Population	The population will be pediatric (<21 years of age) patients who are greater than 48 hours of age, requiring a first cardiovascular sternotomy procedure, on cardiopulmonary bypass and without delayed chest closure.
Sample Size	640 patients randomized and treated with either REPEL-CV (320 patients) or the untreated study-directed control (320 patients), 15 sites
Key Study Endpoints	The primary safety endpoint will be the incidence of a composite measure based on the patient-level incidence of the following two specific adverse events: 1) Re-operation for re-bleeding and/or cardiac tamponade; 2) Mediastinitis: defined as a deep sternal infection. The secondary safety endpoints will be: 1) The individual incidence of re-operation for re-bleeding and/or tamponade, and mediastinitis; 2) The specific incidence of mediastinitis, delayed constrictive pericarditis, sternal non-union, sternal dehiscence, and reoperation for bleeding and/or tamponade.
Follow-up Visits and Length of Follow-up	Patients will be followed for 6 months post initial sternotomy. However, patients who undergo a planned (staged) second sternotomy (not to include: emergent re-entry, or mediastinitis, or re-operation for re-bleeding and/or tamponade) within 6 months of the first sternotomy will be followed for 3 months post the planned second sternotomy.
General
Study Status	Completed
Application Number / Requirement Number	P080015 / PAS001
Date Original Protocol Accepted	03/12/2009
Date Current Protocol Accepted	03/12/2009
Study Name	Cervista HPV HR Assay
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, cohort study. The study consists of women that are 30 years or older with a normal pap test and Cervista HPV test at baseline. The enrolled subjects come back for their routine screening visits on an annual basis and have a Pap test at each follow-up visit.
Study Population	Study Population: Women 30 years or older who have a NILM cytology result at baseline. Indication: The Cervista HPV 16/18 test can be used adjunctively with the Cervista HPV HR test in combination with cervical cytology to screen to assess the presence or absence of high-risk HPV types 16 and 18 in women 30 years and older.
Sample Size	2000 patients, 26 sites
Key Study Endpoints	Safety endpoints do not apply. The effectiveness endpoints include cervical cytology, colposcopy/biopsy, and HPV 16/18 test.
Follow-up Visits and Length of Follow-up	The study required 3 years of follow-up. Follow-up inculdes annual visits.
Interim or Final Data Summary
Interim Results	Saftey information not applicable
Actual Number of Patients Enrolled	2026
Actual Number of Sites Enrolled	26
Patient Follow-up Rate	3 years
Final Safety Findings	The estimates for Cervista HPV 16/18 positive over Cervista 16/18 negative relative cumulative risk at the end of 3 years is 0.015 as compared to 0.009 (p=0.630). Sensitivity = 20.0% (95% CI: 3.6 ¨C 62.4) Specificity = 95.1% (95% CI: 93.8 ¨C 96.1) Positive predictive value = 1.4% (95% CI: 0.0 ¨C 5.0) Negative predictive value = 99.6% (95% CI: 99.6-99.9)
Final Effect Findings	Please see safety findings.
Study Strengths & Weaknesses	The cumulative 3 year incidence for Cervista HPV 16/18 test is based on one HPV positive with CIN2+ were compared to two HPV negative with CIN2+. Thus, it is unclear if data from the PAS supports that Cervista HPV 16/18 test (P80015) is more effective in triaging women to colposcopy. Another weakness is the generalizability of the study as the absolute 3 year cumulative risk of developing ¡ÝCIN2 in Cervista HPV HR [1.1% (4/362)] positive women is lower in the Cervista NILM ¡Ý30 population in comparison to cross-sectional and longitudinal data using other approved assays.
Recommendations for Labeling Changes	The study results for the three year follow-up of women with NILM ¡Ý30 with normal cytology and the uncertainty surrounding the conclusions will be included in the label Study limitations).
General
Study Status	Completed
Application Number / Requirement Number	P080014 / PAS001
Date Original Protocol Accepted	03/12/2009
Date Current Protocol Accepted	03/12/2009
Study Name	Cervista HPV HR Assay
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, cohort study. The study consists of women that are 30 years or older with a normal Pap test and Cervista HPV test at baseline. The enrolled subjects come back for their routine screening visits on an annual basis and have a Pap test at each follow-up visit.
Study Population	Study Population: Women 30 years or older who have a NILM cytology result at baseline. Indication: 1) To screen patients with atypical squamous cells of undetermined significance cervical cytology results to determine the need for referral to colposcopy. 2) In women 30 years and older, the Cervista HPV HR test can be used with cervical cytology to adjunctively screen to assess the presence or absence of high-risk HPV types.
Sample Size	2000 patients, 26 sites
Key Study Endpoints	There are no safety endpoints, The effectiveness endpoints include cervical cytology, colposcopy/biopsy, and high risk HPV test result.
Follow-up Visits and Length of Follow-up	The study required 3 years of follow-up. Follow-up inculdes annual visits.
Interim or Final Data Summary
Interim Results	Saftey information not applicable
Actual Number of Patients Enrolled	2026
Actual Number of Sites Enrolled	26
Patient Follow-up Rate	3 years
Final Safety Findings	The cumulative risk of ¡ÝCIN2 after 3 years among subjects who had a positive Cervista HPV HR result was 0.013 compared to 0.001 among subjects with HPV negative results when followed for 3 years (p=0.002).The clinical sensitivity, specificity, NPV and PPV of the test For detection of >= CIN2, based on 6diseased subjects. Sensitivity = 66.7% (95% CI: 30.0-90.3) Specificity = 81.6% (95% CI: 79.4 ¨C 83.5) Positive predictive value = 1.6% (95% CI: 0.6 ¨C 2.2) Negative predictive value = 99.8% (95% CI: 99.6-100.0)
Final Effect Findings	Please see safety findings.
Study Strengths & Weaknesses	Of the 2026 women enrolled in the PAS, only 6 had the study outcomes/CIN2+, namely 4 HPV positive and 2 HPV negative after 3 years. 36 subjects had missing data for CIN2+ determination in the PAS as compared to the 6 CIN2+ evaluated in the PAS. However, missing data analyses evaluated the study results as robust. Another weakness is the generalizability of the study as the absolute 3 year cumulative risk of developing ¡ÝCIN2 in Cervista HPV HR [1.1% (4/362)] positive women is lower in the Cervista NILM ¡Ý30 population in comparison to cross-sectional and longitudinal data using other approved assays.
Recommendations for Labeling Changes	It is recommended that the label be updated to reflect the study results for the three year follow-up of women with NILM ¡Ý30 with normal cytology.
General
Study Status	Other
Application Number / Requirement Number	P060027 / PAS001
Date Original Protocol Accepted	10/31/2008
Date Current Protocol Accepted	10/31/2008
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 5-year, multi-center, single arm, prospective and retrospective cohort study. All subjects in the study receive the device.
Study Population	Study population same as approved product. Indication for use: Ovatio cardiac resynchronization therapy is indicated for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life threatening arrhythmias. The device is also indicated for the reduction of heart failure symptoms in medically optimized New York Heart Association Functional Class III and IV patients with left ventricular ejection fraction of 35% or less, and a QRS duration of 150 ms or longer. Situs over-the-wire is designed to pace the left ventricle through a coronary vein. It is intended to be used in conjunction with ELA Medical cardiac resynchronization therapy pulse generators.
Sample Size	2260 subjects, 20 sites
Key Study Endpoints	Endpoints include complication free rate at 5 years, individual adverse event rates through 5 years, and system complication free rate at 6 months.
Follow-up Visits and Length of Follow-up	Scheduled follow-up occurs at discharge, one month, 6 months, and every 6 months thereafter, for five years post-implant. Unscheduled visits may occur for adverse events. At each scheduled visit, patients are queried regarding adverse events and device interrogation is performed.
General
Study Status	Completed
Application Number / Requirement Number	P070008 / PAS001
Date Original Protocol Accepted	05/12/2008
Date Current Protocol Accepted	12/23/2010
Study Name	CELESTIAL Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a 5-year, multi-center prospective cohort study designed to follow at least 2,000 patients implanted with BIOTRONIK's Corox OTW(-S) BP left ventricular lead.
Study Population	The study includes patients who require treatment for advanced heart failure through any CRT-P or CRT-D. Patient must be successfully implanted with a BIOTRONIK CRT system, including a Corox OTW(-S) BP left ventricular lead, from 7-180 days prior to enrollment.
Sample Size	This post- approval registry will include a minimum of 2,500 patients from up to 100 sites in the United States with. a minimum of 600 evaluable subjects for the Corox OTW-L BP lead which assumes an equal 1/3 distribution of each lead model (Corox OTW BP LV lead, Corox OTW-S BP LV lead, and Corox OTW-L BP LV lead). The estimated sample size requirement is based on both primary safety endpoints: a non-inferiority comparison (with ä of 5%) of the overall SAE free-rate to 92.5% at 5 years, and a non-powered, superiority comparison for those individual lead-related SAE to 1% at 5 years.
Key Study Endpoints	Primary Endpoint 1 evaluates the overall incidence of serious adverse events related to the Corox over-the-wire BiPolar Left Ventricular leads. Primary Endpoint 2 evaluates the incidence of each type of serious adverse events that contributes to Primary Endpoint 1.
Follow-up Visits and Length of Follow-up	Patients will be seen for routine follow-up visits per their institutional standard of care (typically every 3-4 months for a cardiac resynchronization therapy-defibrillator and every 6 months for a cardiac resynchronization therapy-pacer), but not to exceed every 6 months.
Interim or Final Data Summary
Interim Results	Thirty patients (5.3%) experienced an adverse event; these were reviewed and adjudicated by the Clinical Events Committee. One primary endpoint adverse event was reported in 565 subjects over a cumulative implant duration of 4227.6 months (352.3 years). The adverse event occurred on day 87, and the current estimated freedom from adverse events is 99.8% for implant times 87 days or longer. There were 36 (8%) subjects with elevated thresholds at implant, and 56 (12%) subjects with elevated thresholds at any follow-up. This number includes all subjects with a threshold greater than 3 Volts or 3.5 Volts, at implant or follow-up respectively, regardless of measured pulse width.
Actual Number of Patients Enrolled	2499
Actual Number of Sites Enrolled	97
Patient Follow-up Rate	90.1%
Final Safety Findings	Freedom from complication free rate: 94.19%
Final Effect Findings	The LV lead continued to sense and pace appropriately and the percentage of CRT pacing over time remained high
Study Strengths & Weaknesses	The study was large, prospective and had long-term follow up. Results demonstrated low adverse event rates. There were minimal weaknesses, aside from study duration.
Recommendations for Labeling Changes	Yes, completed
General
Study Status	Terminated
Application Number / Requirement Number	P070016 / PAS001
Date Original Protocol Accepted	11/26/2008
Date Current Protocol Accepted	12/06/2011
Study Name	Longterm PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational cohort of registry patients, chosen from a minimum of 15 multi-national investigative sites, with a maximum number of 25 patients enrolled at any one site.
Study Population	Consecutive patients who meet the inclusion criteria and who are willing to participate will be enrolled in the study. For inclusion in the study, patients must have a descending thoracic aortic aneurysm of at least 5 cm diameter, or with a history of growth of at least 0.5 cm per year, or degenerative or atherosclerotic ulcer of at least 10 mm in depth and 20 mm in diameter, AND patient must not meet any of the general, medical or anatomical exclusion criteria.
Sample Size	300 subjects, up to 50 sites Factoring in a 10% dropout rate, that adds up to 300. This will include 160 endovascular treatment patients from the pivotal clinical trial, plus an additional 125 endovascular patients, which allows for 12 patients lost to follow-up.
Key Study Endpoints	Aneurysm-related mortality is the primary endpoint. Additional endpoints to be assessed include device performance (change in aneurysm size, endoleaks, migration, device integrity, and secondary interventions) and morbidity.
Follow-up Visits and Length of Follow-up	Patients will be followed for a total of five years. Termination of follow-up will occur 30 days following explant, and upon patient withdrawal, death or closure of pre-market study.
General
Study Status	Terminated
Application Number / Requirement Number	P070007 / PAS001
Date Original Protocol Accepted	06/05/2008
Date Current Protocol Accepted	04/05/2016
Study Name	THRIVE Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will examine the post-market performance of the Talent Thoracic Stent Graft System. This study is a prospective non-randomized 5 year trial. A total of 451 subjects will be analyzed that consists of 195 enrolled subjects from the VALOR Test Group of the Talent Thoracic PMA Submission, and 256 new subjects to be enrolled following PMA approval.
Study Population	For purposes of cohort comparability, the inclusion/exclusion criteria will match to those used for the VALOR study with the exception of the removal of the following two parameters from the exclusion criteria: the patient's access vessel (as determined by treating physician) precludes safe insertion of the delivery system and patient requires a planned aortic conduit. Patients diagnosed with a descending thoracic aortic aneurysm are considered candidates for the endovascular repair. ,
Sample Size	195 subjects from the VALOR Test Group of the Talent Thoracic PMA Submission, and 256 new implants, 26 sites
Key Study Endpoints	The primary endpoint of this study is freedom from aneurysm-related mortality at 5 years. The postmarket performance of the Talent Thoracic Stent Graft System will be evaluated by comparing aneurysm-related mortality rates in patients implanted with the Talent Stent Graft System at 5 years versus the rate at 1 year for open surgery. The open surgery aneurysm-related mortality rate is based on the experience collected in 3 Centers of Excellence. Aneurysm-related mortality is defined as: Death from rupture of the thoracic aortic aneurysm or from any procedure intended to treat the descending thoracic aorta
Follow-up Visits and Length of Follow-up	The planned follow-up is 5 years for #2002-07. Participants from the #99-03 study will be followed until the termination of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P010012 S160/ PAS001
Date Original Protocol Accepted	05/16/2008
Date Current Protocol Accepted	01/20/2017
Study Name	ACUITY Long-Term Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	prospective, non-randomized, multi-center registry
Study Population	The study population will consist of patients who: were successfully implanted with the ACUITY Spiral Lead, meet the study criteria.
Sample Size	1,700 patients, 150 sites
Key Study Endpoints	Chronic LV lead-related complication-free rate over a five year follow- up period
Follow-up Visits and Length of Follow-up	Patients will be followed until they have completed five years of follow-up from implant or until death, withdrawal, or closure of the registry. Patients will have an in-clinic follow-up visit one month (15 to 29 days) post implant and then subsequently be followed according to the center¿s standard follow-up schedule, with complete in-clinic system interrogation recommended to be at least once every six months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1308 subjects (out of the required 1700 subjects)
Actual Number of Sites Enrolled	94 sites
Patient Follow-up Rate	57.3%
Final Safety Findings	he one-sided 95% confidence-interval lower bounds for the mean values of the modified complication-free rate (CFR) for the following five different time points are well above the acceptance boundary of 92.5%, as given in Table below. Interval (Years from implant) Statistic 1 2 3 4 5 Mean % Free from Adverse Events 96.8 96.3 96.1 95.7 95.3 Lower One-Sided 95% Confidence Limit 95.9 95.3 95 94.5 94 None of the deaths were reported as LV lead-related. The final death rate per year is 7.23%.
Final Effect Findings	Percentages of patients with out-of-bound measurements are as follows: a voltage threshold (9%), pulse width (2%), pacing impedance (0%, 1 patient with pacing impedance >= 2000 ohms), and sensing amplitude out of performance standards bounds (11%) cumulatively. The 60-month occurrence rates of out-of-bound measurements are the voltage threshold (1%, >3.5V), pulse width (0%, energy output >0.5), pacing impedance (0%, >= 2000 ohms), and sensing amplitude (1%, <= 3mV).
Study Strengths & Weaknesses	The study strengths are 1) the high modified CFR of 95.3% and its lower bound of 94% and 2) the low occurrence rates of out-of-range measurements as listed above for the final effectiveness findings. The study weakness is that only a total of 436 subjects were followed, which is smaller than the minimum 500-subject requirement often seen in other PAS’s for leads.
Recommendations for Labeling Changes	Inclusion of 1) the 5-year modified CFR and corresponding 95% one-sided confidence interval; and 2) a summary of adverse events that were and were not counted towards the 5-year modified CFR along with a clarification on intervention methods (non-invasive vs. invasive).
General
Study Status	Completed
Application Number / Requirement Number	P070009 / PAS001
Date Original Protocol Accepted	09/28/2007
Date Current Protocol Accepted	09/09/2008
Study Name	Realize PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, single-arm, multi-center study designed to look at the long-term re-operation rates seen with the Swedish Adjustable Gastric Band.
Study Population	Study population: Subjects are between the ages of 18 and 60 years old who have been diagnosed with morbid obesity and considered appropriate candidates for surgical weight reduction. Indication: Patients with one or more significant medical conditions related to obesity for which the subject is being treated, and which are generally expected to be improved by weight loss. Body Mass Index (BMI) must be greater than or equal to 35 kg/m2 and less than or equal to 40 kg/m2.
Sample Size	300 patients, 8 sites
Key Study Endpoints	The primary endpoint is the re-operation rate (including band revisions, band replacements, and explants) in years four and five post-implant. Secondary endpoints are: HbA1c levels, serum lipid levels, amount of excess body weight loss, quality of life measured by SF-36, Beck Depression Inventory scale score, adverse event rate, severe adverse event rate
Follow-up Visits and Length of Follow-up	Subjects will be followed for five years. During year 1 following implant, evaluations take place at 1, 2, 4, 6, 8, and 10 months. Evaluations will then take place at 12 months, 24 months, 36 months, 48 months, and 60 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	303
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	77%
Final Safety Findings	The primary safety goal of this study was to determine the reoperation rate (band revision, band replacement, and explants resulting from Serious Adverse Events (SAEs)) of gastric banding at 4 and 5 years post implant. The safety success criterion for this study was an observed device-related reoperations rate significantly lower than 8% for Years 4 and 5 of the study. The observed reoperation rate in the post-approval study was 8.9% with an upper bound 95% confidence interval of 12.08%, which results in failure to reject the null hypothesis (H0: Reoperation rate ? 8%). Therefore, there is no evidence that the reoperation rate is less than 8%. The most commonly occurring AE related to the study device was GI disorders with 1,117 events experienced by 246 (81.2%) subjects. Of all the adverse events that occurred in Years 4 and 5 of the study, the most commonly occurring AE related to the study device was GI disorders with 289 events experienced by 155 (51.2%) subjects. Overall, gastroesophageal reflux disease (14.2%), vomiting (13.5%), esophageal dilation (8.9%), dysphagia (7.9%), and gastric dilatation (6.3%). The overall explant rate was 8.9% with a 95% CI range of 6.0% to 12.08%. Most Frequently Occurring Device Related Serious Adverse Events include: device migration (9.2%), catheter related complication (5.0%), cholelithiasis (4.3%), cholecystitis (2.6%), and gastric dilatation (2.3%) were the most common SAEs reported throughout the entire study.
Final Effect Findings	As a result of the reduction in BMI, important and statistically significant reductions in the lipid profile were achieved and were reported since the first year of follow-up including reductions in LDL, triglycerides, and HbA1c values, which were maintained throughout the remainder of the study. There was a statistically significant change in BMI values between each yearly time point and the value at screening. However, there was not a statistically significant change appreciated in the total cholesterol levels. The following are detailed results at 5-years post- surgery in the ITT population: ? %EWL was 35.6 ± 26.84; ? Mean reduction in BMI (kg/m2) was -7.0 ± 5.45 (95% CI: -7.7 to -6.3); ? Mean reduction in absolute weight (lb) and mean % in weight reduction (%) was -43.1 ± 32.5 (95% CI: -47.3 to -39.0), and 16.0 ± 11.9 (95% CI: 14.5 to 17.6) respectively; ? The Physical Component score and the domain scores for SF-36 showed improvement at every post-surgery visit; ? The total transformed score and the domain scores for the IWQOL-Lite showed improvement at every post-surgery visit in the CI-07-0006 cohort; ? Mean reduction in HbA1c (%) was -0.22 ± 0.823 (95% CI: -0.33 to -0.11), which was statistically significant; ? Mean increase in HDL (mg/dL) was 9.3 ± 11.51 (95% CI: 7.7 to 10.8), which was statistically significant; ? Mean reduction in LDL (mg/dL) was -7.3 ± 31.90 (95% CI: -11.6 to -3.0), which was statistically significant; ? Mean reduction in total cholesterol (mg/dL) was -2.0 (95% CI: -7.8 to 2.0), which was not statistically significant; and ? Mean reduction in triglycerides (mg/dL) was -28.2 ± 110.15 (95% CI: -42.7 to -13.7), which was statistically significant.
Study Strengths & Weaknesses	Enrollment was successful: A sample size of 300 was expected and a total of 303 were studied. A five-year follow-up was achieved providing long-term safety and effectiveness data. Weaknesses: No concurrent comparison group, which limits interpretation of the results. Based on this one study, statements comparing the device to alternative treatments cannot be made. A 77% follow-up rate was attained. Loss to follow-up limit the interpretation of the study results. The subjects that remain in the study may be different to those that were lost, and therefore, the generalizability of results can be limited.
Recommendations for Labeling Changes	PAS study data must be added to the labeling including: description of the study design and methods, and the new safety information through 5 years of follow-up.
General
Study Status	Completed
Application Number / Requirement Number	P020056 / PAS004
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Adjunct
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 84, 329 patients were enrolled in the study; 45,055 in the reconstruction cohort and 39,274 in the revision cohort
Actual Number of Sites Enrolled	2,696 sites
Patient Follow-up Rate	Reconstruction cohort: 54.3% at Year 1, 29.8% at Year 3, 17.8% at Year 5 Revision cohort: 47.9% at Year 1, 26.1% at Year 3, 15.7% at Year 5
Final Safety Findings	The most commonly observed complications in the reconstruction and revision cohorts were capsular contracture, asymmetry, implant palpability/visibility, implant malposition and wrinkling. The cumulative 5-year risk rate for these complications in reconstruction and revision were as follows, respectively; capsular contracture (15.0%, 21.5%), asymmetry (11.1%, 10.6%), implant palpability/visibility (7.1%, 11.5%), implant malposition (6.5%, 7.1%) and wrinkling (5.6%, 8.9%). The rate of any reoperation at 5 years post-implantation was 34.4% in the reconstruction cohort and 30.1% in the revision cohort. The most common reasons by cohort for reoperation were: capsular contracture (30.9%), cosmetic (30.9%), infection (5.1%) in the reconstruction cohort capsular contracture (44.3%), cosmetic (33.6%), and infection (4.8%) in the revision cohort. The incidence of implant removal with replacement at 5 years post-implantation was 18.6% in the reconstruction cohort and in the revision cohort. The incidence of implant removal without replacement at 5 years post-implantation was 5.1% in the reconstruction cohort and 4.3% in the revision cohort. The Kaplan-Meier cumulative rupture rates at 5 years were 1.3% in the reconstruction cohort and 1.5% in the revision cohort.
Final Effect Findings	For the reconstruction cohort, on a 1 (definitely dissatisfied) to 5 (definitely satisfied) scale, the average satisfaction level for patients and physicians was 4.3-4.4 at each follow-up timepoint. For the revision cohort, the average satisfaction level for patients and physicians was 4.4-4.5 at each follow-up timepoint.
Study Strengths & Weaknesses	A large number of patients were enrolled in the adjunct study. However, the study was originally designed to address the public health needs of reconstruction and revision patients before device approval and to gather safety data regarding short-term post-implant complications under a limited clinical protocol without follow-up goals. The follow-up rates of the reconstruction cohort at 1, 3 and 5 years were 54.3%, 29.8%, 17.8%, respectively. The follow-up rates were slightly lower in the revision cohort, i.e., 47.9% at Year 1, 26.1% at Year 3, 15.7% at Year 5. The poor patient compliance provides limited meaningful interpretation of the available safety results.
Recommendations for Labeling Changes	No. The Adjunct Study was designed to address the public health needs of reconstruction and revision patients before device approval. The follow-up rates of the reconstruction cohort and revision cohort were low for the duration of the study. Therefore, there is lack of valuable safety data from the study due to poor patient compliance.
General
Study Status	Terminated
Application Number / Requirement Number	P070012 / PAS002
Date Original Protocol Accepted	10/23/2007
Date Current Protocol Accepted	10/23/2007
Study Name	EMERGE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the EMERGE study is to evaluate the safety of the Exponent Carotid Stent System with distal embolic protection in routine clinical practice for the treatment of carotid stenosis in patients at high risk for carotid endarterectomy and to identify rare or unanticipated device-related events that might occur with use of the devices.
Study Population	This device is indicated for use, in conjunction with a Medtronic Vascular embolic protection system, for improving carotid luminal diameter in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: 1) neurological symptoms and > 50% stenosis of the common or internal carotid artery by either ultrasound or angiogram, or patients without neurological symptoms and > 80% stenosis of the common or internal carotid artery by either ultrasound or angiogram, and 2) having a vessel with reference diameters between 4.5 mm and 9.5 mm at the target lesion.
Sample Size	1500 patients, 50 sites
Key Study Endpoints	The protocol defined primary endpoint for each phase of the trial was the cumulative incidence of major adverse events at 1-year, defined as a composite of all-cause death, MI (Q wave and non-Q wave), and ipsilateral stroke. The primary endpoint is defined as the cumulative incidence of major adverse events at 1-year post-procedure, defined as all-cause death, stroke, or MI at 30 days plus all-cause death, MI or ipsilateral stroke within 31 days to 365 days post-procedure.
Follow-up Visits and Length of Follow-up	All patients will be followed to 30 days, the first 500 patients will be followed for 365 days.
Interim or Final Data Summary
Interim Results	None, no patients were ever enrolled in this study
Actual Number of Patients Enrolled	0
Actual Number of Sites Enrolled	0
Patient Follow-up Rate	Not applicable
Final Safety Findings	None, study was never started.
Study Strengths & Weaknesses	None, study was not conducted.
Recommendations for Labeling Changes	No labeling changes recommended since study was not conducted.
General
Study Status	Completed
Application Number / Requirement Number	P070001 / PAS002
Date Original Protocol Accepted	08/12/2008
Date Current Protocol Accepted	08/12/2008
Study Name	Enhanced Surveillance Study
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an enhanced surveillance system to collect the patietns demographic, clinical and device information for all complaints and adverse events (both MDR and non-MDR) possibly related to the Pro-Disc device up to 5 years after device approval
Study Population	Study population is as per device approval. The study includes all patients who received Prodisc after device approval. This device is indicated for skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable symptomatic cervical disc disease (SCDD). Symptomatic cervical disc disease is defined as neck or arm (radicular) pain and/or a ftmctional/neurological deficit with at least one of the following conditions confirmed by imaging (CT, MRI, or X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or loss of disc height. The ProDiscTM-C Total Disc Replacement is implanted via an open anterior approach. Patients receiving the ProDiscTM-C Total Disc Replacement should have failed at least six weeks of non-operative treatment prior to implantation of the ProDiscTM-C Total Disc Replacement.
Sample Size	n/a
Key Study Endpoints	Complaints and Adverse events
Follow-up Visits and Length of Follow-up	up to 5-year after device approval
Interim or Final Data Summary
Interim Results	From the December 17, 2007 approval of the ProDisc-C device, through December 7, 2009, Synthes has received a total of 65 complaints for this device. Fifteen complaints are currently being investigated internally and additional information will be provided to the agency as it becomes available. Forty-three of the complaints were determined to be MDR reportable. Eight complaints were determined as "non-valid".
Actual Number of Patients Enrolled	Not applicable this is Enhanced surveillance investigation
Actual Number of Sites Enrolled	Not applicable this is Enhanced surveillance investigation
Patient Follow-up Rate	Not applicable this is Enhanced surveillance investigation
Final Safety Findings	Since the PMA approval of December 17, 2007 through November 1, 2012, theinformation on the cumulative total MDRs (n=214) and device sales has been collected and evaluated. During 60-monthds of the study period, no unanticipated adverse events were identified, and the device has not been withdrawn from any of the markets.
Final Effect Findings	Not applicable this is Enhanced surveillance investigation
Study Strengths & Weaknesses	The duration of the Enhanced Surveillance System was 5 years after PMA approval, allowing time to monitor longer term adverse events and complaints received by the company for the device in the post-market setting. There may be under-reporting of adverse events and complaints to the company. Therefore, the true number of adverse events and complaints during the 5-year study period is unknown. In addition, the total number of implants sold may be an overestimate of the number of devices actually implanted.
Recommendations for Labeling Changes	No labeling change is recommended because the adverse events noted in the final report are not unanticipated.
General
Study Status	Hold
Application Number / Requirement Number	P020056 / PAS005
Date Original Protocol Accepted	11/17/2006
Date Current Protocol Accepted	11/17/2006
Study Name	Device failure Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
General
Study Status	Completed
Application Number / Requirement Number	P010012 S230/ PAS002
Date Original Protocol Accepted	09/27/2011
Date Current Protocol Accepted	09/27/2011
Study Name	MADIT-CRT Registry
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	394 patients
Actual Number of Sites Enrolled	49 centers
Patient Follow-up Rate	98.98% (390/394)
Final Safety Findings	The rate of device system related adverse events (number of Events/100 Device Months) is slightly higher in the CRT-D compared to ICD (0.54 in CRT-D vs. 0.36 in ICD) in this PAS Registry that is expected and consistent to the findings in the IDE study. The Registry showed a higher rate of early ERI (elective replacement indicator) in CRT-D group (4.1%) compared to ICD only group (2.7%) with longer follow-up indicating rapid battery depletion secondary to increased amount of pacing needed over time for cardiac resynchronization. The incidence of device-related adverse events for CRT-D in the Registry is in the acceptable range.
Final Effect Findings	The cohort of combined IDE and Registry for followed out through 5 years showed CRT-D reduced a 32% relative risk of all-cause mortality in LBBB subpopulation as compared to ICD (p=0.028). CRT-D was also associated with significant reduction in the risk of a first heart failure event and recurrent heart failure events in both the LBBB subsets and all subjects in combined IDE and Registry.
Study Strengths & Weaknesses	Strength: long-term follow-up (5 years) Weakness: small sample size (394 patients) insufficient to test statistical significance in crossover analysis and efficacy analysis
Recommendations for Labeling Changes	NO
General
Study Status	Completed
Application Number / Requirement Number	P100010 / PAS001
Date Original Protocol Accepted	12/17/2010
Date Current Protocol Accepted	08/31/2016
Study Name	STOP AF PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, one-armed, multi-center, non-randomized study.
Study Population	Patients included in this study will have: A diagnosis of paroxysmal atrial tachycardia, with at least two episodes of atrial fibrillation in the past three months, at least one which is documented with a tracing Age 18 and above. Failure of treatment of atrial fibrillation (AF) with at least one drug indicated for the treatment of paroxysmal atrial fibrillation (PAF) Presence of no exclusion criteria
Sample Size	370 enrolled with procedure attempts at 30 new user investigational sites and up to 15 STOP AF/continued access protocol AF sites with at least 70% of subject enrollment in the study come from the new user sites
Key Study Endpoints	Cryoablation procedure events and chronic treatment failure at 3 years, and major adverse atrial fibrillation events.
Follow-up Visits and Length of Follow-up	The length of follow-up will be three years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	402 subjects. Modified intent-to-treat (mITT) cohort was comprised of 354 subjects that met all eligibility criteria and were treated per protocol. The primary analysis was conducted in this cohort
Actual Number of Sites Enrolled	39 sites
Patient Follow-up Rate	The follow-up for the mITT cohort was 84% (298/354) at 3 years. Overall ECG visit compliance was 95.2% and overall Holter visit compliance was 91.3% in mITT subjects. The mean number of Holter monitors collected per subject was 3.33 across all 354 mITT subjects.
Final Safety Findings	Primary safety endpoint: -The rate of subjects experiencing one or more cryoablation procedure events (CPE) through 12 months was 2.3% (95% confidence interval (CI): 1.1% - 4.5%), which met the performance goal (PG) of 14.8%. Secondary safety endpoint: -The proportion of patients free of major adverse atrial fibrillation (AF) events (MAFE) were (Kaplan-Meier Rate [95% CI]): 90.3% [ 86.6% - 92.9%] , 83.2% [ 78.8% - 86.8%], and 77.8% [ 72.9% - 81.9%], at 1, 2, and 3 years, respectively. The majority of the MAFEs were due to AF recurrence or ablation (69 events in 60 subjects). MAFE component results ([subjects with events]/354]): -Cardiovascular death: 0% [0] -Myocardial infarction: 0.6% [2] -Stroke 0.3% [1] -Hospitalization for (primary reason): *AF recurrence or ablation: 17% [60] *Atrial flutter ablation (excluding Type I): 4% [14] *Systemic embolization (not stroke): 0% [0] *Congestive heart failure: 0.6% [2] *Hemorrhagic event (not stroke): 1.1% [4]
Final Effect Findings	Primary effectiveness endpoint The proportion of subjects free of chronic treatment failure for paroxysmal atrial fibrillation at 36 months was 66.9% (95% CI: 61.6% - 71.7%), which met the PG of 45%. The proportion of subjects with single procedure success at 36 months was 65.5% (95% CI: 60.1% – 70.3%).
Study Strengths & Weaknesses	Strengths: These results provide further evidence of the long-term (3-year) performance and safety of this device. In this Post Approval Study (PAS), the Arctic Front Cardiac CryoAblation Catheter met both its primary effectiveness endpoint (PG: 45%; the lower bound of the 95% CI: 61.6%) and primary safety endpoint by a good margin (PG: 14.8%; upper bound of the 95% CI: 4.5%). This PAS had a low attrition rate (~16%) at 3 years and very good ECG and Holter visits’ compliance (>90%). Subject’s follow-up in this PAS was reduced from 5 years to 3 years in 2016. The justification for this reduction in follow-up was (1) the 3-year follow-up being in line with the minimum follow-up duration recommended in the 2012 Heart Rhythm Society Expert Consensus Statement on AF Ablation for the assessment of long term success, (2) no new safety or effectiveness concerns were shown in the PAS data at the time of the protocol review, and (3) the PAS was demonstrating more favorable results than the pivotal study and meeting primary endpoints with a great margin. Weakness: There was no control group enrolled in this study.
Recommendations for Labeling Changes	This PAS provided important new information about the effectiveness and safety of the device. A labeling update is recommended to include the 3-year data for this device.
General
Study Status	Completed
Application Number / Requirement Number	P070014 S037/ PAS001
Date Original Protocol Accepted	08/31/2016
Date Current Protocol Accepted
Study Name	Popliteal Indication PAS Surv Project
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To conduct long term post-market surveillance of the safety (including stent fractures assessed at revision) and effectiveness of the Bard LifeStent Vascular Stent Systems for the treatment of symptomatic de novo or restenotic lesions in the popliteal artery A prospective surveillance project using the Vascular Quality Initiative (VQI) Peripheral Vascular Intervention (PVI) registry to evaluate consecutive patients treated for symptomatic de novo or restenotic lesions of the popliteal artery with the LifeStent. The surveillance project involves new enrollment. Patient information will be collected according to standard of care practice through 24 months post index procedure
Study Population	All eligible patients with symptomatic de novo or restenotic lesions in the popliteal artery (P2/P3) that receive treatment with the Bard life Stent.
Sample Size	A minimum of 74 patients will be treated with the LifeStent in P2/P3 lesions.
Key Study Endpoints	Primary Post Approval Surveillance Project Endpoints Safety: Freedom from Major Adverse Events (MAE) defined as device and/or procedure-related death or target limb(s) major amputation through 12-months post- index procedure. Effectiveness: Freedom from Target Lesion Revascularization (TLR) and/or Target Vessel Revascularization (TVR) at 12- months post-index procedure. Secondary Post Approval Surveillance Project Endpoints: Acute Lesion Success defined as attainment of < 30% residual stenosis of the target lesion after the index procedure using any percutaneous method and/or non-investigational registry device (i.e., post- dilatation). Acute Procedure Success defined as lesion success and no peri-procedural complications prior to hospital discharge, and the following secondary endpoints assessed at 12 and 24 months post index procedure: Primary Patency assessed with Doppler ultrasound (DUS) Primary Assisted Patency assessed with DUS Secondary Patency assessed with DUS Sustained Clinical Success Sustained Hemodynamic Success Stent fracture rate will be assessed by Core Lab inter- pretation of images obtained during target lesion revascularization classified as Types I to IV.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Seventy-four (74) subjects were enrolled, and 76 legs were treated in the 74 subjects.
Actual Number of Sites Enrolled	Twenty-nine (29) sites were enrolled. Nineteen (19) sites enrolled at least one subject.
Patient Follow-up Rate	87.8% (65/74) and 79.0% (49/62) at 1 year and 2 years, respectively
Final Safety Findings	Primary Safety Endpoint Freedom from device and/or procedure-related death and freedom from target major limb amputation at 1 year by Kaplan Meier estimate was 98.6% and 90.9%, respectively.
Final Effect Findings	Primary Effectiveness Freedom from target vessel revascularization (TVR) and target lesion revascularization (TLR) at 1 year by Kaplan Meier estimate was 84.9% and 86.3%, respectively. Secondary Endpoints Acute lesion success rate was 98.7% (75/76) at pre-discharge Acute procedure success rate was 81.6% (62/76) at pre- discharge. Limb ischemia assessed by change in Rutherford class decreased in 86.5% (45/52) and 86.8% (33/38) of evaluable subjects at 12months and 24 months, respectively. Ankle brachial index increased in 77.3% (17/22) and 86.7% (13/15) of evaluable subjects at 12 months and 24 months. Stent fracture rate at 12 months was 11% (1/9). Primary patency rate at 12 and 24 months by Kaplan Meier estimate was 80.5% and 68.1%, respectively. Primary assisted patency rate at 12 and 24 months by Kaplan Meier estimate was 80.5% and 68.1%, respectively. Secondary patency rate at 12 and 24 months by Kaplan Meier estimate was 89.4% and 78.9% respectively. Sustained clinical success at 12 and 24 months by Kaplan Meier estimate was 98.5% and 95.9% respectively. Sustained Hemodynamic success at 12 and 24 months by Kaplan Meier estimate was 100% and 81.2%, respectively.
Study Strengths & Weaknesses	This is an observational surveillance project involving use of real- world evidence. Therefore, patients were treated according to standard of care practice. The sample size estimation was not hypothesis- driven and the study endpoint results were not evaluated with formal hypothesis testing.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post approval study. The labeling change should include a new section in the label showing a summary of the surveillance objective, design, patient population, data source, sample size including number of sites, endpoints, length of follow-up and frequency of follow-up, final results (final endpoint results, follow-up rate etc.), strengths and limitations of the surveillance project.
General
Study Status	Completed
Application Number / Requirement Number	P030031 S011/ PAS002
Date Original Protocol Accepted	08/12/2009
Date Current Protocol Accepted	01/05/2018
Study Name	Atrial Fibrillation Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, multicenter, non-randomized clinical evaluation of PAF patients treated with the radio frequency ablation with Thermocool catheters.
Study Population	Study Population: Adult patients with paroxysmal atrial fibrillation (PAF).
Sample Size	A minimum of 381 patients, 109 in the MEP group and 272 in the LEP group, enrolled at 40 sites. Since the endpoint is 7-day primary AE rate, it is anticipated that the attrition for this endpoint is minimum. In P030031/S085, it is indicated that a total of 407 subjects received RF ablation procedure with 125 in the MEP group and 282 in the LEP group. Of the 282 subjects in the LEP group, 76 remaining subjects who have not reached 5-year follow-up won’t be followed through 5 years.
Key Study Endpoints	The primary safety endpoints include adverse events that occur within 7 days of an ablation procedure.
Follow-up Visits and Length of Follow-up	Study participants will be followed for 5-years.
Interim or Final Data Summary
Interim Results	No safety data is available for this study.
Actual Number of Patients Enrolled	A total of 437 subjects with the 394 evaluable subjects, which met the required minimum of 381 evaluable subjects, were enrolled by October 01, 2013. The Safety Cohort (SC) included 408 subjects, which included enrolled subjects who received study catheter insertions. The Effectiveness Cohort (EC) included 394 evaluable subjects, with 120 in the more experienced physician (MEP) Group and 274 in the less experienced physician (LEP) Group.
Actual Number of Sites Enrolled	A total of 21 sites.
Patient Follow-up Rate	The 5-year overall follow-up rates in the SC and EC cohorts are 88.35% and 89.05%, respectively. The 5-year follow up rates for the SC are 89.60% and 88.05%, respectively, in the MEP and LEP groups, and for the EC, and 90.83% and 88.07%, respectively.
Final Safety Findings	The study met the primary safety endpoint (i.e., primary adverse events (PAE) within 7 days of operation) for both MEP and LEP groups, with the upper bounds of the one-sided 95% confidence interval for the MEP and LEP being 10.5% and 9.3%, respectively, which are lower than the pre-determined performance goal of 16%. The percentage of PAE, 3.2%, of the MEP is lower than the 6.4% of the LEP as expected. With regards to the secondary long-term safety endpoints, first, by physician experience, the LEP group has a higher percentage of SAEs (39%) than that (32%) of the MEP group. Second, by time interval, the trends of the SAE occurrences (beyond 7 days of index operation) are slightly different between the MEP and LEP groups.
Final Effect Findings	The overall success rates of entrance block for all targeted PVs were comparable between the MEP (95.8%, 115/120) and LEP (94.9%, 260/274) groups. With regards to the long-term effectiveness endpoint (without multiple lesions), the overall cumulative AF occurrence rate (78.3%) over the 5-year period in the MEP group was numerically higher than that (70.4%) in the LEP group, but the difference was not statistically significant. With respect to the long-term effectiveness endpoint with multiple lesions, the percentage for the overall cumulative AF occurrence (84.3%) over the 5-year period in the MEP group was numerically (but not statistically significantly) higher than that (67.3%) in the LEP group. In addition, the 1-, 2-, 3-, 4-year AF occurrence rates were consistently higher in the MEP than the those in the LEP with statistical significance.
Study Strengths & Weaknesses	¿ Study strength: This is a prospective, multi-center, long-term study with high 5-year follow-up rates and sufficient sample size for testing the primary endpoint. ¿ Study weakness: The AF recurrence data were collected based on subjective self- reporting rather than using an objective method such as ECG and Holter monitor. The study did not control for potential confounders for the relationship between physician ablation experience and effectiveness endpoint (i.e., AF occurrence) in the case of multiple lesions.
Recommendations for Labeling Changes	The labeling changes should include new information stemmed from this PAS, such as the safety data with Tables 3.3.7.1A and 3.3.7.2A and the effectiveness data with Table 3.3.6.1 from the final report.
General
Study Status	Completed
Application Number / Requirement Number	P070014 / PAS002
Date Original Protocol Accepted	02/13/2009
Date Current Protocol Accepted	02/13/2009
Study Name	RESILIENT
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	246
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	82%
Final Safety Findings	There is no statistically significant difference in time to MACE between the test and control groups (p = 0.98) for the duration of the study. The 6, 12, 24 and 36-month major adverse clinical event (MACE) rates show no statistical difference (p-values > 0.78) between the control (PTA) arm and the test (LifeStent NT) arm.
Final Effect Findings	The 36-month freedom from re-intervention and clinical success statistically favored the test group. The test group fared better than the control group (p <0.0001) for the study's primary effectiveness endpoint, freedom from TLR/TVR at 6-months.
Study Strengths & Weaknesses	There was no statistical justification for the sample size and no specific hypotheses proposed for the post-market follow-up.
Recommendations for Labeling Changes	Requested by ODE
General
Study Status	Completed
Application Number / Requirement Number	P070015 / PAS004
Date Original Protocol Accepted	07/02/2008
Date Current Protocol Accepted	07/02/2008
Study Name	Fatigue Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an implementation of updated final product testing methodologies.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	This is an implementation of updated final product testing methodologies.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A This is a bench testing study.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Terminated
Application Number / Requirement Number	P070014 / PAS001
Date Original Protocol Accepted	02/13/2009
Date Current Protocol Accepted	07/11/2014
Study Name	CONTINUUM PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm, non-randomized, prospective, multi-center international study in subjects (>=22 years of age) with TransAtlantic Inter-Society Consensus A, B and C lesion(s) in the infra-inguinal segment (SFA and/or Popliteal arteries). Subjects will be treated with PTA followed by the LifeStent Self-Expanding Stent System (FlexStar / FlexStar XL). The primary objectives of this investigation are to provide confirmatory evidence of safety and effectiveness of the LifeStent Self-Expanding Stent System in patients with de novo and restenotic (non-stented) lesion(s) in the infra-inguinal segment (SFA and/or Popliteal arteries). A secondary objective of this investigation is to continue to evaluate the clinical utility of the LifeStent Self-Expanding Stent System.
Study Population	This device is indicated for improvement of luminal diameter in the treatment of symptomatic de-novo or restenotic lesions up to 160 mm in length in the native superficial femoral artery and proximal popliteal artery with reference vessel diameters ranging from 4.0 - 6.5 mm.
Sample Size	170 patients, 20 sites
Key Study Endpoints	The primary safety endpoint is freedom from death at 12-months post-procedure. The primary effectiveness is freedom from procedural device malfunction.
Follow-up Visits and Length of Follow-up	Subjects will undergo a clinical evaluation at baseline (prior to study procedure), prior to hospital discharge, 30 days post-procedure, 12, 24 and 36 months post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 173 subjects were enrolled as follows: 113 enrolled under P070014 (Target Lesion lengths less than or equal to 160 mm), 18 enrolled under subgroup P070014/S010 (Target Lesion lengths >160 - 240 mm) and 41 enrolled under subgroup P070014/S022 (Target Lesions treated with 200 mm LifeStent SOLO). 1 subject had target lesion length of 280 mm that is not included in the subgroup categories.
Actual Number of Sites Enrolled	A total of 30 sites received IRB approval and were enrolled.
Patient Follow-up Rate	Follow-up rates for the combined subgroups at 30 days, and 12, 24, and 36 months was 98.8% (163/165), 98.6% (142/144), 98.3% (115/117) and 97.7% (84/86), respectively.
Final Safety Findings	Primary safety was defined as freedom from occurrence of death at 30 days and 12-months post procedure. The freedom from primary safety event rate at 30 days and 12 months post index procedure was 99.4% (95% confidence interval [CI] 95.9%, 99.9%) and 95.1% (95% CI 90.4%, 97.5%) respectively.
Final Effect Findings	Primary effectiveness (Device Success) for the CONTINUUM study was defined as: freedom from device delivery failure and primary Target Lesion Patency (TLP) at 12-months post-index procedure measured by DUS. TLP was defined as the interval following the index procedure until a DUS assessment indicates that the target lesion(s) is no longer patent; that is, the treated segment has a peak systolic velocity ratio (PSVR) greater than or equal to 2.5. Primary effectiveness at 12 months by Kaplan Meier method was 72.7% (95% confidence interval [CI] 61.8 to 81.0%). Primary target lesion patency (TLP) at 12-Months post-index procedure by Kaplan Meier analysis for CONTINUUM LifeStent group was 75.3% (95% CI: 67.4%, 81.6%) compared to RESILIENT PTA 36.7% (95% CI: 25.1%, 48.4%). The hazard ratio for CONTINNUUM LifeStent over RESILIENT PTA (ITT) was 0.123, P <0.001. For non-inferiority comparison of the CONTINUUM Lifestent to RESILIENT LifeStent, the primary TLP at 12 months for CONTNUUM LifeStent was 81.1% versus RESILIENT LifeStent 73.2% using Cox’s regression model with regression covariates: treatment group, Rutherford Category, target lesion length, total treated segment length, age, and gender. The difference in primary TLP at 12 months between CONTINUUM LifeStent and RESILIENT LifeStent is 0.079 (7.9%). The lower bound of the 95% CI for the difference in TLP between CONTINNUUM LifeStent and RESILIENT LifeStent of -0.006 is greater than -0.075, the non-inferiority margin, indicating that the CONTINUUM arm is not inferior to the RESILENT arm. The Z-test statistic is equal to 2.99, p-value = 0.0014. Freedom from TLR and/or TVR at 12 months post index procedure for the CONTINUUM LifeStent group was 82.2% (95% CI 75.2%, 87.3%) compared to that of RESILIENT PTA (ITT) group 45.2% (95% CI: 33.4%, 56.3%) – (p-value <0.001). The percentage of subjects free from stent fracture at 12- and 24-months post-index procedure was 92.4% (110/119) and 67.6% (69/102) respectively.
Study Strengths & Weaknesses	Overall, approximately 74% (173/234) of required enrollment was achieved in the CONTNUUM study. The target enrollment of at least 64 subjects in each subgroup was not achieved in two subgroups. The two subgroups were: 1) Target Lesion Lengths > 160 mm and = 240 mm, and 2) Target Lesions treated with the 200 mm LifeStent SOLO.
Recommendations for Labeling Changes	Labeling change is not recommended with the post approval study results as the study was not completed.
General
Study Status	Terminated
Application Number / Requirement Number	P040051 / PAS002
Date Original Protocol Accepted	05/12/2006
Date Current Protocol Accepted	04/22/2011
Study Name	Stelkast Surpass Active PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Active surveillance supplemented by prospective multi-center cohort study
Study Population	Patients implanted with the Stelkast Surpass Acetabular System
Sample Size	320 patients active surveillance, 20 patients prospective multi-center cohort Patient sites: sites for the active surveillance component and sites for the prospective multi-center study
Key Study Endpoints	Study endpoints include device related adverse events, device revision, removal. reoperations, and supplemental fixation.
Follow-up Visits and Length of Follow-up	Annual Length of follow up: 10 Years
General
Study Status	Completed
Application Number / Requirement Number	P040013 S016/ PAS001
Date Original Protocol Accepted	05/27/2011
Date Current Protocol Accepted	12/06/2011
Study Name	GEM21S Growth Factor
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Stability testing (bench study)
Study Population	GEM21S (Formulated rhPDGF-BB) 0.5 mL in a 1 mL syringe on Long Term Stability at 2¢ªC - 8¢ªC (horizontal) will undergo stability testing.
Sample Size	Horizontal testing will be performed on at least one production lot annually, and a sample of three production lots will be tested out to 48 months for informational purposes (the current shelf life for the syringe is 42 months).
Key Study Endpoints	pH, bioassay, Chromatographic purity evaluation, Protein concentration by analysis using UV, HPLC purity evaluation, SDS Page purity evaluation, sterility evaluation, and bacterial endotoxin evaluation.
Follow-up Visits and Length of Follow-up	The stability study will follow each lot for at least 42 months 2-8¢ªC. The first three production batches will be tested through 48 months at 2-8¢ªC. Long-term temperature Stability testing will be performed at 3, 6, 9, 12, 18, 24, 42 and 48 months.
General
Study Status	Completed
Application Number / Requirement Number	P110001 / PAS001
Date Original Protocol Accepted	06/26/2012
Date Current Protocol Accepted	06/26/2012
Study Name	HERCULES PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The HERCULES trial is a prospective, non-randomized, multi-center, single-arm clinical trial to demonstrate efficacy and safety of the RX Herculink Elite Renal Stent System (Herculink Elite) in the treatment of suboptimal post-procedural percutaneous transluminal renal angioplasty (PTRA) of atherosclerotic de novo or restenotic renal artery stenoses in patients with uncontrolled hypertension.
Study Population	The population is entirely comprised of the existing 202-patient HERCULES study cohort.
Sample Size	The sample size and power calculation were based on the primary endpoint of binary restenosis rate at 9 months. The OPC for the binary restenosis rate at 9 months was determined to be based on the ASPIRE-2 and SOAR clinical studies.
Key Study Endpoints	Major Adverse Events: (death, nephrectomy, embolic events resulting in kidney damage) reported for all follow up visits up to 36 months. Target lesion revascularization (TLR) for all follow-up visits up to 36 months. Primary patency rate at 24 and 36 months. Secondary patency through 36 months for all visits. Change in blood pressure, anti-hypertensive medication intake, and renal function for all follow up visits up to 36 months.
Follow-up Visits and Length of Follow-up	36 months 12 months (+/- 6 weeks) Physician office visit: Blood pressure measurement, antihypertensive medication review, identification of adverse events, laboratory (sCr) 24 months (+/- 8 weeks) Physician office visit: Blood pressure measurement, antihypertensive medication review, identification of adverse events, laboratory (sCr), duplex ultrasound 36 months (+/- 8 weeks) Physician office visit: Blood pressure measurement, antihypertensive medication review, identification of adverse events, Laboratory (sCr), duplex ultrasound
Interim or Final Data Summary
Actual Number of Patients Enrolled	202
Actual Number of Sites Enrolled	37
Patient Follow-up Rate	73%
Final Safety Findings	The binary restenosis rate at 9 months was 10.5% (22/209), with the upper one-sided 95% CI of 14.7%, which was significantly below the pre-specified PG of 28.6% (p < 0.0001, exact binomial test).
Final Effect Findings	3 year rates: The freedom from TLR Kaplan-Meier Survival Analysis was 87.6%. The study device, procedure, and clinical success rates were high: 96.0% (237/247), 99.2% (238/240) and 98.0% (197/201), respectively. Primary and secondary patency rates at 36 months were 82.9% and 95.8%, respectively. There was a significant improvement in blood pressure from baseline. There was no difference in the mean serum creatinine (sCr) and renal function from baseline.
Study Strengths & Weaknesses	Strengths - Outcome well below performance goal Weakness - High attrition rate (27%).
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P070015 S122/ PAS001
Date Original Protocol Accepted	10/03/2014
Date Current Protocol Accepted	03/03/2017
Study Name	Extended followup of the EXPERT CTO Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is the continued follow-up of the premarket cohort. It is a prospective, multi-center, single-arm study.
Study Population	All patients in whom recanalization and predilatation of CTO are completed and the study stent(s) (XIENCE V and/or XIENCE PRIME) is inserted into the coronary guiding catheter.
Sample Size	A total of 250 patients were enrolled at 20 sites in the United States, with the intention-to-treat population consisting of 222 patients. There are 205 patients available with 1-year follow-up.
Key Study Endpoints	The following outcomes will be reported annually through 5 years: XRate of Major Adverse Cardiac Events (MACE), defined as a composite of death, Myocardial Infarction (MI), or clinically- driven Target Lesion Revascularization (TLR), and individual MACE components ¿XTarget Lesion Failure (TLF), defined as a composite of cardiac death, target vessel-related MI, and clinically-driven TLR and individual TLF components ¿XTarget Vessel Revascularization (TVR) and clinically-driven TVR ¿XTarget Vessel Failure (TVF), defined as a composite of cardiac death, target vessel-related MI, and clinically-driven TVR ¿XOccurrence of stent fracture at target lesion, as assessed by fluoroscopy in patients undergoing clinically-driven angiographic follow-up at any time during the 5-year study period (the same angiographic core lab will continue to be utilized throughout the five-year follow-up period) ¿XStent thrombosis according to Academic Research Consortium (ARC) criteria (all, definite, definite/probable, probable, possible): acute, subacute, late, very late and accumulative rates
Follow-up Visits and Length of Follow-up	3 years post-procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	202 subjects available at 1 year for long term follow- up
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	84.7% (171/202) at 4 years
Final Safety Findings	The EXPERT CTO clinical trial met its primary endpoint. The stent related endpoint result of 1- year MACE [composite of death, myocardial infarction (MI) or clinically driven target lesion revascularization (CD-TLR)] rate was significantly lower than the pre-specified performance goal (PG) of 24.4% in both the intent-to-treat (ITT) population (18.5%, 1 sided UCL= 23.4%, p =0.0248) and the per protocol (PP) population (8.2%, 1 sided UCL = 12.3%, <.0001). The key secondary endpoints based on the ITT population through four (4) years are as follows: MACE (death, MI or CD-TLR) per ARC 31.6% (62/196) per protocol 22.4% (44/196) Target Lesion Failure (cardiac death, Target vessel-MI or CD-TLR) per ARC 24.1% (45/187) per protocol 17.2% (32/186) Target Vessel Failure (Cardiac death, Target vessel MI or CD-TVR) per ARC 26.2% (49/187) per protocol 19.4% (36/186) Death 10.5% (20/191) Cardiac Death 5.5% (10/181) All MI per ARC 20.3% (37/182) Target Vessel MI (TV-MI) per ARC 15.5% (28/181) All TLR (target Lesion revascularization) 11.9% (21/177) CD-TLR 11.3% (20/177) All TVR (target vessel revascularization), inclusive of target lesion) 13.6% (24/177) All TVR (non-target lesion) 2.9% (5/172) Stent Thrombosis (Definite/probable) 1.7% (3/174)
Study Strengths & Weaknesses	Strength: The EXPERT CTO study was a prospective, open-label, multicenter study. The study achieved a follow-up rate greater than 80% at 4 years. An independent clinical event committee performed adjudication of the safety endpoints including all cases of death, Q-wave myocardial infarction (QMI), non Qwave MI (NQMI), stent thrombosis, target lesion revascularization and target vessel revascularization. Weakness: There is no formal hypothesis testing for the long term (4 year) study outcomes. The study is limited by the small sample size. Study Strengths and Limitations: The EXPERT CTO study was a prospective, open-label, multicenter study. All event adjudications were performed by an independent Clinical Event Committee (CEC) with 100% site-reported adjudicable events being source-verified. This study provides important information on clinical outcomes in patients with chronic total occlusions treated with the XIENCE family of stents. The study is limited by being a small study with no head-to-head comparison with other DES platforms. In addition, due to the small population size, subgroup analysis can at best be considered exploratory.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post Approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P070015 / PAS001
Date Original Protocol Accepted	07/02/2008
Date Current Protocol Accepted	07/02/2008
Study Name	Longterm IDE Follow up
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Approximately 1125 subjects were originally planned to be enrolled in the study; however, the study was expanded to 3690 subjects. Subjects in the SPIRIT IV clinical study were randomized 2:1, with 2460 subjects to receive XIENCE V and 1230 subjects to receive TAXUS.
Study Population	This device is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length < 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm. The study population consisted of the long term follow-up of pateints enrolled in the SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 and SPIRIT IV trials.
Sample Size	SPIRIT FIRST: 60 patients, 9 sites, SPIRIT II: 300 patients, no site maximum specified, SPIRIT III RCT: 1002 patients, 65 sites, SPIRIT III 4.0: 80 patients, 30 sites. SPIRIT IV: 3690 patients, 66 sites
Key Study Endpoints	The primary endpoint of the SPIRIT FIRST clinical study was in-stent LL at 180 days on the per-treatment evaluable population. The primary endpoint of the SPIRIT II trial was in-stent LL at 180 days. The primary endpoint of the SPIRIT III RCT was in-segment LL at 240 days and the major secondary endpoint was ischemia-driven target vessel failuer at 270 days. The primary endpoint of the SPIRIT III 4.0 mm trial was in-segment LL at 240 days. The primary endpoint of the SPIRIT IV trial was target lesion failure at 1 year.
Follow-up Visits and Length of Follow-up	SPIRIT FIRST: Patients were evaluated at 30, 180, 270 days and 1, 2, and 3 years following the index procedure. Angiography and IVUS in all patients were performed at 180 days and 1 year post index procedure.; SPIRIT II: Patients were evaluated at 30, 180, 270 days and 1, 2 and 3 years following the index procedure. Angiography in all patients and IVUS on a pre-specified subset of patients (N=152) was performed at 180 days post index procedure. Additionally, 2-year angiography and IVUS was performed in a subset of patients (N=152).; SPIRIT III RCT: Subjects were evaluated at 30, 180, 240, 270 days, one year, and two years following the index procedure. Further clinical observations will be performed at 3 years for all subjects. Angiography was to be performed on all subjects in group A and group B at 240-day follow-up.; SPIRIT III: Subjects were evaluated at 30, 180, 240, 270 days, and one and two years following the index procedure. Further clinical observations will be performed per protocol in newly enrolled subjects and at 3 years for all subjects. Angiography was to be performed on all subjects at their 240-day follow-up. Target enrollment remains 80 subjects
Interim or Final Data Summary
Interim Results	SPIRIT 1st - 87% of patients (49/56) had a 5 yr clinical follow-up (24 for VISION-E and 25 in the VISION control). The target vessel failure (TVF) rates were 17% in the VISION-E test vs. 36% in the VISION control arm. The major adverse cardiac event (MACE) rates were 17% for VISION-E vs. 28% VISION control. Patients enrolled in the VISION-E test arm did not experience any additional MACE or TVF events between 1- and 5-yr follow-up. Due to 2 patients lost to follow-up at 5 yrs, the hierarchical MACE/TVF rates for VISION-E increased from 15% at 1-yr to 17% at 5 yr. All major endpoints for VISION-E were better than VISION control. While the number of patients was small, the results do not raise concerns. SPIRIT II - Results at 4 yrs do not raise any concerns. The rates of ischemia-driven (ID)-TVF, ID-MACE, MI, ID- target lesion revascularization (TLR) and cardiac death are lower in the XIENCE V arm vs. TAXUS arm. Kaplan-Meier (KM) estimates indicated clinical differences in ID-MACE rates in favor of the XIENCE V, 7%, vs. TAXUS, 15% (p=0.042) as well as in cardiac death rates in favor of the XIENCE V, 0.5%,vs. TAXUS, 4% (p=0.024). Non-hierarchical NQMI and non-hierarchical ID-TLR rates were lower in XIENCE V, 4% and 5%, vs. TAXUS, 8% and 10%. Low rates of stent thrombosis were found for XIENCE V and TAXUS for per protocol and ARC definitions. SPIRIT III RCT - Results at 3 yrs do not raise concerns for the safety and effectiveness of the XIENCE V. It exhibits lower rates of TVF, MACE, TLR, and TVR, non-TLR vs. TAXUS. There was a 29% reduction in the 3-yr TVF rates in the XIENCE V vs. TAXUS (14% vs. 20%). There was a 41% reduction in MACE rates for XIENCE V vs. TAXUS arm (10% and 16%). KM estimate indicated clinical difference in TVF and MACE-free survival rates for XIENCE V. XIENCE V had lower TLR (6%) vs. TAXUS, 9%.. The TVR, non-TLR rates were also lower in the XIENCE V arm (7%) vs. TAXUS arm (9%). There were low rates of stent thrombosis for XIENCE V and TAXUS per protocol and ARC definitions. SPIRIT III 4.0mm - Of the 73 enrolled, follow-up rate at 2 yrs was 90% (62/69). The TVF rates were 8% (5/65) for XIENCE V 4.0 mm arm, 16% (50/305) for TAXUS RCT, and 11% (72/637) for XIENCE V RCT. The MACE rates were 8% (5/65) for XIENCE V 4.0 mm, 14% (42/305) for TAXUS RCT, and 8% (49/637) for XIENCE V RCT. The difference in MACE rates between XIENCE V 4.0 mm and TAXUS RCT represented a reduction of 44% for XIENCE V 4.0 mm. TLR rates were 2% (1/65) for XIENCE V 4.0 mm, 8% (23/305) for TAXUS RCT and 5% (29/637) for XIENCE V RCT. The difference in TLR rates between XIENCE V 4.0 mm and TAXUS RCT represented a reduction of 80% in the XIENCE V 4.0 mm arm. XIENCE V 4.0 mm had not TVR procedures (0/65). TVR rates were7% (20/305) for TAXUS RCT and 5% (31/637) for XIENCE V RCT. KM estimates showed that revascularization-free survival rates through 758 days were clinically different for XIENCE V 4.0 mm, (99%) vs. TAXUS RCT (89%). The stent thrombosis rates per protocol for XIENCE V 4.0 mm vs. TAXUS RCT arm were, acute (1% and 0%); subacute (0% and 0%); late (0% and 0.6%), and very late (1.6% and 1.0%), as defined in the protocol. The stent thrombosis rates for XIENCE V 4.0 mm and XIENCE V RCT were comparable. SPIRIT IV - At 1-yr, there was a 29% TVF reduction, 14% DMR reduction, 39% reduction in MACE, and 26% ID-TVR (non-TLR) reduction XIENCE V patients. For stent thrombosis rates, the overall per protocol results were 0.17% for XIENCE V vs. TAXUS (0.85%). The overall ARC-defined (definite/probable) stent thrombosis rate was lower for XIENCE V vs. TAXUS, (0.29% and 1.10%). The results of the SPIRIT IV clinical trial at 1-yr do not raise any concerns in terms of the safety and effectiveness of XIENCE V and demonstrate positive results compared with the TAXUS control.
Actual Number of Patients Enrolled	SPIRIT FIRST: 60 SPIRIT II: 300 SPIRIT III (RCT): 1002 SPIRIT III (4.0mm size): 73 SPIRIT IV: 3687
Actual Number of Sites Enrolled	SPIRIT FIRST: 9 SPIRIT II: 28 SPIRIT III (RCT): 65 SPIRIT III (4.0mm size): 30 SPIRIT IV: 66
Patient Follow-up Rate	SPIRIT FIRST: 87% SPIRIT II: 81% SPIRIT III (RCT): 84.3% SPIRIT III (4.0mm size): 88% SPIRIT IV: 90.9%
Final Safety Findings	SPIRIT FIRST No stent thrombosis events reported in either arm in the SPIRIT FIRST study through the five- year follow-up time point per protocol definition and per ARC definition. SPIRIT II The stent thrombosis rate was numerically lower for XIENCE V compared to TAXUS at 5 years (0.9% vs. 2.8%) per ARC definition. No stent thrombosis events were observed since the 3 year endpoint in the XIENCE V arm. SPIRIT III (RCT) The stent thrombosis rates overall were numerically low and comparable between the XIENCE V and TAXUS RCT arms respectively, (1.55 versus 1.87%) per ARC definition. SPIRIT III (4.0mm size) Overall Stent Thrombosis rates per ARC definitions at 5 years were 0%, suggesting relative safety of the device as compared to the TAXUS RCT arm. SPIRIT IV Overall Stent Thrombosis (ST) rates per ARC definitions at 3 years were 0.62% (14/2263) for XIENCE V arm, and 1.73% (19/1098) for TAXUS arm. ST rates in the XIENCE V arm was < 1% suggesting relative safety of the device as compared to the TAXUS RCT arm.
Final Effect Findings	SPIRIT FIRST The five-year follow-up rates of TVF remained favorable in the XIENCE V arm, 16.7% (4/24) compared to the VISION arm, 36.0% (9/25). The MACE rates were 16.7% (4/24) in the XIENCE V arm and 28.0% (7/25) in the VISION arm. SPIRIT II Five-year cardiac mortality was significantly lower in the XIENCE V arm than in the TAXUS arm (1.5% vs. 7.3%, p=0.015). Cardiac Death and MI was lower, yet not statistically significant (4.8% vs. 11.4%) and lower ID-TLR (4.7% vs. 9.4%) in the XIENCE V arm than in the TAXUS arm. As a result, there was a consistent reduction in ID-MACE for XIENCE V vs. TAXUS (ID- MACE 8.0% vs. 18.1%, p=0.018) SPIRIT III (RCT) At five years, the XIENCE V arm TVF rate was 20.3% (123/605) compared to 26.6% (76/286) in the TAXUS arm. Cardiac death rates in the XIENCE V arm was 2.8% (17/605) and was 4.5% (13/286) in the TAXUS arm through five years with numerically low rates of MI sustained in the XIENCE V arm (4.6% 28/605) compared to the TAXUS arm (7.0% 20/286). TLR rates were also more favorable in the XIENCE V arm through five years in the XIENCE V arm (8.9% 54/605) compared to the TAXUS arm (12.9% 37/286). SPIRIT III (4.0mm size) Rates of key clinical events and angiographic endpoints were lower in the XIENCE V arm than in the TAXUS RCT arm out to 5 years as follows: - MACE Rates at 5 years: 10.4% (as compared to 22% in TAXUS RCT arm) - TLR rates at 5 years: 4.5% (as compared to 12.9% in TAXUS RCT arm) - TVF rates at 5 years: 11.9% ( as compared to 26.6% in TAXUS RCT arm) SPIRIT IV The rates of key clinical events and angiographic endpoints were lower in the XIENCE V arm than in the TAXUS arm out to 3 years as follows: - MACE Rates at 3 years: XIENCE V: 9.8% (231/2348) as compared to TAXUS: 12.3% (142/1158) - TLR rates at 3 years: XIENCE V: 6.3% (148/2348) as compared to TAXUS: 7.9% (92/1158) - TVF rates at 3 years: XIENCE V: 13.3% (312/2348) as compared to TAXUS: 14.5% (168/1158) - TLF rates at 3 years: XIENCE V: 9.5% (233/2348) as compared to TAXUS: 11.9% (138/1158)
Study Strengths & Weaknesses	Results from each of the five clinical studies for XIENCE V® including: SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 mm, and SPIRIT IV provide further evidence of the clinical utility and safety of this device.
Recommendations for Labeling Changes	Post-approval study findings from each of the five clinical studies for XIENCE V® including: SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 mm, and SPIRIT IV should be part of the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P070015 / PAS002
Date Original Protocol Accepted	07/02/2008
Date Current Protocol Accepted	07/02/2008
Study Name	XIENCE Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will 1) evaluate clinical outcomes in a cohort of real-world patients receiving the XIENCE V EECSS during commercial use by various physicians with a range of coronary stenting experiences; 2) Evaluate patient compliance with adjunctive antiplatelet therapy and major bleeding complications;3) Determine clinical device and procedural success during commercial use; and 4) Evaluate patient health status using the Seattle Angina Questionnaire.
Study Population	The XIENCE V Everolimus Eluting Coronary Stent System is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery, lesions (length < 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm.
Sample Size	5000 patients, number of sites not listed
Key Study Endpoints	The primary endpoints of the study are is stent thrombosis rates annually through 5 years as defined by Academic Research Consortium and the composite rate of cardiac death and any myocardial infarction at 1 year.
Follow-up Visits and Length of Follow-up	Clinical follow-up for this cohort will occur at 2, 3, 4, and 5 years.
Interim or Final Data Summary
Interim Results	The rate of definite and probable ST (ARC definition) through 194 days was 0.5% (27/4957). Based on the time window when those definite and probable ST events occurred, 2 patients (0.04%) were adjudicated with acute ST, 20 patients (0.4%) were adjudicated with subacute ST, and 5 patients (0.1%) were adjudicated with late ST.The composite rate of cardiac death and any MI (Q-wave [QMI] and non-Q-wave [NQMI]) and the composite rate of all death and any MI (QMI and NQMI), at the in-hospital, 21-day, 37-day, and 194-day post-procedure time points are provided. The event rates through 37 days were 2.5% (126/5016) for cardiac death and MI, and 2.5% (127/5016) for all death and MI. The event rates through 194 days were 3.7% (183/4983) for cardiac death and MI, and 3.9% (195/4983) for all death and MI, respectively. Through 194 days post-procedure, the composite cardiac death and MI rate were dominated by NQMI (2.5% [124/4983]).
Actual Number of Patients Enrolled	5,020
Actual Number of Sites Enrolled	161
Patient Follow-up Rate	93%
Final Safety Findings	The annual rate of ARC-defined definite and probable ST at 4 years for the first 1500 on-label and near on-label subjects from the long-term follow-up (LTF) cohort was 0.16% (2/1241, upper one-sided 95% CI 0.51%). The 4-year cumulative ARC-defined definite and probable ST rates were 1.56% (64/4093, 95% CI [1.21%, 1.99%]) for the overall LTF cohort, 0.79% (10/1268, 95% CI [0.38%, 1.45%]) for the first 1500 on-label and near on-label population, and 1.91% (54/2825, 95% CI [1.44%, 2.49%]) for the remaining subjects in the LTF cohort. The 1-year adjusted rate of cardiac death and any MI was 6.2% (166/2663) for the SPIRIT study arm, the 1-year event rate was 6.2% (55/881) for the XIENCE V USA test arm (non-inferiority p<0.01).
Final Effect Findings	The cumulative rates of cardiac death and MI through 4 years were 14.9% (676/4530, 95% CI [13.90%, 15.99%] for the overall LFT cohort, 10.1% (139/1373, 95% CI [8.58%, 11.84%]) for the first 1500 on-label and near on-label subjects, and 17.0% (537/3157, 95% CI [15.71%, 18.37%]) for the remaining subjects in the LFT cohort.
Study Strengths & Weaknesses	The study had a low rate of attrition, thus minimizing selection bias. The study met its performance goals and had a large sample size.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term performance of the device from the pre-market cohort.
General
Study Status	Completed
Application Number / Requirement Number	P070015 / PAS003
Date Original Protocol Accepted	07/02/2008
Date Current Protocol Accepted	07/02/2008
Study Name	Dual Antiplatelet Therapy
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to evaluate the effectiveness and safety 12 versus 30 months of dual antiplatelet therapy on the composite of all death, myocardial infarction and stroke free survival, as well as definite or probable ST free survival, in patients treated with drug eluting stents. The patients will be randomized to either their dual anti-platelet therapy or placebo and followed from 12 months to 30 months post index procedure.
Study Population	The Xience V Everolimus Eluting Coronary Stent System was approved on July 2, 2008. This device is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length < 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm.Study population will consist of event free patients at 12 months
Sample Size	Study Phase I (From index procedure to 1 year post stent implantation):8,000 patients, Study Phase II (From 1 year up to 5 years) : All patients enrolled and completed Study Phase I will be evaluated at 1-year to determine their eligibility of participating in one of the three different study cohorts in Study Phase II:1) XIENCE V USA LTF Cohort: The first 1,500 on-label patients and the remaining patients from the initial 5,000 patients who do not participate in the HCRI-DAPT cohort will be included in this cohort. 2) HCRI-DAPT Cohort: Patients who are event free in the first year and are compliant with DAPT will be identified for HCRI. 3) AV-DAPT Cohort: Up to 1,524 patients from the additional 3,000 patients who are event free in the first year and are compliant with DAPT will be included in this cohort. The approximately 440 sequentially enrolled patients from 3,841 to 5,060 that are not included in the HCRI-DAPT study will also be followed to five years post index procedure. Therefore, a total of 4,280 patients (3,840 + 440) will be followed to five years post index procedure by Abbott Vascular. The remaining 780 patients will be followed by HCRI for the HCRI-DAPT study, 275 sites
Key Study Endpoints	Annual rates of ST cardiac death and myocardial infarction will be determined.
Follow-up Visits and Length of Follow-up	Annually to five years. Clinical follow-up will occur at 15, 24, 30 and 33 months.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P970004 S022/ PAS002
Date Original Protocol Accepted	09/24/2002
Date Current Protocol Accepted	10/23/2007
Study Name	Urinary Urge Incontinence (UUI)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
General
Study Status	Delayed
Application Number / Requirement Number	P050050 / PAS002
Date Original Protocol Accepted	05/27/2009
Date Current Protocol Accepted	05/06/2022
Study Name	Actual Conditions of Use Study (STAR 2)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This is a retrospective, Real-World Evidence multi-center study. The purpose of this study is to examine the safety and survivorship of the STAR™ Ankle under actual conditions of use, employing the approved instructions for use, labeling, and instrumentation. This study will enroll a minimum of 500 on-label subjects across approximately 5 sites in the United States, consecutively implanted per site, who are to be assessed in this clinical investigation. Each site will have a minimum of fifty patients, with subject patient primary surgery dates taking place between 2015-2019.
Study Population	A minimum of 500 adult male or female subjects, who meet all the study criteria (listed in 4.6), that received treatment with the STAR ankle implant for ankle replacement for treatment of a painful arthritic ankle joint due to osteoarthritis, posttraumatic arthritis or rheumatoid arthritis. Patients sets at each site will be on-label and consecutive. The study plan is to enroll all on-label, consecutive patients per site with primary STAR surgery dates between 2015 and 2019. With this surgery date range, the potential patient follow-up period should be between approximately two years at a minimum to seven years maximum. With this new patient follow-up range, the longer time periods for this subject study will be between the PAS2 and PAS8 study bounds.
Sample Size	No. of subjects: 500 on-label subjects No. of sites: 5 (Each site will have a minimum of 50 patients). Sites location: US
Key Study Endpoints	Primary Objective: To examine the safety and survivorship of the STAR™ Ankle under actual conditions of use, employing the approved instructions for use, labeling, and instrumentation. The primary endpoint consists of evaluating key safety and survivorship parameters associated with the STAR™ Ankle, with specific elements listed below. 1. Reoperations - incidence rates and times to event will be collected. 2. Revisions - incidence rates and times to event will be collected. 3. Removals - Incidence rates and times to event will be collected. 4. Occurrence and types of serious device-related adverse events. Secondary Objective: Information regarding the following patient and treatment parameters will be gathered and assessed in the course of evaluation: Nature/reason for revision, onset, duration, severity, relationship to the device, relationship to the operative procedure, and outcome of any adverse event
Follow-up Visits and Length of Follow-up	Duration of follow-up will vary based upon date of primary STAR surgery. All available patient records through the present will be collected per patient, such that patients with surgery dates in 2015 may have up to seven years of follow-up, while those patients with surgery dates in 2019 may have approximately two years of follow-up.
Interim or Final Data Summary
Interim Results	Safety Results: 165 adverse events were reported. AEs were associated with 87 of the 197 enrolled patients, such that 44.16% of patients had one or more AEs. Twenty-five (25) reoperations, 14 revisions, and five (5) removals were recorded in the current 197-patient data set.
Actual Number of Patients Enrolled	197
Actual Number of Sites Enrolled	Four (4)
Patient Follow-up Rate	39.4%
General
Study Status	Terminated
Application Number / Requirement Number	P070022 / PAS001
Date Original Protocol Accepted	07/06/2009
Date Current Protocol Accepted	07/06/2009
Study Name	EASE TRIAL
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a continued follow-up of subjects in the premarket EASE trial, a prospective, single-armed, multicenter study. The primary objective of the post-approval study is to determine the 3-year through 10-year, yearly period efficacy rates for subjects enrolled in the premarket EASE study.
Study Population	The device is indicated for women who desire permanent birth control (female sterilization) by occlusion of the fallopian tubes. The study population includes women who are currently relying on the Adiana system for permanent contraception and those who are being followed for safety purposes, all from the premarket cohort.
Sample Size	770 patients, 16 sites
Key Study Endpoints	Effectiveness endpoint is the pregnancy rate during the three through ten year reliance follow-up period for subjects in the EASE study who rely on the device for contraception.Safety endpoints include: (1) Subject satisfaction and comfort with device wearing; (2) Safety of device wearing; and (3) Relevant adverse events: All reproductive adverse events, and all abdominal adverse events reported during the study.
Follow-up Visits and Length of Follow-up	All subjects will be assessed annually in years 3, 4, 5, 6, 7, 8, 9 and 10 post reliance or follow up date (±30 days). All visits will occur via telephone. If there is any indication that the subject may be pregnant, by either verbal admission or unusual menstrual events, an office visit will be scheduled and a pregnancy test administered within one month. The duration of follow-up is ten years.
General
Study Status	Completed
Application Number / Requirement Number	P060008 S011/ PAS001
Date Original Protocol Accepted	07/23/2010
Date Current Protocol Accepted	07/23/2010
Study Name	TAXUS Long (S011)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center study designed to observe clinical outcomes in patients receiving the TAXUS Liberte-Paclitaxel-Eluting Coronary Stent and prasugrel as part of a dual antiplatelet therapy drug regimen. This is a consecutively-enrolled study with follow-up through 5 years. This study will also contribute patient data to an FDA-requested and industry-sponsored research study that will evaluate the optimal duration of dual antiplatelet therapy study.
Study Population	The TAXUS Liberté Long Paclitaxel-Eluting Coronary Stent is an expandable, mesh-like stainless steel tube with a drug (paclitaxel) contained within a thin polymer coating on its surface. The stent is mounted over a deflated balloon attached to the end of a long thin flexible tube called a stent delivery catheter. The stent is indicated for improving luminal diameter for the treatment of de novo lesions in native coronary arteries >=2.75 mm to <=4. 00 mm in diameter in lesions <=34 mm in length.
Sample Size	84 subjects, 100 sites
Key Study Endpoints	Data will be collected on the rate of cardiac death or myocardial infarction through 12 months. This will be compared with the cardiac death or myocardial infarction rates observed through 12 months in control arm of the TAXUS ATLAS Workhorse Clinical Trial and the ARRIVE 1 and 2 registries.
Follow-up Visits and Length of Follow-up	Patient follow up will occur at months 6, 12, 15, 18, 24, 30, 33, 36, 48 and 60 post index procedure, for all enrolled patients. Follow-up for months 15, 33, 36, 48 and 60 may be conducted via telephone. Follow-up for months 6, 12, 18, 24 and 30 must be conducted during a clinical visit for the purposes of study drug dispensing and accountability. The 18-month office visit is intended to serve the purposes of drug dispensing and accountability only.
Interim or Final Data Summary
Interim Results	The study has recently started, no results available.
Actual Number of Patients Enrolled	150
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	90.2%
Final Safety Findings	¿MACE: out-of-hospital MACE to 5 years was comparable for the groups (32.6% for the TAXUS® ATLAS Group and 27.6% for the Control Group, P=0.3790). ¿Stent Thrombosis: Stent thrombosis rates were not statistically different for the TAXUS® ATLAS Group versus the Control Group (2.5% versus 0.9%, P=0.6220) ¿All Death: Rates through 5 years were comparable between the TAXUS® ATLAS Group and the Control Group (11.1% versus 10.9%, P=0.9465). ¿Non-cardiac Death: Rates through 5 years were not statistically different the TAXUS® ATLAS Group and the Control Group (7.0% versus 2.5%, P=0.1054).
Final Effect Findings	¿MACE (cardiac death, MI, and TVR): The rate at 5 years was comparable between the TAXUS® ATLAS Group and the Control Group (32.6% versus 30.7%, respectively). ¿Cardiac Death: Rates through 5 years were comparable for the TAXUS® ATLAS Group and the Control Group (4.5% versus 8.7%). ¿MI: Rates through 5 years were comparable for the TAXUS® ATLAS Group and the Control Group (7.6% versus 11.8%). ¿TVR: The rate at 5 years was comparable for the TAXUS® ATLAS Group versus the Control Group (25.8% versus 20.5%). ¿TLR: The rate at 5 years was comparable for the TAXUS® ATLAS Group versus the Control Group (18.9% versus 14.2%). ¿TVF: The rate at 5 years was comparable for the TAXUS® ATLAS Group versus the Control Group (30.5% versus 28%. *The study was not powered for these endpoints at 5 years
Study Strengths & Weaknesses	Sponsor had a high follow-up rate. The stent thrombosis rate was higher in the treatment group. The study was not adequately powered to detect differences in stent thrombosis rates.
Recommendations for Labeling Changes	Yes, to update with the five year final study results.
General
Study Status	Completed
Application Number / Requirement Number	P070026 S004/ PAS001
Date Original Protocol Accepted	04/02/2013
Date Current Protocol Accepted	03/10/2015
Study Name	Long-Term F/U of IDE COC36 patients
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Multi-center, cohort study
Study Population	Patients will be enrolled from the IDE study
Sample Size	It is anticipated that up to 80 subjects from the IDE study implanted with the 36 mm device will consent to participate.
Key Study Endpoints	Device revision is the primary endpoint; secondary endpoints include Harris Hip Scores and radiographic findings.
Follow-up Visits and Length of Follow-up	Patients will be followed for 10 post-operative years, These subjects will be evaluated at the time of consent (approximately 5 to 7 years post-op), again at a minimum 8 year follow-up interval, and finally at a minimum 10 year follow-up interval.
Interim or Final Data Summary
Actual Number of Patients Enrolled	81 Subjects from among COC36 IDE study subjects.
Actual Number of Sites Enrolled	57 sites were enrolled for the post-approval study.
Patient Follow-up Rate	92% had follow-up with complete datasets at year 8 of follow-up. 81% had follow-up with complete datasets at year 10 of follow-up.
Final Safety Findings	No significant differences were noted in the Harris Hip outcomes (total or any sub-score) as well as the acetabular and femoral radiographic summaries. Those who received all approved components (PMA cohort) had a slightly higher percent with any complication compared to subjects who received at least one non-PMA approved component (non-PMA cohort): 88.2% vs. 66.7% (p-value = 0.0237). The percent of subjects with systemic adverse events was slightly higher among the PMA cohort vs. the non-PMA cohort: 76.5% of Subjects vs. 56.7% of Subjects, respectively (p-value = 0.0825). The percentages of Subjects with Surgical Site adverse events was not significantly different for the PMA cohort vs. the non-PMA cohort: 29.4% vs. 26.7%, respectively (p-value = 1.000).
Final Effect Findings	The 10-year device survivorship estimate is 96.6%, with a lower 95% confidence limit of 89.7% for those who received all approved components (PMA cohort). The 10-year device survivorship estimate is 96.7%, with a lower 95% confidence limit of 87.3% for those who received one or more non-PMA components.
Study Strengths & Weaknesses	Results provided further evidence of the clinical utility and safety of this device.
Recommendations for Labeling Changes	Post-approval study findings should be part of the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P070026 S004/ PAS002
Date Original Protocol Accepted	04/02/2013
Date Current Protocol Accepted	06/26/2020
Study Name	Short-Mid-Term F/u of New COC36 patients
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	A prospective, non-controlled, non-randomized, multicenter study. A minimum of 170 subjects will be prospectively enrolled into the study. Study sites will be comprised of both IDE study sites, as well as newly recruited sites. Subjects will be seen for a preoperative (pre-op) clinic visit at the time of consent, and then at 6-weeks, 1-year, 2-years, 3-years, 4-years and a minimum of 5-years postoperatively (post-op). If Subjects are not willing or able to return for a clinical and radiographic follow-up in the 3- and/or 4-year interval, then a telephone interview may be utilized for the purpose of determining device survivorship/patient satisfaction and case report form (CRF) 4b will be used. It is anticipated that a minimum of 136 unrevised subjects in this PAS will have a minimum 5-year post-op clinic evaluation. Up to fifteen (15) sites will participate, consisting of up to 5 sites who participated in the IDE study and the remainder being newly recruited sites.
Study Population	Newly enrolled subjects at participating sites who meet the inclusion/exclusion criteria for this study.
Sample Size	170 patients
Key Study Endpoints	Primary endpoint: Device survivorship, which will be estimated with a Kaplan-Meier survivorship analysis at 5-years post-operatively. Secondary endpoints: Device survivorship will also be estimated at each year post- operatively. Harris Hip scores, Subject-hip outcomes, radiographic evaluation, and type and frequency of AEs will also be estimated at each year post-operatively.
Follow-up Visits and Length of Follow-up	Study Duration: The anticipated duration of this investigation is approximately seven years from the time of study initiation given that It may take up to a minimum of 2-years from the time of study initiation to enroll new subjects. Each subject will be followed until they have completed their minimum 5-year follow-up. The study will be closed when all subjects are at 5-years post-operatively.
Interim or Final Data Summary
Actual Number of Patients Enrolled	172 hip procedures in 170 subjects (Female: 70, Male: 100)
Actual Number of Sites Enrolled	16 sites (US & Canada)
Patient Follow-up Rate	The 5-year follow-up rate for subjects with all primary and secondary endpoints data is 66% (107/163)
Final Safety Findings	A total of 134 hips (77.9%) had systemic adverse events (AE) and 105 hips (61.0%) had surgical site AEs data at 5 years of follow up. There were 2 deaths (1.2%) unrelated to the device or procedure and 8 revisions (4.7%) to femoral head, acetabular liner and/or acetabular cup and most revisions occurred within the first two (2) years of implantation. At 5 years of follow-up, there were: • 46 device related AEs at the surgical site in 19.2% (33/172) of hips. There were no unanticipated adverse device events. • 11 systemic procedure related AEs in 5.8% (10/172) of hips and 83 surgical site procedure related AEs in 32.0% (55/172) of hips. • The most frequently reported AEs were joint crepitation/noise/squeaking/grinding/vibration.
Final Effect Findings	Survivorship: At 5-years post-surgery, Kaplan-Meier implant survivorship is estimated as 94.9% (95% confidence interval: 90.0%- 97.4%). Functional Outcomes: At 5-years of follow up, 88% (96/109) of patients were reported to have ‘Excellent’ or ‘Good’ modified Harris Hip Score (mHHS) (score >80) and 4.6% (5/109) were reported to have ‘Poor’ mHHS (score <70). Radiographic Outcomes at 5 years: • For Acetabular Component, there were no cases of migration noted, 99.1% (108/109) had no radiolucency, 99.1% (108/109) had no osteolysis, 97.2% (106/109) with no sclerotic lines, and 97.2% (106/109) with no heterotopic ossification greater than grade III. • For Femoral Component, there were no cases of subsidence, osteolysis or radiolucency, 96.3% (105/109) with no heterotopic ossification greater than grade III, 92.7% (101/109) had no sclerotic lines, and 97.2% (106/109) had no calcar resorption
Study Strengths & Weaknesses	Strengths: The US and Canadian study was able to demonstrate device safety and effectiveness through 5 years post-surgery. Overall study success was determinable for 139 subjects. Weaknesses: High loss to follow-up or missing data (e.g., radiographic, mHHS) for 34.4% (56/163) of subjects at 5 years. Caution is advised in generalization of these results to broader US patients or practice. Of note, there were 14 (8.2% of 170) subjects that received one or more non-PMA device component(s) (i.e., femoral stem, femoral head, or acetabular cup), which may have influenced safety and effectiveness findings, which may have influenced safety and effectiveness findings.
Recommendations for Labeling Changes	Yes, a labeling change is recommended to update the device labeling with the final study results.
General
Study Status	Completed
Application Number / Requirement Number	P070026 S004/ PAS003
Date Original Protocol Accepted	04/02/2013
Date Current Protocol Accepted	11/21/2013
Study Name	COC36 PAS: UK & Australian Natl Joint Reg
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Hybrid non-comparator study based on registry data
Study Population	36mm CoC patients in UK and Australia joint registries
Sample Size	At minimum 500 patients
Key Study Endpoints	Device survivorship, revision and death rates
Follow-up Visits and Length of Follow-up	N/A, the study duration is predicted to be 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	427 subjects with PMA approved components and indications from the United Kingdom National Joint Registry.
Actual Number of Sites Enrolled	Not applicable as this is a retrospective registry analysis.
Patient Follow-up Rate	Not applicable as this was a retrospective analysis.
Final Safety Findings	Based on review of patients for between 0 and 11 years, 253 patients with 5 or more years follow-up, there was a revision rate of 0.77/100 patient years (95% confidence interval of 0.47-1.18). The estimated revision rate for patients at 7 years was 4.45% (95% confidence interval of 2.78-7.09%). Reasons for revision included infection, loosening, dislocation, pain and fracture.
Final Effect Findings	The study collected only safety endpoints.
Study Strengths & Weaknesses	The study evaluated the long term revision rate for patients; however, this study did not evaluate patient functional outcomes.
Recommendations for Labeling Changes	no labeling changes recommended
General
Study Status	Completed
Application Number / Requirement Number	P980040 S039/ PAS001
Date Original Protocol Accepted	04/15/2013
Date Current Protocol Accepted	04/23/2018
Study Name	New Enrollment of Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval study is to evaluate the rates of visual distortions for the TECNIS Toric IOLs with >2.0 D of cylinder correction at the corneal plane (Models ZCT300 and ZCT400) in a larger population in clinical practice compared to a non-toric control IOL. The design is a prospective, multi-center, bilateral, non- randomized, open-label, comparative clinical study conducted at up to 80 sites in the USA. Subjects will choose to be bilaterally implanted with either 1) the TECNIS 1-Piece Toric IOLs, Model ZCT300 and/or ZCT400, or 2) the TECNIS Monofocal Model ZCB00 non-toric control IOL, according to subject preference.
Study Population	Patients with bilateral cataracts with corneal astigmatism of approximately 2.00 D to 3.62 D based on the combination of preoperative keratometric cylinder and the expected effect of surgically induced astigmatism.
Sample Size	A sample size of a minimum of 396 enrolled subjects to achieve bilateral implantation of approximately 294 subjects: 169 TECNIS Toric ZCT300 and ZCT400 and 125 control subjects will be enrolled. A two-group large-sample normal approximately test of proportions with a one- sided 0.05 signficance level using only 37 evaluable toric subjects and 27 evaluable control subjects will have a greater than 90% power to detect a rate of severe visual distortions for toric subjects as being 10 percentage points or greater than that for control subjects. This assumes severe visual distortion rates of 1% for both the toric and control subjects. Therefore, the sample size proposed for a minimum of 396 enrolled subjects, assuming a 10% drop out rate for a minimum of 152 toric and 112 control subjects available for evaluation at 6 months, is sufficient to demonstrate a non-inferiority in the rate of severe visual distortions (the primary endpoint of this study) between the two study groups in a larger population in clinical practice, and thereby demonstrate the continued safety of the toric IOLs.
Key Study Endpoints	Primary Endpoint Rate of severe visual distortions; defined as the percentage of subjects who report a severe visual distortion under overall circumstances at 6 months postoperative for any of the following 5 visual distortion items of interest: -lines that slant, tilt, split or separate o flat surfaces appearing curved -objects appearing further away or closer than they actually are -objects appearing to have a different size or shape o physical discomfort related to vision. Other Endpoints Ratings of individual items included on the visual distortion questionnaire Rates of IOL repositioning procedures (secondary surgical intervention) due to IOL misalignment Rates of other adverse events
Follow-up Visits and Length of Follow-up	Six months; any subjects that undergo a lens repositioning procedure due to IOL misalignment or that report a severe visual distortion at six months, will be followed through 1 year postoperatively.
Interim or Final Data Summary
Actual Number of Patients Enrolled	118 (101 patients implanted)
Actual Number of Sites Enrolled	44
Patient Follow-up Rate	Overall follow-up rate among those enrolled: 104% (429/396) The follow-up rate among those implanted was 95.8% at 1-month, 93.8% at 6-month, and 91.3% at 1- year
Final Safety Findings	The rate of severe visual distortion was 0% and 1.4% for the Toric and control groups, respectively; None in the Toric group, and two subjects in the control group reported severe visual distortion under overall circumstances for the 5 items of interest in the questionnaire at 6-months. The percentage of subjects who completed the 6-month questionnaire and reported severe visual distortions at the 6-month visit was 5.9% (11/187) in the Toric group and 5.0% (7/141) in the control group. The 11 Toric subjects reported 14 severe visual distortions while the 7 control subjects reported 22 severe visual distortions. There were no unexpected medical findings. Lens findings of misalignment were the most common finding reported by the investigator. A total of 33 subjects experienced 42 ocular serious/device-related adverse events (SAE/ADEs) in 38 eyes as determined by the investigators. Forty events were categorized as serious by medical monitor(s) based on the definition of SAE per the protocol. These included 12 reports (a rate of 5.6%, 12/214) of IOL misalignment that required secondary surgical intervention to reposition the lens all resolved without sequelae.
Final Effect Findings	No effectiveness study endpoints were included in the approved protocol.
Study Strengths & Weaknesses	Strength: More than 80% follow-up rate, there is a comparator group. Weaknesses: No randomization, lack of representativeness (92% were White).
Recommendations for Labeling Changes	The PAS study design, methods and results must be included in the labeling. Additionally, it should be included in the following: protocol deviations results and sensitivity analysis
General
Study Status	Completed
Application Number / Requirement Number	P070026 / PAS001
Date Original Protocol Accepted	12/23/2010
Date Current Protocol Accepted	03/18/2015
Study Name	Ceramax PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is prospective.
Study Population	Males and females who are appropriate candidates for primary hip replacement with non-inflammatory degenerative joint disease.
Sample Size	A total of 250 Subjects will be enrolled in the investigation 100 subjects recruited from IDE to PAS 150 new PAS subjects There will be 5 sites enrolling IDE patients and 10 sites enrolling newly enrolled patients.
Key Study Endpoints	The main study endpoint is device revision. Secondary endpoints include Harris Hip Score and radiographic findings.
Follow-up Visits and Length of Follow-up	Follow-up to 10 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	179 subjects/181 hips (including 2 bilateral).
Actual Number of Sites Enrolled	13 sites with IRB approvals including 11 activated/ participating sites.
Patient Follow-up Rate	Throughout the study, follow-up rates decreased from 64% at 6 weeks in New PAS subjects and 92% at 7 years in IDE Rollover subjects to levels below 50% at the final study time points in both groups. Considering the decision on close-out of 28mm Ceramax Hip System study, no new follow-up measures were implemented; however, the loss-to-follow-up was considered in the assessment of long-term device survival and overall study findings.
Final Safety Findings	A total of 8 cumulative revisions for any component and any reason were reported throughout the study among IDE Rollover and New PAS subjects. Due to no change in the number of revisions since Year 3, device survival estimates in the 28mm Ceramax Hip System PAS remained at the level of 96.7% (95% CI: 93.4, 98.3) from Year 3 to Year 10. However, the numbers of Hips Remaining at the same time points decreased from 199 to 51, respectively. To enhance the reliability of safety assessment in this PAS, the 10-year survival assessment was complemented by evaluating Ceramax device performance captured within the National Joint Registry of England, Whales, Northern Ireland and the Isle of Man (NJR). The NJR registry-based 10-year cumulative revision rate for 28mm Ceramax bearing was estimated as 4.08% (95% CI: 3.54, 4.69) in 5,724 patients.
Final Effect Findings	Harris Hip Success at 5-years was achieved in 96.2% (76/79) of subjects in the entire 28mm Ceramax hip dataset, with the same number of subjects (96.2%) having total Harris Hip Score >80. However, there were a total of 43 subjects with <80 scores and only 87.7% (64/73) satisfied the criteria for Overall Composite Clinical Success. With the low long-term follow-up affecting subgroup analyses, the Overall Composite Clinical Success rates were much lower in the New PAS subjects (77.8% and 50.0% in IDE Rollover and New PAS subjects, respectively). The 10-year estimates for total Harris Hip Score, Pain Score, and Function and Activity Score were reported as 96.0%, 42.5%, and 44.3%, respectively.
Study Strengths & Weaknesses	The 28mm Ceramax Hip System PAS provided safety and effectiveness data for ceramic hips with smaller size heads as well as identified potential treatment modifying effects (e.g., due to surgical approach). However, due to the low long-term follow-up rates, there was a need for complementary evidence from orthopedic registries to substantiate the assessment of long-term device survival. The NJR 28mm cumulative revision rates should be interpreted with caution because the cases within NJR are from non-US population which includes mostly Non-PMA approved systems (i.e., hip systems with different stems and acetabular cups compared to those approved for use with the Ceramax system in the US). Less than 1% of data points in NJR are representative of the US approved construct. Additionally, evidence from published literature was used to complement the assessment of other safety aspects of ceramic hips such as ceramic fracture and its possible consequences (e.g., third body wear) in subsequent total hip replacements.
Recommendations for Labeling Changes	Post-approval study findings should be part of the device labeling. Additional clarifications on risks and outcomes as identified in the literature review should also be added to the labeling. Labeling update may need to include some results on possible modifying effects as well as warnings regarding the low long-term follow-up and lack of radiographic assessment affecting the assessment of acoustic phenomena (joint crepitation) and other safety and effectiveness outcomes.
General
Study Status	Completed
Application Number / Requirement Number	P100028 / PAS001
Date Original Protocol Accepted	12/05/2011
Date Current Protocol Accepted	12/05/2011
Study Name	REFORM
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	95%
Final Safety Findings	No significant safety problems were reported at 36 months. A clinically significant decrease in systolic blood pressure was sustained for 36 months.
Final Effect Findings	The rate of the primary endpoint was 91.7% and the lower limit of the 95% two-sided confidence interval was 84.2%. The primary premarket hypothesis tested was the 9-month primary patency rate that resulted greater than 60% (p < 0.001). Therefore, the rate was higher than the performance goal. Technical Success was 97.4% (112/115) on a per lesion basis.
Study Strengths & Weaknesses	Results provide further evidence of the clinical utility and safety of this device.
Recommendations for Labeling Changes	Post-approval study findings should be part of the device labeling, including the following key safety findings: the 9-month primary patency rate (table 3.10-1), Major Adverse Events (table 3.11.1-1), technical success, acute procedural success (tables 3.11.2-1 and3.11.3-1), blood pressure results (table3.11.6.1-1) cured and improved hypertension at 36 months (table 3.11.6.3- 1) and renal function results (tables 3.11.7-1 and 3.11.7-2).
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P030011 S011/ PAS001
Date Original Protocol Accepted	05/16/2012
Date Current Protocol Accepted	08/20/2012
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	2-armed (partially retrospective and partially prospective), multi- center, non-randomized, cohort registry study that uses the INTERMACS Registry to compare performance of the TAH-t when supported with the Companion 2 Driver System vs. performance of the TAH-t when supported with the CSS Console.
Study Population	Patients in the INTERMACS Registry who are implanted with the TAH-t.
Sample Size	The study will be composed of 151 patients supported by the Companion 2 Driver System and the last 151 patients supported by the CSS Console
Key Study Endpoints	Primary Endpoint The primary endpoint parallels the study hypothesis: Transplant prior to three months, transfer to the Freedom Driver System prior to three months, continuing implant driver support prior to 3 months, or death prior to any of the endpoints listed. Secondary Endpoints Adverse events and device-related adverse events
Follow-up Visits and Length of Follow-up	3 months, or when one of the primary endpoints is reached ¿ whichever occurs first. Patients will be followed at one week, one month, and three months.
General
Study Status	Terminated
Application Number / Requirement Number	P110032 / PAS001
Date Original Protocol Accepted	11/01/2013
Date Current Protocol Accepted	11/01/2013
Study Name	Aorfix Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective observational study with a historical control, including both prospective follow-up of newly enrolled subjects, plus continued follow-up of the premarket cohort.
Study Population	The study will include 234 prospectively enrolled subjects treated in accordance with the IFU for the device plus all 221 Aorfix¿ subjects enrolled into Lombard Medical¿s IDE study.
Sample Size	455 subjects, including 234 newly enrolled subjects plus 221 from the premarket cohort. A minimum of 20 sites
Key Study Endpoints	 Aneurysm-related mortality at 5 years (primary endpoint)  Major adverse events at 30 days, and annually through 5 years  Type I and III endoleaks  Device migration  Fracture in fixation zone  Conversion to open surgery  Change in aneurysm size  Aneurysm rupture
Follow-up Visits and Length of Follow-up	5 years 30 day post-implant, one year, and annually thereafter
General
Study Status	Completed
Application Number / Requirement Number	P080006 S068/ PAS001
Date Original Protocol Accepted	08/01/2014
Date Current Protocol Accepted	08/01/2014
Study Name	Post-Approval Study Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Attain Performa PAS is a non-randomized, observational, world-wide study with prospective data collection. Data collection will begin at patient enrollment and will continue at six-month intervals through five years post-implant. Follow-up windows consistent with typical practice have been established and will be provided to sites to facilitate a robust data set and ensure reporting consistency. Attain Performa IDE patients are eligible to continue in the PAS upon market approval if they are followed at a participating PAS study site and are consented.
Study Population	All patients who meet eligibility criteria and are implanted with an Attain Performa lead will be included in analysis of the PAS objectives. Inclusion criteria: Patient or legally authorized representative provides written authorization and/or consent per institution and geographical requirements Patient has or is intended to receive or be treated with an eligible product Patient within enrolment window relative to therapy initiation or meets criteria for retrospective enrollment Exclusion criteria: Patient who is, or is expected to be inaccessible for follow-up Patient with exclusion criteria required by local law Patient is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound results There are no comparison groups
Sample Size	A total of 1,778 Attain Performa leads will be enrolled in the PAS. The study will be conducted at 150 study sites located in the United States (US), Canada, and ECA (Europe and Central Asia). Enrollment outside the United States (OUS) will be limited to no more than 50% of the overall sample size. Enrollment of1778 Attain Performa leads results in 1050 leads followed for 5-years. This assumes a 10% per year attrition rate and provides a power of over 80% to test the primary objective. Sample size determinations must satisfy the primary objective analysis requirement and provide a reliable estimate of individual failure mode rates for the general population. The distribution of Attain Performa lead-related complications can be expressed as binomial (n, p=0.4%). Therefore, the probability of detecting a rare event can be calculated as a function of n.
Key Study Endpoints	Study Endpoints Primary Endpoints: To demonstrate that the complication-free probability is greater than 92.5% at five years post-implant for the Attain Performa Model 4298 lead. For the purposes of the PAS, survival from Attain Performa lead-related complications will be based on acute and chronic complications as illustrated in Table below. / Undersensing Table 4 Full Protocol for: Attain PerformaTM Left Ventricular Quadripolar Lead Post- Approval Study Registry Analysis Plan, Version 2, Date July 2, 2014 Study Element Description Secondary Endpoint: ¿ To summarize all Attain Performa lead-related ADEs ¿ To summarize analysis results from explanted and returned Attain Performa leads Additional analysis will be to report on incidence of pacing threshold rise per the following: ¿ At implant, pacing thresholds for the programmed LV pacing vector that are > 3.0 Volts at > 0.4 ms ¿ At 6-months, pacing thresholds for the programmed LV pacing vector that are > 3.5 Volts at > 0.4 ms (6- month threshold values will be regarded as the baseline for chronic thresholds) ¿ At 12-months and all eventual follow-up visits, an observed threshold increase 1.5 Volts over the 6- month values, or an absolute value > 3.5 Volts at > 0.4 ms
Follow-up Visits and Length of Follow-up	5 years post-implant Post-approval reports will be submitted to the FDA every six months for the first two years after the first Attain Performa PMA-S approval, then annually thereafter.
Interim or Final Data Summary
Interim Results	The overall complication free rate for across all leads at 60 months was 98.75% (95% CI: 97.85%, 99.27%).
Actual Number of Patients Enrolled	1900
Actual Number of Sites Enrolled	114
Patient Follow-up Rate	88.43%
Study Strengths & Weaknesses	The progress report was found to be adequate with sufficient follow-up rate and with a complication free rate which is above the approved performance goal (92.5%).
General
Study Status	Completed
Application Number / Requirement Number	P080006 S085/ PAS001
Date Original Protocol Accepted	02/01/2016
Date Current Protocol Accepted
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. ¿ Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P040029 / PAS001
Date Original Protocol Accepted	09/29/2004
Date Current Protocol Accepted	09/29/2004
Study Name	JSZ Orthokeratology Contact Lenses
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort-Study. The study was to evaluate the stability of the treatment post lens removal by analysis of measures such as uncorrected visual acuity, refraction and corneal changes for 150 subjects that have attained a predefined level of refractive stability within a 3 month period. The post approval study was to monitor regression toward pretreatment levels during a one week period following lens removal.
Study Population	The device is indicated for use in the reduction of myopic refractive error in non-diseased eyes. The lenses are indicated for overnight wear for the temporary reduction of myopia up to 5.00 diopters with eyes having astigmatism up to 1.50 diopters. The lenses may only be disinfected using a chemical disinfection system. The PAS was to include patients with documented stability of refraction for the prior 6 months, as demonstrated by spherical equivalent change of less than or equal to 0.50 diopters.
Sample Size	150 subjects
Key Study Endpoints	Data collection included: stability of the treatment post lens removal by analysis of measures such as uncorrected visual acuity, refraction and corneal changes, regression toward pretreatment levels during a one week period following lens removal.
Follow-up Visits and Length of Follow-up	3-months
Interim or Final Data Summary
Interim Results	Study was not conducted because device was not marketed in the US
Actual Number of Patients Enrolled	138
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	70%
Final Safety Findings	[Note: This Post-Approval Study Requirement was fulfilled using data from a post-approval study that was conducted for a similar device approved under a different PMA (P010062). This was considered appropriate because both devices use same design/materials and are approved for the same indication of use.] There were no adverse events related to the study product. Three eyes reported to have a grade 3 slit lamp finding during the Treatment Phase (2 eyes completed, 1 eye discontinued) and no reports of a grade 4 slit lamp finding during the Treatment Phase.
Final Effect Findings	At the initial diagnostic visit, none (0%) of the eyes achieving stability had uncorrected visual acuity (UCVA) of 20/20 or better and only 12 eyes (6.5%) had UCVA of 20/40 or better. By the end of the Treatment Phase, 3-Month Visit, most eyes that achieved stability had an MRSE that was between - 1.00D and +1.00D (177 eyes/ 96.2%). The refractive change from pretreatment resulted in excellent uncorrected distance visual acuity where 144 eyes (78.2%) had UCVA of 20/20 or better and 184 eyes (100%) had UCVA of 20/40 or better. Following lens removal, the stability of the vision was good during the day. At the 5-Hour Visit in the Regression Phase, there were 141 eyes (76.6%) that had UCVA of 20/20 or better and 182 eyes (98.9%) with 20/40 or better. While the MRSE regressed toward the pretreatment MRSE as the Regression Phase continued, there were still 121eyes (66.5%) with UCVA of 20/40 or better at the 24-Hour visit and 52 eyes (28.6%) were 20/20 or better. Although the there was no study requirement for eyes that achieved stability to be followed until complete return to pretreatment status, 128 of 184 eyes (69.6%) had regressed within ± 0.50D of pretreatment MRSE and 172 of 184 eyes (93.5%) had regressed within ± 1.00D of pretreatment MRSE by the 1-Week Regression Phase Visit. The BSCVA comparison of pretreatment to the final Regression Phase demonstrated that 177 eyes (97.8%) had no change (96.7%) or improved a line (1.1%) from the pretreatment BSCVA. The results demonstrated that subject¿s eyes were able to return to pretreatment values.
Study Strengths & Weaknesses	A strength of this study was the large sample size, which was enough to properly evaluate the safety of this device. However, lack of a control group limits interpretation of study results because findings could be due to factors related or unrelated to the device. The follow up rate was only 70%, increasing the likelihood for biased results as usually subjects that remain on the study may differ from those that are lost to follow-up.
Recommendations for Labeling Changes	It is recommended that the label be updated to reflect the long-term results. The post-approval study design, methods, safety and effectiveness results should be included in the labeling from both phases (i.e., treatment and regression phases).
General
Study Status	Completed
Application Number / Requirement Number	P070004 / PAS001
Date Original Protocol Accepted	03/09/2012
Date Current Protocol Accepted	05/29/2012
Study Name	Post-Approval PMA Cohorts Study (PACS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Post-approval PMA Cohorts Study (PACS) will continue to follow subjects from premarket cohorts for 10 years in order to assess the long-term clinical performance of the approved device. The PACS data are to be collected via annual physician follow-up evaluations and all patients in the study will have MRI at years 6, 8, and 10.
Study Population	Women who received Sientra' silicone breast implants and were enrolled in the premarket Core Study and reconstruction cohorts of the Continued Access Study. The data obtained at baseline on each subject will be used as the control data for physical status, cancer history and status, rheumatologic history and status, medical history and status, and CTD history and status.
Sample Size	A total of 1,788 subjects have been enrolled in Sientras PACS at 33 sites throughout the United States.
Key Study Endpoints	The safety endpoints include local complications, implant rupture, connective tissue diseases (CTDs), CTD signs and symptoms, lactation complications, cancer and suicide. Effectiveness will be assessed based on quality of life (QOL) assessments and subject satisfaction.
Follow-up Visits and Length of Follow-up	10 years Annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,788 Primary augmentation: 1,116 Revision-augmentation: 363 Primary reconstruction: 225 Revision-reconstruction: 84 Number of subjects completed 10-year visit: 1,030 Primary Augmentation: 688 (66.8%) Revision Augmentation: 192 (18.6%) Primary Reconstruction: 118 (11.5%) Revision Reconstruction: 32 (3.1%)
Actual Number of Sites Enrolled	61
Patient Follow-up Rate	At year 10, the overall follow-up rate for the PACS Study was 65%. Follow-up calculations were based on the following formula: [(“Seen” (Number of Patients Completed Visit) /”Expected” (Theoretically due – discontinued due to deaths & explants)]. The follow-up rates from year 1 to 10 for primary augmentation are 92%, 84%, 81%, 80%, 78%, 73%, 68%, 60%, 66%, and 67%, respectfully. For revision augmentation the rates are 89%, 85%, 80%, 80%, 76%, 73%, 67%, 57%, 65%, 62%, respectfully. For primary reconstruction, the rates are 90%, 83%, 81%, 78%, 73%, 74%, 66%, 61%, 67%, 65%, respectfully. For revision reconstruction the rates are 87%, 86%, 76%, 76%, 76%, 73%, 66%, 61%, 55%, and 58%, respectfully.
Final Safety Findings	Deaths There were 37 known deaths in the PACS study (10 primary augmentation, 4 revisionaugmentation, 15 primary reconstruction, and 9 revision-reconstruction subjects), which is about 2% of the population. Most are due to cancers (breast, lung, or other cancers) or other comorbidities, 9 were “unknown”; 7 are from the reconstruction or revision-reconstruction cohorts, which may be related to either a recurrence or metastasis of their breast cancer. Suicide There was one “reported possible suicide” in the primary augmentation cohort. Local Complications Besides Baker Grade II capsular contracture, a “mild” event, the most common complication in the primary augmentation, revision-augmentation and primary reconstruction cohorts was Baker Grade III/IV capsular contracture (12.9%, 13.7% and 15.8%, respectively). In the revisionreconstruction cohort, besides Baker Grade II capsular contracture, the most common complication was asymmetry (16.9%), followed by Baker Grade III/IV capsular contracture (14.3%). Implant Rupture The 10-year risk of rupture for the MRI cohort ranged between 6.8% to 16.5% and for the non- MRI cohort between 3.5% and 6.6%. The overall risk of rupture at 10 years is 7.9%. Connective Tissue Diseases (CTD) signs and symptoms The frequency of each CTD Sign/Symptom stratified by Visit & Age Group are within 5% for the primary augmentation cohort (max=4.6%) at year 10, and within 10% for the other cohorts (max=8.3% Revision Reconstruction, max=6.0% Primary Reconstruction, 0.0% Revision Reconstruction). Lactation Complications/Pregnancy Difficulties The incidences of post-operative pregnancy difficulties were 1.7%, 1.7%, 0.9% and 0.0%. The incidences of post-operative lactation difficulties were 11.5%, 10.6%, 0.0% and 0.0% in the primary augmentation, revision-augmentation, primary reconstruction and revisionreconstruction cohorts. Cancer The Kaplan Meier risk for breast cancer is 0.6%, 1.6%, 2.9%, and 3.2% for the primary augmentation cohort, the revision-augmentation cohort, the primary reconstruction cohort, and the revision-reconstruction cohort, occurring anywhere from one to ten years after surgery. Reasons for Reoperation In the primary-augmentation cohort, the most common reasons for reoperation were capsular contracture (24.7%), style/size change (20.6%) and ptosis (10.7%). In the revision-augmentation cohort, the most common reasons remain the same, with style/size change and capsular contracture (17.4% and 16.3%, respectively). In the primary reconstruction cohort, the most common reasons were style/size change (20.2%) and asymmetry (16.1%). In the revisionreconstruction cohort, the most common reasons remain the same with asymmetry (23.6%), capsular contracture (21.8%) and style/size change (16.4%). Reasons for Explantation/Removal In the primary augmentation cohort, the most common reasons for explantation were style/size change (49.1%) and capsular contracture (18.7%). In the revision-augmentation cohort, the most common reasons were style/size change (43.8%) and capsular contracture (11.1%). In the primary reconstruction cohort, the most common reasons were style/size change (36.0%) and asymmetry (16.2%). In the revision-reconstruction cohort, the most common reasons were style/size change (16.4%), asymmetry (23.6%), and capsular contracture (21.8%). Risk Factor Regression Analysis For all four cohorts, Years of Implantation is associated with increased risk (p value <0.001) for reoperation and explantation with or without replacement, and for Baker III/IV Capsular Contracture, statistically significant. Device Surface and Placement were significant for capsular contracture in primary augmentation, Device Surface was also significant for revision reconstruction, and Participant’s Age was a risk factor for the revision augmentation cohort. In
Final Effect Findings	In terms of patient satisfaction at 10 years, overall more than 80% patients feel more feminine and more attractive, and more than 74% feel better. The Mean Cup Change (and standard deviation) was 1.6 +/- 7 and circumference increased about 1-inch post-implant, 35.4 +/- 2.4 vs. 34.2 +/- 2.2. Paired t-test showed both statistically significant improvements in terms of bra cup size and circumference. There were no statistically significant changes in the SF-36 Subscale scores compared to the general female population by the 10-year visit across all four cohorts. The mean Rosenberg Self-Esteem scale scores and changes were within one point of each other across all four cohorts, ranging from 25.7 +/- 4.55 to 26.4 +/- 2.91. Specifically, a score of 26.0 +/- 4.34 was observed in the primary augmentation cohort, 25.9 +- 3.95 in the revision augmentation cohort, 25.7 +/- 4.55 in the primary reconstruction cohort, and 26.4 +/- 2.91 in the revision reconstruction cohort.
Study Strengths & Weaknesses	The PACS study assessed the continued follow-up of premarket cohorts. The participants were followed annually for 10 years to assess the long-term clinical performance of the device with acceptable follow-up rates. The PACS study is limited by its single arm design, i.e. only silicone is used across the four indication cohorts. In addition, the smaller number of reconstruction and revisionreconstruction cohort also limits the generalization of its results. Readers should be cautious in interpreting the data and in making generalizations about the target population because each of the four cohorts mentioned have a different patient profile, and with that, different levels of risk.
Recommendations for Labeling Changes	Labeling update is recommended to reflect the long-term safety and effectiveness results
General
Study Status	Completed
Application Number / Requirement Number	P080013 / PAS001
Date Original Protocol Accepted	09/04/2009
Date Current Protocol Accepted	02/03/2016
Study Name	DuraSeal Exact Spine Sealant System
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: Estimate the rates of post-operative CSF leak, deep surgical site infection and neurological SAEs within 90 days for DuraSeal Exact Spine Sealant and to compare these rates to the corresponding rates for Control. Design: a multi-center, non-randomized, Post Approval study with a prospective treatment arm and a retrospective control arm.
Study Population	For the retrospective controls (standard of care), subjects with fewer than 45 days of follow-up will be considered incomplete.
Sample Size	The DuraSeal Exact Spine Sealant prospective treatment arm will enroll up to 489 subjects in order to obtain a total of 402 evaluable subjects with 90 day follow-up data.
Key Study Endpoints	The primary endpoint is the occurrence of post-operative CSF leaks within 90 days after the spine surgical procedure. A CSF leak is defined as a CSF fistula or a pseudomeningocele* confirmed by clinical examination or diagnostic testing (i.e., MRI or CT) whether or not treatment such as surgical repair or drainage is required. * Pseudomeningocele noted on a diagnostic test must be confirmed by the study investigator Secondary endpoints are the occurrence of the following events (within 90 days following the surgical procedure): Deep Surgical Site Infections (DSSI) as defined per the CDC guidelines All neurological SAEs
Follow-up Visits and Length of Follow-up	For retrospective controls (standard of care), a patient will be considered completed if there is follow-up of at least 45 days. New study sites that do not have 90 day standard of care visits will enroll prospective subjects only (DuraSeal and/or Control). This would allow new sites to contribute subjects prospectively inside the study window (60 to 120 days), and allow control over follow-up compliance.
Interim or Final Data Summary
Actual Number of Patients Enrolled	489 (treatment group) + 435 (control arm)
Actual Number of Sites Enrolled	36
Patient Follow-up Rate	(429+406) / (489+435) * 100% = 90.4%
Final Safety Findings	Primary Endpoint: CSF Leakage DuraSeal Sealant was non-inferior compared with the control device in CSF Leakage in this study. Of the 886 study subjects on whom data were available, 58 (6.6%) subjects (DuraSeal Exact Spine Sealant: 30 [6.6%]; Control arm: 28 [6.5%]) experienced a CSF leak within 90 days after the spine surgical procedure. The difference estimate and its 95% CI (%) between treatment arms was reported as -0.9 (- 3.7, 2.0) from an unstratified analysis and as -0.5 (-3.4, 2.3) from a stratified analysis by propensity score quintile, Surgical Site Infections (SSI): There was no statistically significant difference in distribution of subjects with deep Surgical Site Infection (SSI) between the treatment groups As per CDC guideline, SSIs have been categorized into superficial SSI, DSSI, and organ/space SSI. There was a statistically significant higher proportion of subjects with superficial SSIs in the DuraSeal Exact Spine Sealant arm compared to the Control arm (2.8% versus 0.5%; p = 0.0076). Although the proportion of subjects with DSSI (2.1% versus 1.6%) and organ space SSIs (0.2% versus 0%) was numerically higher in the Control arm against the DuraSeal Exact Spine Sealant arm, the difference was not statistically significant. Adverse Events (AEs) There was no statistically significant difference in the proportion of subjects with any AE between the DuraSeal Exact Spine Sealant and the Control arms Ninety-two (92) subjects experienced at least one AE (DuraSeal Exact Spine Sealant arm: 51 [10.4%] subjects; Control arm: 41 [9.4%] subjects). There was no statistically significant difference in the proportion of subjects with at least one AE between the DuraSeal Exact Spine Sealant and the Control arms (p=0.6109). There was no statistically significant difference in the proportion of subjects with any SAE between the DuraSeal Exact Spine Sealant and the Control arms There were 75 serious AEs reported during the study (DuraSeal Exact Spine Sealant arm: 42 [8.6%] subjects; Control arm: 33 [7.6%] subjects). There was no statistically significant difference in the proportion of subjects with at least one SAE between the DuraSeal Exact Spine Sealant and the Control arms (8.6% versus 7.6%; p=0.5755). No UADEs were reported during this study. There was no statistically significant difference in the proportion of subjects between the treatment groups in terms of AE relatedness to the study device (p = 0.5370) and AE severity (p= 0.5979). By relatedness, the AEs were related to the device in 22 subjects (DuraSeal Exact Spine Sealant arm: 18 subjects; Control arm: 4 subjects); There was no statistically significant difference in the proportion of subjects with definite, probable, possible, or unknown relationship/impossible to determine relatedness to the study device for AEs between the two treatments.
Final Effect Findings	There was no effective endpoints, the primary and secondary endpoints are all safety related.
Study Strengths & Weaknesses	Strength Multi-center prospective treatment group with relatively large sample size so that the study is sufficiently powered and the sample is representative to the general population; Using a large number of patient with standard of care as the control arm; A pre-specified statistical plan in place to test the non-inferiority margin of 5% was in place before the study initiation. Weakness This is not a randomized study. The treatment group was compared with a retrospectively selected historical cohort with the standard of care. As a result, the two groups may be selected from two populations that are not exactly the same, and this may impact the result of the study.
Recommendations for Labeling Changes	It is recommended that the sponsor change the conclusion regarding the risk of Surgical Site Infection to accurately reflect the PAS results. Original language: ‘there was no statistically significant difference in distribution of subjects with any Surgical Site Infection (SSI) between the treatment groups (p=0.2295)’ New language: ‘there was no statistically significant difference in distribution of subjects with deep Surgical Site Infection (SSI) between the treatment groups’.
General
Study Status	Completed
Application Number / Requirement Number	P010031 S232/ PAS002
Date Original Protocol Accepted	04/04/2012
Date Current Protocol Accepted	01/10/2019
Study Name	REVERSE Product Surveillance Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort study
Study Population	All adult patients treated with a Medtronic CRT-D device, meeting the expanded indication with QRS duration < 150ms, enrolled into Medtronics Product Surveillance Registry.
Sample Size	216 investigation sites, 500 patients
Key Study Endpoints	To estimate the 3-year survival probability of freedom from centrally adjudicated heart failure hospitalization or all-cause death for patients implanted with a Medtronic CRT-D device meeting the approved expanded indication criteria with a QRS duration < 150ms. To estimate the 3-year survival probability of freedom from centrally adjudicated heart failure event or all cause death for patients implanted with a Medtronic CRT-D device meeting the approved expanded indication criteria with a QRS duration < 150ms.
Follow-up Visits and Length of Follow-up	3 years, with the potential to be extended out to 5-years every 6 months from implant through a minimum of 3-years
Interim or Final Data Summary
Actual Number of Patients Enrolled	155
Actual Number of Sites Enrolled	189
Patient Follow-up Rate	86.9%
Final Safety Findings	Of the 32 deaths reported, none were adjudicated to be system or procedure related. There were 39 reported heart failure events in 25 patients, of which 38 were adjudicated to be events and 35 were heart failure hospitalizations. The Kaplan Meier survival estimate at 5 years is 66.9%. This is primarily driven by the small sample size. The observed survival rate for the composite endpoint of heart failure event or allcause death was 77.4% at 3 years.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study estimated the 3-year survival probability of freedom from heart failure hospitalization/event or all-cause death. There were no significant safety concerns of device use in the expanded patient population. There were very few deviations and a high follow up rate. The study was limited by the number of enrollments and ultimate size of the analysis cohort.
Recommendations for Labeling Changes	Labeling will be updated with the clinical data available from the completed study
General
Study Status	Completed
Application Number / Requirement Number	P110004 / PAS001
Date Original Protocol Accepted	04/12/2012
Date Current Protocol Accepted	04/12/2012
Study Name	Continued f/u of BLAST Placebo Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a non-randomized, multi-center, prospective, single arm clinical study.
Study Population	Patients with symptomatic ischemic heart disease due to a single de novo stenotic lesion contained within native coronary artery with reference vessel diameter between 2.5 mm and 4.0 mm and lesion length less than or equal to 30 mm that is amenable to percutaneous revascularization with percutaneous coronary intervention with stent deployment.
Sample Size	131 patients enrolled from up to 15 sites in the USA. Assumptions: ¿ Three-year TVF rate for bare metal stents derived from the meta- analysis is 22%. (95% CI 17.7%, 26.4%). ¿ Performance goal for bare metal stents = 33% ¿ Type I error (a) = 0.05 (one-sided) ¿ Statistical power (1 – ß) = 80% ¿ Expected rate for TVF at 3 years for Presillion plus Stent System = 22%
Key Study Endpoints	Primary Endpoint Target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) [Q wave or non-Q wave], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 3 years post-procedure. The secondary safety endpoints are: All Death at 30 days, 1, 2 and 3 years Cardiac Death at 30 days, 1, 2 and 3 years All cause MI at 30 days, 1, 2 and 3 years Target vessel MI at 30 days, 1, 2 and 3 years Clinically driven TVR at 30 days, 1, 2 and 3 years Clinically driven target lesion revascularization (TLR) at 30 days, 1, 2 and 3 years Acute Success Rates Device Success: Attainment of < 50% final residual stenosis of the target lesion using only Presillion plus Stent Systems. Lesion Success: Attainment of < 50% final residual stenosis of the target lesion using any percutaneous method. Procedure Success: Attainment of < 50% residual stenosis of the target lesion and no in-hospital death, MI, or TLR. Stent Thrombosis at hospital discharge, at 30 days, 1, 2 and 3 years.
Follow-up Visits and Length of Follow-up	Patients will be followed-up for 3 years. Follow-up will be performed at 30 days, 1, 2, and 3 years post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	74 subjects
Actual Number of Sites Enrolled	12 sites
Patient Follow-up Rate	93.2% (69/74)
Final Safety Findings	The rates [95% Confidence Interval] through 5 years were: Major Adverse Cardiac Events: 41.7% (30/72) [30.2%, 53.9%] Clinically driven target lesion(s) revascularization: 20.8% (15/72) [12.2%, 32.0%] All-cause mortality: 2.8% (2/72) [0.3%, 9.7%] Myocardial Infarction (MI) (ST-segment elevation MI and non-ST segment elevation MI): 27.8% (20/72) [17.9%, 39.6%] Stent Thrombosis: 2.8% (2/72) [0.3%, 9.7%] Acute: 0.0% (0/72) [0.0%, 5.0%] Sub-acute: 1.4% (1/72) [0.0%, 7.5%] Late: 1.4% (1/72) [0.0%, 7.5%] Very Late: 0.0% (0/72) [0.0%, 5.0%]
Final Effect Findings	The rate of cardiac death and MI through 5 years was 29.2% (21/72) [19.0%, 41.1%].
Study Strengths & Weaknesses	This study provides longer term (5 years) safety and effectiveness results of Presillion CoCr Coronary Stent RX System. The study had a low rate of attrition, thus minimizing selection bias. This study follows up the premarket cohort to provide earlier, descriptive information on long-term performance, as such the study had a small sample size and its results are descriptive. The generalizability of the results from this outside the United States population is limited to Israeli patients. This limitation is being addressed through the conduct of the second condition of approval study, ¿Enrollment of New US Cohort¿. The combined data will provide early information on long-term device performance and generalizable, statistically powered findings.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term (5-years) postmarket performance of the device.
General
Study Status	Other
Application Number / Requirement Number	P110004 / PAS002
Date Original Protocol Accepted	04/12/2012
Date Current Protocol Accepted	04/12/2012
Study Name	Enrollment of New US Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective multi-center, non-randomized, single arm clinical study designed to collect information about the safety and effectiveness of the NIRxcell CoCr Coronary Stent RX System in the treatment of de novo stenotic lesions in native coronary arteries in a newly enrolled US population.
Study Population	A sample size of 131 evaluable patients is needed to demonstrate that the NIRxcell CoCr Coronary Stent RX System TVF rate is less than 33% after three years (80% power and one-sided a=0.05). This sample size accounts for an expected loss to follow-up of approximately 7.5% per year. Patients will be enrolled from up to 15 sites in the USA.
Sample Size	see Study population
Key Study Endpoints	The primary effectiveness endpoint for this study is target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) [Q wave or non-Q wave], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 3 years post-procedure. The secondary safety endpoints are: All Death at 30 days, 1, 2 and 3 years Cardiac Death at 30 days, 1, 2 and 3 years All cause MI at 30 days, 1, 2 and 3 years Target vessel MI at 30 days, 1, 2 and 3 years Clinically driven TVR at 30 days, 1, 2 and 3 years Acute Success Rates Device Success: Attainment of < 50% final residual stenosis of the target lesion using only NIRxcell? Stent Systems. Lesion Success: Attainment of < 50% final residual stenosis of the target lesion using any percutaneous method. Procedure Success: Attainment of < 50% residual stenosis of the target lesion and no in-hospital death, MI, or TLR. Stent Thrombosis at hospital discharge, at 30 days, 1, 2 and 3 years.
Follow-up Visits and Length of Follow-up	Patients will be followed-up for 3 years. Follow-up will be performed at 30 days, 1, 2, and 3 years post-procedure.
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS007
Date Original Protocol Accepted	05/03/2005
Date Current Protocol Accepted	06/12/2012
Study Name	New England Bapt Hospital Joint Registry
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry study
Study Population	The study population is comprised of patients who receive the Duraloc Option hip in the post-market environment.
Sample Size	The sample size is 225 patients.
Key Study Endpoints	The primary endpoint is device revision.
Follow-up Visits and Length of Follow-up	The length of follow-up is 5 years Follow-up visits will occur per standard medical practice.
General
Study Status	Completed
Application Number / Requirement Number	P920015 S055/ PAS001
Date Original Protocol Accepted	01/09/2012
Date Current Protocol Accepted	11/22/2013
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Medtronic Post-Approval Network (PAN) is designed to conduct non-randomized, active prospective post-market Surveillance. The Registry is sponsored by Medtronic and is comprised of a global network of hospitals, clinics and clinicians from which reliable ¿real world¿ product safety and patient clinical outcome information is generated. Primary objective: To demonstrate that the complication- free probability is greater than 92.5% at five years post- implant for the high voltage DF4 connector.
Study Population	This study will consist of 1,778 patients implanted with a DF- 4 connector system, enrolled at one of approximately 150 centers globally. Subjects that meet the following inclusion criteria and do not meet any of the following exclusion criteria are eligible for enrollment. Inclusion Criteria ¿ Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements ¿ Subject is implanted with a DF-4 connector system. ¿ Subject within 30 days of implant Exclusion Criteria ¿ Subject who is, or will be inaccessible for follow-up at a site ¿ Subject with exclusion criteria required by local law (Europe, Central Asia [ECA] only) ¿ Complete implant and follow-up data, including any product-related events at implant through the time of enrollment are unavailable
Sample Size	Accounting for attrition, a minimum enrollment of 1778 DF4 connectors are estimated to be required in order to achieve the desired sample size for the primary objective analysis at five years.
Key Study Endpoints	A list of lead-related events eligible to be included in the primary objective: Failure to capture, Failure to sense/ Undersensing, Oversensing, Threshold rise, Abnormal pacing impedance, Abnormal defibrillation impedance (RV and/or SVC coil), Lead insulation breach, Lead conductor fracture, Extra cardiac stimulation, Lead dislodgement, Cardiac perforation, Structural Lead Failure.
Follow-up Visits and Length of Follow-up	Subjects will be followed for a minimum of 5 years from their implant date. Therefore, the expected duration of the DF4 PAS is approximately 7 years. Frequency of Follow-up Assessments Every 6 months
Interim or Final Data Summary
Interim Results	38.5%
Actual Number of Patients Enrolled	1778
Actual Number of Sites Enrolled	104
Final Safety Findings	The complication-free survival probability in this group was 98.6%.
Final Effect Findings	The sponsor presented Pacing Thresholds, Pacing and Defibrillation Impedance, and Sensing data for the subjects who remained in the study at 6 month intervals by lead type associated with the DF4 connector. The results confirm that the electrical performance of the DF4 connector leads is stable over time and within expected ranges.
Study Strengths & Weaknesses	A strength of this study is that the results reflect what is expected to be observed in routine clinical practice. A weakness includes the premature exit of some study sites and patients due to the longer-term nature of the study, thus limiting patient follow-up. Despite this barrier, the primary objective of the study was met, demonstrating the safety and efficacy of the DF4 connector.
Recommendations for Labeling Changes	Yes, completed.
General
Study Status	Completed
Application Number / Requirement Number	P080030 / PAS002
Date Original Protocol Accepted	06/25/2012
Date Current Protocol Accepted	05/13/2016
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Initial Phase: Prospective, randomized, concurrently controlled, parallel group, multicenter investigation Surgery consisting of implantation of one (1) GTS100 stent in conjunction with cataract surgery, or cataract surgery only 1:1 randomization plan (treatment group to control group) Washout of ocular hypotensive medications at Month 23 (if on medications) Follow-up through 3 years postoperative Revised Phase: Prospective, controlled, multicenter investigation Surgery consisting of implantation of one (1) GTS100 stent in conjunction with cataract surgery (treatment group) Surgery consisting of cataract surgery only in subjects randomized to control group in the GC-007 and GC-008 trials and the initial phase of GTS100-PAS2 (control group) Washout of ocular hypotensive medications at Month 23 (if on medications) Follow-up through 3 years postoperative
Study Population	Males or Females, 22 years of age or older
Sample Size	180 eyes of 180 subjects will comprise the treatment group. In addition, subjects randomized to cataract surgery only during the initial phase of this trial are included in the total study subject population. Subjects will be enrolled at a minimum of 20 sites and up to 45 sites; it is expected that about 400 subjects or more will undergo screening and baseline exams and operative procedures in order to obtain 180 eyes that received a GTS100 stent in conjunction with cataract surgery. With estimated rates of 0.03 (3%) for PT and PC at 5 years, a Type I error rate of 5%, a Type II error rate of 20% (i.e., 80% power), a randomization ratio of 1:1, 1-sided testing, a two-group large-sample normal approximation test of proportions, and a ? of 0.05 (i.e., a non-inferiority margin of 0.05 or 5%), the required sample size is 288 subjects (or 144 per group). Due to the age of the study population, it is estimated that the study will have a drop-out rate of 20%.
Key Study Endpoints	The primary endpoints will be the occurrence of STAEs. The STAEs include best corrected visual acuity (BCVA) loss greater than or equal to 3 lines, endophthalmitis, corneal decompensation, retinal detachment, severe choroidal hemorrhage, severe choroidal detachment, and aqueous misdirection. Other important ocular adverse events includes increase in intraocular pressure (IOP) of greater than or equal to 10 mmHg at any time postoperative, and loss of best spectacle corrected visual acuity of greater than or equal to 2 lines (greater than or equal to 10 letters) postoperative as compared to baseline or best recorded visual acuity measured at any visit postoperative. Additional safety events of interest include findings from IOP, best spectacle corrected visual acuity (BSCVA), visual field, pachymetry, and specular microscopy measurements, stent dislocation, stent migration, stent obstruction, secondary procedures, such as additional surgical procedures to lower IOP, and findings from slit-lamp, fundus and gonioscopic examinations. The effectiveness outcomes, although not the primary endpoint of this safety study, are the outcomes of mean diurnal IOP reduction greater than or equal to 20% vs. baseline IOP without ocular hypotensive medication, and mean diurnal IOP less than or equal to 18 mmHg without ocular hypotensive medication, at 24 months. The rate of these effectiveness outcomes will be compared between the treatment and control groups.
Follow-up Visits and Length of Follow-up	Three years Visit 1 Screening (day -60 to day -5) Visit 2 Baseline (after completion of appropriate medication washout period) Visit 3 - Operative Visit 4 6 Hours (+/- 4 hours) Visit 5 Day 1 (+1 day) Visit 6 Week 1 (7 +/- 2 days) Visit 7 Month 1 (4 weeks +/- 7 days) Visit 8 Month 3 (13 weeks +/- 14 days) Visit 9 Month 6 (26 weeks +/- 30 days) Visit 10 Month 12 (52 weeks +/- 30 days) Visit 11 Month 18 (78 weeks +/- 45 days) Visit 12 Month 23 (Minimum 4 weeks Prior to Month 24 Visit; 96 to 104 weeks) Visit 13 Month 24 (104 weeks +/- 28 days) Visit 14 Month 30 (130 weeks +/- 45 days) Visit 15 Month 36 (156 weeks +/- 45 days)
Interim or Final Data Summary
Actual Number of Patients Enrolled	357 subjects
Actual Number of Sites Enrolled	A total of 47 sites received IRB approval; 40 of the 47 were initiated
Patient Follow-up Rate	Accountability/follow-up rates were 86.5% (154/178) for the treatment group and 86.0% (148/172) for the control group at Month 36.
Final Safety Findings	The primary safety endpoint is the occurrence of sight-threatening adverse events (STAEs). A total of 51 STAEs were reported for 39 treatment subjects (21.3%) and 95 STAEs were reported for 59 control subjects (21.4%). 5 events of loss of BSCVA of 3 lines or more compared to baseline or best recorded visual acuity at any time postoperatively persisting at time of study exit were reported: 1 event involved 1 treated subject (0.5%), and 4 events were reported for 4 control subjects (1.4%). 6 events of IOP increase = 10 mmHg vs. baseline occurring = Month 1 were reported- 2 events for 2 treated subjects (1.1%) and 4 events for 3 control subjects (1.1%); all events resolved within ~4 months except one event in a control subject that was ongoing at study exit. Ten events of IOP increase requiring secondary surgical interventions (SSI) were reported. 3 events involved 3 treated subjects (1.6%) (3/183) and 7 events were reported for 6 control subjects (2.2%)(6/276). Statistical comparison of the STAE rate over 3 years is not statistically different between the groups. The slit lamp examination found no severe corneal edema during the study in any subject. There were no clinically meaningful changes in pachymetry between the groups. The proportion of eyes with a Visual Field mean deviation (MD) decrease of >2 dB was similar among groups: 19.1% (29/152) of stent eyes vs. 22.6% (33/146) of control eyes at Month 36. The proportion of eyes with Visual field pattern standard deviation (PSD) decrease of >2 dB was 5.9% (stent group) (9/152) and 10.3% (control group) (15/146) at Month 36. Specular microscopy showed that three subjects (2.9%) (3/102) in the stent group and 10 control subjects (7.2%) (10/138) had an average endothelial cell loss (ECL) >30% at Month 36. Otherwise, the percent change in average ECL from screening was similar in both groups and stable through the study conclusion aside from an initial reduction in both groups of approximately 10% at Month 3. Postoperative goniosynechiae were reported in 2 treatment eyes and 9 control eyes. A single transient angle abnormality was observed postoperatively in one treatment eye on Day 1 (hemorrhage covering the snorkel). 2 subjects who had stents that were visualized on Day 1 after implantation but after Week 1 were unable to be visualized again by gonioscopy. 1 of these stents was later visualized through Month 36 and the other until ~3 months prior to Month 36 with ultrasound biomicroscopy (UBM). Post-operative AEs also showed stent obstruction was reported for 6 subjects (3.3%)(6/183); 3 of these subjects had an IOP at Month 36 of 17.5mmHg or below without adjunct ocular hypotensive medications. 2 subjects required a single additional ocular hypotensive medication for IOP control, and the final subject had an IOP of 24.5 mmHg at Month 36 with ongoing stent obstruction on two ocular hypotensive medications.
Final Effect Findings	The effectiveness outcomes in this study included mean diurnal IOP reduction >= 20% versus baseline IOP without ocular hypotensive medication and mean diurnal IOP =< 18 mmHg without ocular hypotensive medication at 24 months in the treatment (cataract surgery with iStent) group compared to the control (cataract surgery only) group. The final findings revealed that 77.8% (123/158) of the cataract surgery with iStent group achieved mean diurnal IOP reduction >= to 20% without hypotensive medications compared to 42.7% (106/248) of the cataract surgery only group. In addition, 68.4% (108/158) of the cataract surgery with iStent treatment group achieved mean diurnal IOP <= 18 mmHg without ocular hypotensive medications compared to 33.5% (83/248) of the cataract surgery only group. Therefore, based on the observed rates, the treatment group (cataract surgery and iStent) had a higher rate of achieving both effectiveness outcomes and thus reduction in IOP after 24 months.
Study Strengths & Weaknesses	Strength: This was a new enrollment post approval study that provides further follow up and long-term safety data for the iStent with high rate of subject accountability for both the treatment (86.5%, 154/178) and control (86.0%; 148/172) groups. Weakness: The control group is comprised of three separate randomized groups, with one newly randomized group, and two groups from the prior study, such that there are differences among the control groups. In addition, there was a relatively large number of protocol deviations.
Recommendations for Labeling Changes	Given the significant clinical findings from the post approval study, it is recommended that the device label be updated with long-term device performance results regarding safety.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P080030 / PAS003
Date Original Protocol Accepted	06/25/2012
Date Current Protocol Accepted	07/21/2015
Study Name	Registry Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, single�]arm, multicenter registry of subjects implanted with GTS100 stents. Subjects will be followed for at least 3 months and up to 12 months from the date of implantation. The study will determine the rate of sight�]threatening adverse events for up to 6 months after surgery. The specific question this study will address is: What are the 3�]and 6�] month sight�]threatening adverse event rates after implanting the study device in conjunction with cataract surgery and the corresponding 95% confidence interval?
Study Population	Subjects with implantation of GTS100 in conjunction with cataract surgery.
Sample Size	Not specified
Key Study Endpoints	Sight�]threatening adverse events
Follow-up Visits and Length of Follow-up	3 months or until adverse events related to the study procedure are resolved or stable,
General
Study Status	Completed
Application Number / Requirement Number	P030054 S130/ PAS001
Date Original Protocol Accepted	05/10/2010
Date Current Protocol Accepted	05/10/2010
Study Name	QuickFlex u Model 1258T LV lead
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is designed to characterize the chronic performance of the St. Jude Medical QuickFlex® ì Model 1258T LV Lead.
Study Population	Study Population: Patients with an approved indication, as per cardiovascular society guidelines, for implantation of an ICD or CRT-D system for treatment of heart failure or life-threatening ventricular tachyarrhythmia(s). Indication: The device is indicated for the treatment of heart failure or life-threatening ventricular tachyarrhythmia(s).
Sample Size	1884 patients, 80 sites
Key Study Endpoints	Complication free survival rate at 5 years for complications related to the RV lead or SJ4 connector is greater than 92.5%. The following complications will be included in this analysis: Cardiac perforation, Lead dislodgement that occurred greater than 30 days after implant, Lead insulation damage, Lead fracture, Lead/Port damage, Abnormal RV lead performance (abnormal lead defibrillation impedance, abnormal lead pacing impedance, elevated pacing thresholds, loss of capture, loss of defibrillation output, loss of sensing, oversensing, undersensing), Other unexpected complications that are considered related to the RV lead or SJ4 connector
Follow-up Visits and Length of Follow-up	Patients will be followed every six months for 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	total of 1930 subjects were enrolled.
Actual Number of Sites Enrolled	76 study sites were enrolled.
Patient Follow-up Rate	Follow-up rate at 5 years is 73.2%.
Final Safety Findings	The LV lead-related complication free survival KM probability at 5 year is 94.5% with Lower Confidence Bound of 93.3% which is above the accepted boundary of 92.5%. • 542 deaths were reported during the study. All deaths were adjudicated. 174 deaths were determined to be “Cardiac” while 190 deaths were “Non-Cardiac” and 178 deaths were “Unknown” (178). None of the deaths were reported as LV lead-related • LV lead related complication rates: o The complication rate of lead dislodgement or migration occurred after 30 days from implant is 2.2% which is lower than the expected rate of 3.5%. o The complication rate of diaphragmatic or phrenic nerve simulation is 0.8% which is lower than the expected rate of 1.7%. o The complication rate of loss of capture is 0.5% which is slightly higher than the expected rate of 0.4%. o All other complications rates are less or equal to expected rate of 0.4%: abnormal LV lead performance (0.2%; lead fracture (0.1%); elevated pacing threshold (0.4%); lead insulation damage (0.1%; and all other unexpected LV related complications (0.2%) o No complication of cardiac or coronary sinus perforation is reported.
Final Effect Findings	The mean LV bipolar pacing capture threshold at 0.5ms pulse width was 2.04±1.60V with a 95% CI of 1.93V to 2.16V) (N=774) at 5 years which is within the expectation criteria of less than 3.5V.
Study Strengths & Weaknesses	Strength: The QuickFlex u Model 1258T LV lead post approval study provided 5-year follow-up long term safety and effectiveness data. The primary study endpoints formally evaluated with hypothesis testing and all primary endpoints performance goals were met. Stratified female and male subgroup complication analysis was provided. Weakness: The study weakness is the low sample size of 433 subjects at risk who completed 5- year follow-up, which does not meet the required sample size of 645 patients (500 minimum) for the LV lead related complications rate hypothesis testing.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post- approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Terminated
Application Number / Requirement Number	P090012 / PAS001
Date Original Protocol Accepted	11/01/2011
Date Current Protocol Accepted	10/22/2014
Study Name	PAS of MelaFind
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multicenter, prospective, observational, single arm, post- approval study of MelaFind, which will enroll lesions that meet the labeled Indications for Use. Dermatologists¿ biopsy decisions before and after obtaining MelaFind results will be recorded. Biopsy specimens will undergo central dermatopathology review to determine whether the lesion is melanoma, high-grade, or another type of lesion. Patient follow- up will extend out to 24 months.
Study Population	All patients of any age, race, ethnicity, or gender, presenting with pigmented skin lesions that meet the Indications for Use and lesion Inclusion and Exclusion Criteria, including signing the Informed Consent Form, are eligible to participate in this study. Up to six clinical sites in the US will participate in this study. Three of the sites will be located in urban settings, and three will be located in a suburban or rural setting. At least 50% of the sites will be new, i.e., they did not participate in the MelaFind pivotal study. Some sites will be academic centers and some private practices.
Sample Size	It is anticipated that at least 78 patients with one or more eligible and evaluable histologically-confirmed melanoma and or high-grade lesion will be enrolled.A total of 720 patients and a total number of lesions to range from 720 up to about 3600 are expected to be enrolled in the study.
Key Study Endpoints	The primary objective of this study to test the hypothesis that, among eligible and evaluable lesions with central histological reference standard status melanoma or high-grade lesion, the relative sensitivity ñ comparing enrolling dermatologists after MelaFind use with enrolling dermatologists if MelaFind were not available is greater than 110%.. Secondary Objectives Real-World Use of MelaFind 1. To describe characteristics of patients with lesions imaged with MelaFind, including age, gender, race, ethnicity, and Fitzpatrick skin type 2. To describe characteristics of lesions imaged with MelaFind, particularly the proportion of such lesions that meet the labeled Indications for Use 3. To describe the experience oF/Using MelaFind to image lesions, particularly: a. Number of imaging attempts b. Proportion of lesions for which an image that passes automatic image QC algorithms is not obtained (non-evaluables) 4. To describe the distribution of MelaFind test results (positive, negative) among lesions with images that pass automatic image QC algorithms Safety and Effectiveness of MelaFind 5. To describe the proportion of lesions that are biopsied among lesions with positive MelaFind test results, among lesions with negative MelaFind test results, and among non-evaluables (lesions with images that do not pass automated QC algorithms) 6. Among biopsied lesions: a.To describe biopsy results based on central histological reference standard (melanoma, high-grade lesion [high-grade dysplastic nevus, atypical melanocytic hyperplasia proliferation], other) among lesions with positive MelaFind test results, among lesions with negative MelaFind test results, and among non-evaluables b. To estimate sensitivity of MelaFind to melanomas and high-grade lesions, based on central histological reference standard c. To estimate specificity of MelaFind for non-melanomas and non-high- grade lesions, based on central histological reference standard 7. To describe lesion management decisions of dermatologists before and after MelaFind evaluations: a. For all lesions: among non-evaluable lesions, among evaluable lesions with positive MelaFind test results, and among evaluable lesions with negative MelaFind test results b. For eligible and evaluable lesions that are neither melanomas nor high-grade lesions: ratio of false-positive fraction (FPF) after MelaFind evaluation to FPF if MelaFind were not available. c. For biopsied lesions: true positives, true negatives, false positives, false negatives, and biopsy ratios (number of false positives for each true positive) d. For biopsied lesions: ratio of false-positive fraction after MelaFind evaluation to false-positive fraction if MelaFind were not available (relative false-positive fraction) e. For biopsied lesions: ratio of biopsy ratio after MelaFind evaluation to biopsy ratio if MelaFind were not available (relative biopsy ratio) 8. Among lesions without biopsy after 2-year follow-up, describe the results of all available MelaFind evaluations
Follow-up Visits and Length of Follow-up	Patient follow-up will extend out to 24 months. Patients with lesions evaluated with MelaFind during the enrollment period, but not biopsied at that time, will be scheduled for follow-up appointments at 1 year ±3 months and 2 years ±3 months. If a patient returns to the clinic for a lesion examination anytime between enrollment and the 2 year follow-up visit, per the dermatologists standard of care, follow-up visit data will be collected and analyzed as described in the statistical analysis section.
Interim or Final Data Summary
Actual Number of Patients Enrolled	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Actual Number of Sites Enrolled	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Patient Follow-up Rate	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Final Safety Findings	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Final Effect Findings	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Study Strengths & Weaknesses	The PAS was terminated because the original device was modified in both software and firmware. The safety and effectiveness of the modified device were supported by a reader study, and the changes were approved in PMA supplements (P090012/S010, and P090012/S011) in 2016
Recommendations for Labeling Changes	Labeling update is not needed. The updated User Guide (dated 8/17/2016) already presents relevant instructions on the most recent device model available in the commercial setting.
General
Study Status	Completed
Application Number / Requirement Number	P090013 S202/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. ¿ Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P090013 S205/ PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted
Study Name	PCT Change Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will be conducted within Medtronic’s Product Surveillance Registry (PSR). The PSR platform is designed to conduct non-randomized, active, prospective post-market surveillance. Patients implanted with a MR Conditional CIED system and enrolled in the PSR will be followed per the expected standard of care practice of their care provider. Pacing capture thresholds (PCT) measurements of MR conditional CIED systems enrolled in the PSR will be used to prospectively monitor changes in PCT following 3T MR exposure. Patient status is collected approximately every 6 to 12 months including MRI scan information, if applicable. Sites will report patient baseline information (e.g. height, weight, etc.) the occurrence of a medically indicated MRI scan, reason for scan, anatomical region scanned, magnet strength, and MRI related events. Analysis of the primary objective will be performed 4-years following approval
Study Population	All patients implanted with a MR Conditional CIED system and enrolled in the PSR who subsequently receive an MRI scan using a 3T system within the 4-years post approval that meets approved labelling requirements.
Sample Size	The following assumptions were used to estimate the PAS duration and number of 3T scans projected to be obtained during the 4-years study period: MR Conditional CIED enrollment of approximately 2,400 patients Annual MRI scan rate of 9% Participating sites with 3T scanning capability: 25% - 40% % of patients with a 3T MRI scan: 30% - 45% Table 3: 3T Scan Rate Assumptions Over 4-Year Study Duration Assumptions Year 1 Year 2 Year 3 Year 4 Cumulative MR Conditional Enrollments (*) 1260 1674 2047 2382 Cumulative # of completed MRI Scans 113 264 450 571 Assumption for % centers with 3T capability 25% 25% to 40% % MR scans through 3T in these centers 30% 30% - 45% Cumulative # of completed 3T scans 9 43 to 103 (*) Assumes a 10% annual attrition Contribution from enrollments outside the US to the primary objective will be limited to no more than 50% of the total sample size.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of patients implanted with an MR conditional CEID system with a pre to post MRI scan PCT measure change of more than 0.5 V following 3T scan exposure. Definitions for pre and post PCT measurements Pre-MRI PCT measure: max PCT value preceding the SureScan mode enabled and prior to the 3T MRI scan Post-MRI PCT measure: 1st max PCT measurement at a time point >30 days (chronic PCT) following 3T MRI exposure. Further investigation will be carried out to identify root cause if the observed proportion of PCT changes following 3T scan exposure is greater than 8% (i.e. 2X the observed proportion in the PSR SureScan data) and more than 50% of those observed >0.5V PCT changes reflect an increase.
Follow-up Visits and Length of Follow-up	4 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	8388
Actual Number of Sites Enrolled	191
Final Safety Findings	One patient showed a ¿PCT greater than 0.5V within the analysis window. As this does not meet the 8% threshold proportion of patients and/or scans with a greater than 0.5V change pre- to post-3T MRI, no additional comparative analyses were performed. No adverse events, deaths, or device deficiencies related to 3T scan.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The primary endpoint was acceptable. The results are favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P150030 / PAS001
Date Original Protocol Accepted	10/17/2016
Date Current Protocol Accepted	08/21/2020
Study Name	Long-Term F/u of EU patients PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multicenter, observational study that is currently in the follow-up data collection phase. Five of the seven study sites that contributed data to the PMA cohort will participate in this PAS.
Study Population	All subjects in the investigational group of the PMA Cohort excluding one patient who died and one patient who was revised.
Sample Size	A total of 135 subjects will be followed.
Key Study Endpoints	The primary endpoint is implant survivorship at 10 years post study procedure. Secondary endpoints include the following: Patient outcomes as measured using the modified Harris Hip Score; Radiographic evaluation to assess radiographic success defined as: No radiolucencies greater than 2 mm in 50% or more in any of the cup or stem zones; and No femoral or acetabular subsidence greater than or equal to 5mm from baseline; and No acetabular cup inclination changes greater than 4 degrees (4°)
Follow-up Visits and Length of Follow-up	Patients will be followed for 10 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	135 hips
Actual Number of Sites Enrolled	5 sites
Patient Follow-up Rate	The 10-year follow-up rate for subjects with all primary and secondary endpoints data is 78.6% (99/126).
Final Safety Findings	A total of 130 hips had adverse event data by 10 years of follow-up. There were 14 device-related adverse events (AEs) in 6.2% (8/130) of hips. At 10-year follow-up, 1.5% (2/130) of patients were revised for loosening (one hip was revised for cup loosening failure and one hip was revised for stem loosening failure). There were 24 procedure- related AEs that occurred in 14.6% (19/130) of the hips. The most frequently reported device- and procedure-related AEs were pain, hip discomfort, soreness, and heterotopic ossification.
Final Effect Findings	Survivorship: At 10-years post-surgery, Kaplan-Meier implant survivorship is estimated as 0.98 (95% Confidence interval: 0.950, 1.000). Functional Outcomes: At 10-years of follow up, 89.7% (105/117) of patients were reported to have ‘Excellent’ or ‘Good’ modified Harris Hip Score (mHHS) (score >80) and 3.4% (4/117) were reported to have ‘Poor’ mHHS (score 60-69). Radiographic Outcomes: At 10-years post-surgery, radiographic success was reported 95.1% (97/102).
Study Strengths & Weaknesses	Strength: The study was able to demonstrate long-term device safety and effectiveness through 10 years post-surgery. Weaknesses: The loss to follow-up and missing data (e.g., radiographic, mHHS, and AEs). The results may not be generalizable to US patients or practice (OUS study population).
Recommendations for Labeling Changes	Yes, a labeling change is recommended to update the device labeling with the final study results. Labeling update can identify the impact of protocol deviations including those resulting from COVID-19 (e.g., partial data collection or missing data on device safety and effectiveness).
General
Study Status	Completed
Application Number / Requirement Number	P090013 S225/ PAS001
Study Name	MR conditional Tachy Therapy Systems Stud
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P080030 / PAS001
Date Original Protocol Accepted	06/25/2012
Date Current Protocol Accepted	03/05/2013
Study Name	Extended F/u of IDE Cohort Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Extended follow-up of subjects previously enrolled in Glaukos Study GC-003; Follow-up through 5 years postoperative
Study Population	¿ Inclusion Criteria: Subjects previously enrolled in Glaukos Study GC-003 who are able and willing to participate in this extended follow-up study; ¿ Exclusion Criteria: o Subjects previously enrolled in Glaukos Study GC-003 who are not able or willing to participate in this extended follow- up study o Patients not previously enrolled in Glaukos Study GC-003 Device subjects received the Glaukos iStent in conjunction with cataract surgery and controls subjects received cataract surgery alone.
Sample Size	Of 290 subjects enrolled in Study GC-003, extended follow-up is planned on subjects eligible to participate in this extended follow-up study.
Key Study Endpoints	The safety measurement listed in the outline section as: ¿ Postoperative ocular adverse events ¿ Findings from OR medication use, BSCVA, VF measurements and pachymetry ¿ Findings from slit-lamp, fundus and gonioscopic measurements
Follow-up Visits and Length of Follow-up	5 years postoperative. 2 years from completion of the IDE study Annual
Interim or Final Data Summary
Actual Number of Patients Enrolled	108
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	Only 42.35% (108/255) enrolled at the beginning of the IDE cohort continuation study. Of those 108 subjects enrolled, 100% of subjects were followed through the fifth year post procedure.
Final Safety Findings	Kaplan-Meier (K-M) analyses for the sight-threatening adverse event rate at 5 years are provided by randomized groups: all eyes with cataract surgery and iStent versus randomized cataract surgery only. The cumulative Kaplan-Meier probability that a patient experienced a sight-threatening adverse event is 26.0% (95% CI 15.6%, 36.3%) in the randomized cataract surgery with stent group (stent group) and 42.8% (95% CI 27.9%, 57.8%) in the cataract surgery only group (control group). These results indicate that the stent group is non-inferior to the control group (p=0.009). Based on the upper 1-sided 90% confidence limit (CL), the stent group has a lower incidence of sight-threatening adverse events than the control group. Analyses presented for the comparison of all eyes with cataract surgery and iStent versus randomized cataract surgery only provide cumulative Kaplan-Meier probability that a patient experienced a sight-threatening adverse event is 28.5.0% (95% CI 19.6%, 37.4%) in the Overall Cataract Surgery with iStent (stent group) and 42.8% (95% CI 27.9%, 57.8%) in the Randomized Cataract Surgery Only (control group). These results indicate that the stent group is non-inferior to the control group (p=0.015). Based on the upper 1-sided 90% confidence limit (CL),the stent group has a lower incidence of sight-threatening adverse events than the control group.
Final Effect Findings	This study does not include any effectiveness endpoints
Study Strengths & Weaknesses	Strength: The continued IDE study is an observational study with a clinical trial design with longer term follow-up of safety data. Weakness: The enrollment rate from the premarket cohort for the eligible subjects is only 42%. The low enrollment rate could introduce bias to the study.
Recommendations for Labeling Changes	As a result, upon completion of the post approval studies with significant clinical findings, labeling changes is recommended to update the labeling with long-term device performance results regarding safety
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS002
Date Original Protocol Accepted	04/20/2010
Date Current Protocol Accepted	04/20/2010
Study Name	Prospective Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Prospective Post-Approval Study is a single-arm observational study
Sample Size	Approximately 100 qualified subjects, at up to 10 centers, previously enrolled in the original prospective post-approval study will be longitudinally followed after their primary total hip replacement surgery.
Key Study Endpoints	Clinical data (hip function), radiographic evaluations, an outcomes questionnaire, and subject self-assessment information was/will be collected for each subject. Key endpoints include device survival, Harris Hip Score, and radiographic assessment.
Follow-up Visits and Length of Follow-up	The length of follow-up for this study is 5 years. A quality of life survey (SF-12) was/will be completed by the subject for all post-operative visits up to the 5-year follow-up interval. The Subject Outcomes Questionnaire was/will be completed by the subject at the one year follow-up interval and annually after that up to the 5-year follow-up interval. The (modified Harris) Hip Function Evaluation was/will be used to clinically assess each subject pre-operatively, and at 6 weeks, 6 months, and annually for five years postoperatively. High quality anteroposterior pelvis (AP-pelvis) and lateral radiographs of the operative hip were/will be obtained during the same postoperative follow-up intervals as for the clinical evaluations.
General
Study Status	Terminated
Application Number / Requirement Number	P040023 / PAS003
Date Original Protocol Accepted	04/20/2010
Date Current Protocol Accepted	04/20/2010
Study Name	DePuy Outcome Tracking Sys Registry(DOTS)
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry study
Sample Size	Approximately 80 subjects at multiple clinical sites who have previously received a DURALOC Option implant will be longitudinally followed after their primary total hip replacement surgery.
Key Study Endpoints	DePuy will provide annual reports from the DOTS registry patients and provide these reports to the FDA in annual progress reports. DePuy will provide the following information: ¿ Femoral Stem types ¿ The years in which the surgeries were performed ¿ Patient demographic summaries (age, gender, diagnosis, height, weight, BMI) ¿ Patient listing of reasons for revisions ¿ Revision rate ¿ Death rate ¿ Kaplan-Meier survival estimates ¿ Harris Hip Score over time ¿ Adverse Events ¿ Radiographic results
Follow-up Visits and Length of Follow-up	The length of follow-up for this study is 5 years.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P090018 / PAS002
Date Original Protocol Accepted	03/17/2010
Date Current Protocol Accepted	03/18/2016
Study Name	New Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Post-Approval Study is similar to the PMA pivotal clinical trial, which was designed as a prospective, multi-center, non-randomized, clinical trial to evaluate the safety and efficacy of the Esteem® System. For this trial the subject acts as his or her own control.
Study Population	Subjects 18 years of age and older who have moderate to severe sensorineural hearing loss (HL) defined by PTA, have a healthy middle ear, have an unaided speech discrimination score of equal to or better than 40%, and have previously worn a hearing aid for a minimum of 30 days are eligible for inclusion in the Post Approval Study. Inclusion Criteria Subject must meet all of the following criteria to be eligible for treatment in the trial: a) Subject is ≥ 18 years old b) Subject understands the nature of the procedure and has signed the Subject Informed Consent Form prior to the procedure c) Subject is willing and able to comply with specified follow-up evaluations and understands the audiological test procedures and use of the Esteem® System. d) Subject has moderate to severe sensorineural hearing loss in the ear to be implanted defined by pure tone average air-conduction threshold level. e) Subject has an unaided maximum word recognition score of greater than or equal to 40% with recorded delivery using a phonetically balanced word list at SRT + 40 dB or at maximum tolerable presentation level. f) Subject is a current user of a properly functioning and appropriately fit hearing aid for at least one (1) month in the ear to be implanted. g) Subject has normally functioning eustachian tube h) Subject has normal tympanic membrane i) Subject has a normal middle ear anatomy j) Subject has adequate space for Esteem® System implant determined via fine cut temporal bone CT scan k) Subject is a native speaker of the English language. Exclusion Criteria Subjects will be excluded from the trial if any one of the following criteria is met: a. Subject has a history of post-adolescent chronic middle ear infections, inner ear disorders or recurring vertigo requiring treatment, disorders such as mastoiditis, Hydrops or Meniere¿s syndrome or disease b. Subject has a history of otitis externa or eczema for the outer ear canal and the investigator believes this will affect the Esteem® System implantation c. Subject has cholesteatoma or destructive middle ear disease d. Subject has life expectancy of < two (2) years due to other medical conditions e. Subject has retrocochlear or central auditory disorders f. Subject is known to be suffering from any psychological, developmental, physical, or emotional disorder that the investigator feels would interfere with the surgery or follow-up testing g. Subject has a known history of fluctuating air conduction and/or bone conduction hearing loss over a one-year period of 15 dB in either direction at 2 or more frequencies (from 500 ¿ 4000 Hz) h. Subject has sudden hearing loss due to unknown cause i. Subject has a history of disabling tinnitus, defined as tinnitus which required treatment. j. Subject is unable to adequately perform audiological testing k. Subject has a medical condition or undergoing a treatment that may affect healing and the investigator does not believe the subject is a good candidate for the trial. l. Subject has diabetes that is not well controlled with medication or diet and the investigator does not believe in his best medical judgment that the subject would be a good candidate for the trial m. Subject is pregnant at the time of device implant n. Subject has a history of keloid formation o. Subject has known hypersensitivity to silicone rubber, polyurethane, stainless steel, titanium and/or gold
Sample Size	A minimum total of 120 new subjects will be enrolled and implanted in this study by newly trained surgeons at 5 to 10 investigational sites on a consecutive consenting basis. For the effectiveness objectives, based upon the following analysis and pre-market clinical data, a sample size of 45 new subjects meets the guidelines for statistical power. For the facial pareses/paralysis objective with an end point of 1 month, a sample size of 109 subjects is required as shown below. As a result, the sample size enrollment of 120 subjects is adequate to assure minimums that account for attrition through 5 year follow-up for effectiveness and 1 month follow-up for facial pareses/paralysis.
Key Study Endpoints	1) To demonstrate that the Esteem® System improves the speech threshold of sensitivity for hearing and identifying speech signals as well as or better than the pre-implant hearing aid (aided condition). Endpoint: Comparison of the speech reception threshold (SRT) using the Esteem® System as compared to the pre-implant aided condition. 2) To demonstrate that the Esteem® System is as effective as or better than the hearing aid for improving speech discrimination (intelligibility). 3) To determine the incidence of Serious Adverse Device Effects. Endpoint: The analysis of the incidence of SADEs and device failures and replacements at each follow-up. 4) To demonstrate that the incidence of facial pareses/paralysis is no greater than the 7% incidence experienced in the PMA clinical trial. Endpoint: The analysis of the incidence of facial pareses/paralysis at 1 month follow-up. Secondary Objectives:
Follow-up Visits and Length of Follow-up	The goal will be to monitor the subjects through their five (5) year follow-up. Patients will be evaluated at screening, implantation, activation, 1 month, 4 months, 10 months post-implant and yearly thereafter.
General
Study Status	Completed
Application Number / Requirement Number	P090018 / PAS003
Date Original Protocol Accepted	04/16/2010
Date Current Protocol Accepted	02/24/2020
Study Name	Esteem New Enrollment 2
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a new enrollment study. It is a prospective, non-randomized, multicenter study, and it aims to evaluate the safety and efficacy of the device implanted by newly-trained surgeons in subjects suffering from moderate to severe hearing loss.
Study Population	Subjects 18 years of age and older who have moderate to severe sensorineural hearing loss (HL) defined by Pure Tone Average (PTA), have a healthy middle ear, have an unaided speech discrimination score of equal to or better than 40%, and have previously worn a hearing aid for a minimum of 30 days are eligible for inclusion in the Post Approval Study.
Sample Size	120 subjects in 5 to 10 investigational sites. The sample size is based on testing the following hypothesis: Facial Pareses/paralysis: Based upon a null hypothesis of 7% and a hypothesized true rate of 2% of facial paresis/paralysis, 109 subjects at 1 month would provide at least 80% power for testing the hypothesis.
Key Study Endpoints	To demonstrate that the Esteem® System is as effective as or better than the hearing aid for improving speech discrimination (intelligibility) as shown by the word recognition score at 50 dB. Primary Endpoints: 1) Comparison of the speech reception threshold (SRT) using the Esteem® System as compared to the pre-implant aided condition. 2) Comparison of word recognition score using the Esteem® as compared to the pre-implant aided condition. 3) The analysis of the incidence of SADEs and device failures and replacements at each follow-up. 4) The analysis of the incidence of facial pareses/paralysis at 1 month follow-up. 5) Comparison of the bone conduction threshold with forehead placement compared to the pre-implant bone conduction threshold. Secondary Endpoints: 1) To show that the Esteem® System improves Quality-of-Life when compared to the baseline aided condition as shown by APHAB scores. 2) To gather subject feedback and comments on the use of the Esteem® System relative to the pre-implant hearing aid (aided condition) as shown by the Esteem® Questionnaire.
Follow-up Visits and Length of Follow-up	The subjects will be followed for 1 year. Device will be activated during activation visit (8weeks+/- 2week post implant. Subjects will be followed at 1, 4 and 10 months post-activation.
Interim or Final Data Summary
Actual Number of Patients Enrolled	59
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	85% at 4-month timepoint, 84% at 10-month timepoint
Final Safety Findings	Serious Adverse Events Two adverse events were reported as serious adverse events. One event was related to extensive fibrotic tissue discovered after the patient reported diminished performance with the device. This device was explanted. The other event was related to persistent acoustic feedback, which was resolved when the patient received a new external processor. There were three other serious adverse events adjudicated to be procedure, and not device-related, and therefore removed from the safety analysis. These three events were reported to be due to infection, and the devices were ultimately explanted. Facial Nerve Injury A total of 110 Subjects contributed to this endpoint. There were three reported events of facial paresis/ weakness. All three reported events resolved with no residual side effects. There were no reported events of facial paralysis or lasting facial paresis. Statistical analysis shows the incidence of facial paresis/paralysis is no greater than was reported in original Esteem PMA pivotal clinical trial.
Final Effect Findings	Final effectiveness findings (key endpoints): Speech Reception Threshold (SRT) This co-primary effectiveness endpoint is a comparison of the speech reception threshold (SRT) using the Esteem as compared to the pre-implant aided condition. Both non-inferiority and superiority hypotheses were evaluated. Mean improvement at the 4-month timepoint was 1.1 dB, and 5.3 at the 10-month timepoint. In total, 72% of subject SRTs improved or were the same at the 4-month timepoint, and 78% improved or were the same at the 10-month timepoint, meeting the non-inferiority criterion. Neither timepoint met the superiority criterion. Word Recognition Score This co-primary effectiveness endpoint is a comparison of the word recognition score using the Esteem compared to the word recognition score in the preimplant aided condition at 50 dB. Both non-inferiority and superiority hypotheses were evaluated. The mean difference for WRS at the 4-month timepoint was -4.7% and for the 10-month timepoint it was -2.2%. In total, at the 4-month time point 80% of subjects performed better or the same compared to their hearing aid, and 84% at the 10-month timepoint. Both of these values are greater than the -10 criterion set for non-inferiority. Neither timepoint supported a superiority claim.
Study Strengths & Weaknesses	This study met its non-inferiority criterion for effectiveness, but not the superiority criterion. The safety endpoints were also met, though throughout the study duration there were inconsistences in designation of serious adverse events. Due to a slow rate of enrollment, the study modified it’s long-term endpoint from 5 years to 1 year, which limits interpretation of long-term safety and effectiveness.
Recommendations for Labeling Changes	The labeling should be changed to reflect the final study results for each endpoint. The sponsor should add results from the safety (i.e., facial paresis) and effectiveness endpoints out to 1-year (SRT and WRS endpoints).
General
Study Status	Ongoing
Application Number / Requirement Number	P150026 / PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted	07/01/2020
Study Name	PAS of HeartLight Endoscopic Ablation Sys
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to evaluate the long-term safety and effectiveness of the device in a commercial population and to clarify the safety profile of the device among females. This will be accomplished through a new enrollment prospective single-armed study.
Study Population	The study population will be subjects clinically eligible for the treatment of paroxysmal atrial fibrillation with the HeartLight Endoscopic Ablation System.
Sample Size	250 subjects will be enrolled at up to 25 sites in the US, and a minimum 135 of those subjects will be female, will accommodate the hypothesis testing with 80% power and an alpha of 0.025 for each of the hypotheses.
Key Study Endpoints	The primary effectiveness endpoint will be freedom from symptomatic Atrial Fibrillation at one-year, and will be compared to a performance goal of 55% of subjects free from symptomatic AF at one year. The primary safety outcome for the entire cohort will be the percentage of subjects experiencing a Primary Adverse Event by one-year of follow-up, and will be compared to a performance goal of PAE rate of 14% at one year. The same safety outcome will be assessed for females with the same performance goal. Longer term (three year) safety and effectiveness will be assessed as secondary outcomes. The long-term effect of operator experience will also be assessed as a secondary outcome. If there are gender differences in safety outcomes, the factors contributing to these differences will be evaluated as secondary outcomes.
Follow-up Visits and Length of Follow-up	Three years All subjects will undergo clinical follow-up pre-discharge, at 30 days, 90 days, 12 months, 24 months, and 36 months.
Interim or Final Data Summary
Interim Results	Safety Results There have been no unanticipated adverse events. The number of participants with at least one AE is 46 (40.0%), with 14 having a serious event. There have been 2 deaths. Effectiveness Results Overall, acute success is 94.2%.
Actual Number of Patients Enrolled	124
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	Follow-up rate remains adequate.
General
Study Status	Completed
Application Number / Requirement Number	P090029 S003/ PAS001
Study Name	10 Year Extended f/u of IDE Subjects
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	10 Year Extended Follow-up of IDE Subjects Treated with the PRESTIGE LP™ Cervical Disc at Two Contiguous Levels is a 10-year post-approval study (PAS) to evaluate the longer term safety and effectiveness of the PRESTIGE LP™ Cervical Disc. This study has a multi-center, prospective, randomized, controlled design. The bi-level ACD-LP treatment will be compared to the control treatment, a bi-level anterior cervical fusion procedure involving cortical ring allograft and the ATLANTIS® Cervical Plate System.
Study Population	Patients who have been diagnosed with symptomatic cervical degenerative disc disease at two adjacent levels (from C3-C7) according to the specified inclusion/exclusion criteria as stated in the protocol (Version G).
Sample Size	397 subjects treated in the pivotal investigational device exemption (IDE) study (209 2-level PRESTIGE LP™ subjects and 188 2-level ACDF control subjects)
Key Study Endpoints	The primary endpoint was (individual subject) overall success at 24 months, a composite variable which included safety and effectiveness considerations, and was defined as follows: 1. Postoperative Neck Disability Index (NDI) score improvement of at least a 15-point increase from preoperative; 2. Maintenance or improvement in neurological status; 3. No serious adverse event classified as implant associated or implant/surgical procedure associated (as determined by an independent clinical adjudication committee); and 4. No additional surgical procedure classified as a “failure. Secondary endpoints, measured in both treatment groups, included neck pain, arm pain, quality of life (SF-36 Physical Component Score [PCS] and Mental Component Score [MCS]), gait assessment (Nurick’s classification), subject satisfaction, subject perceived effect, physician perception of results, radiographic success (defined differently in the two treatment groups), range of motion, Functional Spinal Unit (FSU) height, implant condition, heterotopic ossification, and return to work.
Follow-up Visits and Length of Follow-up	120 months (+/-3 months)
Interim or Final Data Summary
Actual Number of Patients Enrolled	181 subjects in the Investigational (INV) cohort (down from 209 enrolled in the IDE trial due to clinical sites not participating at 120 months); 160 subjects in the Control (CTR) cohort (down from 188 enrolled in the IDE trial)
Actual Number of Sites Enrolled	19 investigational sites
Patient Follow-up Rate	INV follow-up rate was reported as 86.0% at 120 months; CTR follow-up rate was reported as 84.9% at 120 months
Final Safety Findings	There was no difference in the risk of subjects experiencing an adverse event between the INV group and the CTR group. There were fewer subjects experiencing a secondary surgical intervention in the INV group compared to the CTR group
Final Effect Findings	Bayesian analyses shows a posterior probability of non-inferiority of essentially 100% and a posterior probability of superiority of 99.9% for overall success of the INV group compared to the CTR group.
Study Strengths & Weaknesses	This Extended Follow-up study successfully demonstrated superiority of the 2-level Prestige LP disc compared to the 2-level ACDF control group. While the closure of several clinical sites introduce a potential source of bias related to possible clinical differences between patients in the 120 month PAS group and patients not participating, an analysis of the baseline demographic data and last observed effectiveness outcomes for missing subjects compared to subjects observed at 120 months indicate that there is no statistically significant difference between groups. Additional results of a tipping point sensitivity analysis show that the non-inferiority and to a lesser degree the superiority conclusions, are robust to the missing data.
Recommendations for Labeling Changes	Labeling changes were recommended to reflect the 120 month outcomes.
General
Study Status	Completed
Application Number / Requirement Number	P090029 S003/ PAS002
Date Original Protocol Accepted	02/13/2018
Date Current Protocol Accepted	07/12/2019
Study Name	PRESTIGE LP 2-Level Metal Concentrations
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	a one-arm cohort study
Study Population	Patients diagnosed with degenerative disc disease and two (2) contiguous levels in the cervical spine from C3 to C7 and implanted with Prestige LP
Sample Size	30 subjects
Key Study Endpoints	The main study end-point is assessment of metal concentrations (titanium, vanadium, and aluminum) and their changes over time in blood serum. Additional Study endpoints are as follows: Overall success rate with overall success defined as: NDI score improvement of at least 15 points from baseline Maintenance or improvement in neurological status No serious AE classified as implant associated/related or implant/surgical procedure associated/related No secondary surgical procedure classified as a treatment “failure” o Neck Disability Index (NDI) score improvement from baseline; o Neurological Status change from baseline o Neck and Arm Pain score change from baseline o Safety of the PRESTIGE LP™ Cervical Disc as reported through AEs and secondary surgeries.
Follow-up Visits and Length of Follow-up	12 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	25 subjects enrolled, 26 subjects have been treated and in follow-up. (8 subjects failed screening, 1 dropped out)
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	72% @ 3mo; 68% @ 6mo; 79.2% @ 12mo.
Final Safety Findings	No major safety concerns observed from limited study
Study Strengths & Weaknesses	Protocol modified to increase enrollment results in some confounding factors, small sample size. COVID19 pandemic also introduced follow-up challenges and reduced data points.
General
Study Status	Completed
Application Number / Requirement Number	P090029 / PAS001
Date Original Protocol Accepted	07/24/2014
Date Current Protocol Accepted	07/24/2014
Study Name	Extended Follow-Up
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	280 subjects in the Investigational (INV) cohort, 30 in the Metal Ion cohort, and 24 in the Continued Access cohort.
Actual Number of Sites Enrolled	20 clinical sites have received IRB approval, 15 of them have been enrolled.
Patient Follow-up Rate	INV follow-up rate was reported as 82.2% and 90.9% for 84 months (± 3 months) and 120 months (± 6 months), respectively.
Final Safety Findings	No alarming safety trends were identified. However, there is a need to further address higher cumulative rate for vascular adverse events in INV group vs. controls and explore its possible reasons other than by a chance finding.
Final Effect Findings	Bayesian analyses showed a posterior probability of non- inferiority of essentially 100.0% and a posterior probability of superiority of 98.5% for overall success without Functional Spine Unit (FSU) and a posterior probability of non-inferiority of 94.5% with FSU. Both non-inferiority and superiority of the Prestige lp disc over the control treatment were established for overall success without FSU. Non-inferiority of the Prestige lp disc was missed by 0.5% for overall success with FSU (based on the success criteria of posterior probability of 95%) due to the low rate of the FSU success in the Prestige lp disc group vs. control (83.8% vs. 96.9%, respectively). Angular motion among subjects with the Prestige lp disc was higher at superior, but not inferior, adjacent level.
Study Strengths & Weaknesses	This Extended Follow-up study successfully demonstrated non- inferiority of overall Prestige LP disk performance compared to comparator. However, longer-term device performance needs further evaluation, especially taking into account that this follow-up study was based on historical control and therefore lacked comparator data beyond the 84-month timepoint.
Recommendations for Labeling Changes	Labeling changes were recommended to reflect that FSU non- inferiority in the INV group was missed at the 84 months as well as refer to some other study findings such as higher cumulative rate for vascular adverse events in the INV group.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P090029 / PAS002
Date Original Protocol Accepted	04/06/2015
Date Current Protocol Accepted	04/06/2015
Study Name	Enhanced Surveillance Study
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objectives- to fully characterize adverse events and complaints when the device is used in the intended use population in the United States and in the rest of the world. Medtronic will attempt to collect the following information for any adverse events and complaints, including those complaints which are not associated with any adverse clinical effect. Design-enhanced surveillance
Study Population	All device users
Sample Size	N/A
Key Study Endpoints	All adverse event data including subsequent surgeries, heterotopic ossification, device malfunction, and other serious device-related complications. Information will be actively collected from annual surgeon surveys and on the company website. Information will also be collected passively through complaints, MDRs, and annual systematic literature reviews. All of the surgeons who have been trained on the use of PRESTIGE® LP Cervical Disc Prosthesis in the U.S. will be surveyed annually and the number of surveys issued and received will be reported. If a survey response includes any information related to an adverse event, you will collect additional data as specifically outlined in the ESS protocol and report that data to FDA.
Follow-up Visits and Length of Follow-up	The study duration is 10 years.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P090029 / PAS003
Date Original Protocol Accepted	03/11/2016
Date Current Protocol Accepted	12/15/2016
Study Name	Device Failure
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Objective: to assess long-term modes of device failure. the Design: the study incorporates explant analysis, histopathological analysis using periprosthetic tissues removed during explant surgery, and metal ion testing using blood samples analyzed for trace metal concentrations.
Study Population	Retrievals from Extended Follow-up of Premarket Cohort, New Enrollment study and other sources (no comparator group)
Sample Size	All explanted and retrieved device components which were returned to the company
Key Study Endpoints	Effectiveness endpoints ? N/A; Safety endpoints: outcomes of explant analysis, histopathological analysis, and metal ion testing with regards to device failure modes
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P100003 / PAS001
Date Original Protocol Accepted	09/28/2012
Date Current Protocol Accepted	07/16/2014
Study Name	Extended f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study includes investigational and control patients from the US IDE pivotal study (G050075), which was a multi-center, prospective, randomized clinical study conducted to compare the safety and effectiveness of SECURE®-C Cervical Artificial Disc to control Anterior Cervical fusion surgery. The first subjects enrolled at each center were nonrandomized subjects receiving the SECURE®-C device.
Study Population	Secure C patients and ACDF patients from IDE investigation
Sample Size	The IDE study invovled 380/Subjects: 89 non-randomly assigned to SECURE®-C, 151/Randomized to SECURE®-C, and 140/Randomized to ACDF (control). Of these, 220/SECURE®-C patients (91.7%) and 114/ACDF patients (81.4%) yielded 24 month primary outcomes. As a result, the observed rate of missingness was (380 ¿ 220 ¿ 114) 380 = 12.1%. The IDE study was originally designed to randomize 280/Subjects with 80% study power in a 1:1/Ratio of treatment to control. For power calculation purposes, it was assumed that these 220 + 114/Subjects will constitute the beginning sample size for the PAS1.
Key Study Endpoints	Primary Endpoints This study is required to evaluate overall success (protocol- specified primary endpoint) for each patient. The definition of success for an individual patient is based on meeting the following primary outcome measures of safety and effectiveness: Pain Disability Improvement of at least 25% in the Neck Disability Index (NDI) at 5 years and 7 years compared with the score at baseline. No device failures (at the index level) requiring revision, re- operation, removal, or supplemental fixation. Absence of major complications defined as major vessel injury, neurological damage, or nerve injury; and For control fusion patients only, radiographic fusion, as defined by the presence of bridging trabecular bone, without evidence of pseudoarthrosis. The FDA has also required the evaluation of overall success in which an individual patient is considered a success if the following primary (FDA-specified) outcomes measures of safety and effectiveness are met: Pain Disability Improvement of at least 15 points in the Neck Disability Index (NDI) at 5 years and 7 years compared with the score at baseline No secondary surgery at the index level, including revision, removal, reoperation, and supplemental fixation No potentially device-related adverse events Maintenance or improvement in all components of neurologic status No SECURE®-C intraoperative changes in treatment Overall study success criteria are based on a comparison of individual patient success rates, such that the patient success rate for the SECURE®-C investigational group is no worse than that of the ACDF cervical fusion control group, using a delta of 10%.
Follow-up Visits and Length of Follow-up	7 years Follow-up is annual (3- 7 year) (±4 months window).
Interim or Final Data Summary
Actual Number of Patients Enrolled	Out of 380 subjects enrolled in IDE, a total of 334 subjects: 220 SECURE-C patients (91.7%) and 114 ACDF patients (81.4%), were available at the 24-month timepoint for enrollment into the Extended Follow-Up Study.
Actual Number of Sites Enrolled	Out of 18 sites from the initial IDE study, the current Extended Follow-Up Study involved a total of 16 sites.
Patient Follow-up Rate	With a total of 288 subjects followed up until 84 months, the overall follow up rate at the final timepoint was 75.8%, per the initial number of IDE patients (380) and the 7-year follow-up visits: 186 Secure-c (61 nonrandomized, 125 randomized) patients and 102 ACDF patients. However, the follow-up rate at interim visits was much lower, with the Actual in window % follow-up rates reaching only 20-25% for the most of Secure-c visits.
Final Safety Findings	No evidence raising serious concerns on Secure-c safety was found. However, a continuing long-term follow-up through the on-going 10-year ESS study is considered imperative for further assessment of this device and the relatively new TDR technology in general. MDRs reporting posterior expulsion/migration suggested a particular need for the further assessment and labeling update as well as for other possible regulatory actions (if needed) to address this particular AE that was not anticipated upon pre-market approval of the Secure-c disc. A higher rate for cardiovascular adverse events (mostly, in mild category) was observed among Secure-c versus ACDF patients. In addition, clinically-relevant Heterotopic Ossification (Grade III-IV) was found in every fifth Secure-c patient at the 60-months and in every fourth Secure-c patient at the 84 month. Based on the corresponding ROMs, the premise of maintained motion is not fulfilled after 5 years in at least 20-25% of Secure-c patients.
Final Effect Findings	Overall success outcomes including the FDA-defined criteria clearly demonstrated non-inferiority of Secure-c compared to ACDF. Superiority of the investigational group to the control was established for overall success at 24, 60 and 84 months. Superiority in Patient Satisfaction in the Secure-c group compared to the control group was achieved at 24 and 84 months. The changes in NDI score from baseline were not statistically different between Secure-c and control groups, but showed greater improvement for the SECURE-C group at 84 months. The change in global ROM was statistically greater for SECURE-C than ACDF at 24, 36, and 48 months, but was not different at 60, 72, and 84 months. Mean disc height was greater for the Secure-c group at all postoperative time points. However, the lack of correlation between ROMs and overall success, NDI, and VAS pain scores suggested the need for further scrutiny over the Secure-c ability to benefit clinical outcomes via the motion preservation.
Study Strengths & Weaknesses	This Extended Follow-Up study was capable of demonstrating non-inferior, and in some instances superior, performance of the investigational Secure-c device compared to ACDF as control. However, a further comparative analysis of the Secure-c disc vs. cervical fusion as the current standard of care is still warranted, particularly with regard to the premise of preserved motion and subsequent clinical benefits that are anticipated as a result of the TDR procedure.
Recommendations for Labeling Changes	The current labeling is recommended to be updated based on long-term device performance (7-years).
General
Study Status	Delayed
Application Number / Requirement Number	P100006 S005/ PAS001
Date Original Protocol Accepted	06/11/2019
Date Current Protocol Accepted	06/11/2019
Study Name	Long-term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is designed to assess the long-term (out to 6 years post-op) performance of AUGMENT Injectable compared to autograft by continued follow-up of available subjects from several prospective clinical studies (protocols BMTI-2009-01, BMTI-2010-01, and BMTI-2006-01 (autograft only)). No new subjects will be enrolled. Subjects and radiologists will remain blinded. Subjects will be informed of their treatment after the last evaluation. Study is intended to address the following questions: Can it be assessed and confirmed that bridging bone occurs in the long-term after AUGMENT® Injectable has been resorbed? Are the improvements in clinical outcomes associated with the use of AUGMENT® Injectable sustained long-term? Does the promotion of existing tumors from a nonmalignant to malignant state at longer time-points in patients treated with AUGMENT® Injectable exceed the expected rate of promotion in patients not treated with AUGMENT® Injectable or other growth factors used to promote fusion?
Study Population	study group: AUGMENT Injectable graft with fused joints stabilized by metallic fixation hardware control group: autograft with fused joints stabilized by metallic fixation hardware
Sample Size	88 projected from 179 potential prior subjects actual sample size may be modified to address discrepancies
Key Study Endpoints	Primary Effectiveness Endpoints: Pain on weight bearing (via VAS) Confirmation of bridging bone via CT Subject function as determined by AOFAS, FFI Primary Safety Endpoints: Presence of all treatment related adverse events (i.e., description, frequency, incidence, time to onset of first event, severity, duration, treatments administered, etc.) Presence of serious unanticipated adverse device effects rhPDGF-BB antibody status Significant medical conditions, including incidence of cancer Presence of clinically important events Functional Assessments Subjects will assessed using the pain, function and quality of life data instruments: Fusion Site Pain via VAS score (FSP) Weight Bearing Pain Assessment at Fusion Site via VAS score (WBP) Graft Harvest Site Pain via VAS score (GHSP) Foot Pain and Disability Index (FFI) AOFAS Hindfoot/Ankle Score (AOFAS) Safety Assessments Subjects will be assessed for safety parameters and events, including: Presence of all treatment related adverse events Presence of serious unanticipated adverse device effects (UADE) rhPDGF-BB antibody status Presence of clinically important events as defined below: - Musculoskeletal and connective tissue disorders (severe pain, swelling and/or arthralgia in the treated foot/ankle joint(s)); - Additional surgery of the original treated joint due to non-union. - Neoplasms benign, malignant and unspecified (including cysts and polyps) (all lower level terms associated with neoplasms) - Complications related to bone graft harvest site
Follow-up Visits and Length of Follow-up	Subjects will be followed out to at least 5 years post-op
Interim or Final Data Summary
Actual Number of Patients Enrolled	One hundred and thirty-one (131), 53 AUGMENT® Injectable and 78 Autograft
Actual Number of Sites Enrolled	15
Patient Follow-up Rate	Follow-up Rate Follow-up rate is 139% (131/94)
Final Safety Findings	Safety Results 109 adverse events (AEs) were reported in 41 subjects (31.78%), with the autograft group exhibiting a higher overall event rate (58 events in 27 subjects, 35.06%) compared to the AUGMENT® Injectable group (51 events in 14 subjects, 26.92%), and musculoskeletal/connective tissue disorders representing the largest event category. Only 3 events in 2 AUGMENT® Injectable subjects, with a single case of Staphylococcal osteomyelitis classified as possibly device-related. Secondary surgical interventions revealed a higher hardware removal rate in the AUGMENT® Injectable group (17.31%, 9 procedures) versus autograft (9.09%, 7 procedures), while revision rates were slightly higher in the autograft group (3.90%, 3 procedures vs. 1.92%, 1 procedure). No unanticipated adverse device effects (UADEs) identified. No serious or unanticipated adverse events related to AUGMENT® Injectable were reported during this reporting period. Thirteen deaths were reported across both groups (5 AUGMENT® Injectable, 8 autograft), with no AEs classified as resulting in death during the study period.
Final Effect Findings	Primary endpoint was met. Change in WBP from baseline: AUGMENT® Injectable –53.4±3.42 mm vs. autograft –55.1±2.73 mm; LS mean difference 1.7 (95% CI: –7 to 11); 1-sided 95% UCL = 9 < NI margin of 15 mm (Table 10). This demonstrates non-inferiority. Clinically significant WBP improvement (=20 mm decrease) also met non-inferiority: 1-sided 95% LCL = 0.71 > 0.50; PS-adjusted AI 88.63% vs. autograft 80.91%. However, three binary secondary endpoints were not met (clinically significant AOFAS improvement; clinically significant FFI improvement; CT FCOJ maintenance/improvement).
Study Strengths & Weaknesses	Strengths: Prospective, Randomized, Controlled, Multi-Center study. Weaknesses: Lack of diversity, because the majority are Caucasian (95.35%) and non-Hispanic/Latino (97.67%), limiting generalizability. The autograft group is disproportionately composed of subjects from BMTI-2006-01 whose index surgeries occurred 14–18 years prior to evaluation, versus 8–11 years for the comparator cohort, introducing temporal heterogeneity and cohort-level confounding across age-related bone metabolism, peri-operative care standards, and competing risks that were not present in the original pivotal design. Additionally, two subjects were excluded from the PS-matched cohort due to missing covariates, yielding a final 1:1.48 AI-to-autograft ratio that, while accommodated by the PS subclassification design, further reflects the structural imbalance of the dataset.
Recommendations for Labeling Changes	A labeling change is recommended to update the device labeling with the final study results to ensure that patients and providers are aware of the long-term risk of device failure.
General
Study Status	Completed
Application Number / Requirement Number	P100006 / PAS001
Date Original Protocol Accepted	03/16/2016
Date Current Protocol Accepted	03/18/2016
Study Name	Extended f/u of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to evaluate the long-term effectiveness and safety of AUGMENT® Bone Graft vs. autoglogous bone graft. This study is a continued follow-up of the pre-market cohort.
Study Population	investigational graft – Augment Bone Graft control graft – autograft bone
Sample Size	A total of 169 subjects (109 investigational and 69 control) from the original population of 414 subjects (272 investigational and 142 control) have been enrolled.
Key Study Endpoints	The primary effectiveness endpoints will consist of the following: - Demonstration of bridging bone via CT - Patient Function as determined by Pain on Weight Bearing (via VAS), AOFAS Score and Foot Function Index (FFI) The primary safety endpoints will consist of the following: - Presence of all adverse events (i.e., description, frequency, incidence, time to onset of first event, severity, duration, treatments administered, etc.) - Presence of serious unanticipated adverse device effects (UADE) - rhPDGF-BB antibody status - At evaluation, subjects will be interviewed regarding significant medical conditions, including incidence of cancer - Presence of clinically important events as defined below: o Musculoskeletal and connective tissue disorders (severe pain, swelling and/or arthralgia in the treated foot/ankle joint(s)); o Additional surgery of the original treated joint due to non-union. o Neoplasms benign, malignant and unspecified (including cysts and polyps) (all lower level terms associated with neoplasms) o Complications related to bone graft harvest site
Follow-up Visits and Length of Follow-up	The patients will have one study visit at >5 years post-op. Frequency of Follow-up Assessments The patients will have one study visit at >5 years post-op.
Interim or Final Data Summary
Actual Number of Patients Enrolled	169
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	100%
Final Safety Findings	Subjects implanted with AUGMENT Bone Graft experienced a higher rate of “Medically Relevant Adverse Events” compared to the autograft control group, 42.2% compared to 28.3%, respectively. No unanticipated adverse device effects (UADE) were reported for subjects in either group. rhPDGF-BB antibodies were found in 13.7% of the subjects treated with AUGMENT Bone Graft. None of these subjects reported detectable levels of neutralizing antibodies. Clinically important events:AUGMENT Bone Graft - 23 secondary surgical interventions (SSIs) in 109 cases (21.1%). This rate was double that observed in the autograft control subjects - 6 SSIs in 60 cases (10%). o Neoplasms benign, malignant, and unspecified (including cysts and polyps) (all lower level terms associated with neoplasms) were more than twice as common in the subjects implanted with AUGMENT Bone Graft (26.6%) compared to the autograft control group (11.7%). o Complications related to bone graft harvest site of the autograft control subjects included a 5% rate of significant pain at more than 5 year follow up. o The subjects implanted with AUGMENT Bone Graft reported a similar number of events characterized as “Musculoskeletal and connective tissue disorders” (severe pain, swelling and/or arthralgia in the treated foot/ankle joint(s)) compared to the autograft control subjects (26 of 109 (23.9%) compared to 13 of 60 (21.7%), respectively).
Final Effect Findings	The rate of fusion for the subjects implanted with AUGMENT Bone Graft was numerically lower, but not statistically significant (not below the 10% non-inferiority margin) when compared to the autograft control subjects - (92.7%-92.8%) compared to (95.0%-96.6%), respectively. Function outcomes as determined by Pain on Weight Bearing via VAS, AOFAS Score and Foot Function Index (FFI) exhibited lower scores or less improvement in subjects implanted with AUGMENT Bone Graft compared with to the autograft control subjects, but these differences were not significantly different (not below the 20 point non-inferiority margin). Significant graft site pain was still reported in 5% of autograft control subjects at timepoints out to at least 5 years post-op. As outlined in the approval order, the intent of the PAS was to collect longer-term data in an attempt to address the following specific clinical questions: • Can it be assessed and confirmed that bridging bone occurs in the long-term after Augment has been resorbed? As with the original PMA radiographic assessments, the sponsor was not able to directly confirm the presence of bridging bone. The followup radiographic evaluations did, however, allow them to demonstrate that detrimental changes to the treated joints did not occur, i.e., subjects reporting initial healing did not progress to non-unions. This observation can be used to satisfy the first clinical objective of the PAS. In order to definitively address graft resorption and fusion mass formation as evidenced by radiographically-visible bridging bone, it would have been necessary for the sponsor to perform the types of radiographic assessments requested in PAS #2, which based on agreement with FDA, was ultimately not performed. • Are the improvements in clinical outcomes associated with the use of Augment sustained long-term? The PAS has demonstrated that the early clinical observations, e.g., VAS pain and the various function assessments, were maintained over the longer-term follow-up period. As a result, the second clinical objective has been satisfied. • Does the promotion of existing tumors from a nonmalignant to malignant state at longer time-points in patients treated with Augment exceed the expected rate of promotion in patients not treated with Augment or other growth factors used to promote fusion? The minimal amount of data related to tumors does not support a difference in behavior between subjects receiving AUGMENT Bone Graft compared to subjects receiving autograft bone. As part of the continued annual reporting requirements, the sponsor will continue to report on incidences of tumors. The third clinical objective has been satisfied.
Study Strengths & Weaknesses	Strength: 100% follow-up rate, there is a comparator group. Weaknesses: Small sample size (169), lack of representativeness, e.g., 94% of subjects were White. Labeling Change Recommended: The PAS study design, methods and results must be included in the labeling.
Recommendations for Labeling Changes	Yes
General
Study Status	Terminated
Application Number / Requirement Number	P100006 / PAS002
Study Name	2-year New Enrollment Study
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P100009 S028/ PAS001
Date Original Protocol Accepted	03/14/2019
Date Current Protocol Accepted
Study Name	Cont f/u of the COAPT Trival Pivotal Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the COAPT Trial pivotal cohort. The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE pivotal cohort.
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, stroke, single leaflet device attachment, device embolization, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, heart failure (HF) related hospitalization, New York Heart Association (NYHA) classification, 6-Minute Walk Distance (6MWD) through 2 years, Kansas City Cardiomyopathy Questionnaire (KCCQ) score through 2 years, 36-Item Short Form Survey (SF-36) score through 2 years, mitral valve surgery (including type of surgery), new use of Cardiac Resynchronization Therapy (CRT), new use of single or dual chamber pacemaker, permanent left ventricular assist device (LVAD) implant, heart transplant, additional MitraClip device intervention or de novo MitraClip device intervention, including reason for intervention, number of hospitalizations and reason for hospitalization (i.e., heart failure, cardiovascular, non-cardiovascular) through 2 years, number of days alive and out of hospital, number of days hospitalized, proportion of subjects living in the baseline location, new onset of permanent atrial fibrillation, mitral stenosis, clinically significant atrial septal defect (ASD) that requires intervention, and dosages of guideline directed medical therapy (GDMT).
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	665 subjects were enrolled or treated in the study, including subjects randomized for test group – MitraClip (302), subjects randomized for control – GDMT (312), and roll-in subjects (51).
Actual Number of Sites Enrolled	Eighty-four (84) sites enrolled at least 1 Roll-In or Randomized subject
Patient Follow-up Rate	Test group (MitraClip): 75% (104/139); Control group (GDMT): 59% (75/128)
Final Safety Findings	The Kaplan-Meier curve showed the freedom from the primary safety endpoint (Composite of Single Leaflet Device Attachment (SLDA), device embolization, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, and any device-related complications requiring non-elective cardiovascular surgery) in the safety analysis population as 89.2% (event rate was 10.8%). No new SLDAs (0.7%), embolization (0.3%) and device related complications requiring non-elective cardiovascular surgery (0.3%) were reported between 12 months and 60 months. 93.5% of subjects treated with the study device were free from LVAD implantation and 93.5% of subjects treated with the study device were free from heart transplant at 5 years. Kaplan-Meier estimate of all-cause mortality at 5 years was 57.3% for the Device group, compared to 67.2% for the Control group. The rate of cardiovascular mortality was 48.8% in the Device group and 57.2% in the Control group, and the rate of heart failure mortality was 30.9% in the Device group and 42.8% in the Control group, respectively, at 5 years.
Final Effect Findings	26.4% of the Device group subjects and 8.5% of the Control group subjects were alive or free from a HF related hospitalization after 5 years. A higher proportion of subjects in the Device group achieved =1+ secondary mitral regurgitation (SMR) compared to the Control group, and the reduction in MR was durable through 5-year follow-up in the Device group: 89.5% of the subjects in the Device group and 78.3% of the subjects in the Control group had MR < 2+.
Study Strengths & Weaknesses	Strength: This study was able to follow the enrolled and treated subjects in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation trail (The COAPT Trial) per protocol through 5 years. The data reported demonstrate that the safety and effectiveness of the MitraClip System is maintained through 5 years, with favorable results compared to Guideline Directed Medical Therapy (GDMT) alone. Weakness: Deaths occurring over the 5-year follow-up reduced the number of available subjects for long-term assessment, reducing randomized subjects with a visit completed at 5 years to 179 (67% follow-up rate adjusted for deaths). Sample sizes for other endpoints, such as echocardiographic endpoints, were further reduced due to missing endpoint data deviations. For example, only 5% (14/267) and 39% (103/267) of subjects (adjusted for death) contributed to Effective Regurgitant Orifice Area and Mitral Regurgitation analyses at 5 years. Although the primary safety and effectiveness endpoints were demonstrated over the COAPT Trial 5-year follow-up, the lower samples sizes in echocardiographic endpoints due to deaths confounds interpretation of long-term clinical effectiveness
Recommendations for Labeling Changes	Yes, labeling change recommended to update the device labeling with the final, long-term study results
General
Study Status	Ongoing
Application Number / Requirement Number	P100009 S028/ PAS002
Date Original Protocol Accepted	07/26/2019
Date Current Protocol Accepted
Study Name	Registry-Based CAP Cohort and RWU Surveillances
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillances. The objectives of the surveillances are to characterize the clinical outcomes of the continued access protocol (CAP) cohort annually through 5 years post-procedure and to assess the real-world use of the commercial MitraClip System to ensure that the device is used in appropriate circumstances.
Study Population	Patients with symptomatic, moderate-to-severe or severe secondary (or functional) mitral regurgitation (MR; MR greater than or equal to Grade III per American Society of Echocardiography criteria) in patients with a left ventricular ejection fraction (LVEF) greater than or equal to 20% and less than or equal to 50%, and a left ventricular end systolic dimension (LVESD) less than or equal to 70 mm whose symptoms and MR severity persist despite maximally tolerated GDMT as determined by a multidisciplinary heart team experienced in the evaluation and treatment of heart failure and mitral valve disease.
Sample Size	All living CAP subjects who were enrolled at participating institutions and a total of 5000 consecutively treated patients at a minimum of 100 representative institutions across the United States.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry. The follow-up data (including all-cause mortality, stroke, repeat procedure for mitral valve-related dysfunction, and hospitalization) from year 2 through year 5 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	COAPT CAS Cohort: At 1-year follow up, Kaplan Meier estimated events were 24.1% death, 0.6% stroke, and 25.4% % heart failure hospitalizations. Based on reported events, 2.5% (4 of 162 subjects) experienced mitral valve reintervention. At 4-year follow up, Kaplan Meier estimated events were 57.3% death, 2.6% stroke, and 63.2% % heart failure hospitalizations. Based on reported events, <10% (less than 11 of 107 subjects, due to CMS data (cell size) policy) experienced mitral valve reintervention. RWU Surveillance Cohort: At 1-year follow up, Kaplan Meier estimated events were 22.0% death, 2.4% stroke, 19.0% heart failure hospitalizations, and 3.5% need for repeat procedure for mitral valve-related dysfunction. At. 3-year follow up, Kaplan Meier estimated events were 49.2% death, 7.7% stroke, 80.3% all-cause hospitalizations, and 7.5% need for repeat procedure for mitral valve-related dysfunction. Based on reported events, 840 patients had heart failure hospitalizations
Actual Number of Patients Enrolled	COAPT Continued Access Study (CAS) Cohort = 162; Real World Use (RWU) Surveillance Cohort = 5000
Actual Number of Sites Enrolled	COAPT CAS Cohort = 32 sites; RWU Surveillance Cohort = 406 hospitals
Patient Follow-up Rate	COAPT CAS Cohort: 89% at 1 year (excluding deaths), with 5 withdraws, 2 lost-to-follow up- and 6 missed visits. RWU Surveillance Cohort: 66% at 1 year (excluding 921 deaths), with 12 withdraws, 302 lost-to-follow up, and 1064 missed visits
General
Study Status	Ongoing
Application Number / Requirement Number	P180036 / PAS001
Date Original Protocol Accepted	03/21/2019
Date Current Protocol Accepted	04/08/2025
Study Name	OPTIMIZER Smart System PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center, single-arm open label study to provide long-term safety and effectiveness data.
Study Population	Patients to be included will have NYHA functional class III symptoms and reduced (HFrEF) or moderately reduced (HFmrEF) ejection fraction (25-45% inclusive).
Sample Size	up to 650 patients. No limit on sites.
Key Study Endpoints	Safety Endpoints The powered safety endpoint is a composite incidence of device- or procedure-related complication free rate at 12 months post-index implantation procedure compared to a performance goal of 75%. 1. Procedure related complications occurring through the end of 30 days following the index procedure. 2. Optimizer device-related complications occurring through the end of 1-year following the index procedure. Observed mortality will be compared to predicted mortality for the patient group according to the Seattle Heart Failure Model (SHFM) at 1 year and 3 years post-implant. Effectiveness Endpoints Change in QOL, as measured by MLWHFQ, from baseline to 9 months, 2-years and 3-years following index implantation procedure. Clinician assessment of functional class. A one – class change in functional class at 9-months, 2-years and 3-years following index implantation. Change in LVEF and ESV at 9-months, 2-years and 3-years following index implantation. Change in NT-proBNP at 9-months, 2-years and 3-years following index implantation. Change in QRS duration at 9-months, 2-years and 3-years following index implantation. Additional: An assessment of the incidence of Optimizer device-related “complications” (SADEs) and “observations” (ADEs) occurring during the 3-year period following the index procedure.
Follow-up Visits and Length of Follow-up	Followed ups are scheduled: 9-month, 2-year and 3-year 3 years
Interim or Final Data Summary
Interim Results	Safety Results: 167 serious adverse events (SAEs) through 2 years were reported during the current period. Of these, 7 were considered either system- or procedure- related (4.2% of all SAEs). To date, there have been 29 lead dislodgements total (4.2% of total subject enrollment). Primary Safety: • 6.1% rate of procedure-related adverse events through 30 days or device-related adverse events through the end of 1 year All-cause mortality: • At 1-year, 90.90% Kaplan-Meier actual survival vs. 93.56% predicted mortality using Seattle Heart Failure Model (N=567) • At 3-year, 78.10% Kaplan-Meier actual survival vs. 82.37% predicted mortality using Seattle Heart Failure Model (N=275) Effectiveness Results: MLWHF • Baseline to 1-year: –16.9 ± 24.0 (N=482) • Baseline to 2-year: –18.4 ± 25.0 (N=380) NYHA Classification • Baseline to 1-year: –0.9 ± 0.8 (N=503) • Baseline to 2-year: –0.9 ± 0.8 (N=387) LVEF (%) • Baseline to 1-year: 2.9 ± 8.1 (N=219) • Baseline to 2-year: 3.6 ± 9.0 (N=139) LVESV (cm3) • Baseline to 1-year: –13.8 ± 27.5 (N=219) • Baseline to 2-year: –19.3 ± 30.0 (N=139) NT-proBNP (pg/mL) • Baseline to 1-year: 49.6 ± 5467 (N=449) • Baseline to 2-year: –101 ± 3930 (N=355) QRS width (ms) • Baseline to 1-year: –1.0 ± 28.8 (N=346) • Baseline to 2-year: –1.0 ± 36.5 (N=320) Results displayed in Mean ± SD with number of subjects (N)
Actual Number of Patients Enrolled	692
Actual Number of Sites Enrolled	91
Patient Follow-up Rate	1 Year: 510 actual follow up (FU) (92.1%), 64* deaths, 39 withdrawals*, 1 lost to FU* 2 Year: 395 actual FU (90.8%), 100 deaths*, 68* withdrawals, 3 lost to FU* 3 Year: 221 actual FU (86.3%), 125 deaths*, 78 withdrawals*, 13 lost to FU* * denotes cumulative counts
General
Study Status	Ongoing
Application Number / Requirement Number	P100009 / PAS001
Date Original Protocol Accepted	10/24/2013
Date Current Protocol Accepted	06/13/2014
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objectives: to assess long term safety and effectiveness of the MitraClip device in a broad patient population and to study how prohibitive risk is interpreted in real-world use of the MitraClip device to ensure the device is used in appropriate circumstances. Study design: a prospective, single-arm, multi-center, observational study of a minimum of 2,000 MitraClip patients consecutively entered into the TVT Registry. A new enrollment study.
Study Population	Patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation; patients treated in accordance with the MitraClip Clip Delivery System labeling, formal protocol- specific inclusion and exclusion criteria will not be used. Cohort A: Patients treated per the MitraClip Clip Delivery System indication approved on October 24, 2013 will comprise Cohort A. Patients will be identified as Cohort A for analyses if the data collected on the eCRFs identify symptomatic DMR ≥3+ and at least one reason for prohibitive risk. Cohort B: patients from the PAS 1 Device Registry who are not included in Cohort A.
Sample Size	Subjects: 2,000 MitraClip patients consecutively entered into the TVT Registry. Sites: This study will include all sites participating in the STS/ACCF TVT Registry and trained by Abbott Vascular to implant the MitraClip device. A minimum of 2,000 patients will allow detection of low frequency safety events and provide improved precision for the rates of safety events that have previously been characterized.
Key Study Endpoints	Primary Safety/Effectiveness Endpoints: The following endpoints will be reported through 1 year follow-up from data extracted from the TVT-R: ¿ All-cause mortality at 30 days and 1 year ¿ Stroke at 30 days and 1 year ¿ NYHA Functional Class at 30 days and 1 year ¿ Hospitalizations (All-cause and HF-related) at 1 year ¿ The echo parameters of MR severity, left ventricular end-diastolic volume (LVEDV) and Left Ventricular Internal Dimension-Diastole (LVIDd) at baseline, 30 days and 1 year in all patients and in the subset of patients who undergo mitral valve (MV) surgery within the first year The following endpoints will be reported for years 2 - 5 post-implant by linking data extracted from the TVT Registry to the Center for Medicare and Medicaid Services (CMS) Claims database: ¿ All-cause mortality ¿ Stroke ¿ Hospitalizations (All-cause and HF-related) ¿ Surgical interventions Secondary Safety/Effectiveness Endpoints: Interpretation of the definition of prohibitive risk status in commercial use will also be reported on. Prohibitive risk status will be audited by a qualified MitraClip Registry Audit Committee Charter (MRAC) that meets quarterly. The composition and the schedule for auditing is described in the MRAC Charter document (received on June 10, 2014).
Follow-up Visits and Length of Follow-up	5 years Discharge, 30 days, 1 year annually through 5 years
General
Study Status	Completed
Application Number / Requirement Number	P100009 / PAS002
Date Original Protocol Accepted	10/24/2013
Date Current Protocol Accepted	04/05/2016
Study Name	New EnrollMitraClip Analysis Cohort (MAC)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective cohort study, a subset of patients entered into the MitraClip TVT-Registry who fulfill the enrollment criteria and from sites/centers of excellence and experienced with performing and collecting 6MWT data and KCCQ data (i.e. sites/centers with at least 75% completion rate in terms of collecting both 6MWT and KCCQ data) will be included in MAC. This is a new-enrollment study. NOTE: Annual follow up (e.g. death, stroke, surgical intervention, hospitalizations) from year 2 through year 5 post-implant through linkage to the CMS database will be reported as part of P100009/PAS001- OSB-lead Comprehensive/Linked-Registry Based Surveillance. PAS1
Study Population	A subset of approximately 420 patients entered into the MitraClip TVT-Registry who fulfill the following criteria in MAC: Significant symptomatic MR (greater than or equal to 3+) due to primary abnormality of the mitral apparatus, otherwise known as Degenerative Mitral Regurgitation (DMR). Prohibitive risk for mitral valve surgery (MV) as determined by a heart team, which includes a cardiologist experienced in MV disease and a cardiac surgeon experienced in MV surgery, and existing comorbidities that would not preclude the expected benefit from reduction of the MR. Perform the 6MWT at baseline or unable to perform the 6MWT due to cardiac reasons. No comparator group.
Sample Size	Assuming 10% withdrawal at 12 months, a sample size of 420 patients from the Prohibitive Risk DMR Patient Registry (PAS 1 Device Registry) is expected to provide 420 evaluable patients (not lost-to-follow-up or discontinued) at 12 months post procedure. Assumptions: The reported death rate at 30 days was 6.3% in the Prohibitive Risk DMR Cohort (Lim et al 2013); the all-cause mortality rate at 30 days was assumed to be 6.5%. The device- related complication rate was assumed to be ~6% at 12 months. Because a majority of device-related complications are expected to occur within 30 days of the MitraClip procedure, the rate at 30 days was also assumed to be ~6%. Two thousand (2,000) simulations were performed to calculate sample size and power for the primary safety endpoint. A sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the 5% significance level. Two thousand (2,000) simulations were performed to calculate sample size and power for the primary effectiveness endpoint. Assuming 37% attrition (25% death, 10% withdrawal, and 2% missing data) at 12 months, a sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the 5% significance level. There will be a minimum of 15 sites and a maximum of 40 sites, with no more than 10% of patients (up to 46) from each site. Sites selected for participation in this study will be centers of excellence and experienced with performing and collecting 6MWT data and KCCQ data.
Key Study Endpoints	Main safety endpoints: A composite of death and device-related complications at 30 days post-procedure. The device-related complications include single leaflet device attachment (SLDA), device embolization, device thrombosis, and other device-related events (e.g., endocarditis, MV stenosis), which result in MV re-intervention, unplanned other cardiac surgery, or unplanned vascular surgery or intervention through 30 days post-procedure. Secondary safety endpoints: All-cause mortality at 12 months, and device-related complications at 12 months. Main effectiveness endpoints: The change in 6MWT distance at 12 months over baseline. Secondary effectiveness endpoints: MR severity at 12 months Change in LVEDV at 12 months over baseline Change in LVIDd at 12 months over baseline Change in KCCQ QoL at 12 months over baseline NYHA Functional Class at 12 Months
Follow-up Visits and Length of Follow-up	5 years Active follow-up of patients will be performed through 12 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total 554 study subjects who entered into STS/ACC Transcatheter Valve Therapy (TVT) registry between November 04, 2013 and July 29, 2015 and met eligibility criteria for this study were enrolled in this post-approval study.
Actual Number of Sites Enrolled	A total of 50 sites (sites with at least 75% data completeness of both baseline 6-minute walking test and KCCQ data) were included in this post-approval study.
Patient Follow-up Rate	The overall follow-up rate at 1-year through the Mitral Module of the TVT registry is 78.2%.
Final Safety Findings	The primary safety endpoint of rate of freedom from composite of death and device-related complications at 30 days was 95.5% (529/554), which was significantly higher than the pre-specified performance goal of 80% (P<0.0001). For secondary safety endpoints, freedom from all-cause mortality at 12 months was 80.2% (SE: 1.85%; performance goal=66%, P<0.0001), and freedom from the composite device-related complications at 12 months was 98.9% (SE: 0.45%; performance goal=90%, P<0.0001). All primary and secondary safety endpoints were successfully met.
Final Effect Findings	The primary effectiveness endpoint of mean improvement in 6-minute walking test (6MWT) at 12 months from baseline was 31.56±115.24 meters. The results showed significantly improvement at 12 months (one-sided p-value=0.0001). Analysis of secondary effectiveness endpoints shows significant mitral regurgitation (MR) reduction (P<0.0001) and improvement in NYHA class (P<0.0001) at 12-months from baseline, reduction in left ventricular size at 12-months from baseline as per LVEDV (-10.9 ± 48.9 ml, P=0.0111) and LVIDd (-0.22±0.72 cm; P<0.0001) measurements as well as improvement of Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months over baseline (30.40±25.77, P<0.0001).
Study Strengths & Weaknesses	Strength: This study was able to demonstrate the safety and effectiveness of Mitral Valve Repair and Clip Delivery Systems (MitraClip®) using real-world data collected through the national STS/ACC TVT Registry. Weakness: Sample size for some of the subgroup analyses, such as recurrent mitral regurgitation subgroup, was relatively small, resulting in large standard deviations for the estimates. Although primary effectiveness endpoint was successfully met, only about 62.1% patients among those who have completed 12-month visit had 6MWT information available (including patients who performed 6MWT or were unable to perform due to cardiac reasons). High proportion of missing values were also reported for LVEDV endpoint at 12 months (36.8% of patients who completed 12-month have information available). Patients included in this study were enrolled from sites with at least 75% completion rate in terms of collecting both baseline 6MWT and KCCQ data, and results may not be generalizable to patients enrolled from sites with less experience performing and collecting 6MWT and KCCQ data. Finally, the data available are limited to 1-year follow-up currently; additional data on longer term (5- year) safety and effectiveness remain to be assessed.
Recommendations for Labeling Changes	Yes, labeling change recommended to update the device labeling with the final study results.
General
Study Status	Completed
Application Number / Requirement Number	P050023 S105/ PAS001
Date Original Protocol Accepted	05/04/2017
Date Current Protocol Accepted	09/24/2019
Study Name	QP ExCELS Sentus QP Ext CRT w/Quad LV
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Confirm long-term safety of the Biotronik Sentus OTW QP left ventricular pacing leads. The evaluation of safety will be freedom from Sentus QP related complications at 5 years post-implant.
Study Population	CRT-eligible Heart Failure patients
Sample Size	Postmarket Sample Size Required: 979 Postmarket Sample Size Required including attrition = 1754
Key Study Endpoints	Primary Endpoint: The purpose is to evaluate the long-term Sentus related complication-free rate through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	2872
Actual Number of Sites Enrolled	N/A - RWE
Patient Follow-up Rate	N/A - RWE
Final Safety Findings	Primary safety objective of complication-free rate (CFR) greater than 92.5% at 5 years post-implant for Sentus LV leads was met. 84 complications noted in 2920 Sentus leads. Lower bound of the two-sided 95% confidence interval of CFR was 92.72%.
Final Effect Findings	N/A
Study Strengths & Weaknesses	This study’s use of real-world data captures a large representative assessment of device performance. While data granularity is limited, the study confirms there are no significant safety concerns with the device’s long term performance.
Recommendations for Labeling Changes	Labeling changes should include the study design, results, and strengths and weaknesses of the PAS.
General
Study Status	Ongoing
Application Number / Requirement Number	P180035 / PAS001
Date Original Protocol Accepted	07/26/2021
Date Current Protocol Accepted	12/17/2025
Study Name	MiSight 1 Day PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a multicenter, parallel-group, controlled, double-masked (subject and investigator), randomized clinical trial with a total duration of four years. Part 1 will study effectiveness of MiSight 1 Day in slowing myopia progression over three-years in a US population. Subjects in Part 1 will wear MiSight 1 Day lenses or Proclear 1 day lenses. Part 2 will study the stability of the effectiveness result over a one-year post-treatment period. All subjects in Part 2 will wear Proclear 1 day lenses. Subjects and investigators will remain masked from Part 1. The primary objectives of this study are: (1) to confirm in the U.S. population that there are clinically meaningful differences (super-superiority margin of 0.50D) in the mean change of cycloplegic refractive error and axial length change from baseline after three years of using MiSight 1 Day lenses among intended patient population compared to the mean changes in a control group using conventional daily disposable lenses; (2) to assess the stability of the myopia reduction over 1-year post-treatment among those who completed the 3-year confirmation study follow-up. Secondary objectives of this study are: (1) to estimate the effects of race, baseline cycloplegic spherical equivalent refractive error, and baseline age on the treatment effect; (2) to assess the effects of the MiSight 1 Day on the patients’ visual symptoms and the effects on patients’ activities of daily living, using an appropriately validated patient-reported outcome (PRO) measure.
Study Population	The eligible study population will be children ages of 8-12, who have best corrected visual acuity of at least 20/25 bilaterally with refractive error between -0.75 D to – 4.00D spherical equivalent and = 0.75 D of astigmatism at the initiation of treatment, who are free of ocular disease or abnormalities (including any corneal scar), who are not under medication that would interfere with contact lens wear or are using or have used any pharmaceuticals or other methods for control of myopia, and who have no other contraindications per product labeling.
Sample Size	Part 1 will enroll a minimum of 675 patients in the MiSight 1 Day treatment group and 225 in the control group from all eligible patients in clinical sites and will have a target minimum of 664 total number of evaluable patients (498 patients in the treatment group and 166 patients in the control group) completing 3 years of wear. All of those who completed the 3-year confirmation study follow-up will be continuously followed into Part 2. A target minimum number of 598 evaluable patients (with 448 in the treatment group and 150 in the control group) will complete this phase of the study
Key Study Endpoints	The primary endpoints for Part 1 of this study are: Mean difference in cycloplegic SERE change from baseline between the MiSight 1 Day group and control lens group after 3 years. Mean difference in axial length change from baseline between the MiSight 1 Day group and control lens group after 3 years. In addition, an estimate of the effects of race, baseline cycloplegic spherical equivalent refractive error, and baseline age on the treatment effect will be provided. The primary endpoints for Part 2 of this study will be: Mean difference in rate of cycloplegic SERE change between the Part 1 MiSight 1 Day group and the Part 1 control lens group over one-year post-treatment. Mean difference in rate of axial length change between the Part 1 MiSight 1 Day group and Part 1 control lens group over one-year post-treatment. Secondary endpoints for Part 1 of this study include: A comparison of the rates of the patients’ visual symptoms and the effects on patients’ activities of daily living between the MiSight 1 Day and control lens groups using a validated PRO measure; Comparison of percentage of subjects in the MiSight 1 Day group and control lens group with no appreciable myopic progression (-0.25D change or less) over the 3 years.
Follow-up Visits and Length of Follow-up	Part 1: 3-year Part 2: 1-year
Interim or Final Data Summary
Actual Number of Patients Enrolled	868
Actual Number of Sites Enrolled	32
Patient Follow-up Rate	206 subjects exited early. 89 subjects exited at the initial visit, due to not meeting enrollment criteria (e.g., refractive error, strabismus). 61 exited at the fitting/training or contact lens follow-up or follow-up visits and 56 exited at or after the six months visit.
Final Safety Findings	N/A
Final Effect Findings	N/A
General
Study Status	Terminated
Application Number / Requirement Number	P070014 S010/ PAS001
Date Original Protocol Accepted	12/23/2010
Date Current Protocol Accepted	07/11/2014
Study Name	CONTINUUM Long Lesion PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm, non-randomized, prospective, multi-center international study in subjects (>=22 years of age) with TransAtlantic Inter-Society Consensus A, B and C lesion(s) in the infra-inguinal segment (SFA and/or Popliteal arteries). Subjects will be treated with PTA followed by the LifeStent Self-Expanding Stent System (FlexStar / FlexStar XL). The primary objectives of this investigation are to provide confirmatory evidence of safety and effectiveness of the LifeStent Self-Expanding Stent System in patients with de novo and restenotic (non-stented) lesion(s) in the infra-inguinal segment (SFA and/or Popliteal arteries). A secondary objective of this investigation is to continue to evaluate the clinical utility of the LifeStent Self-Expanding Stent System.
Study Population	The study population will be comprised of subjects who present with lifestyle-limiting claudication or ischemic rest pain and are candidates for PTA and stenting. A minimum number of patients with longer lesions will be enrolled.
Sample Size	170 patients; 20 sites
Key Study Endpoints	The primary safety endpoint is freedom from death at 12 months post-procedure. The primary effectiveness is freedom from procedural device malfunction.
Follow-up Visits and Length of Follow-up	Subjects will undergo a clinical evaluation at baseline (prior to study procedure), prior to hospital discharge, 30 days post-procedure, 12, 24, and 36 months post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 173 subjects were enrolled as follows: 113 enrolled under P070014 (Target Lesion lengths less than or equal to 160 mm), 18 enrolled under subgroup P070014/S010 (Target Lesion lengths >160 - 240 mm) and 41 enrolled under subgroup P070014/S022 (Target Lesions treated with 200 mm LifeStent SOLO). 1 subject had target lesion length of 280 mm that is not included in the subgroup categories.
Actual Number of Sites Enrolled	A total of 30 sites received IRB approval and were enrolled.
Patient Follow-up Rate	Follow-up rates for the combined subgroups at 30 days, and 12, 24, and 36 months was 98.8% (163/165), 98.6% (142/144), 98.3% (115/117) and 97.7% (84/86), respectively.
Final Safety Findings	Primary safety was defined as freedom from occurrence of death at 30 days and 12-months post procedure. The freedom from primary safety event rate at 30 days and 12 months post index procedure was 99.4% (95% confidence interval [CI] 95.9%, 99.9%) and 95.1% (95% CI 90.4%, 97.5%) respectively.
Final Effect Findings	Primary effectiveness (Device Success) for the CONTINUUM study was defined as: freedom from device delivery failure and primary Target Lesion Patency (TLP) at 12-months post-index procedure measured by DUS. TLP was defined as the interval following the index procedure until a DUS assessment indicates that the target lesion(s) is no longer patent; that is, the treated segment has a peak systolic velocity ratio (PSVR) greater than or equal to 2.5. Primary effectiveness at 12 months by Kaplan Meier method was 72.7% (95% confidence interval [CI] 61.8 to 81.0%). Primary target lesion patency (TLP) at 12-Months post-index procedure by Kaplan Meier analysis for CONTINUUM LifeStent group was 75.3% (95% CI: 67.4%, 81.6%) compared to RESILIENT PTA 36.7% (95% CI: 25.1%, 48.4%). The hazard ratio for CONTINNUUM LifeStent over RESILIENT PTA (ITT) was 0.123, P <0.001. For non- inferiority comparison of the CONTINUUM Lifestent to RESILIENT LifeStent, the primary TLP at 12 months for CONTNUUM LifeStent was 81.1% versus RESILIENT LifeStent 73.2% using Cox’s regression model with regression covariates: treatment group, Rutherford Category, target lesion length, total treated segment length, age, and gender. The difference in primary TLP at 12 months between CONTINUUM LifeStent and RESILIENT LifeStent is 0.079 (7.9%). The lower bound of the 95% CI for the difference in TLP between CONTINNUUM LifeStent and RESILIENT LifeStent of -0.006 is greater than -0.075, the non-inferiority margin, indicating that the CONTINUUM arm is not inferior to the RESILENT arm. The Z-test statistic is equal to 2.99, p-value = 0.0014. Freedom from TLR and/or TVR at 12 months post index procedure for the CONTINUUM LifeStent group was 82.2% (95% CI 75.2%, 87.3%) compared to that of RESILIENT PTA (ITT) group 45.2% (95% CI: 33.4%, 56.3%) – (p-value <0.001). The percentage of subjects free from stent fracture at 12- and 24-months post-index procedure was 92.4% (110/119) and 67.6% (69/102) respectively.
Study Strengths & Weaknesses	Overall, approximately 74% (173/234) of required enrollment was achieved in the CONTNUUM study. The target enrollment of at least 64 subjects in each subgroup was not achieved in two subgroups. The two subgroups were: 1) Target Lesion Lengths > 160 mm and less than or equal to 240 mm, and 2) Target Lesions treated with the 200 mm LifeStent SOLO.
Recommendations for Labeling Changes	Labeling change is not recommended with the post approval study results as the study was not completed.
General
Study Status	Terminated
Application Number / Requirement Number	P100012 / PAS001
Date Original Protocol Accepted	10/26/2012
Date Current Protocol Accepted	08/25/2015
Study Name	PCM Cervical Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is enhanced surveillance.
Study Population	Skeletally mature patients for reconstruction of a degenerated cervical disc at one level from C3-C4 to C6-C7 following single-level discectomy for intractable radiculopathy (arm pain and or a neurological deficit), with or without neck pain, or myelopathy due to a single-level abnormality localized to the disc space.
Sample Size	The sample size is comprised of all patients who receive the device after its approval. All US physicians who utilize the device will be surveyed.
Key Study Endpoints	Subsequent surgeries, heterotopic ossification, and other device related adverse events
Follow-up Visits and Length of Follow-up	Surgeons will be surveyed on an annual basis and for ten (10) years from the PMA approval date.
Interim or Final Data Summary
Interim Results	A total of 128 physicians were identified to survey. Of the surgeons surveyed, 8 responded. The overall response rate was 6.25% (8/128).
Actual Number of Patients Enrolled	N/A There is no enrollment of patients. All patients who have received this device in the post-market environment, i.e. all patients who are implanted with the device. The intended patient population under general conditions of use in the United States and in the rest of the world.
Actual Number of Sites Enrolled	N/A Annual surgeon survey: active collection of surgeon feedback annually to elicit information related to heterotopic ossification, device malfunction, device removal, or other serious devicerelated complications.
Patient Follow-up Rate	Numbers of sites, IRB approvals and study participants are not available, since this ESS does not include enrollment of sites/patients. There is no enrollment of patients.
Study Strengths & Weaknesses	N/A
General
Study Status	Completed
Application Number / Requirement Number	P100012 / PAS002
Date Original Protocol Accepted	10/26/2012
Date Current Protocol Accepted	02/06/2013
Study Name	PCM Cervical Long Term
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multi-center randomized clinical trial
Study Population	The study population is comprised of patients who received the device during the IDE or controls that underwent ACDF during the IDE.
Sample Size	The sample size is comprised of 142 PCM cervical disc patients and 110 controls that underwent ACDF.
Key Study Endpoints	The primary endpoint will be individual subject success at the 7 year visit. ¿Success¿ is defined as: Improvement of at least 20% on the Neck Disability Index (NDI) at 7 years compared to baseline; No device failures (at the index level) requiring revision, re-operation, removal, or supplemental fixation; No major complications such as vascular or neurological injury; Radiographic success Secondary endpoints include neurological assessment, Neck and Arm Pain Visual Analog Scale, and Short-Form-36 Health Survey Questionnaire.
Follow-up Visits and Length of Follow-up	7 years. Patients will undergo follow-up assessments at 5, 6, and 7 post-operative years..
Interim or Final Data Summary
Actual Number of Patients Enrolled	205 investigational and 172 control subjects (per protocol – withdrawals).
Actual Number of Sites Enrolled	18
Patient Follow-up Rate	At 84 months, the follow-up rate (for the Primary Endpoint) was 86.0% (166/193) for the investigational group and 75.0% (117/156) for the control group.
Final Safety Findings	Based on the data available, the rate of implant related serious adverse events was 4.1% in the investigational group and 3.8% in the control group. The overall (84-month) rate of secondary surgical intervention (SSSI) device removals was 13.2% (for training group subjects), 7.3% (for the PCM investigational group) and 8.8% (for training and investigational groups combined). For SSSI device removals, it is unknown whether clinically acceptable fusion occurs or if fusion after PCM removal is deleteriously impacted. For the additional individual radiographic safety endpoints (e.g., migration, radiolucency, heterotopic ossification, adjacent level degeneration), no serious safety concerns were evident, though the radiographic data availability was low (49%-73%). A possible association between radiolucency and failure of the device (i.e., device migration) that may require a secondary surgical intervention (SSSI) cannot be ruled out based on the data available.
Final Effect Findings	Based on the data available, the study met its primary objective by demonstrating that for the primary endpoint (clinical composite success defined as 20% NDI improvement, no reoperations, removals or revisions, and no major complications*), PCM is non-inferior to ACDF at 84 Months. Statistical superiority of the primary endpoint was achieved. The primary endpoint at 84 months, using the 20% NDI definition of success, was 67.5% (112/166) for the investigational group compared to 50.8% (60/118) for the control group. The primary endpoint at 84 months, using the alternative 15-point NDI definition, was 64.53% (107/166) for the investigational group compared to 50.0% (59/118) for the control group. These results are based on data availability rates of 87% for the PCM group and 75% for the control group at 84 months. For additional, individual effectivness endpoints (e.g., NDI, VAS, SF36, Dysphagia, and Patient Satisfaction, time to recovery, radiographic effectiveness measures), based on the data available, the PCM group tended to reveal better performance than the control group. However, these data are based on low data availability rates and/or highly discrepant data availability rates between PCM and control groups. *Complications: Defined as major vessel injury, neurological damage, or nerve injury; Maintenance or improvement in all components of neurologic status; and Radiographic success (for PCM patients, defined as lack of evidence of continuous bridging bone between the adjacent endplates of the involved motion segment or >2° of segmental movement on lateral flexion/extension radiographs; for ACDF patients defined as evidence of continuous bridging bone between the adjacent endplates of the involved motion segment, radiolucent lines at =50% of the graft-vertebral interfaces, and less than or equal to 2° of segmental movement on lateral flexion/extension radiographs).
Study Strengths & Weaknesses	This long term (7 year) extended follow-up study was able to demonstrate comparable safety and effectiveness outcomes (non-inferiority) between the PCM device and anterior cervical discectomy and fusion (ACDF). The study retained 91.5% of investigational subjects, and 89.6% of the control subjects from the original IDE study. The data are limited however to the subjects in the IDE study, which may not be necessarily be representative of real world use. There was a low rate of data availability for many endpoints and substantially different rates between the PCM and control group; as such, the data for additional measures (including patient satisfaction and radiographic measures) cannot be heavily interpreted. There was no requirement or prespecified methodology for investigator- performed radiographic assessments so the data regarding migration or HO as indication for SSSI may not be accurate. Also, fusion outcomes on those subjects undergoing removal SSSI were not captured during the study and so the study does not permit a conclusion regarding possible deleterious effect on fusion if performed after device removal.
Recommendations for Labeling Changes	The labeling should be updated to include the long-term follow-up data generated in this Post-Approval study.
General
Study Status	Completed
Application Number / Requirement Number	P070015 S054/ PAS001
Date Original Protocol Accepted	05/24/2011
Date Current Protocol Accepted	05/24/2011
Study Name	SPIRIT Small Vessel (SV) Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single-arm, open-label, US multi-center registry study to evaluate the safety and effectiveness of the 2.25 mm XIENCE V Everolimus Eluting Coronary Stent System (XIENCE V EECSS) in improving coronary luminal diameter in subjects with ischemic heart disease due to a maximum of two de novo native coronary artery lesions in small vessels, each in a different epicardial vessel.
Sample Size	150 subjects enrolled at up to 75 sites in the United States
Key Study Endpoints	The primary endpoint is the composite rate of cardiac death, target vessel myocardial infarction (MI) (per protocol definition), and clinically indicated target lesion revascularization (CI-TLR) at 1 year. This endpoint meets a pre-specified performance goal of 20.4% derived from the 2.25 mm DES data that was obtained in a literature review.
Follow-up Visits and Length of Follow-up	Clinical F/U: 30 days (clinic visit), 240 days and 1 year (clinic visit), 2, 3 years (clinic or telephone visit). Angiographic F/U: 240 days (only subjects in the angiographic cohort who received a 2.25 mm XIENCE V EECS are eligible).
Interim or Final Data Summary
Actual Number of Patients Enrolled	150
Actual Number of Sites Enrolled	33
Patient Follow-up Rate	88.2%
Final Safety Findings	The overall (0 - 1123 days) definite/probable stent thrombosis rate per ARC was 1.5% (2/130).
Final Effect Findings	-MACE Rates at 3 years: 12.1% (16/132) -TVR rates at 3 years: 13.6% (18/132) -TLF rates at 3 years: 12.1% (16/132) -Cardiac Death rates at 3 years: 3.8% (5/132)
Study Strengths & Weaknesses	Results provide further evidence of the clinical utility and safety of this device. The study had an acceptable rate of attrition, thus minimizing selection bias.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term performance of the device from the pre-market cohort.
General
Study Status	Completed
Application Number / Requirement Number	P100014 / PAS001
Date Original Protocol Accepted	05/27/2011
Date Current Protocol Accepted	02/26/2014
Study Name	Solesta - Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single-arm, multicenter, observational clinical study.
Study Population	Adults 18-75 years old with FI who have failed conservative therapy.
Sample Size	It is anticipated that at least 244 patients and as many as 293 patients may be enrolled in this Solesta PAS to obtain at least 150 evaluable patients from approximately 15-20 sites with more sites to be added if necessary to meet accrual within the 2-3 year target
Key Study Endpoints	The primary efficacy endpoint of this study is freedom from FI reintervention. The primary safety endpoint will be the occurrence of device-related AEs. Secondary Endpoints: The secondary safety endpoint will be the occurrence of peri-injection device-related infectious AEs. The secondary performance endpoints will be: 1) the presence or absence of implants (as assessed by the clinician) and 2) determine if any local shift has occurred at 6 and 36 months after the last Solesta treatment (as assessed by the clinician). Secondary Efficacy Endpoints: ¿ Fecal Incontinence Quality of Life will be assessed by the Rockwood instrument, at baseline, 6, 12, and 36 months after last Solesta treatment. ¿ Cleveland Clinic Florida Fecal Incontinence Score will be collected at baseline, 6, 12, and 36 months after last Solesta treatment. ¿ A patient global assessment of improvement (i.e., GPE-Score; 7- Point Scale) will be performed at 6, 12 and 36 months after last Time to FI reintervention will be measured from the date of last treatment with Solesta to the date of first FI reintervention.
Follow-up Visits and Length of Follow-up	36 months 3, 6, 12, 24 and 36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	283 subjects enrolled
Actual Number of Sites Enrolled	18 sites enrolled
Patient Follow-up Rate	67.6%
Final Safety Findings	Overall, 72 AEs related to the injection were reported in the study: 58 during the injection interval; 8 during the peri-injection interval and 6 during the long-term interval. There were 43 device-related AEs during the injection interval (less than or equal to 2 days post-Solesta injection); 9 during the peri-injection interval (> 2 days and greater than or equal to 2 weeks post-Solesta injection) and 6 during the long-term interval (> 2 weeks post-Solesta injection). There was also a total of 98 SAEs reported in 51 subjects (18.0%), none of which were device or injection related. Most of the device related events were gastrointestinal disorders that resolved quickly, and none were serious. The results for the secondary safety endpoint only include one patient with a device/procedure related infectious AE that was mild and resolved with antibiotic treatment.
Final Effect Findings	The primary objective was reached because at 36 months, 152 (79.2%) subjects were free from FI re-intervention and 40 (20.8%) were not. The rate of re-intervention 95% confidence interval was between 14% to 24.4% which is below 50%. Therefore, the primary effectiveness endpoint was achieved before and after sensitivity analysis considering the potential bias effect of missing values. The results regarding performance endpoints to assess the relative anatomic stability of the device were evaluated by the presence of implants and any local shift in the implant(s). Although technical difficulties with the ultrasound scans, in general, it was possible to notice that the device did not shift from one anatomic position to another. Additionally, the low rate of FI re-interventions (up to 24%) confirms that the device has a reasonable performance level.
Study Strengths & Weaknesses	Sample size and power were adequate throughout the study and until the end of the follow-up. Weaknesses: No concomitant comparator group was included; the follow-up rate was low (67%).
Recommendations for Labeling Changes	Labeling changes including the design, methods and results of the post-approval study are recommended given the importance of the postapproval results including the effectiveness, the adverse events and FI intervention rates.
General
Study Status	Terminated
Application Number / Requirement Number	P090002 / PAS001
Date Original Protocol Accepted	11/04/2011
Date Current Protocol Accepted	11/04/2011
Study Name	Pinnacle CoMplete Acetabular Hip System
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is a prospective, multi-center cohort study
Study Population	The study population is comprised of patients implanted with the Pinnacle CoMplete Acetabular System.
Sample Size	The sample size is 250 patients.
Key Study Endpoints	The primary endpoint is device survivorship. The secondary objective is to evaluate five year cobalt and chromium median metal ion levels along with renal function indicators to include BUN levels and creatinine levels.
Follow-up Visits and Length of Follow-up	10 years. Patients will receive clinical examination postoperatively at 4 weeks, 3 months, and 1, 2, 3,4, 5, 8, and 10 years. Patients will undergo radiographic examination at 4 weeks, and 1, 2, 3, 4, 5, 8, and 10 postoperative years. For patients in the metal ion study, metal ion testing and renal function testing will occur preoperatively and postoperatively at 1, 2, 5, 8, and 10 postoperative years.
General
Study Status	Hold
Application Number / Requirement Number	H190001 / PAS002
Date Original Protocol Accepted	12/05/2021
Date Current Protocol Accepted	10/16/2023
Study Name	HF PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objectives of the summative usability evaluation are to: 1. Demonstrate that the device can be used by representative intended users under simulated and actual use conditions, without producing patterns of failures that could result in a negative clinical impact to patients or harm to users or patients; 2. Demonstrate that the device design, representative training and labeling are effective in mitigating all use-related risks to an acceptable level; 3. Demonstrate that no new use-related hazards or hazardous scenarios have emerged, and evidence supports that benefits outweigh the residual use-related risks; and 4. Demonstrate that operators are able to prepare the solvent mixture correctly, including verification of the mixture.
Study Population	1. Age: 18+ years old 2. Gender: Male or Female 3. Education: Undergraduate degree 4. Experience: unrestricted 5. Primary Duties: Performs laboratory procedures, including preparing and testing specimens and recording results 6. Training: on-the-job instrument training, aseptic technique, blood/plasma handling procedure 7. Hearing: unrestricted 8. Vision: corrected vision or no impairments 9. Permissible impairments: appropriate to the job 10. Language: English 11. Cultural Background: unrestricted
Sample Size	The sample will consist of trained HDL Therapeutics professionals, N=5.
Key Study Endpoints	The summative usability study data collection and analysis is intended to provide sufficient and appropriate data to facilitate identification and understanding of the root causes of any use failures or problems that occur, including usability issues. The root cause analysis is intended to identify causes that are related to the design of the system, the system labeling (including IFU), and the training of test participants. Only the completion of the task without any observed use difficulties, use errors, or assistance from the moderator will be deemed a successful outcome. All other outcomes will be considered degrees of failure for which the moderator will observe and report the nature of the issues in greater detail. A failure can be classified as any assistance provided by the moderator to a test participant for any specific task, beyond what is provided during the training session. A failure can also result if the participant performs a task incorrectly and does not request help. The acceptable range for the number of attempts for this system is three. There will be a limit of 3 times a participant can attempt a task.
Follow-up Visits and Length of Follow-up	The follow-up will be immediately after the 8 hour training evaluation.
General
Study Status	Terminated
Application Number / Requirement Number	P100010 S110/ PAS001
Date Original Protocol Accepted	12/16/2021
Date Current Protocol Accepted	03/25/2024
Study Name	STOP AF First PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The primary objective is to estimate the 36-month freedom from AF/AFL/AT recurrence.
Study Population	Subjects greater than or equal to 18 years of age (or minimum age as required by local regulations) who have a recommendation for a pulmonary vein ablation with the Arctic Front™ Cardiac Cryoablation Catheter System may be approached regarding enrollment in this study.
Sample Size	Up to 200 subjects will be enrolled to ensure up to 175 subjects are treated.
Key Study Endpoints	Primary Safety Endpoint The occurrence of a Primary Safety Event defined as a serious cryoballoon procedure-related or serious cryoballoon system-related AE including the following; • Transient ischemic attack (within seven days of ablation procedure). • Cerebrovascular accident (within seven days of ablation procedure). • Major bleeding that requires transfusion (within seven days of ablation procedure). • Cardiac perforation, tamponade, or pericardial effusion (within seven days of ablation procedure). • Pulmonary vein stenosis (> 70% reduction within 6-months of ablation procedure). • Myocardial infarction (within seven days of ablation procedure). • Phrenic nerve injury (unresolved at 12-months). • Atrio-esophageal fistula (within 6-months of ablation procedure). • Death (within seven days of ablation procedure). Secondary Safety Endpoint • Characterize all reported AEs through 36-months. Main Effectiveness Endpoints Recurrent AF/AFL/AT recurrence through 36 months (after 90-day blanking period), defined as: • Documented recurrent AF/AFL/AT on a rhythm monitoring device. • Repeat ablation for the treatment of AF/AFL/AT. • Cardioversion for the treatment of AF/AFL/AT. Secondary Effectiveness Endpoints • Characterize the cryoablation procedure • Change in Quality of Life through 36-months • Estimate the freedom from symptomatic AF/AFL/AT recurrence through 36 months. • Estimate the freedom from AF/AFL/AT recurrence through 36 months for subjects on/off all Class I/III AADs after the 90-day blanking period. • Characterize data pre- and post- ablation captured by sensor device
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	93
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	91.2% (subjects with status unknown at 6 months)
General
Study Status	Completed
Application Number / Requirement Number	P100020 S017/ PAS001
Date Original Protocol Accepted	07/03/2018
Date Current Protocol Accepted
Study Name	COB-HPV-301 Post Approval Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study includes 10,000 women, 25 years or older from a general screening population for cervical disease. All subjects have results of the cytology test from specimens collected in Sure PathPreservative Fluid and cobas HPV Test results with SurePath specimens. Subjects with either abnormal or UNSAT Pap or positive cobas HPV Test results are referred to colposcopy/biopsy procedures. In addition, 250 subjects with NILM cytology and negative HPV results will be referred to colposcopy/biopsy. The study provides additional data regarding the clinical performance of the cobas HPV Test with SurePath samples as sensitivity, specificity, likelihood ratios, and predictive values for women 30 years or older and for women 25 years or older with ASC-US (atypical squamous cells of undetermined significance) cervical cytology test results.
Study Population	Women 25 years of age or older from a general screening population for cervical disease
Sample Size	10,000 or more
Key Study Endpoints	greater than or equal to CIN2 (Cervical Intraepithelial Neoplasia) and greater than or equal to CIN3 by colposcopic examination
Follow-up Visits and Length of Follow-up	A need for the follow-up study and the length of the follow-up depends on the estimates of clinical performance of the cobas HPV Test with SurePath specimens. Decision about the need of a follow-up study will be made based on the difference in risks of cervical disease for women with negative cobas HPV Test results and/or with positive Other 12 HR HPV cobas HPV Test and NILM cytology results estimated in the study in comparison with the risks for similar groups of women in the ATHENA study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	8095 women aged 30 years and older with NILM cytology were enrolled in the clinical study. Of those enrolled, 8088 women were evaluable.
Actual Number of Sites Enrolled	Subjects were enrolled at 11 U.S. sites.
Patient Follow-up Rate	Not applicable.
Final Safety Findings	No severe adverse events were reported.
Final Effect Findings	In the current study, it was demonstrated that the risks of cervical disease (greater than or equal to CIN2 and greater than or equal to CIN3 determined by colposcopy/biopsy) for women with HPV 16/18 positive results or with 12 Other HR HPV positive results obtained by cobas HPV Test in SurePath Preservative Fluid were higher than the risk of the cervical disease for women with cobas HPV Test negative results. In addition, these risks were compared to the corresponding risks when using an FDA-approved HPV test and the study demonstrated that these risks were similar.
Study Strengths & Weaknesses	Study strength: Women who were HPV negative and had NILM cytology were sent to colposcopy in the clinical study. The colposcopy results allowed estimation of the sensitivity and specificity of the device. Study weakness: Biopsy results of greater than or equal to CIN2 in NILM HPV negative women may not be definitive of cervical disease without follow-up information.
Recommendations for Labeling Changes	Labeling incorporating the data from post approval study was submitted and approved.
General
Study Status	Completed
Application Number / Requirement Number	P100021 S063/ PAS001
Date Original Protocol Accepted	09/29/2017
Date Current Protocol Accepted	05/28/2021
Study Name	Cont f/u ANCHOR Reg Short Neck Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to evaluate the long-term safety and effectiveness outcomes on the use of the Endurant II/IIs Stent Graft System to treat short neck infrarenal abdominal aortic aneurysms when used in conjunction with the Heli-FX EndoAnchor System. The study was originally approved with enrollment of 70 subjects to be followed for up to 5 years. Clinical safety and effectiveness outcomes from the 70 subjects were used to seek an indication expansion for the Endurant II/IIs Stent Graft System to treat short (proximal neck lengths greater than or equal to 4 mm and < 10 mm) neck infrarenal abdominal aortic aneurysms when used in conjunction with the Heli-FX EndoAnchor System. In May 2021, FDA approved a study expansion to include clinical data for 60 additional core lab-verified short neck subjects from the ANCHOR registry to support the long-term safety and effectiveness for the short neck indication. These additional 60 subjects will be followed through 5 years as per the ANCHOR clinical investigation plan requirements.
Study Population	Patients with an abdominal aortic aneurysm with an infrarenal neck length measured as greater than or equal to 4 to <10mm by the core laboratory, who met the selection criteria and who were treated with an Endurant or Endurant II/IIs Stent Graft System and the Heli-FX EndoAnchor System during the initial repair of their aneurysm.
Sample Size	70 patients were enrolled in Short Neck Cohort. Follow-up data on the surviving patients in this cohort will be reported in this PAS.
Key Study Endpoints	Clinical outcomes will include aneurysm-related mortality, aneurysm rupture, aneurysm expansion, Type Ia endoleak, migration, Type III endoleak, re-intervention, device-related adverse events, and device integrity.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	130 [70 original Short Neck (SN) subjects + 60 supplemental SN ANCHOR Registry subjects]
Actual Number of Sites Enrolled	40 sites (total contributing subjects to either original SN cohort or supplemental ANCHOR registry cohort)
Patient Follow-up Rate	All eligible subjects completed 5 years of follow-up. Of the 33 eligible subjects from the original SN cohort, 28 subjects (85%) completed clinical follow-up and 23 subjects (70%) completed imaging (including CT, DUS, and/or MRA) follow-up. Of the 35 eligible subjects from the supplemental SN ANCHOR Registry cohort, all 35 subjects (100%) completed clinical follow-up and 27 subjects (77%) completed imaging (including CT, DUS, and/or MRA) follow-up.
Final Safety Findings	Safety and Effectiveness Results The summary of results below includes events occurring between day 1 through day 2009 for endoleaks and aneurysm expansion, and events occurring between day 0 through day 1826 for aneurysm-related mortality, reintervention, aneurysm ruptures, migration, device-related adverse events and loss of device integrity. Aneurysm Related Mortality: Six subjects from the original SN cohort experienced aneurysm related mortality. The rate of freedom from aneurysm related mortality through 5 years in the original SN cohort was 90.1%. One subject from the supplemental SN ANCHOR cohort experienced aneurysm related mortality. The rate of freedom from aneurysm related mortality through 5 years in the supplemental SN ANCHOR cohort was 97.4% Reintervention: Eleven subjects from the original SN cohort had a total of 16 secondary procedures. Of the 16 procedures, 11 were secondary endovascular procedures, 3 were conversions, and 2 were other open surgical procedures. This cohort experienced a 76.9% rate of freedom from any secondary procedure through 5 years. One additional original SN cohort subject had a secondary endovascular procedure reported after the 5-year cutoff day. Eleven subjects from the supplemental SN ANCHOR cohort had 13 secondary procedures performed. Of the 13 procedures, 11 were secondary endovascular procedures and 2 were other open surgical procedures. The supplemental SN ANCHOR cohort experienced a 75.6% rate of freedom from any secondary procedures through 5 years. Aneurysm ruptures: Two subjects from the original SN cohort experienced ruptures. This cohort experienced a 95.6% rate of freedom from aneurysm rupture through 5 years. One additional original SN cohort subject experienced a rupture after the 5-year cutoff day. Two subjects from the supplemental SN ANCHOR cohort experienced ruptures. This cohort experienced a 96.6% rate of freedom from ruptures through 5 years. Aneurysm expansion: Nine subjects from the original SN cohort and eight subjects from the supplemental SN ANCHOR cohort experienced new aneurysm expansion through 5 years. Migration: None reported in either cohort through 5 years. Endoleaks: Nine subjects from the original SN cohort experienced 8 Type Ia endoleaks through 5 years. Four subjects from the supplemental SN ANCHOR cohort experienced Type Ia endoleaks through 5 years, including one reported on day 0 post implant. No Type III endoleaks were reported in either cohort through 5 years. Device Related Adverse Events (AEs): Six subjects from the original SN cohort experienced a total of 10 device-related AEs through 5 years. One additional original SN cohort subject had 2 device-related AEs after the 5-year cutoff day. Seven subjects from the supplemental SN ANCHOR cohort experienced a device-related AE through 5 years. Loss of Device Integrity: One subject in the original SN cohort experienced an EndoAnchor fracture through 5 years. No losses of device integrity events were reported in the supplemental SN ANCHOR cohort.
Study Strengths & Weaknesses	Strengths: The study SN cohort, which adhered to standard of care for clinical and imaging visits, was prospectively analyzed from the ANCHOR registry, a large, real-world, non-interventional study. No new safety or effectiveness concerns were observed in either real-world cohort over the long-term follow-up period. The outcomes were consistent and similar between the two study cohorts and demonstrated the long-term safety and effectiveness of the device combination and indication (Endurant II/IIs stent graft system in conjunction with the Heli-FX EndoAnchor system) in real-world use. Weaknesses: Visit windows were not prospectively defined in the ANCHOR protocol, and the timing and method of imaging collection were completed per local institution standard of care. The ANCHOR protocol included recommendations on imaging follow-up per the regional societal guidelines (SVS or ESVS) or local institutional guidelines but did not require investigators to follow specific imaging recommendations or bring subjects in for follow-up at specific timepoints. Overall, at all timepoints, imaging included a mix of CT scans and/or DUS modalities, and imaging visit compliance was lower than clinical visit follow-up compliance. Because imaging modalities such as DUS are not sensitive for detection of all endograft performance events (e.g., migration, stent fracture, fabric tear, etc.), under-reporting of these events may have occurred.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P100021 / PAS001
Date Original Protocol Accepted	05/09/2011
Date Current Protocol Accepted	01/24/2014
Study Name	ENGAGE
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 372 subjects were enrolled for the Engage PAS. The ENGAGE PAS cohort comprised of 328 subjects from the All Bifurcated arm and 44 subjects from the AUI IDE arm. The All Bifurcated arm included 178 de novo subjects and 150 Endurant IDE study subjects.
Actual Number of Sites Enrolled	All Bifurcated arm: A total of 27 sites enrolled the Endurant IDE cohort subjects and 24 sites enrolled the de novo cohort. Aorto-Uni-Iliac (AUI) IDE Arm: A total of 15 sites enrolled the (AUI) IDE arm.
Patient Follow-up Rate	The clinical follow up rate at 5 years was 90% (99/110) for de novo cohort, 94% (95/101) for Endurant IDE cohort, and 93% (27/29) for AUI IDE cohort.
Final Safety Findings	Aneurysm-related mortality (ARM)-All Bifurcated arm-The freedom from ARM at 5 years (Kaplan-Meier (KM) estimate) for all bifurcated arm subjects was 99% (95% CI: 97.9%, 100%). AUI IDE arm-The freedom from ARM at 5 yrs (KM estimate) for the AUI IDE subjects was 97.7% (95%CI: 93.3%, 100%). The lower 95% confidence limit for the 5-yr survival estimate for both the Bifurcated & AUI IDE cohorts were greater than the pre-specified performance goal of 92%. All-Cause Mortality-All Bifurcated arm-The freedom from all-cause mortality (KM estimate) thru 5 yrs for the All Bifurcated subjects was 76.8% (95%CI: 72.0%, 81.6%). In total 74 deaths were reported for the All Bifurcated arm, 48 in the de novo cohort & 26 in the Endurant IDE cohort. Two deaths in de novo cohort were adjudicated by the clinical event committee (CEC) as aneurysm and procedure-related deaths and one death in Endurant IDE cohort was adjudicated by the CEC as device and aneurysm related death. The remaining deaths were adjudicated by the CEC as not aneurysm, device, or procedure related. AUI IDE arm-The freedom from all-cause mortality (KM estimate) thru 5 yrs in the Endurant AUI cohort was 67.6% (95% CI: 53.5%, 81.6%). There were 14 deaths in this cohort and the CEC adjudicated one death as related to the procedure. The remaining 13 deaths were adjudicated by the CEC as not related to aneurysm, device or procedure. Aneurysm Rupture (AR)-All Bifurcated arm-No AR (0%) was reported for the de novo subjects in this cohort. Two Endurant IDE subjects experienced AR. The AR rate at 1 and 4 yrs for the All Bifurcated arm subjects were 0.3% (1/314) and 0.4% (1/251) at 1 and 4 yrs respectively. There were no reports of AR (0.0%) at 2, 3 and 5 yrs. AUI IDE arm-There were no AR thru 5 yrs (0%) in the AUI IDE cohort. Major Adverse Events (MAE)-All Bifurcated arm-The percentage of subjects in the All Bifurcated arm that experienced one or more MAE (including all-cause mortality, bowel ischemia, myocardial infarction, paraplegia, stroke, renal failure & respiratory failure) at 5 yrs follow-up was 8.8% (20/226). AUI IDE arm-The percentage of subjects in the AUI IDE arm that experienced one or more MAE at 5 yrs follow-up was 12.5% (4/32). Gender Analysis: A total of 45 females were enrolled in the All Bifurcated arm (32 in the de novo subjects and 13 Endurant IDE subjects), and 14 subjects enrolled in the AUI IDE arm. ARM-All bifurcated arm-Thru 5 yrs the freedom from ARM rate in both genders were similar. The freedom from ARM at 5 yrs (KM estimate) for female All Bifurcated subjects was 97.8% (95% CI: 93.5% to 100%), and for male All Bifurcated subjects was 99.2% (95% CI: 98.1% to 100%). AUI IDE arm-There was no ARM observed in female AUI IDE subjects. ARM occurred in only 1 male subject which resulted in freedom from ARM of 96.7% [95% CI: 90.2% to 100%] at 5 yrs. All Cause-Mortality-The percentage of female subjects that experienced all-cause mortality in All Bifurcated arm at 5 yrs was 11.1 % (3/27) in the AUI IDE arm at 5 yrs was 0.0% (0/11). MAE-The percentage of female subjects that experienced one or more MAEs in All Bifurcated arm at 5 yrs follow up was 14.8% (4/27), and 0% (0/11) in the AUI IDE Arm. Race Analysis-A total of 11 (9 de novo subjects and 2 Endurant IDE subjects) non-white subjects were enrolled in the All Bifurcated cohort and 2 non-White subjects were enrolled in the AUI IDE cohort ARM-The freedom from ARM at 5 yrs (KM estimate) for white subjects in All Bifurcated arm was 99% [95% CI: 97.8% to 100%] and in AUI IDE arm was 97.6% [95% CI: 93% to 100%]. There was no ARM reported for non-white subjects in All Bifurcated arm and AUI IDE arm. MAEs-All bifurcated arm-The percentage of non-white subjects in All Bifurcated arm that experienced one or more MAEs at 5 yrs follow up was 50.0% (2/4). AUI IDE arm-The percentage of non-white subjects in the AUI IDE arm that experienced one or more MAEs at 5 yrs follow -up was 0.0% (0/2).
Final Effect Findings	Aneurysm Expansion greater 5mm: The percentage of subjects with aneurysm expansion greater than 5mm at 5 years for All Bifurcated cohort was 5.8% (10/173) [95% CI, 2.8%, 10.4%] and 4.2% (1/24) [95% CI, 0.1%, 21.1%] for the AUI IDE cohort. Aneurysm Decrease greater 5 mm or stable: In both All Bifurcated cohort and AUI IDE cohorts, the majority of the subjects had aneurysm diameter decrease greater than 5mm or no change in size - All Bifurcated subjects 94.2%, and AUI IDE cohort 95.8%. Conversion to Open Surgical Repair - There were no conversions to open repair (0.0%) through 5 years in the All Bifurcated subjects or the AUI IDE subjects. Secondary Endovascular Procedure-The percentage of subjects that had secondary endovascular procedure at the 5-year time interval was 3.6% (8/220) for All Bifurcated cohort and 3.2% (1/31) for the AUI IDE cohort. Stent Graft Migration-Two (2) stent graft migrations greater than 10 mm occurred at days 1499 and 1479 (4 years) in two patients for de novo subjects. There was no stent graft migration greater than 10 mm in Endurant IDE subjects or in the AUI IDE subjects through 5 years. Endoleaks-All Bifurcated arm-In total nine (9) Type I endoleaks were reported in All Bifurcated subjects. The Type I endoleak rates reported for the timepoints were 0.3% (1/311) at 1 month, 0.7% (2/279) at 1 year, 0.8% (2/266) at 2 years, 0.5% (1/208) at 3 years, 1.6% (3/189) at 4 years and 0.0% (0/166) at 5 years. The Type II endoleak rates reported for All Bifurcated subjects at the timepoints were 11.3% (35/311) at 1 month, 9.3% (26/279) at 1 year, 9.4% (25/266) at 2 years, 10.1% (21/208) at 3 years, 11.6% (22/189) at 4 years and 9.6% (16/166) at 5 years. There were no Type III, Type IV, or Type V endoleaks reported for All Bifurcated subjects. AUI IDE arm-The type II endoleaks rate reported for AUI IDE subjects at the time points were 7.0% (3/43) at 1 month, 13.9% (5/36) at 1 year, 6.1% (2/33) at 2 years, 10.7% (3/28) at 3 years, 7.7% (2/26) at 4 years and 5.0% (1/20) at 5 years. There were no Type I, Type III, Type IV, or Type V endoleaks reported AUI IDE subjects. Technical observations-There were no stent graft twisting, stent graft kinking, and stent graft stenosis reported at 5 years for All Bifurcated subjects and AUI IDE subjects. Technical success-The technical success rate was 99.1% (325/328), 95% CI (97.4%, 99.8%) for All Bifurcated subjects and 97.7% (43/44), 95% CI (88.0%, 99.9%) for AUI IDE subjects indicating the successful delivery and deployment of the Endurant Stent Graft System in the planned location. Subgroup Analysis: Gender Analysis: Stent Graft Occlusion/ Loss of Stent Graft Patency There were no stent graft migration, no stent graft integrity, or no twisting reported in any of the female All Bifurcated subjects and AUI IDE arm at any time point. Aneurysm Expansion greater 5mm-One (1) female subjects in All Bifurcated arm experienced aneurysm expansion greater than 5 mm at the 3, 4, and 5-year time point, as compared to 1 month. There was no aneurysm expansion greater than 5mm reported for female AUI IDE subjects. Endoleaks-All bifurcated arm-Overall endoleaks were reported in 7 of 45 (15.6%) female All Bifurcated subjects. Type I endoleaks were reported in 2 of the 45 (4.4%) female All Bifurcated subjects. There were no Type III, Type IV, or Type V endoleaks reported at any time point. AUI IDE arm-The Type II Endoleaks were reported in 2 of 14 (14.3%) female AUI IDE subjects. There were no Type I, Type III, Type IV, or Type V endoleaks reported for female AUI IDE subjects at any time point. Race Analysis-There were no technical observations, aneurysm expansion >5mm, migration, stent graft integrity, kinking, twisting, occlusion, or stenosis reported in any of the non-white subjects for all bifurcated arm and AUI IDE arm.
Study Strengths & Weaknesses	Strength: The ENGAGE PAS was a prospective, longer term, multicenter study. The study met the primary endpoint and provided long-term data. Weakness: The sample size for AUI arm cohort is too small to make any definitive conclusion of safety and effectiveness. There were too few non-whites in both all bifurcated cohort and AUI IDE cohort to draw meaningful conclusions about the relationship between race/ethnicity and the device performance.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Other
Application Number / Requirement Number	P890055 S026/ PAS001
Date Original Protocol Accepted	03/15/2011
Date Current Protocol Accepted	03/15/2011
Study Name	Long-Term Surveillance of MedStream
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, single arm, multi-center study with consecutive enrollment. The null hypothesis for this study states that subjects implanted with the MedStream system will have a MedStream system-related AE rate that is greater than or equal to an Objective Performance Criterion (OPC).
Study Population	The study population included patients presenting for de novo implant or replacement of an implantable programmable infusion pump for intrathecal therapy.
Sample Size	Subjects will be enrolled in the study to account for loss to follow-up and for ineligibility to achieve evaluable subjects. The study will be conducted at a minimum and a maximum number of centers in the U.S. with prior IRB approval for this study.
Key Study Endpoints	The primary endpoint is based on Clinical Events Committee determination of relationship.
Follow-up Visits and Length of Follow-up	All subjects are to be followed for a few months and are required to have a minimum of office or hospital-based visits every few months as long as he/she is enrolled in this study. These visits will be documented in the study records, and data will be collected on the Subject's current intrathecal drug therapy. Follow-up visits will be scheduled as deemed necessary by the treating Clinician.
General
Study Status	Completed
Application Number / Requirement Number	P890055 S026/ PAS002
Date Original Protocol Accepted	12/17/2010
Date Current Protocol Accepted	03/15/2011
Study Name	Leachables Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The non-clinical study includes extraction and leachables testing. There are no stated hypotheses.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	Not applicable. This is a bench/lab study.
Key Study Endpoints	In order to determine the endpoints extraction testing and leachable testing will be performed.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A Bench Study
Actual Number of Sites Enrolled	N/A Bench Study
Patient Follow-up Rate	N/A Bench Study
Final Safety Findings	1. Leachables assessment of MedStream infusion pumps at intervals of 4 months, 8 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months, 84 months and 96 months 2. All results acceptable through 8 years.
Final Effect Findings	. Leachables assessment of MedStream infusion pumps at intervals of 4 months, 8 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months, 84 months and 96 months 2. All results acceptable through 8 years.
Study Strengths & Weaknesses	N/A Bench Study
Recommendations for Labeling Changes	No labeling change recommended.
General
Study Status	Completed
Application Number / Requirement Number	P100022 / PAS001
Date Original Protocol Accepted	11/14/2012
Date Current Protocol Accepted	02/15/2013
Study Name	New US Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multicenter study of newly enrolled U.S. patients.
Study Population	Patients with symptomatic vascular disease of the native above-the-knee femoro-popliteal arteries with a reference vessel diameter 4- 7 mm and total lesion lengths up to 140 mm per limb and 280 mm total. The study has no control group. The comparator is performance goal of 83.1% at 1 year.
Sample Size	200 new patients enrolled from a minimum of 10 sites across the United States.
Key Study Endpoints	Primary Endpoint: Target lesion Revascularization (TLR) at 1 year. Secondary Endpoints: thrombosis, stent fracture other adverse events.
Follow-up Visits and Length of Follow-up	1 year TLR assessment at 1 year. Stent thrombosis and other adverse events assessments at pre-discharge and 1 year.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of two hundred (200) patients were enrolled for this PAS. This includes 149 patients treated with stents less than or equal to 80 mm in length and 51 patients treated with stents greater than or equal to 100 mm in length.
Actual Number of Sites Enrolled	Seventeen (17) investigational sites were enrolled across the United States for the post -approval study (US PAS).
Patient Follow-up Rate	One hundred and ninety-four (194) of the 200 enrolled patents were eligible for 12 months visit and 175 patients completed the follow-up at 12 months for a rate 90.2% (175/194).
Final Safety Findings	safety and effectiveness endpoints: All patients The 12-month freedom from target lesion revascularization (TLR) rate in patients treated with the Zilver PTX stent (91.8%, 95% confidence interval:87.2%, 94.8%) met the non- inferiority performance goal of 83.1% (z test statistics, p<0.001). Study lesion thrombosis rate at 12 months was 2.5% (5/200). Stent fracture rate at 12 months was 0.4 (1/276). The rate of amputation of study limb at 12 months was 2.5% (5/200). The rate of worsened claudication/rest pain at 12 months was 13.5% (27/200). Subgroups: Short stent group- patients treated with stents less than or equal to 80 m m in length vs. long stent group- patients treated with stents greater than or equal to 100 mm in length The Kaplan-Meier estimates for freedom from TLR at 12 months for patients treated with stents less than or equal to 80 mm in length and those treated with stents greater than or equal to 100 mm in length were 91.9% and 92.2%, respectively (p=0.94, Log-Rank test), indicating no significant difference in the TLR rates between the subgroups. The 12-month rate of study lesion thrombosis was 2.7% (4/149) for the short stent group and 2.0% (1/51) for the long stent group (p > 0.99). Stent fracture rate at 12 months was 0.5% (1/214 stents) for the short stent group and 0% (0/62 stents) for the long stent group (P > 0.99). The rate of amputation of study limb at 12 months was 3.4% (5/149) for the short stent group and 0% (0/51) for the long stent group. The rate of worsened claudication/rest pain at 12 months was 14.8% (22/149) for the short stent group and 9.8% (5/51) for the long stent group.
Study Strengths & Weaknesses	This was a single-arm, non-randomized multicenter study involving United States patients with follow- up up to 12 months (available patients will be followed through 5 years in the Zilver PTX Stent PAS or PAS2). The follow up rate at 12 months exceeded 80%. The study met the primary endpoint hypothesis with freedom from TLR rate greater than the 83.1% performance goal, therefore confirms the safety and effectiveness of the Zilver PTX stent in the post-approval setting.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the data from the post-approval study. The labeling change should include a new section in the label showing a summary of the post Approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P100022 / PAS002
Date Original Protocol Accepted	11/14/2012
Date Current Protocol Accepted	01/13/2015
Study Name	Zilver PTX Stent PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multi-center study. Includes all subjects from the new US enrollment study, the Zilver PTX subjects from the premarket study, the Japanese post-approval study.
Study Population	Comprises of PAS 1 subjects, the Zilver PTX subjects from the pivotal study, and earliest sequentially enrolled subjects in the Japan PAS that are consistent with the US PAS selection criteria with the exception that lesion length per limb may extend up to 200 mm. Patients with symptomatic vascular disease of the native above-the-knee femoropopliteal arteries with a reference vessel diameter 4 to 7 mm and total lesion lengths up to 140 mm per limb and 280 mm total will be enrolled; for patients enrolled from the Japan PAS, lesion length per limb may extend up to 200 mm.
Sample Size	The sample size will comprise of 200 patients from the new US Enrollment enrolled from minimum of 10 sites, 300 premarket RCT patients enrolled at 47 sites in the US, and approximately 400 patients from the Japan postmarket study enrolled at 60-90 sites.
Key Study Endpoints	Target lesion revascularization (TLR), patency by duplex ultrasonography, and stent thrombosis assessed annually through 5 years in 900 subjects. Stent integrity assessed by x-ray imaging at 1, 3, and 5 years in 600 patients.
Follow-up Visits and Length of Follow-up	5 years Annual follow-up through 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Combined Cohort - 904 Pivotal – 305 Japanese Post-Approval Study – 399 US Post-Approval Study - 200
Actual Number of Sites Enrolled	Combined Cohort – 158 Pivotal – 52 Japanese Post-Approval Study – 89 US Post-Approval Study - 17
Patient Follow-up Rate	Combined Cohort Baseline 100% (904/904); 1 Year 96.3% (810/841); 2 Years 93.0% (681/732); 3 Years 92.9% 588/633); 4 Years 94.0% (513/546) 5 Years 451 completed study Pivotal Baseline 100% (305/305); 1 Year 98.2% (277/282); 2 Years 93.1% (228/245); 3 Years 95.7% (198/207); 4 Years 91.3% (167/183) 5 Years 146 completed study Japanese PAS Baseline 100% (399/399); 1 Year 97.6% (359/368); 2 Years 94.0% (297/316); 3 Years 90.9% (250/275); 4 Years 96.0% (218/227) 5 Years 190 completed study US PAS Baseline 100% (200); 1 Year 91.1% (174/191); 2 Years 91.2% (156/171); 3 Years 92.7% (140/151); 4 Years 94.1% (128/136) 5 Years 115 completed study
Final Safety Findings	Safety endpoints assessed for the combined cohort included: adverse events, occurrence of TLR, thrombosis, and stent integrity through 5 years. The primary safety hypothesis was freedom from TLR at 12-months against a performance goal of 83.1%. 12-month TLR rate of 91.8% met the non-inferiority performance goal of 83.1% (p < 0.0001). 5-year freedom from TLR rate - 80.8%. Through 5 years, the freedom from thrombosis rate - 96.5%. Stent integrity was assessed by X-ray at 1, 3, and 5 years. 5-year freedom from stent fracture rate of 98.5% 1 year – 3 fractures total 3 years – 12 fractures total 5 years – 14 fractures total > 5 years – 16 fractures total
Final Effect Findings	Effectiveness endpoint for the combined cohort was primary patency assessed by duplex ultrasound (PSVR < 2.0). Patency data were only available for the pivotal and US PAS studies; patency assessment was not required in the Japanese PAS. 5-year primary patency estimate - 59.3%.
Study Strengths & Weaknesses	The follow-up compliance and study deviations were within reasonable expectations
Recommendations for Labeling Changes	Additional information is available from these results that supplements information already contained in the publicly available SSED and labeling. Therefore, labeling changes are recommended
General
Study Status	Completed
Application Number / Requirement Number	P100018 / PAS001
Date Original Protocol Accepted	04/06/2011
Date Current Protocol Accepted	06/27/2011
Study Name	Continued Follow-up of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Single arm prospective cohort
Study Population	Pipeline Embolic Device pivotal study cohort and the (device and control continued access cohort follow up. These were patients group) with wide-necked intracranial aneurysms in the internal carotid artery from the petrous to the superior hypophyseal segments.
Sample Size	(no. 134 subjects, 2-subgroup analyses by aneurysm location study sites and and by hypertension status patients)
Key Study Endpoints	Ipsilateral stroke or neurovascular death Secondary: complete occlusion of treated aneurysm, stenosis of the parent artery in PED, and device-related adverse events.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Out of 138 consented patients, 135 patients were enrolled in the PUFS-PAS (108 PUFS between November 2008 and July 2009 + 27 PUFS-CA between May 2010 and April 2011) of which 134 PUFS- PAS patients were treated with the PED and 1 PUFS patient was not treated with the PED.
Actual Number of Sites Enrolled	12 centers (10 US, 2 OUS (1 Hungary, 1 Turkey)).
Patient Follow-up Rate	3- year follow-up rate: 107 / 130 (82.3%) 5-year follow-up rate: 100/128 (78.1%) Note: These are general follow-up rates. For specific endpoints (e.g. safety and effectiveness endpoints requiring the use of angiography), the follow-up rate may be less, potentially leading to selection bias, which may leads to an underestimate of rates for adverse events or complications.
Final Safety Findings	The primary endpoint (incidence of ipsilateral stroke or neurovascular death at 5-year follow-up) was 8.3% (11/134; 95% CI: 4.7%-14.4%), meeting the threshold of success of < 25%. There was no significant difference according to aneurysm location (at or below cavernous segment vs. at or above ophthalmic segment) in incidence of ipsilateral stroke or neurovascular death at 5-year follow-up. There was a significantly higher incidence of ipsilateral stroke or neurovascular death at 5- year follow-up (P=0.0067) among patients with a history of hypertension (10/70 (14.3%)) vs. patients without a history of hypertension (1/64 (1.6%)). Seven device related adverse events were observed during the long-term follow-up period: 5-year follow-up: 7 / 106 (6.6%) 0- to 3-year follow-up: 5/106 (4.7%) 4- to 5-year follow-up: 2/99 (2.0%) Parent artery stenosis: 3 years 5 years 0-25% 80% (80/100) 80% (64/80) >25-50% 8.0% (8/100) 5.0% (4/80) >50%-75% 0.0% (0/100) 1.3% (1/80) >75% 3.0% (3/100) 2.5% (2/80) Indeterminate 9.0% (9/100) 11.3% (9/80) Note: A total of 100 out of 106 patients had available parent artery stenosis data at 3 years of follow- up and a total of 80 out of 99 patients had available parent artery stenosis data at 5 years of follow- up. Therefore, follow-up rate is less than the overall follow-up rate at 3 years and 5 years. The finding that parent artery stenosis is less problematic at 5 years of follow-up as compared to 3 years of follow-up may be explained by selection bias. Opthalmic artery flow at 1-year follow-up was 49 / 65 or 75.4% of patients.
Final Effect Findings	Complete aneurysm occlusion at 3-year follow-up was 90 / 100 or 90.0%. Complete aneurysm occlusion at 5-year follow-up was 75 / 80 or 93.8%.
Study Strengths & Weaknesses	Strengths: The prospective cohort design may be less prone to bias. Long-term follow-up of patients until 5 years post-procedure. Powered to meet objective performance criterion for primary endpoint. Definitions of safety and effectiveness endpoints facilitate comparison with literature. Pre-specified primary, secondary and descriptive safety and effectiveness endpoints as well as sub- group analyses. Follow-up rates were acceptable, limiting selection bias. Independent assessment of endpoints, limiting misclassification bias. Sensitivity analyses were performed to account for losses to follow-up. Weaknesses: Primary endpoint is composite in nature and there is not enough power to evaluate components of this safety endpoint. Findings from worst-case imputation were inconsistent with findings from optimistic, completers, Kaplan-Meier and predictive distribution, with regard to 5-year complete occlusion rate and 5-year parent artery stenosis of 0-25%. The 3-year follow-up rate was 107 / 130 (82.3%) and the 5-year follow-up rate was 100/128 (78.1%). However, these are general follow-up rates. For specific endpoints (e.g. safety and effectiveness endpoints requiring the use of angiography), the follow-up rate may be less, potentially leading to selection bias.
Recommendations for Labeling Changes	A history of hypertension is associated with increased risk of ipsilateral stroke or neurovascular death following PED treatment.
General
Study Status	Completed
Application Number / Requirement Number	P010012 S212/ PAS001
Date Original Protocol Accepted	11/10/2010
Date Current Protocol Accepted	01/14/2011
Study Name	Longitudinal Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The LSS of 4-SITE is a prospective, nonrandomized, multi-center registry of patients implanted with the 4-SITE Lead/Header system.
Study Population	Patients implanted with the 4-SITE Lead/Header system
Sample Size	1,780 patients.(assuming an annual attrition rate of 10%, a minimum of 1,780 patients implanted with the 4-SITE lead is necessary to obtain 5-year follow-up data on approximately 1050 patients)
Key Study Endpoints	For the 4-SITE Lead/Header system, the primary endpoint for this registry will evaluate the proportion of patients without a chronic 4-SITE Lead/Header-related complication within five years post-implant.
Follow-up Visits and Length of Follow-up	Five-years post implant Every six months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1820 subjects
Actual Number of Sites Enrolled	111 sites
Patient Follow-up Rate	5 years post-implant
Final Safety Findings	The sponsor reported a complication-free rate through 60 months for the 4-SITE Lead/Header system of 98.9% with a one-sided 95% lower confidence limit of 98.5%. The lower confidence limit is higher than the performance goal of 92.5%. The sponsor also reported 17 adverse events that contributed to the primary endpoint. All lower confidence limits for all events types are within 1% of the complication free rate.
Final Effect Findings	Please see above
Study Strengths & Weaknesses	The sponsor has collected sufficient data to address the primary objective of the study which was to estimate the five year Endotak Reliance 4-Site defibrillation lead related chronic complication-free rate. The Agency recommends that the sponsor update the labeling to incorporate the study findings.
Recommendations for Labeling Changes	FDA recommends that the sponsor update the labeling for these devices to reflect the long-term data from the Post Approval Study.
General
Study Status	Completed
Application Number / Requirement Number	P100023 / PAS001
Date Original Protocol Accepted	04/22/2011
Date Current Protocol Accepted	04/22/2011
Study Name	PERSEUS Workhorse and Small Vessel (SV)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	PERSEUS Workhorse: 1,249 PERSEUS Small Vessel: 223
Actual Number of Sites Enrolled	PERSEUS Workhorse: 90 PERSEUS Small Vessel: 28
Patient Follow-up Rate	PERSEUS Workhorse: 92% at five years PERSEUS Small Vessel: 93.7% at five years
Final Safety Findings	PERSEUS Workhorse: Results at five years: -MACE (cardiac death, MI, TVR) TAXUS Express (18.2%) and TAXUS Element (18.6%) -All death TAXUS Express (6.9%) and TAXUS Element (6.8%) -All death and MI TAXUS Express (9.6%) and TAXUS Element (10.6%) -Non-cardiac death TAXUS Express (2.9%) and TAXUS Element (3.3%) -ARC stent thrombosis, definite/probable TAXUS Express (0.7%) and TAXUS Element (1.1%) At five years, there were no statistically significant differences between the groups in any of the safety outcomes examined. PERSEUS Small Vessel: Results at five years: -MACE (cardiac death, MI, TVR) TAXUS Element (30.2%) and BMS (41.3%, P<0.05) -All death TAXUS Element (14.9%) and BMS (9.6%) -All death and MI TAXUS Element (15.9%) and BMS (15.2%) -Non-cardiac death TAXUS Element (15.9%) and BMS (15.2%) -ARC stent thrombosis, definite/probable TAXUS Element (0.6%) and BMS (2.1%)
Final Effect Findings	PERSEUS Workhorse: Results at five years: -Target lesion failure (TLF) TAXUS Express (13.7%) and TAXUS Element (12.8%) -Target vessel failure (TVF) TAXUS Express (17.9%) and TAXUS Element (17.5%) -Target vessel revascularization (TVR) TAXUS Express (13.3%) and TAXUS Element (13.3%) There was no statistically significant difference between the groups in any of the effectiveness outcomes examined. PERSEUS Small Vessel: Results at five years: -Target lesion failure (TLF) TAXUS Element (21.5%) and BMS (35.2%, P<0.05) -Target vessel failure (TVF) TAXUS Element (30.2%) and BMS (39.4%) -Target vessel revascularization (TVR) TAXUS Element (23.6%) and BMS (34.9%, P<0.05)
Study Strengths & Weaknesses	The PERSEUS Workhorse study was prospective, randomized, controlled, single-blind, non-inferiority trial with a sample size of 1,262 subjects. The PERSEUS Workhorse study met its performance goals. The PERSEUS Workhorse PAS included only subjects with a study stent implanted (n=1,249) and followed them up to five years. Strengths of this PAS include randomized treatment assignment; a low rate of attrition in both treatment groups, thus minimizing selection bias; and a large sample size. The PERSEUS Small Vessel study was a prospective, single-aim, superiority trial with an historical control. A total of 223 subjects were implanted with the TAXUS Element stent and compared with 125 matched bare metal (BMS) Express stent subjects from the TAXUS V trial. The subjects were followed-up to five years. Strengths of this PAS include a control group; and a low rate of attrition, thus minimizing selection bias.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term performance of the device from the pre-market cohorts.
General
Study Status	Completed
Application Number / Requirement Number	P100023 / PAS002
Date Original Protocol Accepted	04/22/2011
Date Current Protocol Accepted	12/18/2014
Study Name	ION Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, open-label, multi-center cohort study
Study Population	Newly Enrolled Post-approval Study Population Consecutive patients who are eligible to receive a ION Stent as indicated by the product labeling will be evaluated for enrollment into the study ION US Post Approval Study (PAS). Only those participants in the PAS cohort that are identified as PERSEUS-like will contribute towards the primary endpoint and the main secondary endpoint. Data from the entire PAS cohort will be used in the additional secondary endpoints. PERSEUS-like has been defined as all patients without acute MI, graft stenting, chronic total occlusion, in-stent restenosis, failed brachytherapy, bifurcation, ostial lesion, severe tortuosity, moderate or severe calcification by visual estimate in target lesion or target vessel proximal to target lesion, multivessel stenting, Reference Vessel Diameter (RVD) < 2.25 mm, RVD > 4.00 mm, lesion length > 28 mm, cardiogenic shock, acute or chronic renal function (serum creatinine > 3.0mg/dl or patient on dialysis). PERSEUS-like TAXUS Element Population The new PERSEUS-like ION US PAS cohort participants will be combined with the following extant cohorts of the TAXUS Element (ION) patients from the TAXUS PERSEUS Workhorse (WH) and Small Vessel (SV) Clinical Trials and the TAXUS Element PERSEUS-like patients from the TAXUS Element EU COA study (TE-Prove). This will constitute the PERSEUS-like TAXUS Element total study population evaluated under the Primary Endpoint, Main Secondary Endpoint, and Diabetic Subset analysis.
Sample Size	The ION US PAS uses data from their newly enrolled subjects and other ION studies. The newly enrolled ION PAS US cohort will be 1,115 subjects enrolled at up to 65 U.S. sites. The ION population is expected to be approximately 1,901 subjects with 12- month follow-up. This includes the 1,140 ION subjects from the TAXUS PERSEUS WH and SV Clinical Trials with 12-month follow-up, 360 ION PERSEUS-like subjects from the TAXUS Element EU COA study (TE-Prove) and approximately 401 ION PERSEUS-like subjects from the ION US Post- Approval Study. To allow for approximately 3.5% attrition per year, 2,012 PERSEUS-like subjects will be required to provide at least 1,660 PERSEUS-like subjects through 3-year follow-up. This will include 1,166 subjects enrolled in the TAXUS PERSEUS WH and SV Clinical Trials, 400 ION PERSEUS-like subjects from the TAXUS Element EU COA study (TEProve) and approximately 446 ION PERSEUS-like subjects from the ION US Post Approval Study. Assuming that 40% of the total enrolled population is on-label subjects, a total enrollment of 1,115 subjects will be required in the ION US post-approval study.
Key Study Endpoints	Primary Endpoints The 12-month CD/MI rate for ION Secondary Endpoints Annual increase in Academic Research Consortium (ARC) (definite/probable) ST rate in the PERSEUS-like ION population, starting at 24 months. Additional secondary endpoints include: 1. Stent Thrombosis (ST) rate, using Academic Research Consortium (ARC) definition (definite/probable) in the following populations: overall subject population, ION on-label subject population and off- label subject population. 2. Rate of longitudinal stent deformation. 3. Overall and ION stent-related MACE rates (cardiac death, MI, TVR). 4. Overall and ION stent-related cardiac death or MI rates. 5. Overall and ION stent-related target vessel failure (TVF) rates. 6. Overall and ION stent-related TVR rates. 7. Overall and ION stent-related cardiac death rates. 8. Overall and ION stent-related MI rates. 9. All death rates 10. Non-cardiac death rates 11. All death or MI rates 12. Historical TAXUS definition stent thrombosis rates
Follow-up Visits and Length of Follow-up	2 years 30-Day, 6-Month, and 1 and 2 Years
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 1,111 subjects were enrolled in the ION post-approval study. The ION PERSEUS-like population for the primary and primary secondary endpoint analysis (n=1,789) comprised of 1,166 subjects enrolled in the TAXUS PERSEUS Workhorse and Small Vessel Clinical Trials, 306 ION PERSEUS-like subjects from the TAXUS Element EU COA study and 317 ION PERSEUS-like subjects from the ION US Post Approval Study.
Actual Number of Sites Enrolled	49 sites
Patient Follow-up Rate	At two years the follow-up rate was 92.26% (1025/1111). This study was originally designed to follow-up the subjects five years post-procedure. The study follow- up was reduced to two years post-procedure because available long-term evidence showed that the rate of late stent thrombosis for this device was not expected to substantially increase after 2 years.
Final Safety Findings	The annual increase in Academic Research Consortium (ARC)-defined (definite/probable) stent thrombosis (ST) for the ION stent from the pooled ION PERSEUS-like subjects is 0.23% (4/1720) with an upper 1-sided 95% confidence interval of 0.37% which is less than the pre-specified performance goal of 1% (p<0.0001).
Final Effect Findings	The overall cardiac death or myocardial infarction rate for the ION PERSEUS-like subjects is 2.3% (40/1729) with an upper one-sided 95% confidence interval of 2.9% which is less than the pre-specified performance goal (p < 0.0001).
Study Strengths & Weaknesses	This study met its performance goals and had a large sample size. This study demonstrated that the ION Paclitaxel-Eluting Coronary Stent System had a rate of ARC-definite/probable ST to be significantly less than 1% year-to-year. The study also had a low rate of attrition, thus minimizing selection bias. Subject follow-up was only for two-years. However, this device has been assessed long-term in other studies.
Recommendations for Labeling Changes	A labeling change is not recommended because the results of this post-approval study are consistent with those of the PERSEUS Clinical Trial Program. The current label of the ION Paclitaxel-Eluting Platinum Chromium Coronary Stent System includes longer-term (5 years) results on the PERSEUS Clinical Trial Program.
General
Study Status	Delayed
Application Number / Requirement Number	P100026 / PAS002
Date Original Protocol Accepted	11/14/2013
Date Current Protocol Accepted	09/28/2020
Study Name	New Enrollment - All Comers
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objectives The primary safety objective is to characterize the annual serious adverse event (SAE) rate over 5 years. The secondary safety objective is to demonstrate that there is not a worsening in seizures over time in patients treated with the RNS® System beginning at 6 to 12 months post-implant and extending to 3 years. The primary effectiveness objective will be to estimate the median percent reduction in seizures from baseline (3 months pre-implant) to 3 years in the PAS, and evaluate if this reduction is comparable to the median percent reduction in seizures from baseline to 3 years in the controlled clinical study (51.3%). The secondary objective will be to characterize observed battery longevity overall and in relation to total stimulation time and stimulation programming at 5 years. Additional objectives will be to describe the demographic and clinical characteristics of treated patients, additional procedures including explants and re-implants (reasons, associated complications, and resolution), responder rate, antiepileptic drug (AED) use, discontinuations, and autopsy data. Design An All-comer, 5-year, non-randomized open-label prospective observational study in newly implanted patients treated with the RNS System. .
Study Population	The study population will consist of individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to 2 or more antiepileptic medications, and currently have frequent and disabling seizures.
Sample Size	Up to 375 subjects may be enrolled from up to 30 sites in order that a minimum of 300 subjects be implanted, with no individual investigational site implanting more than 15 subjects. Assumptions: The sample size calculation is based on the endpoint related to the secondary safety onjective (seizure worsening). Sample size calculation for a regression model with a log link and including a term for linear slope in the dependent variable indicates that 240 patients will provide over 80% power for the ability to detect a possible slope equivalent to a 20% cumulative increase in seizures over the period from pre-implant to 30 to 36 months post-implant. The sample size calculation assumes a linear regression t test of the slope with a one sided alpha of 0.05, and a standard deviation of 0.28 applicable to the term for linear slope. Conservatively assuming approximately 25% of patients do not contribute the full 3 years of data leads to selection of 300 implanted patients as the sample size.
Key Study Endpoints	Primary Safety Endpoint: Severe adverse event rate; Secondary Safety Endpoints: Seizure worsening Primary effectiveness endpoint: Median percent reduction in seizures Additional endpoint: Neurostimulator batter longevity patients characteristics, all-cause mortality, antiepileptic drug (AED) use, subject disposition, RNS system explant/revision, SUDEP rate, responder rate, seizure frequency.
Follow-up Visits and Length of Follow-up	Enrollment plan: 2 patients every other month after the first site is enrolled, 12 patients per month after all sites are enrolled. The study consists of: (a) pre-implant criteria Informed consent process Review medical/seizure history (b) initial implant, Perform examination Review medications Review seizure data Administer Columbia suicide severity rating scale (C-SSRS) Review adverse events Perform surgery activities and (c) post-implant follow-up. Complete implant registration form Distribute Magnet/Remote Monitor Manage Neurostimulator Up to 5 years
General
Study Status	Delayed
Application Number / Requirement Number	P100026 / PAS003
Date Original Protocol Accepted	11/14/2013
Date Current Protocol Accepted	09/28/2020
Study Name	New Enrollment -Performance & Programming
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Objectives The primary safety objective is to characterize the annual serious adverse event (SAE) rate over 5 years in patients treated with the RNS System. The primary effectiveness objective is to demonstrate the median percent reduction in disabling seizures from baseline (3 months pre-implant) to 3 years in the PAS, and evaluate if this reduction is comparable to the median percent reduction in seizures from baseline to 3 years in the LTT controlled clinical study. The secondary safety objective is to demonstrate that there is not a worsening in seizures over time in patients treated with the RNS® System beginning at 6 to 12 months post implant and extending to 3 years. Additional objectives include characterizing, describing, and evaluating: Patient characteristics Adverse events of particular relevance All-cause mortality Anti-epileptic drug (AED) use Subject disposition RNS System explant/revision Sudden unexpected death in Epilepsy (SUDEP) rate Median percentage change Responder rate Seizure frequency in sub-populations of subjects treated with the RNS® System. Programming-related: The primary safety objective is to demonstrate that there is no difference in safety in the 6-week perioperative period based on the experience of NeuroPace qualified and trained implanting physicians. The co-primary safety objective is to demonstrate that there is no difference in safety 1 year post implant on the experinece of NeuroPace qualified and trained treating physicians and Comprehensive Epilepsy Centers. The primary effectiveness objective is to demonstrate that the stimulation programming classes have similar effects on the overall seizure frequency. The secondary objective is to characterize the effects of the stimulation programming classes on the overall 5 year rate of SAEs and device related non serious AEs. Design: A 5 year, non randomized open label prospective observational study in newly implanted patients treated with the RNS system.
Study Population	The study population will consist of individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to 2 or more antiepileptic medications, and currently have frequent and disabling seizures.
Sample Size	Sample size: Up to 375 subjects may be enrolled from up to 30 sites in order that a minimum of 300 subjects be implanted, with no individual investigational site implanting more than 15 subjects. Assumptions: The sample size calculation is based on the endpoint related to the secondary safety objective (seizure worsening) Sample size calculation for a regression model with a log link and including a term for linear slope in the dependent variable indicates that 240 patients will provide over 80% power for the ability to detect a possible slope equivalent to a 20% cumulative increase in seizures over the period from pre-implant to 30 to 36 months post-implant. The sample size calculation assumes a linear regression t test of the slope with a one sided alpha of 0.05, and a standard deviation of 0.28 applicable to the term for linear slope. Conservatively assuming approximately 25% of patients do not contribute the full 3 years of data leads to selection of 300 implanted patients as the sample size.
Key Study Endpoints	Primary Safety Endpoint: SAE rate; Secondary Safety Endpoins: Seizure worsening Primary effectiveness endpoint: Median percent reduction in seizures Programming-related endpoints: Primary Safety Endpoint - Neurosurgeon Experience Primary Safety Endpoint - Physician Experience Primary Effectiveness Endpoint - Neurostimulator Programming Secondary Safety Endpoint - Neurostimulator Programming
Follow-up Visits and Length of Follow-up	5 years Patients will be followed through 5 years with assessments at 15 days, 1 month, 3 months, 6 months, 9 months, 12 months, and then every 4 months until 60 months upon conclusion of the study.
General
Study Status	Completed
Application Number / Requirement Number	P100026 / PAS004
Date Original Protocol Accepted	11/14/2013
Date Current Protocol Accepted	02/18/2014
Study Name	Lead Extraction Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is an open-label prospective observational study of patients treated with the RNS System. Patients are from both continued follow-up of premarket cohorts and new enrollment.
Study Population	All patients implanted with the RNS Neurostimulator and/or Lead(s), including patients in the LTT study and the RNS System PAS2 study, as well as non-study patients whose product data are monitoring systems that consent and have surgical procedures for explant/removal, reimplantation, or revision of the Neurostimulator and Lead(s).
Sample Size	A minimum of 20 procedures to remove a Lead must be collected.
Key Study Endpoints	The incidence and number of adverse events related to surgical procedures associated with implant, explant/removal, reimplantation, and revision of the Neurostimulator and Lead(s) Two groups of adverse events will be presented: (1) adverse events that lead to a surgical procedure, and (2) adverse events that occur as a consequence of a surgical procedure (i.e. complication). Within each of the 2 adverse event groups, the incidence and number of events will be presented for 3 categories: ¿ Serious adverse events ¿ Serious device-related adverse events ¿ Non-serious adverse
Follow-up Visits and Length of Follow-up	N/A and N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	The pool of subjects enrolled could originate from the other ongoing post-approval clinical studies as well as from commercial use; the number of subjects enrolled was not a reporting requirement for this PAS. During the time period studied, a total of 745 patients underwent 823 surgeries related to the RNS NeuroPace system and were eligible for PAS 4. For this lead extraction study, there were 54 attempts in 53 patients to extract a lead.
Actual Number of Sites Enrolled	The pool of study sites could originate from the other ongoing post-approval clinical studies as well as from commercial use. The number of study sites enrolled was not a reporting requirement for this PAS 4.
Patient Follow-up Rate	NA. Follow-up rate is only relevant to those PAS 4 participants who originated from PAS 1 and PAS 2, but not also commercial use participants. Follow-up was not part of this PAS reporting requirements.
Final Safety Findings	There was a cumulative total of 104 adverse events (AEs) reported as occurring with an RNS System surgery for an incidence of 12.6% (104/823 surgeries). 76 of the 104 events (73%) were serious AEs for (SAE incidence of 76/823 or 9.2%). 56 of the 104 events (53.8%) (28/56 serious) were attributed directly to the RNS System surgery (a consequence of surgical procedure). 21 of the 104 events (20.2%) were not related to a prior RNS System surgery but led to a procedure involving the RNS System (all serious). 27 of the 104 events (26%) were both a consequence of a prior RNS System surgery and led to one or more subsequent RNS System surgeries (all serious). The frequency of AEs was comparable to the incidence of AEs reported in the PMA. Infection was the highest reported adverse event. Lead revision rate remained low. Reasons for explantation and analysis of devices returned revealed no concerns related to the device. There were no unexpected adverse events reported.
Final Effect Findings	The study was designed to evaluate safety only.
Study Strengths & Weaknesses	Adverse events related to the surgical procedures related to the implant, explant or revision of the RNS neurostimulator and leads were characterized in 823 surgeries from 745 eligible patients including long term treatment, new enrollment (all comers), and commercial use patients. The study also provided lead extraction data on 54 lead extraction attempts in 53 patients. A study weakness is that the study only reported deaths if they were related to the device; this PAS was not designed to capture possible cofounders that could be contributing to cause of death.
Recommendations for Labeling Changes	NONE
General
Study Status	Completed
Application Number / Requirement Number	P100026 / PAS005
Date Original Protocol Accepted	11/14/2013
Date Current Protocol Accepted	02/14/2014
Study Name	Autopsy Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is a non-randomized, open-label, observational study of patients treated with the RNS System.
Study Population	All patients implanted with the RNS Neurostimulator and/or Lead(s) who die and in whom it is possible to obtain an autopsy, including patients in the LLT study and the RNS System PAS2 study, as well as non-study patients whose product data are tracked via the NeuroPace customer service and product monitoring systems.
Sample Size	A minimum of 15 autopsies must be conducted as part of the study
Key Study Endpoints	1. Data from autopsies obtained from any patient implanted with the Neurostimulator and Lead(s). 2. Secondary endpoint - additional data. Demographic and other data for each patient whose autopsy data are included in the primary endpoint
Follow-up Visits and Length of Follow-up	N/A and N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	19
Actual Number of Sites Enrolled	NA
Patient Follow-up Rate	NA
Final Safety Findings	No safety concerns
Final Effect Findings	No effectiveness concerns
Study Strengths & Weaknesses	Descriptive data provided
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P100034 / PAS002
Date Original Protocol Accepted	02/09/2016
Date Current Protocol Accepted	02/09/2016
Study Name	Registry Study for Optune System
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a new enrollment, non-randomized, open label, post-approval registry study of Optunein recurrent glioblastoma multiforme (GBM) patients. Treatment group is prospectively enrolled, the historica control ground is from the IDE study. Primary objective: To confirm that the efficacy of Optunein patients with recurrent GBM treated in a real life setting following approval is comparable to that of Best Standard of Care (BSC) chemotherapy patients in the pivotal trial. Secondary objective: •To collect additional data on the safety profile of the Optune in a real life setting •To define Optune overall survival (months) by MGMT methylation status (where available). •To define Optune overall survival (months) by baseline MMSE score (where available) •To compare time to treatment failure (months) on Optune to that of BSC chemotherapy patients. •To evaluate Optune functional impairment using Karnofsky Performance Score (KPS) (where available)
Study Population	The treatment group will consist of 192 patients who will receive Optune monotherapyuntil clinical disease progression. Minimal recommended treatment duration – 4 weeks. Patients in the Optune group will be encouraged to use the device for at least 18 hours a day(monthly average). Patients will be enrolled through the PRiDe registry, sponsored by Novocure. Best standard of care chemotherapy (control) group from the EF-11 pivotal study control group. The control arm consisted of the 117 BSC group patients. These patients were treated with the best standard of care chemotherapy available in the US at the time of the study. Inclusion Criteria: •22 years of age or older •Histological diagnosis of GBM (WHO grade IV) •Tumor located in the supra-tentorial region of the brain •Received maximal, safe, surgical resection •Received maximal radiation therapy (45-70Gy) •Received concomitant Temozolomide (75mg/m^2/day for 6 weeks) •Received maintenance Temozolomide (150-200 mg/m^2 daily for 5 days followed by 23 days without treatment for 6 cycles or until disease progression) •Any recurrence (based on radiological or histological evidence of recurrence) •Karnofsky performance score 70 or above •Women of childbearing age must be on effective contraception •Signed consent to use PHI in the Optune registry Exclusion Criteria •Implanted electronic medical device in the brain: oDeep brain stimulator oVagus nerve stimulator oProgrammable shunt •Skull defect without replacement •Receiving concomitant chemotherapy •Unable to comply with treatment with Optune •Pregnant •Actively participating in another therapeutic clinical trial •Radiological suspicion of pseudoprogression or radionecrosis (a cold PET scan or negative biopsy are required in order to rule out these conditions if radiological suspicion exists) •Any serious co-morbidity which is expected to affect survival more adversely than GBM
Sample Size	Treatment arm: N1=192 Optunepatients Comparator arm: N2=117 best standard of care control patients from the EF-11 pivotal study Assumptions: ¿2 = 0.1083 (hazard of death in the recurrent GBM pivotal study BSC control group) Type I error: 0.05 Power: 0.80 Test statistics: Log-rank test Lost to follow-up: 10% in the Optune arm only
Key Study Endpoints	Primary endpoint: Overall survival Secondary endpoints: • Adverse event incidence by body system and term, • including: o Incidence of seizures and headaches • Overall survival (months) by MGMT methylation status (where available) • Overall survival (months by baseline MMSE score (where available) • Time to treatment failure (months)
Follow-up Visits and Length of Follow-up	The range of follow-up is from 12 months to three years. Patients will be followed until death or the end of the study (up to three years). The last patient enrolled will be followed up to 12 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	192
Actual Number of Sites Enrolled	Registry study with all optune certified sites in the U.S.
Patient Follow-up Rate	26 out of 192 subjects censored at 12-months follow-up. Follow-up rate is unavailable for survival study.
Final Safety Findings	A total of 33 patients experienced serious adverse events (SAEs) in the Optune registry population, compared to 41 patients in the EF-11 Best Standard of Care (BSC) population, respectively. The incidence of patients with SAEs was lower in Optune registry arm compared to the EF-11 BSC arm (17% vs. 45%, respectively). No Optune-related SAEs were reported in the registry dataset.
Final Effect Findings	The study used historical control, which is associated with potential limitations such as selection bias, differences in baseline characteristics, diagnosis, and outcome assessment. The length of median 12-month overall survival (OS) in the Optune registry arm was numerically longer than that in the BSC group but does not meet statistical significance (log-rank p=0.053), suggesting Optune treatment is not worse (or non-inferior) than the BSC treatment.
Study Strengths & Weaknesses	Study Strength: The registry Study for Optune System is a prospective registry study with subjects enrolled from all Optune certified oncology centers in the U.S. The study has a prespecified statistical analysis plan to assess non-inferiority of the Optune treated group compared to the BSC group. Study Weaknesses: 12-months overall survival (12- months) by baseline MMSE score is not available due to limited information on MMSE score at baseline. The study does not provide adequate evaluation on the change of KPS score overtime due to limited KPS reported at follow-up.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P100040 S012/ PAS002
Date Original Protocol Accepted	06/23/2014
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv.
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The purpose of this surveillance project, using the Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) registry, will be to obtain data that can be used to refine the selection of and treatment strategy for patients with Type B aortic dissections managed through endovascular graft repair. Data will also be evaluated to identify any signals of device-specific safety or effectiveness issues. This project will be used to establish performance goals for future studies. Specifically, the project will evaluate the short- and long-term clinical performance of endovascular grafts for the treatment of Type B thoracic aortic dissection, following premarket approval. This is a cohort study of patients entered into the VQI registry, treated for Type B thoracic aortic dissection. The project will be comprised of (1) a cohort of patients followed through five years post-implant procedure (this will include a sub-cohort of the 1-year cohort); and (2) a cohort of all-comers followed through one year post-implant procedure.
Study Population	Inclusion criteria: Patients whose index procedure is on or after September 10, 2013 (date of first device approval) for treatment with an endovascular stent-graft used to repair Type B dissections in the descending thoracic aorta may be included in the 1-year or 5-year cohort. Patients diagnosed with classic “double-barrel” Type B thoracic aortic dissection in the descending thoracic aorta and an identifiable intimal flap, with visible contrast enhancement in the false lumen that are treated with endovascular grafts at centers participating in the VQI registry. For the 5-year cohort, subjects will be considered enrolled in the study after arterial cut- down and introduction of the endovascular graft. Data will be collected for unsuccessfully implanted patients through their in-hospital stay. Exclusion criteria: Medial disruption with formation of intramural hematoma/hemorrhage. Plaque rupture leading to aortic ulceration, penetrating aortic atherosclerotic ulcer with surrounding hematoma, usually subadventitial. Iatrogenic and traumatic dissection.
Sample Size	Two surveillance arms: Five (5)-year cohort: Data will be captured on a minimum of 194 chronic and 200 acute patients with Device Technical Success, and treated at centers agreeing to participate in the Surveillance Project through the VQI registry. At least 60 patients treated with the final device design of a participating manufacturer will be enrolled in each surveillance arm (i.e., acute and chronic). If the total sample size of 200 or 194 patients has been reached for one arm (acute or chronic, respectively) of the 5-year surveillance arm, but an individual device has not met the 60 patients minimum required for that arm, enrollment will only continue for that specific device. One (1)-year: All-comers until 200 patients have been surveilled into the VQI registry during the specified enrollment period.
Key Study Endpoints	The sponsor will report any significant observations from the surveillance described below of the use of the TAG device to repair Type B dissections in the descending thoracic aorta. Specifically, this surveillance should monitor: Primary Safety (All devices combined) 5-year arm: Freedom from dissection-related mortality at 5 years 1-year arm: Freedom from dissection-related mortality through 1 year Primary Effectiveness 5-year arm: Device technical success at the time of the procedure (successful delivery, successful and accurate deployment, and successful withdrawal of the delivery system) Device procedural success at 30 days (device technical success with absence of the following at 30 days: major adverse events [MAE] subset, primary intimal tear false lumen perfusion [PIT FLP], retrograde extension of the dissection, and unintentional dissection septum rupture). 1-year arm: Device technical success at the time of the procedure (successful delivery, successful and accurate deployment, and successful withdrawal of the delivery system) Secondary endpoints 5-year arm: Elements of device technical and procedural success Additional endovascular and surgical dissection-related interventions pre-procedure, index-procedure, and post-index procedure (within 30 days, 1 year, yearly) The following endpoints at 30 days, 1 year and yearly assessments: Dissection treatment success and its individual elements: Aortic enlargement in the region encompassed by the initial dissection (1 year and yearly only) Aortic rupture Dissection-related mortality Extension of the dissection (proximally or distally) with or without complications False lumen perfusion (FLP) primary intimal tear Proximal aorta Distal aorta Proximal branch Distal branch Fistula formation (e.g., aorto-esophageal, aorto-tracheal) MAEs subset Unintentional dissection septum rupture Conservative estimate of dissection-related mortality All-cause mortality False lumen patency Endovascular device penetration of the aortic wall Loss of device integrity 1-year arm: Elements of device technical success The following endpoints at procedure and 1 year assessments: FLP (all elements) Aortic enlargement in the region encompassed by the initial dissection (1 year only) Aortic rupture Dissection-related mortality Conservative estimate of dissection-related mortality All-cause mortality MAEs subset Additional endovascular and surgical dissection-related interventions Major adverse events are pre-specified as: paraplegia*† paraparesis*† disabling stroke* non-preexisting and sustained contrast-induced renal failure requiring dialysis not due to malperfusion of the kidneys present at presentation* new ischemia (i.e., not evident at the time of the index procedure) due to branch vessel compromise (malperfusion of organ, upper limb, or lower limb)† *Subset of MAEs for device procedural success †Subset of MAEs for dissection treatment success and 1-year arm
Follow-up Visits and Length of Follow-up	5-year cohort: 30 days, 1 year, and annually through 5 years following the index procedure. 1-year cohort: 30 days and 1 year following the index procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	246 subjects enrolled total: 5-year Acute cohort: 80 subjects 5-year Chronic cohort: 79 subjects 1-year Acute cohort: 62 subjects 1-year Chronic cohort: 25 subjects
Actual Number of Sites Enrolled	1-year cohorts: 28 sites 5-year cohorts: 55 sites
Patient Follow-up Rate	Any data | Imaging data 5 Year Acute Cohort at 1 year*: 80.3% (53/66) | 60.6% (40/66) 5 Year Acute Cohort at 5 years**: 56.8% (25/44) | 25.0% (11/44) 5 Year Chronic Cohort at 1 year: 80.3% (57/71) | 66.2% (47/71) 5 Year Chronic Cohort at 5 years***: 70.8% (34/48) | 47.9% (23/48) 1 Year Acute Cohort at 1 year: 80.0% (44/55) | 65.5% (36/55) 1 Year Chronic Cohort at 1 year: 81.0% (17/21) | 71.5% (15/21) *1 subject in the 5 Year Acute cohort was lost to follow-up at 1 year (2 consecutive visits missed) **14 subjects in the 5 Year Acute cohort were lost to follow-up at 5 years (2 consecutive visits missed) ***10 subjects in the 5 Year Chronic cohort were lost to follow-up at 5 years (2 consecutive visits missed)
Final Safety Findings	N/A - Data for the primary safety endpoints were collected for all study devices combined; device-specific safety data is not available for presentation.
Final Effect Findings	Primary Effectiveness: Device Technical Success during procedure: 5 Year Acute: 97.5% (78/80) 5 Year Chronic: 100% (79/79) 1 Year Acute: 95.2% (59/62) 1 Year Chronic: 100% (25/25) Device Procedural success at 30 days: 5 Year Acute: 92.5% (62/67) 5 Year Chronic: 94.7% (71/75) Secondary Endpoints: Technical Success Elements (5 Year Acute | 5 Year Chronic) Successful device delivery: 98.8% | 100% Successful and accurate deployment: 98.8% | 100% Successful withdrawal of delivery system: 100% | 100% Procedural Success Elements (5 Year Acute | 5 Year Chronic) Freedom from retrograde extension of dissection: 98.1% | 94.7% Freedom from unintentional dissection septum rupture: 100% | 100% Freedom from PIT FLP: 93.6% | 98.2% KM estimate of freedom from dissection-related interventions (5 Year Acute | 5 Year Chronic) Through 1 year: 85.2% | 79.2% Through 5 years: 77.3% | 72.3% Dissection Treatment Success Elements (5 Year Acute | 5 Year Chronic) Freedom from aortic enlargement in the region encompassed by the treated section (range across all timepoints): 52.4-74.5% | 52.9-83.3% Freedom from aortic rupture: 97.5-100% | 98.6-100% KM estimate of freedom from dissection-related mortality: Through 1 year: 90.0% (SE=3.4%) | 96.2% (SE=2.2%) Through 5 years: 90.0% (SE=3.4%) | 96.2% (SE=2.2%) Freedom from extension of the dissection (range across all timepoints): 76.9-100% | 79.5-100% KM estimate of freedom from all-cause mortality: Through 1 year: 82.5% (SE=4.2%) | 89.9% (SE=3.4%) Through 5 years: 72.3% (SE=5.0%) | 72.5% (SE=5.1%) Complete false lumen thrombosis within the treated segment (range across all timepoints): 54.5-95.2% | 38.5-75.9% Partial false lumen thrombosis within the treated segment (range across all timepoints): 0-36.4% | 17.2-23.1% Loss of device integrity (range across all timepoints): 0% | 0% 1 Year Cohort Endpoints (1 Year Acute | 1 Year Chronic) Aortic enlargement in the region encompassed by the initial dissection at 1 year: 39.4% | 33.3% Aortic rupture at discharge: 1.6% | 4.0% Aortic rupture at 1 year: 0% | 0% KM estimate of freedom from dissection-related mortality through 1 year: 90.3% (SE=3.8%) | 91.6% (SE=5.7%) KM estimate of freedom from all-cause mortality through 1 year: 86.8% (SE=4.3%) | 87.3% (SE=6.9%) KM estimate of freedom from dissection-related interventions through 1 year: 85.8% (SE=4.7%) | 75.8% (SE=9.5%) MAE subset (1 Year Acute at discharge / at 1 year | 1 Year Chronic at discharge / at 1 year) Paraplegia: 0% / 0% | 0% / 0% Paraparesis: 0% / 0% | 0% / 0% Stroke or transient ischemic attack: 1.6% / 0% | 0% / 0% Dialysis dependent renal failure: 0% / 0% | 4.0% / 0% Spinal cord deficit: 1.6% / 0% | 0% / 0% Upper limb ischemia: 3.2% / 0% | 4.0% / 0% Lower limb ischemia: 0% / 0% | 0% / 0% Mesenteric ischemia: 3.2% / 0% | 0% / 0%
Study Strengths & Weaknesses	Strengths: Study gathers and separately presents results on acute and chronic dissections through five years, represents geographically diverse health centers in the US, includes representation of some patients with connective tissue disorders, and maintains standard definitions and reporting among the manufacturers participating in the registry. The study compares patient baseline characteristics and outcomes between the VQI study sites and the all-comer VQI population. Weaknesses: The follow-up compliance, particularly for imaging data, is very low, which leads to uncertainty in the longer-term outcomes due to a large portion of missing data. Enrollment of subjects in the 5-year cohorts was non-consecutive, which may introduce selection bias. The study sample size is not powered to determine event rates for each device. The patient population treated was heavily represented by male (68.7%) and Caucasian (56.5%) patients, with reasonable representation from female (31.3%) and African American (30.1%) patients. Limited data was available for other races or ethnicities.
Recommendations for Labeling Changes	Labeling changes are recommended to present the long-term outcomes of this device while acknowledging the limitations of this post-market registry.
General
Study Status	Completed
Application Number / Requirement Number	P100040 S036/ PAS001
Date Original Protocol Accepted	10/19/2018
Date Current Protocol Accepted
Study Name	Continued f/u Valiant EVO Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to obtain longer-term follow-up on the use of the Valiant Navion Stent Graft System to treat descending thoracic aortic aneurysms. There will be no new patient enrollment for this study; instead, five-year follow-up will be reported on the surviving patients from the 100 subjects enrolled in the IDE study, in accordance with the IDE protocol.
Study Population	Patients with descending thoracic aortic lesions who have appropriate anatomy.
Sample Size	100 patients were enrolled in this IDE. Follow-up data on the surviving patients will be reported in this PAS.
Key Study Endpoints	Clinical outcomes will include aneurysm-related mortality, aneurysm rupture, aneurysm expansion, Type Ia endoleak, migration, Type III endoleak, re-intervention, device-related adverse events, and device integrity.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	100 (53 US, 47 OUS)
Actual Number of Sites Enrolled	33
Patient Follow-up Rate	Follow-up rate: 1 month: 98/99 (99%) 6 month (required for US only): 56/91 (62%) 1 year: 79/87 (91%) 2 year: 50/52 (96%) 3 year: 46/49 (94%) 4 year: 41/44 (93%) 5 year: 36/38 (95%) Between the index procedure and the 1-year follow-up visit, 10 subjects died, 2 subjects withdrew, and 1 subject was lost to follow-up. 59 subjects reconsented for 5-year follow-up following completion of the 1-year visit. Between the 1- and 5-year visits, 13 subjects died, 5 subjects withdrew from the study, and 3 subjects were lost to follow-up
Final Safety Findings	The study used a composite safety and effectiveness endpoint: Access and/or deployment failures: 0% (0/100) Major device effects (MDEs) within 30-days of the procedure: 2.0% (2/100) Device-related secondary procedures: 2.0% (2/100) Device-related mortality: 1.0% (1/100) Conversion to open surgery: 0% (0/100) Thoracic aortic aneurysm rupture: 1.0% (1/100) 30-day secondary endpoints: Perioperative mortality: 2.0% (2/100), Major adverse events: 29.0% (29/100), Serious adverse events: 32.0% (32/100), Secondary procedures: 2.0% (2/100), Loss of stent graft patency: 0.0% (0/95), Endoleaks: 4.3% (4/94) Secondary endpoints through 5 years: All-cause mortality: Kaplan-Meier estimate of freedom from all-cause mortality at 1 year: 89.8%, 5 years: 70.9%. Aneurysm-related mortality: Kaplan-Meier estimate of freedom from aneurysm-related mortality at 1 year: 97.0%, 5 years: 95.1%. MDEs: Kaplan-Meier estimate of freedom from MDEs at 1 year: 95.8%, 5 years: 22.4%. Secondary Procedures: Kaplan-Meier estimate of freedom from secondary procedures at 1 year: 0.948%, 5 years: 21.7%. Endoleaks: 6.4% (5/78) at 1 year, 23.5% (8/34) at 5 years Stent graft migration: 0.0% (0/79) at 1 year, 5.7% (2/45) at 5 years Aneurysm expansion: 5.1% (4/78) at 1 year, 14.7% (5/34) at 5 years Aortic rupture: 1 rupture event at 28 days from the procedure Loss of device integrity: 11 device integrity events: 3 stent fractures, 2 stent graft ruptures, 2 stent graft fabric defects, 4 stent ring enlargements, 1 stent wire detachment Loss of stent graft patency: 0.0% at 1 through 5 years Conversion to open surgery: 0.0% at 1 through 5 years
Study Strengths & Weaknesses	Study strengths: This study has a high rate of clinical follow-up for eligible subjects through 5 years, collects imaging data for high rate of eligible subjects through 5 years, and includes representation of patients from both North America and Europe. Study weaknesses: The study is a non-randomized study with inherent biases. There is a low patient sample size reconsented for 5-year follow-up, and the subject race/ethnicity demographics biased toward White patients compared to the total US population
Recommendations for Labeling Changes	No labeling changes are recommended. The Navion device (commercial version of the Valiant Evo Thoracic Stent Graft) is no longer marketed following voluntary removal of the device from global markets in March 2021.
General
Study Status	Completed
Application Number / Requirement Number	P160054 S008/ PAS001
Date Original Protocol Accepted	01/18/2019
Date Current Protocol Accepted
Study Name	Continued f/u of Premarket Pivotal Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To characterize the clinical outcomes through 5 years post implantation by continuing to follow the premarket pivotal cohort of patients.
Study Population	Subjects (both HeartMate 3 and HeartMate II) who were enrolled in the premarket pivotal cohort.
Sample Size	All living subjects (about 533).
Key Study Endpoints	The composite endpoint of survival to transplant or recovery, or on left ventricular assist device (LVAD) support free of debilitating stroke (Modified Rankin Score > 3) or reoperation to replace the pump; mortality; bleeding; major infection; hemolysis; device thrombosis; neurological dysfunction; and any other serious adverse events; as well as New York Heart Association (NYHA) classification and 6-minute walk distance (6MWD).
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	295 subjects enrolled
Actual Number of Sites Enrolled	53
Patient Follow-up Rate	The follow-up rate through 5 years was 98.67%.
Final Safety Findings	Survival Free of Debilitating Stroke or Reoperation at 5 years The Kaplan- Meier estimate of survival free of debilitating stroke or reoperation to replace the pump was higher for the HM3 LVAS (69.7%) compared to the HMII LVAS (41.9%). Survival and Subject Outcomes at 5 years The number of at risk subjects is reduced for both HM3 (134) and HMII (82) subjects. The percent survived for HM3 is 73.7% and HMII 55.6%. The sponsor reports subjects with HM3 LVAD have a statistically significant higher, p=0.0001, survival rate than subjects with HMII. Subgroup Analyses There was no difference in outcomes based on gender. The sponsor reports male and female subjects who received HM3 had statistically significant higher, p<0.0001, survival free of debilitating stroke or reoperation than subjects receiving HMII. In addition the sponsor reports for INTERMACS 1-2 and 3-7 profiles, subjects who received HM3 had statistically significant higher survival (p=0.0223 INTERMACS 1-2, p<0.0001 INTERMACS 3-7) free of debilitating stroke or reoperation than subjects receiving HMII. Device related SAEs The sponsor reports HM3 had significantly less bleeding (p<0.001), stroke (p=0.035) and confirmed device thrombosis events (p<0.001) than HMII subjects. Although, the sponsor reports significantly less bleeding with the HM3, bleeding and major infection are still a risk. Major Infection HMII: # of subjects 34; % of subjects 29.1%; # of events 67; EPPY 0.228, HM3: # of subjects 70; % of subjects 39.3%; # of events 122; EPPY 0.263, p- value 0.348 Bleeding HMII: # of subjects 38; % of subjects 32.5%; # of events 124; EPPY 0.4228, HM3: # of subjects 50; % of subjects 28.1%; # of events 99; EPPY 0.213, p- value <0.001
Final Effect Findings	The NYHA classification and six-minute walk distance assessments were not completed consistently at follow-up visits. Limited data points and comparisons can be made. Overall, both HM3 and HMII subjects had improvements in NYHA classification and 6MWD assessment throughout the 5 year follow-up compared to baseline.
Study Strengths & Weaknesses	This extended follow-up study provides continued evaluation through five years post implant on the safety and effectiveness of the HM3 LVAS. The study provides additional data on the composite endpoint as well as mortality, bleeding, major infection, hemolysis, device thrombosis, neurological dysfunction, device related serious adverse events and functional status. Of note, there was delayed site activation, sites declined to participate, not all subjects reconsented from the MOMENTUM 3 IDE and the COVID-19 pandemic, which attributed to data not being collected and impact the results.
Recommendations for Labeling Changes	A labeling update will be requested to add five-year performance data to inform clinicians and patients of benefit risk profile for the device
General
Study Status	Completed
Application Number / Requirement Number	P100041 / PAS002
Date Original Protocol Accepted	11/02/2011
Date Current Protocol Accepted	08/28/2014
Study Name	Newly Enrolled Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: a non-randomized, retrospective, consecutively enrolled STS/ACC TVT Registry of all patients undergoing SAPIEN transcatheter heart valve replacement therapy.
Study Population	Patients must meet the fundamental enrollment criteria of severe, symptomatic, calcific aortic stenosis with quantifiable and documented source records. Upon meeting these eligibility criteria, the heart team shall then determine the patients risk for operative morbidity and mortality. Details of eligibility including contraindications are provided in the product Instructions for Use which are included with each SAPIEN THV and delivery system. No comparator group.
Sample Size	A total of 5000 subjects combined for P110021 & P100041 patients enrolled into the STS/ACC TVT Registry in all US sites.
Key Study Endpoints	Primary Safety Endpoints: The primary safety endpoint is the clinical event of stroke at 30 days, and again at 1 year. 2. Additional Safety Endpoints: Additional safety endpoints will be evaluated at 30 days and one year: VARC composite safety: o all-cause mortality stroke; o life-threatening (or disabling) bleeding o acute kidney injury - Stage 3 (including renal replacement therapy) o peri-procedural MI o repeat procedure for valve-related dysfunction (surgical or interventional therapy) Major vascular complications Stroke (as defined in the STS/ACC TVT Registry) 3. Additional Effectiveness Endpoints: Additional effectiveness endpoints will be evaluated at 30 days and one year: Total days alive and out of hospital (from date of implant) Clinical improvement per NYHA Class (from baseline) Mean ICU and total index procedure hospital length of stay 4. Learning Curve Assessment: The learning curve assessment will be made by analyzing the composite safety outcome according to the VARC guidelines. Additional evaluation will be performed for stroke and vascular complication. The rationale for assessment the composite at 30 day is that it is reflective of acute procedure outcomes, device performance and important potential procedure complications addressed in the Edwards SAPIEN THV Training program
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	4994
Actual Number of Sites Enrolled	209
Patient Follow-up Rate	year 1: >80%; year 2-5: <80%
Final Safety Findings	All-cause mortality at 5 years: 64.2% Stroke at 5 years: 13.9% TIA at 5 years: 4.2% Aortic Valve Re-intervention at 5 years: 3.1% Re-intervention on Unspecified Valve at 5 years: 0.5% New Requirement for Dialysis at 5 years: 4.8%
Final Effect Findings	Survival at 5 years: 35.8%
Study Strengths & Weaknesses	Strength: Large number of real-world patients enrolled in a relatively short period of time (about 10 months). Weakness: Drop in follow-up rate post 1 year due to the inherent limitations in linking the TVT Registry with the CMS claims database.
Recommendations for Labeling Changes	No. Device has been discontinued due to obsolescence.
General
Study Status	Completed
Application Number / Requirement Number	P100041 / PAS001
Date Original Protocol Accepted	11/02/2011
Date Current Protocol Accepted	01/31/2012
Study Name	Continue Follow-Up of Premarket Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of Cohort B device patients from premarket study. Premarket study was a prospective, controlled, multi-center pivotal trial.
Study Population	Cohort B ¿ Non-surgical patients undergoing transcatheter aortic valve implantation (treatment) via transfemoral delivery vs. best medical management (control)
Sample Size	350 patients in the best medical therapy cohort (Cohort B). 25 sites
Key Study Endpoints	Cohort B: (1) Freedom from death, over the duration of the trial and (2) Composite of death and recurrent hospitalization
Follow-up Visits and Length of Follow-up	Minimum of 5 years
General
Study Status	Completed
Application Number / Requirement Number	P100045 / PAS001
Date Original Protocol Accepted	05/28/2014
Date Current Protocol Accepted	02/14/2017
Study Name	Newly Enrolled Champion
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objectives are to confirm the safety and effectiveness of the CardioMEMS HF System in subjects with New York Heart Association (NYHA) Class III heart failure (HF) (a minimum of 35% of enrolled patients are to be women) who experienced a heart failure hospitalization in the previous year. The purpose of the sub study was to evaluate the use of CardioMEMS HF system in patients with NYHA Class III heart failure who are optimally managed in are clinically similar to the Control group and the CHAMPION study based on pre-enrollment data.
Study Population	Adults with New York Heart Association (NYHA) Class III Heart Failure (HF) who have experienced a heart failure hospitalization within the past 12 months. At least 35% of the enrolled patients will be women.
Sample Size	1,200 enrolled (at least 420 women) at no more than 150 sites. The sponsor states that the 2-year attrition rate in CHAMPION was 49.1% (228/550). At least 35% of the enrolled patients will be women (206 completing the trial) and this data is based on the proportion seen premarket. This sample size of 206 female patients for gender evaluation will provide greater than 90% power to meet the goal for effectiveness and greater than 90% power to detect a difference as small as 0.06 from the null proportion rate of 0.90 for safety.
Key Study Endpoints	Primary Safety Endpoints: 1) Freedom from device/system related complications (DSRC) over 2 years in study compared to the objective performance criterion (OPC) used in the CHAMPION trial; 2) Freedom from Pressure Sensor Failure over 2 years in study compared to the OPC used in the CHAMPION trial. Primary Effectiveness Endpoint: Heart failure (HF) hospitalization rate over 1 year in study compared to the HF hospitalization rate in the year prior to enrollment. Substudy Same Primary Safety Endpoints Effectiveness Endpoint: 1 year HFH rate in PAS study compared to the 1-year HFH rate in the randomized portion of the CHAMPION study Control cohort.
Follow-up Visits and Length of Follow-up	All subjects were followed until completion of their 24 month visit or withdrawal from the study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 1200 subjects were enrolled. Additionally, 387 patients were selected by the independent committee for inclusion in the sub-study.
Actual Number of Sites Enrolled	This study was conducted in 104 centers.
Patient Follow-up Rate	The follow-up rate was 96.3% (684/710) at 24-months.
Final Safety Findings	The primary safety outcomes for this study are 1) freedom from device/system related complications (DSRC) at 24 months and 2) freedom from pressure sensor failure at 24 months. For freedom from DSRCs at 24 months, the results show that freedom from DSRCs at 24 months was 99.6% (1209/1214) with a lower confidence bound of 99.0%, thus allowing the null hypothesis to be rejected. For freedom from pressure sensor failure at 24 months, the results show that freedom from pressure sensor failure at 24 months was 99.9% with a lower confidence bound of 99.5%, thus allowing the null hypothesis to be rejected.
Final Effect Findings	The primary effectiveness endpoint for this study compares the annualized HFH rate including recurrent events at 12 months post implant with the rate including recurrent events 12 months prior to implant. The HFH rate prior to sensor implant was 1.249 HFHs per patient year. After sensor implant, the rate of HFHs was reduced to 0.535 HFHs per patient year. This is a reduction of 57% in HFHs after treatment using the CardioMEMS sensor.
Study Strengths & Weaknesses	Data from the CardioMEMs PAS demonstrates clinically meaningful benefits that include a reduction in the rate of HFH and clinically relevant improvement in quality of life. In CardioMEMs PAS there was a significant reduction of 57% in the HFH rate at 12 months. This result was similar in males and females. There was no significant difference in HFH amongst any of the subgroup analysis. A limitation of the CardioMEMs PAS single arm design is that there is no direct competitor provided within the study population for outcomes. However, results from the CardioMEMs PAS are supported by results from the CHAMPION trial and the MEMS-HF study.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P100045 / PAS002
Date Original Protocol Accepted	05/28/2014
Date Current Protocol Accepted	02/14/2017
Study Name	Champion Substudy
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this sub-study is to confirm the postmarket safety and effectiveness of the CardioMEMS¿ HF System to premarket. This is a prospective, multi-center, open-label trial conducted in the US.
Study Population	The sub-study patient population will consist of patients selected by an independent committee from the PAS (Main Cohort) who are optimally managed and are clinically similar to the Control group in the CHAMPION study based on pre- enrollment data. The independent committee will identify these patients from the main cohort with NYHA Class III HF who have experienced a HF hospitalization within the past 12 months.
Sample Size	A minimum of 256 patients will be selected by the independent committee for inclusion in the sub-study
Key Study Endpoints	Primary safety endpoints will be evaluated at 2 years: 1) Freedom from device/system related complications 2) Freedom from pressure sensor failure The primary effectiveness objective is to demonstrate that there is not a worsening in HF hospitalization rate at 1 year in the sub-study compared to the 1 year HF hospitalization rate in the CHAMPION study Control group (Part 1).
Follow-up Visits and Length of Follow-up	2 years Implanted subjects will be evaluated at Month 1 (± 7 days) and at Months 6, 12, 18, and 24 (± 30 days)
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 1200 subjects were enrolled. Additionally, 387 patients were selected by the independent committee for inclusion in the sub-study
Actual Number of Sites Enrolled	This study was conducted in 104 centers.
Patient Follow-up Rate	The follow-up rate was 96.3% (684/710) at 24-months.
Final Safety Findings	The primary safety outcomes for this study are 1) freedom from device/system related complications (DSRC) at 24 months and 2) freedom from pressure sensor failure at 24 months. For freedom from DSRCs at 24 months, the results show that freedom from DSRCs at 24 months was 99.6% (1209/1214) with a lower confidence bound of 99.0%, thus allowing the null hypothesis to be rejected. For freedom from pressure sensor failure at 24 months, the results show that freedom from pressure sensor failure at 24 months was 99.9% with a lower confidence bound of 99.5%, thus allowing the null hypothesis to be rejected.
Final Effect Findings	The primary effectiveness endpoint for this study compares the annualized HFH rate including recurrent events at 12 months post implant with the rate including recurrent events 12 months prior to implant. The HFH rate prior to sensor implant was 1.249 HFHs per patient year. After sensor implant, the rate of HFHs was reduced to 0.535 HFHs per patient year. This is a reduction of 57% in HFHs after treatment using the CardioMEMS sensor.
Study Strengths & Weaknesses	Data from the CardioMEMs PAS demonstrates clinically meaningful benefits that include a reduction in the rate of HFH and clinically relevant improvement in quality of life. In CardioMEMs PAS there was a significant reduction of 57% in the HFH rate at 12 months. This result was similar in males and females. There was no significant difference in HFH amongst any of the subgroup analysis. A limitation of the CardioMEMs PAS single arm design is that there is no direct competitor provided within the study population for outcomes. However, results from the CardioMEMs PAS are supported by results from the CHAMPION trial and the MEMS-HF study.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P010047 S010/ PAS001
Date Original Protocol Accepted	12/21/2011
Date Current Protocol Accepted	03/16/2015
Study Name	NeoMend ProGel Pleural Air Leak Sealant
General Study Protocol Parameters
Study Design	Case Control Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, observational cohort study with a ProGEL Sealant group and a comparison group of standard-of-care.
Study Population	267 ProGEL Sealant + 133 Comparison Group. Subjects in the comparison group follow the current standard of care to treat IOAL after lung resection is defined by techniques involve suturing, stapling, and cauterization of the lung parenchyma where the leak is detected
Sample Size	267 ProGEL Sealant + 133 Control
Key Study Endpoints	Study Endpoints 1. Pneumothorax 2. Air leak, persistent 3. Air leak, late onset 4. Residual pleural space 5. Acute respiratory distress syndrome (ARDS) 6. Post-surgical renal abnormalities 7. Myocardial infarction 8. Atrial arrhythmia requiring treatment 9. Ventricular arrhythmia requiring treatment 10. Cardiac arrest (resuscitated) 11. Death (all causes) 12. Hospital readmission (related to pulmonary surgery)
Follow-up Visits and Length of Follow-up	90 days
General
Study Status	Completed
Application Number / Requirement Number	P030054 S173/ PAS001
Date Original Protocol Accepted	11/29/2011
Date Current Protocol Accepted	03/02/2012
Study Name	QUAD PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective multi-center study
Study Population	Patients can be approached in one of two ways for enrollment: ¿ Through patient participation in the Promote Q CRT-D and Quartet Left Ventricular Heart Lead Study (IDE Study patients); or ¿ Through participating centers with newly implanted patients.
Sample Size	1,884 new patients will be enrolled to achieve an evaluable sample size of 1,036 patients. In addition, patients will be included for total sample size. 80 active centers enrolled in this study.
Key Study Endpoints	Primary endpoints: to estimate: ¿ Freedom from system-related complications through 5 years. ¿ Freedom from system-related complications through 5 years. ¿ Mean of programmed LV lead pacing capture threshold across 10 pacing configurations at 5 years. Secondary endpoints: To characterize the complication rate of the Quartet Model 1458 LV Lead and to perform a trend analysis of all complications.
Follow-up Visits and Length of Follow-up	All patients will have a total duration of follow-up of 5 years from the date of implant Patients who have a successful system implant will be seen at 6 months (+ 45 days) after implant and every 6 months (+ 60 days) thereafter until the patient reaches the 5 year visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,970
Actual Number of Sites Enrolled	71
Patient Follow-up Rate	796 completed at 5 year follow up
Final Safety Findings	The freedom from complications rate is 89.6%, which exceeds the 80% primary endpoint 1. There was no significant difference between the IDE rollover and newly enrolled subjects regarding freedom from system-related complications through 5 years. The freedom from lead complications rate is 95.9%, which exceeds the 92.5% primary endpoint 2. Primary lead complication is dislodgement. None of the deaths were related to the system.
Final Effect Findings	Mean lead pacing capture threshold met endpoint 3.
Study Strengths & Weaknesses	This is a prospective, multicenter study that provides long term data up to 5 years on the safety and effectiveness of the device. The study outcomes are positive. The follow up rate was a challenge.
Recommendations for Labeling Changes	The labeling will be updated based on the 5 year safety and effectiveness results reported in the PAS final report.
General
Study Status	Completed
Application Number / Requirement Number	P100046 / PAS001
Date Original Protocol Accepted	12/14/2011
Date Current Protocol Accepted	06/13/2014
Study Name	AtriCure Synergy Ablation System
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, observational, single arm registry study.
Study Population	Subjects who are at least 18 years old, have non-paroxysmal forms of atrial fibrillation, are scheduled to undergo a primary open cardiac surgical procedure requiring cardiopulmonary bypass, including valve surgery, and or coronary artery bypass grafting (CABG), and who do not meet any of the exclusion criteria. There is no control group
Sample Size	The sample size of 350 subjects obtained from 50 different U.S. sites is driven by the need to test the safety hypothesis, which is that one-month serious device- and procedure-related adverse events will occur in no greater than 10% of the study population. The calculation assumes a one-sided test for statistical significance at the p < 0.05 level, 80% power, an estimated rate of 6.25%, and a maximum of 5% subject attrition at one month, providing a sample size at one month of at least 333 subjects.
Key Study Endpoints	Main Endpoints Safety: Serious device and procedure-related adverse events (not including pacemaker implantation) at one month post-procedure or during hospitalization for the procedure (whichever is longer). An independent Clinical Events Committee (CEC) will review all reported potential endpoint adverse events that occur within 30 days post-procedure, in order to make a determination on the device- or procedure-relatedness and the seriousness of the AE. Effectiveness: Freedom from AF (i.e. no episodes lasting > 30 seconds of either atrial fibrillation, atrial flutter, or atrial tachycardia) while off of Class I and III anti-arrhythmic drugs for at least 4 weeks (except amiodarone, which the subject must be off of for 12 weeks prior to assessment), as determined by an independent core lab assessment of 48 hour Holter monitor, Zio Patch, or PPM interrogation recording, at one, two and three years post-procedure. Secondary Endpoints Proportion of subjects free from AF regardless of AAD usage, at one, two and three years post-procedure. Major adverse events within 30 days post-procedure or by hospital discharge, whichever is longer, including: Death (Included even if greater than 30 days if procedure-related) Stroke TIA Myocardial infarction Bleeding requiring > 2 units of blood and surgical intervention Any adverse event Serious device- and procedure-related adverse event by type of mprimary cardiac surgical procedure
Follow-up Visits and Length of Follow-up	3 years post-procedure Clinical follow-up will be at 30 days, 4 months, and 1, 2, and 3 years post-procedure. At least three unsuccessful attempts to contact a subject who has missed a clinic visit, by telephone and certified mail, must be made before a subject will be classified as lost to follow-up.
Interim or Final Data Summary
Actual Number of Patients Enrolled	365 subjects enrolled for this study.
Actual Number of Sites Enrolled	40 sites enrolled for this study.
Patient Follow-up Rate	The follow-up rate is 85.1% (309/363) at 36 months.
Final Safety Findings	1.1% (4/365, [90% CI: 0.4%,2.5%]) subjects experienced 4 serious device or ablation procedure-related adverse events within 30 days post-procedure, which met the primary safety endpoint performance goal (PG) of 10%. All the events were procedure related. 8.8% (32/365) subjects developed a total of 36 acute Major Adverse Events within 30 days post-procedure ( 5.5% (20/365) death, 1.9% (7/365) excessive bleeding, 1.6% (6/365) strokes with significant permanent disability, and 0.8% (3/365) Myocardial Infarction (MI)). No TIA was reported. A total of 2352 adverse events were reported in 95.1% (347/365) subjects. Of which, 47.1% (1108/2352) of the events reported occurred during the initial hospitalization or within the 30-day follow-up.
Final Effect Findings	The proportion of patients free from AF, off antiarrhythmic drugs was 66.2% [90% CI: 61.2%, 70.9%] at 12 months, 64.9% [90% CI: 59.6%, 70.0%] at 24 months, and 62.9% [90% CI :57.4%, 67.2%]. at 36 months. The primary effectiveness endpoint PG of 47.8% at 36 months was met.
Study Strengths & Weaknesses	Strength: The ABLATE PAS study evaluated 3-year long term safety and effectiveness of the device. The primary study endpoints were formally evaluated with hypothesis testing and all primary endpoints performance goals were met. Subgroup analysis based on gender, AF type, procedure type, and user experience were provided and did not raise any concerns. Weakness: In the statistical analysis plan (SAP), the specific analysis method to evaluate the primary effectiveness endpoint at 36 months was not clearly specified (e.g., calculating either Kaplan-Meier probability rate or proportion of subject free of AF).
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P100047 S090/ PAS001
Date Original Protocol Accepted	03/15/2018
Date Current Protocol Accepted	08/06/2018
Study Name	Cont F/u of HW004-A ENDURANCE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was designed to evaluate longer-term safety and effectiveness outcomes of patients receiving an HVAD for Destination Therapy through continued follow-up of all living subjects who were enrolled in the ENDURANCE Supplemental trial under G090243.
Study Population	All subjects who were enrolled in the ENDURANCE Supplemental trial and alive at 12 months post-original implant.
Sample Size	All subjects who were alive at 12 months post-original implant are eligible for continued follow-up.
Key Study Endpoints	Subjects will be followed out to five years post-original implant and descriptive data will be collected in accordance with the protocol.
Follow-up Visits and Length of Follow-up	5 years post-original implant procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	494 subjects were enrolled, of which 475 were randomized and 465 (HVAD n=308, Control n=157) were implanted.
Actual Number of Sites Enrolled	50 sites were activated for enrollment. Of these, 48 sites enrolled a subject into the trial.
Patient Follow-up Rate	95% Follow-up for HVAD and 98% Follow-up for Control
Final Safety Findings	For both the HVAD and Control groups, the most common Intermacs adverse events by event rate at 60 months were, by decreasing order: infections (76.3% HVAD, 75.8% Control), bleeding (66.6% HVAD, 68.2% Control), device malfunction/failure (44.8% HVAD, 40.8% Control), and cardiac arrythmia (41.9% HVAD, 42.0% Control). Neurological Adverse Events: The overall stroke rate at 60 months was 26.3% for HVAD and 23.6% for Control. The overall incidence of ICVA was 17.9% for HVAD and 13.4% for Control. The overall incidence of HCVA was 12.0% for HVAD and 12.7% for Control. The overall incidence of TIA was 10.4% for HVAD and 5.1% for Control. Of the total deaths that occurred in the study for each group, 25 HVAD patients (15.3%) and 15 Control patients (17.6%) had their CEC adjudicated cause of death attributed to stroke. Device Malfunction: There were a total of 138 (44.8%) HVAD and 64 (40.8%) Control subjects who experienced a device failure/malfunction during the study. The most common event in both arms was pump thrombosis (51.4% HVAD, 56.3% Control). Freedom from thrombus on the original device at 60 months was 62.2% for HVAD and 68.7% for Control. The second most common event in both arms was Controller Fault (33.3% HVAD, 31.3% Control). Device Exchange: For the HVAD subjects, there were 54 pump exchanges in 45 subjects (14.6%), compared to 37 pump exchanges in 28 Control subjects (17.8%).The most common reason for device exchange was Device Thrombosis (including both Elective and Emergent procedures). At 60 months, 76.2% of HVAD subjects and 75.1% of Control subjects were free from exchanges.
Final Effect Findings	At the completion of this study, 144 (46.8%) HVAD subjects and 71 (45.2%) Control subjects were still alive. Of those, 77 (53.5%) HVAD subjects and 42 (59.2%) Control subjects were still alive on the original device. The Kaplan-Meier survival estimate at 60 months was similar between the HVAD and Control groups: 36.7% for subjects on the HVAD and 37.4% for subjects in the Control group. The primary cause of death in both arms was cardiovascular related (82.4% HVAD, 75.6% Control). The most common non-cardiovascular related death in both arms was infection (11.1% HVAD, 11.0% Control). Functional Capacity: Of the patients who were alive at 60 months and had a follow up, available data for NYHA classification at baseline and 60 months was 65/77 (84.4%) for HVAD and 35/42 (83.3%) for Control. Of the 65/308 subjects in the HVAD group, there were 100% in Class III and IV at baseline and 41.6% at month 60. Of those 42/157 subjects in the Control group, 100% of subjects had Class III and IV at baseline and 31.4% at month 60.
Study Strengths & Weaknesses	The strengths of the study include extended follow-up with high follow-up rates. This means longer-term data and results, including adverse events and survival, should be considered reliable estimates for the studied patients. Additionally, the majority of events were CEC adjudicated. Study weaknesses include a high number of study deviations where assessments were not done. The completion rates for mRS assessment after stroke (a known and very serious risk associated with this device) were low (48.1% for HVAD and 45.9% for Control at 12 weeks, and 46.9% for HVAD at 51.4% for Control at 24 weeks). This makes it challenging to reliably interpret stroke severity. Additionally, quality of life measures were only reported up to 24-months post-implant.
Recommendations for Labeling Changes	Even though this device is no longer being marketed, device performance data will still be of use to patients with the device implanted, and their treating physicians. A labeling update will be requested.
General
Study Status	Ongoing
Application Number / Requirement Number	P100047 S090/ PAS002
Date Original Protocol Accepted	07/26/2018
Date Current Protocol Accepted	02/12/2021
Study Name	ENDURANCE PAS
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to estimate patient survival free of death, disabling stroke, or device malfunction or failure requiring exchange, explantation or urgent transplantation following HeartWare Ventricular Assist Device (HVAD) implantation for destination therapy (DT). This post-approval study (PAS) is a prospective, observational, multi-site study conducted through Medtronic’s Product Surveillance Registry (PSR).
Study Population	Patients using the HVAD system as destination therapy.
Sample Size	The PAS cohort will be comprised of 300 newly enrolled patients. This sample size will estimate the primary endpoint rate at 24 months post-original implant within 6.0%. The following assumptions were used: - Two-sided 95% confidence intervals will be computed - Goal is to estimate the primary objective survival rate at 2 years - Survival rate at 24 months is 59.2%, which is based on the Endurance Supplemental HeartWare success rate using data through March 27, 2017 (data pull May 30, 2017). - Attrition will be 10% from implant to 24 months, primarily consisting of transplants Approximately 50 sites will participate in the PAS.
Key Study Endpoints	The primary endpoint/objective is survival free of disabling stroke or device malfunction requiring exchange, explant, or urgent transplant. Secondary endpoints: - Observed early stroke rate (stroke occurring =2 years post-implant), and stroke risk factors. - Late stroke rate (stroke occurring >2 years post-implant) and to evaluate risk factors for late stroke. - Stroke severity for all subjects who experience a stroke on device while in this study. Stroke severity will be assessed through modified Rankin Scale (mRS) scoring. Additional endpoints: Effectiveness of Invasive Blood Pressure Monitoring (IBPM), a summary of neurologic dysfunction events (ischemic cerebrovascular accidents, hemorrhagic cerebrovascular accidents, and transient ischemic attacks), overall survival on device, INTERMACS adverse event rates, quality of life measures (measured by EuroQol EQ-5D-DL and Kansas City Cardiomyopathy Questionnaire), and functional status (measured by the 6-minute walk test).
Follow-up Visits and Length of Follow-up	Subjects will be followed through five years post-implant
General
Study Status	Completed
Application Number / Requirement Number	P080006 S004/ PAS001
Date Original Protocol Accepted	03/31/2011
Date Current Protocol Accepted	06/29/2015
Study Name	Attain Ability Straight Model 4396
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study
Study Population	Inclusion Criteria Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements Subject is implanted with the Model 4396 LV lead connected and used for a pacing or sensing. Subject within 30 days of implant Exclusion Criteria Subject who is, or will be inaccessible for follow-up at a site Subject with exclusion criteria required by local law (Europe, Central Asia [ECA] only) Complete implant and follow-up data, including any product-related events at implant through the time of enrollment are unavailable
Sample Size	This study will consist of 1,016 patients implanted with Model 4396 lead enrolled from approximately 150 centers globally. The minimum Model 4396 enrollment of 1,016 leads results in approximately 600 leads followed for 5-years.
Key Study Endpoints	The primary objective of the PAS is to demonstrate that the Model 4396 lead-related complication-free rate is greater than 92.5% at five years post-implant.
Follow-up Visits and Length of Follow-up	Subjects in the PAS will be followed for a minimum of 5 years from their implant date. Study follow-up visit schedules are based on a rolling visit window with the visit frequency: The required visit window is 210 days in length or approximately every 6 months from implant.
Interim or Final Data Summary
Actual Number of Patients Enrolled	368 leads in 366 patients
Actual Number of Sites Enrolled	65 sites
Patient Follow-up Rate	The overall follow-up rate was 87.56%
Final Safety Findings	As of the data cut-off date, there have been 45 Model 4396 LV lead events reported to Medtronic, all of which have been reviewed by the CEC. Among the 45 CEC adjudicated events, 18 (in 18 leads / 18 patients) were adjudicated as Model 4396 lead related complications and 27 were classified as observations. The complication free rate at 60 months was 98.54%.
Final Effect Findings	There are 34 (9.6%) leads with elevated thresholds. There were 2 leads with Elevated Impedance out of range at implant and at 60 month follow-up. There were 22 leads with sensing value out of range at 60 month follow-up.
Study Strengths & Weaknesses	The study results, along with the previous IDE results and approval, demonstrate that the Model 4396 LV Lead is safe and effective for pacing and sensing the left ventricle via a cardiac vein. Safety was demonstrated by the complication-free rate from Model 4396 lead-related complications at five years (98.54%, Table 21). The results of the secondary objectives confirm that the general electrical performance (e.g. threshold, sensing, impedance, etc.) of the Model 4396 LV lead is stable over time and within expected values. The main weakness of the study was the low sample size due to low utilization of the Model 4396 LV Lead.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P100047 / PAS001
Date Original Protocol Accepted	11/20/2012
Date Current Protocol Accepted	02/21/2019
Study Name	Newly Enrolled (HW-PAS-01)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the safety and efficacy of the HeartWare System in a commercial setting using data from patients enrolled in the INTERMACS database. The HeartWare VAS performance in a ¿real world¿ setting will be compared to other continuous flow, intra-corporeal left ventricular assist devices in the INTERMACS database, as assessed by primary endpoint of success and secondary endpoints including INTERMACS adverse event rates. Design: This is a multi-center, prospective, contemporaneously controlled trial of newly enrolled patients. There will be two groups - the Treatment group, patients who receive a HeartWare VAS, and a contemporaneous Control group, patients who receive a continuous flow, intra-corporeal LVAD other than the HeartWare VAS.
Study Population	Patients entered into the INTERMACS database who receive a HeartWare System (treatment group) and contemporaneous patients who receive a continuous flow, intra-corporeal LVAD other than HeartWare (control). Inclusion criteria: ¿ FDA approved durable mechanical circulatory support device implanted after PMA approval of the HeartWare System ¿ Signed consent for registry Exclusion criteria: ¿ Prisoner ¿ Consent form not signed
Sample Size	600 HeartWare patients and 600 control patients of continuous flow, intra- corporeal LVADs other than the HeartWare System. A total of 1200 patients are required to satisfy the subgroups of interest (i.e. gender and race). For Scenarios 1-2: At least 310 implanted females and at least 310 implanted non-whites (155 HeartWare and 155 Control), calculated using a non-inferiority with a 10% margin, using a one-sided 5% significance level, will provide 90% power at 180 days. At least 12 non-IDE sites will be included. For Scenarios 3: The sample size of 155 patients will provide greater than 90% power to test the study hypothesis that the lower 95% (5% significance level) one-sided confidence limit is greater than 80%.
Key Study Endpoints	The primary endpoint is success (alive, transplanted, or explanted for recovery) at 180 days on the originally implanted device. Patients who are explanted for recovery must survive at least 60 days post-explant. The denominator of the simple proportion includes all enrolled and implanted patients. This will be stratified by gender and race. Secondary endpoints are: ¿ Overall survival on device ¿ Re-hospitalizations ¿ INTERMACS adverse events ¿ Quality of Life measures (as measured by the EuroQol EQ-5D-5L and KCCQ) ¿ Functional Status (as measured by the 6 minute walk and / or VO2 max) ¿ Post-stroke QOL, Functional and Neurocognitive assessments Device Malfunction and thrombus are also captured. The INTERMACS database does not capture Modified Rankin Scale (MRS) scores, but it does capture data from which an MRS score may be derived. An independent neurologist will analyze on a blinded basis INTERMACS data for patients who have experienced a stroke event to impute MRS scores.
Follow-up Visits and Length of Follow-up	Two years post implant Follow-up will occur at discharge, 1 week, 1 month, 3 months, 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1200 total. 600 HVAD and 600 Competitor Device
Actual Number of Sites Enrolled	68 for HVAD patients and 114 for Competitor Device patients
Patient Follow-up Rate	96.7% Follow-up for HVAD and 97.6% Follow-up for Competitor Device
Final Safety Findings	SURVIVAL 6-month survival for HVAD and the competitor device were similar and the HVAD 6-month patient success rate (87.6%) was within the pre-specified 10% margin compared to the 6-month success rate for patients treated with the competitor device (90.1%). Two-year survival was numerically lower for the patients treated with HVAD (71.8%) compared to the competitor device (77.4%). However, the study was not statistically powered to test if this was a statistically significant difference. REHOSPITALIZATION The sponsor reported a statistically significant differences in the proportion of patients undergoing unplanned rehospitalization within 6 months after implant. With HVAD patients undergoing more unplanned rehospitalizations (65.9% undergoing unplanned rehosp.) compared to patients treated with the competitor device (57.0% undergoing unplanned rehosp.), p=0.0148. ADVERSE EVENTS Adverse Event Rate Per Patient Year (In one year a single patient would average this number of events) Total Adverse Events HVAD: 3.72 events/patient-year Control: 3.05 events/patient-year Device Malfunction/Failure &/or Pump Thrombosis HVAD: 0.23 events/patient-year Control: 0.29 events/patient-year Neurologic Dysfunction (includes CT confirmed ICVA or HCVA, Ischemic/Embolic CVA, Hemorrhagic CVA, and TIA) HVAD: 0.29 events/patient-year Control: 0.24 events/patient-year Infection HVAD: 0.85 events/patient-year Control: 0.69 events/patient-year Respiratory Failure HVAD: 0.26 events/patient-year Control: 0.16 events/patient-year Acute Cardiac Failure HVAD: 0.02 events/patient-year Control: 0.00 events/patient-year SUBGROUP ANALYSIS BY GENDER Female patients treated with the HVAD device appeared more likely than female patients treated with the competitor device to die or to need a device replacement within 6-months. Event Rates were Compared for Males and Females in the HVAD and Competitor Device Group. Through 2-years follow-up Using an event rate p-value cut-off of any p value less than 0.01, Women supported by HVAD were more likely than men supported by HVAD to have the following Adverse Events [Hemorrhagic CVA (Women 0.16 events/patient-year; Men 0.08 events/patient-year), Infection (Women 1.05 events/patient-year; Men 0.76 events/patient-year), Respiratory Failure (Women 0.38 events/patient-year; Men 0.21 events/patient-year), Venous Thromboembolism (Women 0.08 events/patient-year; Men 0.02 events/patient-year), Supraventricular Cardiac Arrhythmia (Women 0.15 events/patient-year; Men 0.08 events/patient-year)] Using an event rate p-value cut-off of any p value less than 0.01, Men supported by HVAD were more likely than women supported by HVAD to have the following Adverse Event: Ventricular Cardiac Arrhythmia (Women 0.08events/patient-year; Men 0.17 events/patient-year) Using an event rate p-value cut-off of any p value less than 0.01, Women supported by Competitor Device were more likely than men supported by Competitor Device to have the following Adverse Event: CT Confirmed ICVA or HCVA (Women 0.21 events/patient-year; Men 0.12 events/patient-year)
Final Effect Findings	Quality of life measures including KCCQ and EQ-5D-3L were not uniformly assessed at every follow-up visit and many assessments were not completed during study visits (including baseline) for both HVAD and competitor device patients. Therefore, effectiveness findings provided are uninterpretable.
Study Strengths & Weaknesses	This study followed a relatively large number of patients treated with HVAD and provided contemporaneous comparison group data on similar patients treated with a competitor device. Patient baseline characteristics bydevice type (HVAD or competitor) were determined to not be significantly different based on propensity score analysis with C-statistic comparisons. Therefore, comparisons in outcomes and adverse events can be reasonably made with the caveat that, because patients were not randomized to HVAD or competitor device, factors other than device type could influence these results. Follow-up rates were high. This means longer-term data and results, including adverse events and survival, should be considered reliable estimates for the studied patients. However, while this study had high follow-up rates, a lot of important data on effectiveness, quality of life, and patient outcomes after stroke (a known and very serious risk associated with this device), were inconsistently collected or largely missing across study visits. This meant that longer term results for endpoints other than survival and adverse events, were uninterpretable.
Recommendations for Labeling Changes	Even though this device is no longer being marketed, device performance data will still be of use to patients with the device implanted, and their treating physicians. A labeling update will be requested.
General
Study Status	Completed
Application Number / Requirement Number	P100047 / PAS002
Date Original Protocol Accepted	11/20/2012
Date Current Protocol Accepted	09/25/2015
Study Name	Training Program (HeartWare-PAS-02)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objectives: To assess the effectiveness of current HeartWare training procedures for the HeartWare VAS, and to assess learning curve analysis for the non-IDE centers. Design: A multi-center, prospective, contemporaneous control trial that will use the INTERMACS registry protocol. This study consists of four parts to provide adequate training prior to use of the device, during initial implants, and in follow-up and continuing education: (a) Surgical training, (b) On-site staff training, (c) Initial implant support and (d) Continuing education and support. New enrollment.
Study Population	Study groups: Patients and operators in the Newly Enrolled Cohort PAS (HW-PAS-01) including IDE and non-IDE centers. The inclusion and exclusion criteria for patients enrolled in the New Cohort Post Approval Study (HW-PAS-01) are defined in that protocol.
Sample Size	At least 150 subjects are required to be enrolled at 12 new centers (non-IDE). The sample size for this trial is based on the patient population from HW-PAS-01 that requires enrollment of 600 HeartWare VAS patients, of which approximately 25% (or 150) of the 600 HeartWare patients will be enrolled at non-IDE centers.
Key Study Endpoints	Primary effectiveness: outcomes for the IDE Experienced centers and the Non-IDE centers. The analysis involves the time and incidence associated with the following: 1. Adverse events occurring from the date of implant to patient discharge: o Bleeding o Infection o Neurologic events o Thromboembolism o Arrhythmias o Device malfunctions 2. Cardiopulmonary bypass (CPB) time by patient cohort 3. Acute care (ICU / CCU) duration of post implant by patient cohort 4. Incidence and rate of intra-operative device exchange by patient cohort
Follow-up Visits and Length of Follow-up	24 months post-implant. Baseline - prior to implant, then follow-up will be conducted at 1 week, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months after the initial implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	343 subjects were enrolled at IDE experienced sites, and 150 subjects were enrolled at non-IDE sites.
Actual Number of Sites Enrolled	28 IDE Experienced Sites and 21 non-IDE sites in the study
Patient Follow-up Rate	IDE experienced sites had the following follow-up rates: Baseline (100%), Week 1 (100%), Month 1 (91.4%), Month 3 (95.2%), Month 6 (92.5%), Month 12 (96.3%), Month 18 (93.6%), Month 24 (95.4%). Non-IDE experienced sites had the following follow-up rates: Baseline (100%), Week 1 (100%), Month 1 (97.9%), Month 3 (98.5%), Month 6 (98.2%), Month 12 (98.7%), Month 18 (100%), Month 24 (97.4%).
Final Safety Findings	The three most common INTERMACS adverse events were similar between the IDE Experienced and Non-IDE centers. For the IDE Experienced centers these were infection (52.8%), bleeding (35.7%), and cardiac arrhythmia (29.4%). For Non-IDE centers, the three most common events were infection (42.0%), bleeding (36.0%), and cardiac arrhythmia (31.3%). Neurologic dysfunction adverse event incidence and per person year rate were not statistically significantly different between the IDE-Experienced cohort (Incidence: 27.7% of patients, Rate per person-year: 0.29) and the non-IDE cohort (Incidence: 26.0% of patients, Rate per person-year: 0.34) through two years.
Final Effect Findings	The overall survival for both IDE Experienced and Non-IDE groups was similar, with no statistically significant difference between the two groups at 24 months (p=0.8895). The overall survival rate for IDE Experienced centers was 70.9% at 24 months and for the Non-IDE centers it was 72.4% at 24 months (Kaplan-Meier estimates). From implant through two-years, the rate per person-year of rehospitalization was higher for the Non-IDE cohort (0.40 Non-IDE vs. 0.26 IDE-Experienced), but the percentage of patients experiencing rehospitalization was higher for the IDE-Experienced cohort (19.2 IDE-Experienced vs. 17.3 Non-IDE).
Study Strengths & Weaknesses	Overall, the study followed a good number of patients at IDE Experienced and Non-IDE Experience centers with a high follow-up rate for each cohort and follow-up visit. However, much of the data completeness for Quality of Life and Functional Assessments were missing across study visits and centers.
Recommendations for Labeling Changes	A labeling update is recommended with the outcomes of this study.
General
Study Status	Completed
Application Number / Requirement Number	P100047 / PAS003
Date Original Protocol Accepted	02/14/2014
Date Current Protocol Accepted	02/14/2014
Study Name	Continued Follow-Up (HW-PAS-03)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multicenter, prospective, a continued follow-up study consisting of patients from the HeartWare Trials under IDE G070199
Study Population	patients at risk of death from refractory, advanced heart failure and implanted with a HVAS under IDE G070199
Sample Size	at the time of PMA and Protocol approval a total of 152 patients (30 from the HW 003 BTT study and 122 from the CAP study) were potentially eligibile for participation
Key Study Endpoints	Main: Transplant, explant, death Observational: Overall survival on device, Final patient status, Re- hospitalizations, INTERMACS adverse events, Quality of Life (QOL) measures (KCCQ and EuroQol EQ-5D-5L), Functional Status (NYHA and 6- minute walk (6MW)).
Follow-up Visits and Length of Follow-up	5 years post implant of original device and every 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	This Post Approval Study is a continued follow-up of subjects from the IDE study (n=140) and the Continued Access Program (CAP) cohort (n=242). Of those subjects (n=382), only 152 (approximately 40%) were potentially eligible for continued follow-up at the time of the PAS enrollment. Additionally, after excluding subjects (a) who had been off the device (transplanted, or explanted for recovery) for greater than six months, (b) subjects who had their device exchanged to a non HeartWare device, (c) subjects at study sites where PAS participation was declined, and (d) subjects who declined participation only 101 subjects (approximately 26% of the original IDE and CAP subject population) were enrolled in the continued follow-up PAS. Twenty-two subjects from the original IDE clinical study participated in this continued follow-up study, and 79 subjects from the CAP cohort participated in this continued follow-up study. Seventeen of the 101 enrolled subjects had the device explanted in order to receive a heart transplant at the time of PAS enrollment (1 from BTT, and 16 from CAP). Thus 84 subjects (approximately 22% of the original IDE and CAP cohorts) were utilizing the HeartWare device at time of PAS enrollment. All subjects from the IDE cohort had survived at least 36 months post-implant to be eligible for this study, and all subjects from the CAP cohort had survived at least six months post-implant to be eligible for this study.
Actual Number of Sites Enrolled	The HeartWare Continued Follow-Up Post Approval Study 3 (HW-PAS-03) enrolled 25 study sites
Patient Follow-up Rate	The overall follow up rate for this study is (n= 98/101) 97%. Three subjects withdrew and one relocated out of the vicinity of a study site.
Final Safety Findings	The safety endpoints of interest are overall survival on device, final patient status, re-hospitalization and INTERMACs-defined adverse events. Overall Survival on Device Subjects in this PAS were followed for up to five years post original HVAD implant. As noted above, in the section detailing the number of subjects enrolled, subjects from the IDE had survived at least 36 months on device to be eligible for this PAS, and subjects from the CAP cohort had survived at least six months on device to be eligible for this PAS. Therefore the survival rates presented here are more representative of late (greater than six or 36 months on device) survival rather than overall survival on device. The Kaplan-Meier survival rate is 50.3% for the up to 20 month additional follow-up period that the BTT patients were followed in this PAS. For the CAP cohort, the Kaplan-Meier survival rate is 44.3% for the up to 54-month additional follow-up period in this PAS. Final Patient Status Sixty-seven subjects were alive at study completion from both on-device and off-device populations. Twenty-six were still utilizing an HVAD (21 were on their original device and five had at least one HVAD exchange) and 41 subjects were alive after being explanted for transplant. In the IDE cohort 8/22 (36.4%) died during continued follow-up, and in the CAP cohort 26/79 (32.9%) died during continued follow-up. Of the 34 total subjects who died, 64.7% died on the original device, 17.6% died post HVAD-explant for transplant and 17.6% died post HVAD-exchange. Rehospitalization Seventy-eight patients out of 84 subjects (approximately 93%) supported by HVAD at the beginning of this PAS had at least one re-hospitalization while on device, and 44 (approximately 52% ) had three or more re-hospitalizations while on-device during this PAS. INTERMACS Adverse Events Device Malfunction/Failure -- Of the 84 subjects supported by HVAD at the beginning of this PAS, there were 36subjects (approximately 43%) who had at least one device malfunction/failure events (number of events= 49) during this PAS. The three most common adverse events were infection, device malfunction/failure and bleeding. Of those 36 subjects with device malfunction/failure events, 34 had at least one serious device malfunction/failure events (number of events=44).. Neurological Dysfunction Adverse Events – Of the 84 subjects supported by HVAD at the beginning of this PAS, 16 (19.0%) had at least one neurological dysfunction events (number of events=23) during this continued follow-up. Six of the 84 subjects (7.1%) had at least one CT confirmed ischemic cerebrovascular accidents (ICVAs) (number of events=7), nine(10.7%) subjects had at least one who had 12 CT confirmed hemorrhagic cerebrovascular accidents (HCVAs) (number of events=12), and 4 had a transient ischemic attacks (TIAs) (number of events=4).
Final Effect Findings	The effectiveness endpoints of interest are quality of life measures, functional testing scores (KCCQ, 6 Minute Walk Test and NYHA Class), NIH Stroke Scale, and the modified Rankin Score. Quality of Life Across all study visits, 68% or more of study subjects completed the EQ-5D-DL assessment. The CAP cohort had a EQ-5D-DL score ranging from 70 at 18 months post-implant to 82 at 12 months post-implant. BTT cohort scores range from 58 at 60 months-post-implant to a high of 70 at 48 months post-implant. Functional Status Testing Across all study visits, approximately 75% of subjects or more had a KCCQ completed. The average KCCQ score increased from 36.8 at baseline to 60.6 at 60-months post-implant. In the CAP cohort, the average KCCQ score increased from 36.9 at baseline to 57.6 at 60 months post-implant. The BTT cohort average KCCQ score increased from 36.6 at baseline to 66.4 at 60 months post-implant. All subjects completed the 6 Minute Walk Test at follow-up visits except for the Baseline where 97% completed the Test, and at six months where 94% completed the Test. The overall average distance walked for the 6 Minute Walk Test increased from baseline at 55 meters to 200 meters at 60 months post-implant. In the CAP cohort, the average distance walked increased from 37 meters to 195 meters from baseline to 60 months post-implant. In the BTT cohort, it increased from 115 meters to 209 meters from baseline to 60 months post-implant. Across all study visits, approximately 75% of subjects or more had a NYHA class assessment completed. The overall NYHA class changed from 95% NYHA Class IV at baseline to 5.6% NYHA Class IV at 60 months post-implant. In the BTT cohort, NYHA class change from 90.5% NYHA Class IV at baseline to 12.5% NYHA Class IV at 60 months post-implant. In the CAP cohort, NYHA Class changed from 96.8% NYHA Class IV at baseline to 0% NYHA Class IV at 60 months post-implant. NIH Stroke Scale Over 70% of the subjects completed the NIH Stroke Scale, with more than half of the visits having greater than 80% completion. The average NIH Stroke Scale score was between 0-0.5 at all timepoints where results were available, and no subjects reported a score greater than 6 at any timepoint. Modified Rankin Scale Score Over 85% of subjects completed the mRS assessment at all timepoints, with most of the visits having over 95% completion. Over 75% of subjects who completed the mRS assessment had an mRS of 0 at all timepoints and over 90% of all subjects who completed the mRS assessment had an mRS less than or equal to 3 at follow-up timepoints. During this PAS, seven subjects had an mRS score greater than 3. Of these seven subjects, six had scores of higher than 3 after a neurologic adverse event and one subject was enrolled in the PAS with an mRS of 4. Fifteen of 16 subjects who had a neurological adverse event during this PAS, had an mRS score assessed in association with the event. Of those, six subjects had a score of greater than 3 after the event.
Study Strengths & Weaknesses	Strengths: The HeartWare Continued Follow up study (HW-PAS-03) is the first long-term follow-up study of HVAD as a Bridge to Transplant device. For patients similar to those enrolled in the IDE study and who survive an intermediate duration (six months or longer), or a long duration (36 months or longer) on HVAD support, this study provides a good estimate of longer-term patient outcomes and incidence of adverse events. Additionally, this study’s utilization of a standardized set of Adverse Event definitions (INTERMACs’ Adverse Event definitions) allows for comparison to other studies. The completion of Quality of Life Measures (e.g. KCCQ) and Functional Status assessments (e.g. Six Minute Walk Test, mRS scores, and NIH Stroke Scale) was high. Weaknesses: Only a small proportion of the IDE and CAP subjects (approximately one quarter or 101/382) were followed in this PAS due to competing risks (e.g. transplant or death) and low enrollment for this continued follow-up study. Survival estimates and longer-term safety and effectiveness results can only be interpreted from the time of enrollment into this PAS study (all subjects enrolled in this study had already survived at least for 6-months on HVAD support). Additionally, results should be interpreted with caution because of the opportunity for selection bias. Approximately 33% (51/152) of subjects potentially eligible for continued follow-up were not enrolled in the study. We do not know all the longer-term results for those subjects or if they differed from the subjects who did agree to be followed longer-term.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P100049 / PAS002
Date Original Protocol Accepted	03/22/2012
Date Current Protocol Accepted	01/29/2018
Study Name	Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multicenter, single-arm study, with patients as their own control.
Study Population	The study population will consist of patients who have signed the informed consent form, meet the eligibility requirements and have been implanted with the LINX device. Each patients baseline assessments will serve as the comparator post-implant to evaluate the treatment effect. Inclusion Criteria - Patient is a candidate for treatment with the LINX Reflux Management System. - Patient has provided written informed consent for participation in the post-approval study. - Patient has indicated a willingness to comply with study requirements and the follow-up schedule and assessments. - Patient has been diagnosed with GERD as defined by abnormal pH testing. - Patient continues to have chronic GERD symptoms despite maximum medical therapy for the treatment of reflux Exclusion Criteria - Patients with suspected or known allergies to titanium, stainless steel, nickel, or ferrous materials - Known circumstances that would make it unlikely for the patient to complete follow-up through 60 months (e.g. life expectancy <5 years)
Sample Size	A total of 200 patients will be implanted with the LINX device and followed per protocol. At least 20 study centers throughout the US will participate. The study centers will include pivotal IDE centers and at least 10 centers with no prior LINX experience.
Key Study Endpoints	Device related serious adverse events (SAEs) evaluated at 6 months, 12 months and then repeated annually through 60 months. No formal statistical hypothesis test will be conducted. Number of events, number of study patients with event, and the percent of study patients implanted with an event will be summarized. A sufficient number of study patients will be enrolled and followed to ensure a high probability of the detection of rare adverse events through 5 years of follow up, defined as an expected incidence rate of implanted study patients. At least of evaluable study patients will have at least a reduction in total GERD HRQL score off PPIs, as indicated by the lower bound of a confidence interval. Endpoint to be evaluated at 6 months, 12 months and then repeated annually through 60 month. Evaluated at 6 months, 12 months and then repeated annually through 60 months. Safety - Incidence rate of device- and/or procedure-related adverse events Efficacy - pH measurements: Total % time pH, DeMeester components and DeMeester score. (NOTE: not done at 6 months) - Symptoms: From the Foregut Symptom Questionnaire (FSQ), the frequency and severity of regurgitation and % patients reporting extra-esophageal symptoms - GERD medications: % patients free from daily use of acid suppression therapy
Follow-up Visits and Length of Follow-up	The length of follow up will be 60 months post-implantation. Visits are at screening/baseline, implant/discharge, 6-months and annually with last visit scheduled at the end of the study (60 months).
Interim or Final Data Summary
Actual Number of Patients Enrolled	200 patients enrolled and implanted
Actual Number of Sites Enrolled	22 sites obtained IRB approval
Patient Follow-up Rate	5-Year follow-up rate is 68% (136/200)
Final Safety Findings	The 5-year rate of device and/or procedure-related SAEs (primary safety endpoint) was 5.5%. The rate of device-related SAEs at 36 months was 4.5% (95% CI: 2.1%, 8.4%), which did not exceed the upper confidence limit (12.6%) reported through 12 months in the IDE study. The rate of all device and/or procedure related adverse events (including serious and non-serious AEs) was 26.5%. Rate of device explant was 13% and the rate of device erosion was 2.0%. Overall, the types and rates of safety events reported in the PAS were comparable to what was reported in the IDE premarket study with the exception of device explants, which occurred in nearly twice as many PAS patients compared to IDE patients (13% vs. 7%).
Final Effect Findings	For the primary effectiveness endpoint (total GERD-HRQL Score at each follow-up visit), 83-89% of patients reported a successful reduction in GERD symptoms, 6 months to 5 years after device implant. In addition, there was clinical improvement for the other key indicators of reflux control when compared from baseline in secondary effectiveness measures including: esophageal acid exposure, extra-esophageal symptoms, severity and frequency of heartburn and regurgitation, and PPI usage at 6 months and all subsequent follow-up visits through 60 months.
Study Strengths & Weaknesses	A key strength of this study is the long, 5-year follow-up and the demonstration of longer-term treatment safety and effectiveness of LINX treatment. However, given that 32% of the PAS cohort (64 patients) were not included in the 5-year follow-up, there is concern about the possibility of patient selection bias leading to overestimated treatment effects.
Recommendations for Labeling Changes	FDA recommends updating the labeling with the final PAS results
General
Study Status	Terminated
Application Number / Requirement Number	P050039 / PAS002
Date Original Protocol Accepted	07/05/2007
Date Current Protocol Accepted	04/03/2017
Study Name	Novation PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multi-center active surveillance study. The primary objectives of the study is to examine long-term device performance device survival under actual conditions of use.
Study Population	Patients who receive the Novation Ceramic Articulation Hip System in the post-market environment.
Sample Size	The sample size is 375 hips.
Key Study Endpoints	The main study endpoint is device survival. Secondary endpoints include adverse radiographic changes.
Follow-up Visits and Length of Follow-up	The length of patient follow-up is 10 years.
General
Study Status	Completed
Application Number / Requirement Number	P090013 / PAS001
Date Original Protocol Accepted	02/08/2011
Date Current Protocol Accepted	02/08/2011
Study Name	Chronic Lead Performance/Multiple MRI
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	Total number of patients enrolled is 2483. This number comprised of 2323 patients in the Chronic Performance cohort and 160 patients in the Multiple Scan Characterization cohort. Of the Chronic Performance cohort patients, 407 patients had at least one MRI and 71 of the 407 patients were implanted with Advisa MRI IPG. Of the Multiple Scan Characterization cohort patients, 146 patients had at least one MRI and 15 of the 146 were implanted with Advisa MRI IPG.
Actual Number of Sites Enrolled	Seventy-five (75) sites were enrolled including 3 sites from Canada and 5 sites from India.
Patient Follow-up Rate	Of 827 eligible Chronic Performance Subjects at 5 years, 702 completed the expected visit for a follow- up rate of 84.9% (702/827) at 5 years.
Final Safety Findings	Primary Objective no. 1 Primary objective no. 1, which was defined as ”the MRI complication rate is less than 2% at 5 years” was met. The 5-year MRI complication free rate was 0.0% with 95% confidence interval (CI) of 0.00% - 0.73%. The upper bound of the 95% CI of 0.73% was below the pre-specified performance goal of 2%. Primary Objective no.2 Primary objective no. 2, which was defined as “the complication free survival probability for Model 5086MRI lead in the right ventricle (RV) is greater than 92.5% at 5 years post-implant” was met. The 5- year complication-free estimate for Model 5086MRI leads in the RV was 99.3% (95% CI: 98.7%, 99.6%). The lower bound of the 95% CI of 98.7% was above the performance goal of 92.5%. Twelve (12) RV lead related complications contributed to the study primary endpoint. Chronic performance of the Model 5086 MRI RV lead stratified by MRI scan exposure (i.e. whether or not the lead had MRI exposure during follow-up) in a survival analysis yielded a log rank p-value of 0.71, indicating that RV lead survival times were not significantly different by lead MRI scan exposure. Primary Objective no. 3 Primary objective no. 3, which was defined as “complication free survival probability for Model 5086MRI leads placed in the right atrium (RA) is greater than 92.5% at 5 years” was also met. The 5-year complication-free estimate for Model 5086MRI leads placed in the RA was 99.0% (95%CI: 98.3%, 99.4%). The lower bound of the 95% CI of 98.3% was above the performance goal of 92.5%. Sixteen (16) of the 17 RA lead related complications contributed to the study primary endpoint. Chronic performance of the Model 5086 MRI RA lead stratified by MRI scan exposure in a survival analysis yielded a log rank p-value of 0.39, indicating that RA lead survival times were not significantly different by lead MRI scan exposure.
Study Strengths & Weaknesses	The Chronic Lead Performance Multiple MRI study was a large (n= 2483), prospective, global, multicenter study with 5-year long term follow-up. The follow up rate at nearly all timepoints exceeded 80%. All events adjudication was performed by the Clinical Event Committee (CEC). The primary study endpoints were formally evaluated with hypothesis testing and all primary endpoints objectives were met. This study provides important information on clinical outcomes in patients implanted with the Medtronic’s Revo/Advisa MRI SureScan Systems. The absence of MRI-related complications, and the high complication-free rate from RA lead-related complications at 5 years (lower bound of 95% CI: 98.3%), and from RV lead-related complications at 5 years (lower bound of 95% CI: 98.7%) support the safety of the Medtronic SureScan pacing system. The study limitations/weaknesses include visit non- compliance 47.4% (1178/2483), incomplete data collection/testing 36.0% (895/2483), and missing source document 2.0% (50/2483). The percentages were calculated based on number of subjects with the specified deviation as the numerator and total number of subjects enrolled as the denominator.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post Approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P020024 S037/ PAS001
Date Original Protocol Accepted	08/18/2013
Date Current Protocol Accepted	11/08/2013
Study Name	Continued F/u of the Premarket ADO II PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	To examine the long term safety and effectiveness of the ADO II through continued follow-up of the 178 subjects from the ADO II IDE study in whom device placement has occurred.
Study Population	Subjects implanted with an ADO II device. No comparison group.
Sample Size	A total of 178 subjects were enrolled in the ADO II IDE study and were implanted with the device.
Key Study Endpoints	The primary ADO II PAS safety objective is to evaluate the rate of device serious adverse events (SAE) reported from the procedure through 5 years post-procedure.
Follow-up Visits and Length of Follow-up	5 years post-procedure - annual visits
Interim or Final Data Summary
Actual Number of Patients Enrolled	178 subjects implanted with the AMPLATZER Duct Occluder II constituted the post-approval study population
Actual Number of Sites Enrolled	25 sites
Patient Follow-up Rate	84.3% (150/178)
Final Safety Findings	Freedom from device- and procedure-related serious adverse events through 5 years was 97.9% (95% CI: 94.4 – 99.2).
Final Effect Findings	A total of 150 patients had their 60-month visits and 5 did not complete their echocardiograms. The rate of complete closure of the ductus arteriosus at 60 months post-procedure was 100% (145/145).
Study Strengths & Weaknesses	The study had a low rate of attrition, thus minimizing selection bias. It also provided results on the long- term (5 years) safety and efficacy of the device. A weakness of this study is that it did not collect data on race and/or ethnicity.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and efficacy results from the pre-market cohort.
General
Study Status	Terminated
Application Number / Requirement Number	P040043 S051/ PAS001
Date Original Protocol Accepted	09/10/2013
Date Current Protocol Accepted
Study Name	TAG Post-Approval Study
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P110040 / PAS001
Date Original Protocol Accepted	09/19/2013
Date Current Protocol Accepted	09/19/2013
Study Name	Complete SE SFA Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective To evaluate the safety and effectiveness of the Complete SE SFA Stent System in the treatment of de novo and/or restenotic lesions or occlusions in the superficial femoral (SFA) and/or proximal popliteal (PPA) in subjects with symptomatic peripheral artery disease (PAD). Study Design Extended follow-up of premarket cohort enrolled in a prospective, multicenter, single arm study. There are no new enrollments.
Study Population	All subjects with symptomatic ischemic PAD and above-the-knee lesions enrolled in the Complete SE SFA IDE study treated with the Complete SE Vascular stent. Comparator: Performance goal (PG) of 35% event-free rate from acute death, amputation and TLRs.
Sample Size	196 subjects enrolled at 28 sites in the US, Germany and Belgium. Assumptions for sample size calculation ¿ 30% attrition of original 196 IDE subjects at 36 month yields 137 PAS subjects ¿ PG: 35% event-free rate from acute death, amputation and TLRs ¿ CSE Stent true event-free rate from acute death, amputation and TLRs = 55.0% ¿ Study Power > 95% ¿ One-sided alpha error of 2.5% ¿ Sample size = 137 subjects evaluable for analysis based on the Exact test of the binomial distribution
Key Study Endpoints	Primary endpoint: composite of freedom from acute death, amputation, and TLR events at 36 months. Secondary endpoints evaluable at 24 and 36 months post implantation: ¿ All-cause mortality ¿ Stent integrity by flat plate x-rays ¿ Acute death, amputation and TLR event rates.
Follow-up Visits and Length of Follow-up	3 years post treatment yearly
Interim or Final Data Summary
Actual Number of Patients Enrolled	196 187 subjects were available at 12 months for follow-up though 36 month post procedure
Actual Number of Sites Enrolled	28 (23 in the United Sates and 5 in Belgium and Germany)
Patient Follow-up Rate	84.5% (131/151) at 36 months
Final Safety Findings	Primary Endpoint The event free major adverse event (MAE) rate (composite of acute death, target lesion or vessel revascularization and target limb Amputation) at 36 months was 69.8%. The lower bound of the 97.5% confidence interval was 62% which is greater than pre-specified performance goal of 35%. Secondary Endpoints All-cause mortality at 24 and 36 months was 9.8% (18/184) [95% CI: 5.95%, 15.0%] and 14% (25/178) [95% CI: 9.3%, 20.0%], respectively. Stent Integrity at 24 and 36 months was 100% (159/159) [95% CI: 97.7%, 100%] and 100% (145/145) [95% CI: 97.5%, 100%], respectively. Acute death, amputation and TLR events rate at 24 and 36 months was 22.5% (38/169) [95% CI: 16.4%, 29.5%] and 30.2% (48/159) [95% CI: 23.2%, 38.0%], respectively.
Study Strengths & Weaknesses	The study involved formal hypotheses testing and it met its primary endpoint at 36 months. Weakness The PAS population comprised of the premarket cohort that was required to meet certain eligibility criteria. Thus, the study results may not reflect the device performance in routine clinical device.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the 3-year long term results from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow ¿up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P110002 / PAS001
Date Original Protocol Accepted	05/27/2014
Date Current Protocol Accepted	05/27/2014
Study Name	Extended f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study is to evaluate the overall long-term success rate (see primary end-points for the definitions) of the investigational device as compared to the control in subjects enrolled in the pivotal IDE study of the Mobi-C (1-levels) device (IDE Number G050212). Design-Prospective Cohort (extended follow-up of IDE patients)
Study Population	All eligible Mobi-C patients treated at one level. All eligible fusion patients treated at one level under the LDR-001 Pivotal Study (IDE G050212)
Sample Size	245 subjects are still enrolled in the study (at the time of the Primary Endpoint 24 month analysis) and eligible for long term follow-up in the post-approval study. This includes 155 randomized investigational subjects, 75 randomized control subjects, and 15 non-randomized training case (investigational) subjects.
Key Study Endpoints	The primary endpoint of the study is individual patient success which is defined using the two measures of composite study success. 1. When assessing the composite endpoint, all components need to be successful for the endpoint to be considered a success. However, only 1 component needs to be a failure for the endpoint to be considered a failure. 2. Note: the data will be also analyzed for the primary outcome based on the 2nd definition for the success. See approval condition #1 and page 18 for the current submission.
Follow-up Visits and Length of Follow-up	7-years At 7th year
Interim or Final Data Summary
Actual Number of Patients Enrolled	Out of a total of 260 subjects from the pivotal study, 245 subjects were enrolled at 24 months and were eligible for long-term follow-up in the PAS: 155 randomized investigational subjects, 75 randomized control subjects, and 15 non-randomized training case (investigational) subjects.
Actual Number of Sites Enrolled	The pivotal clinical study on one-level Mobi-c involved 24 sites.
Patient Follow-up Rate	Out of 245 subjects enrolled in the PAS, there were 51 cumulative discontinuations. The follow up rate varied based on the follow up timepoint, study subgroup and data category. The Actual, efficacy in window follow up rate at the study’s end point (84-months) was reported as 60.3% for the Mobi-c group and 50% for the ACDF group.
Final Safety Findings	No unexpected adverse events were identified based on the overall results from this PAS. As a result, one-level Mobi-c TDR is rendered as a safe alternative to the ACDF procedure using anterior plating with allograft.
Final Effect Findings	Based on the overall success, as defined by the protocol-specified composite primary endpoint and alternative primary endpoints, the one-level Mobi-C device was shown to be as effective as the standard of care (ACDF). Non-inferiority for the one-level Mobi-C compared to ACDF with respect to individual subject success was demonstrated up to the study’s end point of 84 months.
Study Strengths & Weaknesses	This Extended Follow-Up study was capable of demonstrating non-inferior, and in some instances superior, performance of the investigational one-level Mobi-c device compared to ACDF as control. However, a further performance analysis of the one-level Mobi-c disc may help with elucidating possible long-term complications such as underdiagnosed Adjacent Level Disease and progressing Heterotopic Ossification, which can hamper long-term motion preservation as the general premise of TDR. In addition, further research on possible sex-based differences in the performance of one-level Mobi-c and cervical fusion may augment the current device indications and may enable more informed pre-implantation risk-benefit assessment for the sex-stratified patient subgroups. Further research efforts may be also recomended for clarifying possible sex-related differences in Mobi-c performance at one level vs. two contigious levels: in contrast to a trend to higher overall success rates among males with one-level Mobi-c (P110002), males with the two-level Mobi-c experienced overall success less frequently, compared to their female counterparts (P110009).
Recommendations for Labeling Changes	The current labeling for one-level Mobi-c is recommended to be updated based on long-term device performance (7-years). The labeling changes should include the following in particular: • Language that reflects that owing to possible indeterminate results of radiographic imaging (i.e., shoulder obstruction), the actual incidence of Adjacent Level Disease may be higher than that reported in both study groups. • Language describing the progression of Heterotopic Ossification which is statistically significant over time (i.e., 84 months vs. 24-months), but for which the clinical significance (e.g., possible ROM limitation despite the anticipated motion preservation in Mobi-c patients) has not been determined. • Language that mentions the possibility of some sex-related trends in device performance, such as a trend of higher likelihood of heterotopic ossification (=5 years post-implantation) in males vs. females with one-level Mobi-c.
General
Study Status	Completed
Application Number / Requirement Number	P110002 / PAS002
Date Original Protocol Accepted	05/16/2014
Date Current Protocol Accepted	06/03/2014
Study Name	Enhanced Surveillance System
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A 10-year Enhanced Surveillance Study (ESS) of the Mobi-C® Cervical Disc Prosthesis to fully characterize adverse events and complaints when the device is used in the intended patient population under general conditions of use in the United States and in the rest of the world. The objective is to collect, analyze, and submit all adverse event data.
Study Population	All patients who are implanted with the device The data on AEs will be collected by the company and reported to the FDA: 1. Through literature search (every 6 months for first 2 years and then annually thereafter) 2. AEs reported through company website 3. MDR reports 4. Annual survey of all USA physicians who were trained with the device
Sample Size	N/A
Key Study Endpoints	All adverse Events will be reported including HO, neurological complications, subsequent surgeries and etc. The data will be categorized based on severity, and device and MDR relevancy.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	3246 surgeons sent 21854 surveys
Actual Number of Sites Enrolled	N/A Annual surgeon survey: active collection of surgeon feedback annually to elicit information related to heterotopic ossification, device malfunction, device removal, or other serious device related complications.
Patient Follow-up Rate	15.5% survey response rate
Final Safety Findings	No new questions of safety or raised. Highest AE rates regarded device positioning or migration, heterotopic ossification, continuing pain, and general technical difficulty with the surgery. The sum total of all AE responses was 0.61%.
Final Effect Findings	This Enhanced Surveillance Study did not survey effectiveness.
Study Strengths & Weaknesses	Returns represent a small percentage of patients
Recommendations for Labeling Changes	No labeling change is recommended
General
Study Status	Completed
Application Number / Requirement Number	P110002 / PAS003
Date Original Protocol Accepted	07/15/2014
Date Current Protocol Accepted	07/15/2014
Study Name	Retrieval Analysis
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Retrieval Analysis: to asses device failure modes or adverse event profile with a possible relationship to the clinical and demographic characteristic (if the data permits) for one and two level patients with the device. Design-case series (if clinical data is available) premarket cohorts, new enrollment or both.
Study Population	All patients with Mobi-C Cervical Disc whose device has been removed and subjected to retrieval analysis.
Sample Size	NA (bench study)
Key Study Endpoints	Implant Failure Modes Adverse Event Profile Possible relationship of the mechanical wear to the clinical characteristics of the patient (if data is available)
Follow-up Visits and Length of Follow-up	10 years f/u
Interim or Final Data Summary
Actual Number of Patients Enrolled	This is a retrieval study and so this section is not applicable.
Actual Number of Sites Enrolled	This is a retrieval study and so this section is not applicable.
Patient Follow-up Rate	This is a retrieval study and so this section is not applicable.
Final Safety Findings	This is a retrieval study and so this section is not applicable.
Final Effect Findings	This is a retrieval study and so this section is not applicable.
Study Strengths & Weaknesses	This is a retrieval study and so this section is not applicable.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P110009 / PAS003
Date Original Protocol Accepted	08/23/2013
Date Current Protocol Accepted	07/15/2014
Study Name	Retrieval Analysis
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Retrieval Analysis: to asses device failure modes or adverse event profile with a possible relationship to the clinical and demographic characteristic (if the data permits) for one and two level patients with the device. Design-case series (if clinical data is available) premarket cohorts, new enrollment or both.
Study Population	All patients with Mobi-C Cervical Disc whose device has been removed and subjected to retrieval analysis.
Sample Size	NA (bench study)
Key Study Endpoints	Implant Failure Modes Adverse Event Profile Possible relationship of the mechanical wear to the clinical characteristics of the patient (if data is available)
Follow-up Visits and Length of Follow-up	10 years (length of f/u)
Interim or Final Data Summary
Actual Number of Patients Enrolled	This is a retrieval study and so this section is not applicable.
Actual Number of Sites Enrolled	This is a retrieval study and so this section is not applicable.
Patient Follow-up Rate	This is a retrieval study and so this section is not applicable.
Final Safety Findings	This is a retrieval study and so this section is not applicable.
Final Effect Findings	This is a retrieval study and so this section is not applicable.
Study Strengths & Weaknesses	This is a retrieval study and so this section is not applicable.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P120020 / PAS001
Date Original Protocol Accepted	03/28/2014
Date Current Protocol Accepted	10/20/2014
Study Name	SUPERB Extended F/U Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohorts
Study Population	Subjects with SFA and proximal popliteal artery lesions treated with the Supera stent. There is no comparator group.
Sample Size	All remaining study subjects: 212 ITT subjects and 44 Roll-in Subjects as of July 2013
Key Study Endpoints	Safety Endpoint Composite of amputation and clinically-driven target lesion revascularization (TLR) evaluated at 2 and 3 years. Secondary Endpoints include Clinically driven TLR through 3 years Stent Fracture Rate at 2 and 3 years by X-ray evaluation Core Laboratory, defined as type I, II, III, IV or V. Composite endpoint of Death, Amputation and TLR Adverse and Serious Adverse events through 3 years. Unanticipated Adverse Device Effect (UADE) through 3 years
Follow-up Visits and Length of Follow-up	3 years 2 and 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	264 subjects enrolled; 208 subjects were eligible for the 2-year PAS.
Actual Number of Sites Enrolled	46 Investigational Sites
Patient Follow-up Rate	Follow-up rate- (ITT population) - Compliance rate at 36 months was 98.9% (177/179) Follow-up rate- (Roll-in population) - Compliance rate at 36 months was 100% (39/39)
Final Safety Findings	(ITT Population) Primary Endpoint The long term composite safety endpoint of clinically driven TLR and Index limb amputation at 36 months was 22.3% (41/184) [ 95% CI:16.5%,29.0%]. Secondary Endpoints The clinically driven TLR rate at 36 months was 21.3% (39/183) [95% CI: 15.6%, 28.0%]. The safety composite secondary endpoint (Death at 1 month, TLR, Index limb Amputation and RB Classification increase by 2 classes at 36 months) event rate at 36 months was 24.16% (43/178) [95% CI: 18.07%, 31.13%]. The index limb amputation at 36 months was 1.2% (2/173) [95% CI: 0.1%,4.1%], and Rutherford Becker classification increase by 2 classes as compared to pre-procedure at 36 months was 1.20% (2/167) [0.15%,4.26%]. Stent fracture rate at 36 months was 0.6% (1/162) [95% CI: 0.0%, 3.4%]. The proportion of patients with any adverse event and any serious adverse event through 36 months cumulative was 97.2% (211/217) and 91.5% (151/165), respectively. There were no unanticipated adverse device effect events reported through 3 years. Major adverse vascular event (MAVE) rate at 36 months was 6.3% (11/175) [95% CI: 3.2%, 11.0%] Target Vessel Revascularization at 36 Months was 25.8% (48/186) [95% CI: 19.7%, 32.7%]. (Roll-in Population) Secondary Endpoints The long term composite safety endpoint of clinically driven TLR and Index limb amputation at 36 months was 27.9% (12/43) [95% CI: 15.3%, 43.7%]. Clinically driven TLR rate at 36 months was 26.2% (11/42) [95% CI: 13.9%, 42.0%]. The safety composite secondary endpoint (Death at 1 month, TLR, Index limb Amputation and RB Classification increase by 2 classes at 36 months) event rate at 36 months was 29.27% (12/41) [ 95% CI: 16.13%,45.54%]. The index limb amputation at 36 months was 2.5% (1/40) [95% CI: [95% 0.1%,13.2%], and Rutherford Becker classification increase by 2 classes as compared to pre-procedure at 36 months was 0.0% (0/37) [95% CI: 0.00%, 9.49%]. The Stent fracture rate at 36 months was 0% (0/31). The proportion of patients with any adverse event and any serious adverse event through 36 months cumulative was 98.1% (51/52) and 85.7% (36/42), respectively. There were no unanticipated adverse device effect events reported through 3 years. Major adverse vascular event (MAVE) rate at 36 months was 5.0% [95% CI: 0.6%, 16.9%] Target Vessel Revascularization at 36 Months was 32.6% (48/186) [95% CI: 19.1%, 48.5%].
Study Strengths & Weaknesses	The study achieved adequate compliance rate at 3 years (98.9% for the ITT population)
Recommendations for Labeling Changes	Labeling change is recommended to reflect the 3-year long term results from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow ¿up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P090016 / PAS002
Date Original Protocol Accepted	11/14/2011
Date Current Protocol Accepted	03/08/2013
Study Name	Concentration and Molecular Weight
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Bench/Lab study to evaluate the concentration and molecular weight distribution of low molecular weight hyaluronic acid fragments in Belotero Balance as a function of time.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	Not applicable. This is a bench/lab study.
Key Study Endpoints	Not applicable. This is a bench/lab study.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	n/a - bench study
Actual Number of Sites Enrolled	n/a - bench study
Patient Follow-up Rate	The concentration and molecular weight distribution of low MW hyaluronic acid (HA) fragments in three Belotero Balance batches are determined in a laboratory study as a function of time during 18 months.
Final Safety Findings	¿The study results fulfilled the second condition of approval: the sponsor should provide ¿results of studies to evaluate the concentration and molecular weight (MW) distribution of low MW hyaluronic acid (HA) fragments in Belotero Balance as a function of time.¿ HA is a listed ingredient and not a proprietary ingredient. This study reports in each additional time point, during 18 months, additional information about the nature of the soluble fraction HA degradation. ¿Changes in soluble HA fraction are due to degradation of soluble HA within the device, as well as conversion of crosslinked HA to soluble HA. Both effects are linked to hydrolysis of the HA molecule. The mechanism for these increased degradation periods remains unclear. ¿As HA degrades, the % and average MW of the soluble HA fraction increases. However, this increase appears to be temporary as degradation of newly soluble HA occurs. Polydispersity is also lowered as high MW HA fragments degrade over time. ¿Because only soluble HA was evaluated (and not the crosslinked portion), and because the nature of the soluble HA was variable from time point to time point, it is difficult to draw correlations between the viscosity of the material and the network structure/MW distribution of the product. Generally speaking, physical properties arise from chemical characteristics. In this case, there are multiple factors, chiefly the distribution and degradation of the soluble HA component (and secondarily the apparent burst release of soluble HA), that may ultimately lead to the decrease in material properties.
Study Strengths & Weaknesses	A. Strengths: ¿The evaluation methods used in this study effectively evaluated the concentration and distribution of the MW of HA, and revealed certain empirical information regarding the behavior and properties of this device as it age, particularly the potential for stepwise changes in chemical and mechanical properties. ¿The methodology used in this study could be helpful in the evaluation of this class of devices (HA filler products) and may provide the opportunity to compare results with each other. B. Weaknesses: ¿The methodology used was limited in scope to evaluate soluble HA.
Recommendations for Labeling Changes	No labeling changes are recommended because no unexpected findings were reported and no additional information from the PAS is needed in the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P090016 / PAS003
Date Original Protocol Accepted	05/01/2012
Date Current Protocol Accepted	05/01/2012
Study Name	Belotero Balance PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	117 adults
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	97% (113/117)
Final Safety Findings	Re-treatment with Belotero Balance did not result in an increase in ¿severe¿ adverse events (AEs). Total percentage subjects with severe ¿common¿ AEs was 15.6% after the initial treatment, during the pre-approval study, and 7.7% with re-treatment during the post-approval study (p<0.0085). Specifically, the incidence rates of severe adverse events after re-treatment were 11.5% and 5.4% for subjects with Fitzpatrick Skin Type Grades I-III and Grades IV-VI respectively. The duration of ¿severe¿ adverse events with re-treatment was generally short (mean 10.2 days, SD = 5.6, 95% CI = 8.2, 12.2) and none of these events required treatment.
Final Effect Findings	No effectiveness endpoints were included in the study.
Study Strengths & Weaknesses	The post-approval study sample size was 117 exceeding the minimum requirement of 104 subjects. A total of 113 re-treated subjects completed the study achieving a 97% follow-up rate. Adverse events occurring beyond one month after re-treatment were not captured because the length of follow-up was restricted to one month.
Recommendations for Labeling Changes	Labeling changes are recommended to reflect severe adverse event incidence rates after re- treatment.
General
Study Status	Completed
Application Number / Requirement Number	P100003 / PAS002
Date Original Protocol Accepted	09/28/2012
Date Current Protocol Accepted	05/08/2014
Study Name	Enhanced Surveillance
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Objectives-To assess safety profile of the secure-C disc under general condition of use. Design- ESS
Study Population	All patients who have received secure-C
Sample Size	N/A
Key Study Endpoints	Anticipated and un-anticipated adverse events including, but not limited to major vessel injury, neurological damage, or nerve injury, device migration, removal, revision, and heterotopic codification.
Follow-up Visits and Length of Follow-up	10 years Assessments: Annual for surgeon surveys, ongoing for the complains, explants and MDRs
Interim or Final Data Summary
Actual Number of Patients Enrolled	Not applicable
Actual Number of Sites Enrolled	Not applicable
Patient Follow-up Rate	Not applicable
Final Safety Findings	A cumulative total of 7318 implants have been sold in the U.S. since the PMA approval date of September 28, 2012, to September 13, 2022. A cumulative total of 78 MDRs have been reported for the SECURE-C system sold in the U.S. since the approval date to September 13, 2022. 74 of the US MDRs were device related while 4 were instrument related. A cumulative total of 594 implants have been sold outside of the U.S. since the PMA approval date of September 28, 2012, to September 13, 2022. A cumulative total of 1 MDRs have been reported outside of the U.S since the approval date to September 13, 2022, and it was instrument related.
Final Effect Findings	Not applicable
Study Strengths & Weaknesses	The study permitted monitoring of the AEs occurrence in the broader population of the device users. Due to the study design, it is impossible to meaningfully evaluate the AEs rates. Further, due to study design and lack of clinical information reported to the company it is difficult to find any particular trends in occurrence of heterotopic ossification and osteolysis.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P960009 / PAS002
Date Original Protocol Accepted	04/16/2010
Date Current Protocol Accepted	04/16/2010
Study Name	Mortality and Autopsy
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A This is a bench study.
Final Effect Findings	N/A
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P120006 / PAS001
Date Original Protocol Accepted	10/05/2012
Date Current Protocol Accepted	06/21/2013
Study Name	Long Term Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, consecutively enrolling, single-arm, non-randomized, multi- center study
Study Population	Patients with an abdominal aortic aneurysm with vascular morphology suitable for endovascular repair with the Ovation/Ovation Prime Abdominal Stent Graft System. Eligible patients must have met or must meet all of the inclusion criteria and none of the exclusion criteria. Comparator: Performance Goal of 92%
Sample Size	A total 320 subjects yielding at least 192 evaluable subjects at 5 years. Comprises of 161 pivotal cohort subjects, all continued access subjects, all subjects from the HDE PAS and at least 59 de novo subjects enrolled from a minimum of 15 U.S. sites.
Key Study Endpoints	Primary Endpoint: Aneurysm-related mortality at 5 years Secondary Endpoints: ¿ Serious Adverse Events (SAEs) assessed through 30 days, 12 months then annually until 5 years post initial implant. ¿ Mortality (AAA-related and all-cause) ¿ Device Patency ¿ Conversion to open surgical repair ¿ Endoleak ¿ AAA enlargement ¿ Stent Graft Migration ¿ Device integrity ¿ Secondary endovascular procedures ¿ Aneurysm rupture All endpoints assessed at 30 days and 12 months, then annually thereafter through 5 years post initial implant.
Follow-up Visits and Length of Follow-up	5 years 30 days, 12 months and annually thereafter.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 320 subjects were enrolled. This includes 161 Pivotal subjects; 77 Continued Access (CA) Subjects; 82 de novo subject.
Actual Number of Sites Enrolled	49 sites (13 US de novo clinical sites, 36 worldwide clinical sites)
Patient Follow-up Rate	The 5-year clinical follow-up rate for each cohort is as follows: 94% (87/93) of available subjects in the 5 year follow up interval for the Pivotal Cohort 95% (37/39) of available subjects at the 5-year follow-up interval for the Continued Access Cohort 100% (41/41) of available subjects at the 5-year follow-up interval for the de novo Cohort The 5-year CT imaging compliance rate for each cohort is as follows: 90% (84/93) of available subjects in the 5 year follow up interval for the Pivotal Cohort 79% (31/39) of available subjects at the 5-year follow-up interval for the Continued Access Cohort 78% (32/41) of available subjects at the 5-year follow-up interval for the de novo Cohort
Final Safety Findings	Primary Endpoints Aneurysm-Related Mortality: Survival from aneurysm-related mortality by Kaplan Meier (KM) estimate at 5 years was 98.9% for all cohorts. Through 5 years there were three (3) aneurysm-related deaths all in the pivotal cohort. One subject had a death at day 17 from abdominal sepsis and disseminated intravascular coagulation (DIC). A death secondary to suprarenal aneurysm rupture at day 368 was also seen in a subject. An additional AAA-related death was reported for the pivotal cohort at day 1499 due to aneurysm rupture. There were no other aneurysm-related deaths in the other cohorts. Secondary Endpoints: All-Cause Mortality: Through 5 years of follow-up, a total of 67 deaths (67/320, 20.9%) have been reported for the combined cohorts; 35 in the Pivotal cohort (35/161, 21.7%). 17 in the Continued Access cohort (17/77, 22.1%), and 15 in the de novo cohort (15/82, 18.3%). Individually, the all-cause mortality rates for the Pivotal, Continued Access, and de novo cohorts through 365 days is 2.5% (4/161), 5.2% (4/77), and 3.7% (3/82), respectively; the combined all-cause mortality for all cohorts at 365 days is 3.4% (11/320). Surgical Conversion One (1) surgical conversion was reported in the PAS, which was in the de novo cohort. The subject experienced with progressive enlargement due to Type II endoleak through 4-year follow-up and was converted to open repair. The surgical conversion rate at 5 years is 0.5% (1/206). AAA Rupture Two (2) AAA ruptures have been reported in the PAS; one (1) rupture in the Pivotal Cohort and one in the Continued Access cohort. The pivotal study subject died from rupture 1499 days post implant; the patient had Type IA, IB and II endoleaks (previously treated) that were persistent, and the patient refused further endoleak treatment. The continued access subject experienced a contained rupture at day 1486. The subject had a Type IA endoleak which was resolved after repeated coil embolization, yet likely contributed to the rupture. The combined AAA rupture rate at 5 years is 1.0% (2/206). Polymer Leaks There has been two incidence of polymer leaks in the study, occurring at the procedure timepoint in the pivotal cohort and continued access cohort (1 in each). The Ovation/Ovation Prime products were not included in the 2020 Class I Recall regarding the next generation Ovation iX device.
Final Effect Findings	AAA Enlargement: Through 5 years, the total number of patients that experienced aneurysm size enlargement (>5mm) was 24/226 (10.6%) for pivotal and CA combined; 11.5% in the pivotal study cohort (18/156) and 8.6% CA (6/70). In the de novo cohort, 10/67 (14.9%) patients experienced AAA size enlargement, but this was not confirmed by a corelab. Through 5 years, the total number of patients that experienced aneurysm size decrease (>5mm) was 106/226 (46.9%) for the pivotal and CA cohorts; 42.3% in the pivotal cohort (66/156), 57.1% CA (40/70). In the de novo cohort, 32/67 (47.8%) patients experienced aneurysm size decrease. Through 5 years, the total number of patients that experienced no change in aneurysm size was 96/226 (42.5%) for the pivotal and CA cohorts; 46.1 % in the pivotal study cohort (72/156), 34.3% CA (24/70). In the de novo cohort, 25/67 (37.3%) patients experienced no change in aneurysm size. Endoleaks No Type I, III, or IV endoleaks were identified by the imaging Core Laboratory through 5 year follow up in the Pivotal and CA cohorts. In the de novo cohort, 1 Type IIIA endoleak was identified at 5 years (1/82, 1.2%), and 2 type I endoleaks were identified in the same 2 patients at 30-days and persistent through 5-year (2/82, 2.4%). In total, the rate of type I and type III endoleaks through 5-years is 0.6% (2/320) and 0.3% (1/320), respectively, for all cohorts combined In total, 113/232 (48.7%) patients were reported to have Type II endoleaks by the Core Lab in the combined cohorts (pivotal and CA); 49.0% in the pivotal study cohort (77/157) and 48.0% CA (36/75). Twenty-nine patients (29/77, 46.0%) were identified in the de novo cohort with Type II endoleaks but were not confirmed by the corelab. In total, 5/238 (2.1%) patients were reported to have indeterminate endoleaks by the Core Lab in the pivotal and CA cohorts; 1.2% in the pivotal study cohort (2/161), and 0% CA (0/77). Three patients (3/82; 3.7%) were identified in the de novo cohort but were not confirmed by the corelab. Loss of Device Integrity Stent fractures were identified by the imaging Core Laboratory through 12 months post-treatment in 1.9% (6 of 315) of all subjects treated in the Pivotal, CA, and de novo cohorts. Stent fractures were identified by the imaging Core Laboratory through 5-years post-treatment in 17/238 (7.1%) of all subjects treated in the Pivotal and CA cohorts, combined. Of the 11 Pivotal subjects with reported stent fractures through 5 years, six patients had 1 reported stent fracture, four had 2 reported stent fractures, and one had >2 reported stent fractures. In the patients with more than 1 stent fracture, the stent fractures initially occurred in the same axial region of the proximal stent. There were 6 subjects having stent fractures in the CA cohort. There were no stent graft fractures for the de novo cohort. The stent fractures were not associated with clinical sequelae or associated with intervention. There were no reports of loss of integrity (e.g., holes, tears) of the PTFE graft material. Secondary Interventions The freedom from secondary interventions through 5 years [Kaplan-Meier (KM) estimate] for all cohorts was 87.1%; 89.7% for pivotal, 82.5% for CA, and 85.4% for the de novo. Reinterventions occurred over all follow-up time periods. The primary reason for reinterventions were Type II Endoleaks treated with embolization. Stent Graft Migration There have been no device migrations (defined as evidence of proximal or distal movement of the stent graft >10mm relative to fixed anatomic landmarks) reported in any cohort. Loss of Device Patency Loss of device patency is defined as complete occlusion of the treated vessel. The freedom from occlusion through 5 years [KM estimate] for the combined cohorts was 96.1%; 96.3% for the pivotal cohort, 93.4% for the CA cohort, and 98.8% for the de novo cohort.
Study Strengths & Weaknesses	Study Strengths: This study is a multicenter study involving 49 investigational sites, 13 sites in the US and 36 sites outside of the US. Study Weaknesses: Due to loss to subject during follow-up and withdrawal, Endologix did not meet the pre-determined goal of 192 evaluable subjects at the 5-year follow-up visit, which was the original post-market target set to perform the primary endpoint analysis of freedom from aneurysm related mortality. However, Endologix performed a tipping point analysis, in which it was concluded that given that it took 10.5% of “missing” subjects (12/114) to fail the endpoint, and that this is substantially higher than the 1.1% 5-year rate provided by the Kaplan-Meier estimate, the analysis supports that the conclusions of the primary endpoint analysis remain valid. It is also important to note that the Core Lab did not evaluate the de novo cohort. Although we have presented KM estimates and cumulative rates above, there was not adequate follow-up at all timepoints for all patients to assess each of the endpoints. Therefore, the rates provided may be an underestimate of the actual rates of events.
Recommendations for Labeling Changes	Not Recommended, as the Ovation/Ovation Prime devices are no longer marketed.
General
Study Status	Completed
Application Number / Requirement Number	P110009 / PAS001
Date Original Protocol Accepted	08/23/2013
Date Current Protocol Accepted	05/08/2014
Study Name	Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study is to evaluate the long-term overall success rate (see primary end-points for the definitions) of the investigational device as compared to the control in subjects enrolled in the pivotal IDE study of the Mobi-C (2- levels) device (IDE Number G050212). Design-Prospective Cohort, a long term follow-up of the IDE patients ( investigational and controls)
Study Population	All eligible Mobi-C patients (n=221 -randomized and n=8 - training cases) treated at two contiguous levels All eligible fusion patients (n=99- randomized at 24-months) treated at two contiguous levels under the LDR-001 Pivotal Study (IDE G050212)
Sample Size	Investigational¿n=221 -randomized and n=8 -training cases at treated at two contiguous levels. Control¿ all eligible fusion patients (n=99) treated at two contiguous levels
Key Study Endpoints	For Mobi-C: Pain/Disability Improvement of at least 25% in the Neck Disability Index (NDI) at 5 years and 7 years; no device failures at the index level requiring revision, re-operation, removal, or supplemental fixation; absence of major complications defined as 1) neurologic deterioration, 2) radiologic failure and 3) adverse events determined to be major complications and related to the study For Fusion ACDF: evidence of bridging trabecular bone and <2º total angular motion (from flexion to extension) and <50% radiolucency along the graft/endplate interface and for Mobi- C® subjects radiologic failure is defined as evidence of continuous bridging bone and <2º total angular motion.
Follow-up Visits and Length of Follow-up	7 years at 7th year
Interim or Final Data Summary
Actual Number of Patients Enrolled	Out of a total of 339 subjects from the IDE study, 328 subjects were eligible for the PAS, as Mobi-C (221 randomized and 8 training) or ACDF (99) patients treated at two contiguous levels.
Actual Number of Sites Enrolled	The pivotal clinical study on two-level Mobi-c involved 24 sites.
Patient Follow-up Rate	At the 84-months, the total follow up rate was 82%; however, only 136 two-level Mobi-C subjects (66.3%) and 48 ACDF subjects (57.1%) had Actual ‘in-window’ efficacy data at the final timepoint.
Final Safety Findings	No unexpected Mobi-related adverse events were identified in this PAS. As a result, two-level Mobi-c TDR is rendered as a safe alternative to the standard of care procedure (ACDF).
Final Effect Findings	Based on the overall success as defined by the protocol-specified composite primary endpoint and alternative primary endpoints, the two-level Mobi-C TDR was shown to be as effective as control ACDF treatment. Non-inferiority for the two-level Mobi-C compared to ACDF with respect to individual subject success was demonstrated up to the time point of 84 months.
Study Strengths & Weaknesses	Although this Extended Follow-Up study demonstrated non-inferiority of the investigational two-level Mobi-c device, a further performance analysis of the two-level Mobi-c disc may help with elucidating possible long-term complications such as underdiagnosed Adjacent Level Disease and progressing Heterotopic Ossification, which can hamper long-term motion preservation as the general premise of TDR. In addition, further research on possible sex-based differences in the performance of two-level Mobi-c may augment the current device indications and may enable more informed pre-implantation risk-benefit assessment for the sex-stratified patient subgroups. Further research efforts may be also recommended for clarifying possible sex-related differences in Mobi-c performance at one level vs. two contigious levels: in contrast to a trend to higher overall success rates among males with one-level Mobi-c (P110002), males with the two-level Mobi-c experienced overall success less frequently, compared to their female counterparts (P110009).
Recommendations for Labeling Changes	The current labeling for two-level Mobi-c is recommended to be updated based on long-term device performance (7-years). The labeling changes should include the following in particular: Language that reflects that owing to possible indeterminate results of radiographic imaging (i.e., shoulder obstruction), the actual incidence of Adjacent Level Disease may be higher than that reported in both – Mobi-c and ACDF - study groups. Language describing the progression of Heterotopic Ossification which is statistically significant over time (i.e., 84 months vs. 24-months), but for which the clinical significance (e.g., possible ROM limitation despite the anticipated motion preservation in Mobi-c patients) has not been determined. Language that mentions the possibility of sex-related trends in two-level Mobi-c performance, including the following: long-term (84-month) overall success outcomes were more frequent among females with two-level Mobi-c vs. females with two-level ACDF, whereas the same trend for males did not reach statistical significance; males with two-level Mobi-c were less likely to have long-term (84-month) overall success outcomes compared to females with two-level Mobi-c; long-term, clinically significant Heterotopic Ossification (Grade 3-4) was more likely to occur in males with two-level Mobi-c, compared to their female counterparts
General
Study Status	Completed
Application Number / Requirement Number	P110009 / PAS002
Date Original Protocol Accepted	08/23/2013
Date Current Protocol Accepted	05/19/2014
Study Name	Enhanced Surveillance System
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	A 10-year Enhanced Surveillance Study (ESS) of the Mobi-C® Cervical Disc Prosthesis to fully characterize adverse events and complaints when the device is used in the intended patient population under general conditions of use in the United States and in the rest of the world. The objective is to collect, analyze, and submit all adverse event data.
Study Population	All patients who are implanted with the device The data on AEs will be collected by the company and reported to the FDA: 1. Through literature search (every 6 months for first 2 years and then annually thereafter) 2. AEs reported through company website 3. MDR reports 4. Annual survey of all USA physicians who were trained with the device
Sample Size	N/A
Key Study Endpoints	All adverse Events will be reported including HO, neurological complications, subsequent surgeries and etc. The data will be categorized based on severity, and device and MDR relevancy.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A There is no enrollment of patients. All patients who have received this device in the post-market environment, i.e. all patients who are implanted with the device. The intended patient population under general conditions of use in the United States and in the rest of the world.
Actual Number of Sites Enrolled	N/A Annual surgeon survey: active collection of surgeon feedback annually to elicit information related to heterotopic ossification, device malfunction, device removal, or other serious device related complications.
Patient Follow-up Rate	Numbers of sites, IRB approvals and study participants are not available, since this ESS does not include enrollment of sites/patients. There is no enrollment of patients.
Final Safety Findings	Not evaluated, this is a surveillance study
Final Effect Findings	Not evaluated, this is a surveillance study
Study Strengths & Weaknesses	The strength of this study is that the data is collected from real world usage of this device and used by practitioners with a variety of experience and familiarity with the device. The weakness is that this study is highly dependent on surgeon feedback, so the response rate may be low.
Recommendations for Labeling Changes	N/A Labeling was updated with 7-year follow-up data and no new issues or concerns have been found since that time
General
Study Status	Completed
Application Number / Requirement Number	P110010 S001/ PAS001
Date Original Protocol Accepted	06/01/2012
Date Current Protocol Accepted	08/24/2012
Study Name	PROMUS Element Plus US PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, open-label, multi-center registry study
Study Population	PLATINUM-like patients, including at least 200 patients treated with PROMUS Element Plus long lesion stents 32/38 mm lengths (2.50-4.0mm diameters).
Sample Size	2,689 consecutive, consented patients from up to 65 sites in order to attain 906 PLATINUM like patients from the US PAS (33.7% of the enrolled patients)
Key Study Endpoints	Primary: Cardiac death or myocardial infarction rate through 12 months post stent implantation among all PLATINUM-like patients Secondary: Stent thrombosis rate, longitudinal stent deformation, and PROMUS Element plus related MACE, cardiac death/MI, TVF, TVR, cardiac death, and MI.
Follow-up Visits and Length of Follow-up	5 years 30- days, 180-days, and annually through 5 years post intervention
Interim or Final Data Summary
Actual Number of Patients Enrolled	Three hundred and forty-three (343) subjects were enrolled including platinum-like patients (n=13) and non-platinum like patients (n=328) Two patients with unknown reference vessel diameter were not included in either group but included in the overall Long Lesion population.
Actual Number of Sites Enrolled	Fifty-three (53) sites
Patient Follow-up Rate	84% (246/293) at 5 years
Final Safety Findings	Final safety and effectiveness findings (key endpoints) through 5 years: All Subjects Stent thrombosis (ST) rate, using ARC definition (definite/probable) in the overall patient population was 3.6% (11/304). Stent thrombosis (ARC definition, definite/probable) related to PROMUS Element plus rate was 2.6% (8/304). The overall rate of longitudinal stent deformation was 0.15% (1/670). The overall major adverse cardiac event (MACE, composite of cardiac death, myocardial infarction or MI, and target vessel revascularization or TVR) rate was 29.6% (90/304). PROMUS Element Plus-related MACE rate was 24.7% (75/304). The overall cardiac death or MI rate was 12.8% (39/304). PROMUS Element Plus-related cardiac death or MI rate was 10.5% (32/304). The overall target vessel failure (TVF) rate was 28.6% (87/304). PROMUS Element Plus-related TVF rate was 24.7% (75/304). TThe overall cardiac death rate was 9.2% (28/304). PROMUS Element Plus-related cardiac death rate was 8.9% (27/304). The overall MI rate was 5.6% (17/304). PROMUS Element Plus-related MI rate was 3.3% (10/304). All death rate was 16.4% (50/304). Non-cardiac death rate was 7.2% (22/304) All death or MI rate was 20.1% (61/304). Subgroup Outcomes: Platinum-like and Non-Platinum like Patient Populations Stent thrombosis (ARC, Definite/Probable) rate in PLATINUM-like patients was 0.0% (0/12) and in non-PLATINUM-like patients was 3.8% (11/290). MACE rate related to PROMUS element Plus in PLATINUM-like patients was 33.3% (4/12) and in non-PLATINUM-like patients was 24.5% (71/290). Cardiac death or MI rate related to PROMUS element Plus in PLATINUM-like patients was 8.3% (1/12) and in non-PLATINUM-like patients was 10.7% (31/290). TVR rate related to PROMUS element Plus in PLATINUM-like patients was 33.3% (4/12),he overall TVR rate was 21.7% (66/304). PROMUS Element Plus-related TVR rate was 17.8% (54/304). and in non-PLATINUM-like patients was 17.2% (50/290). TVF rate related to PROMUS element Plus in PLATINUM-like patients was 33.3% (4/12), and in non-PLATINUM-like patients was 24.5% (71/290).
Study Strengths & Weaknesses	Strengths: The PROMUS Element Plus US post-approval Long Lesion study was a prospective, open-label, multi-center study that evaluated outcomes data of patients treated with at least one PROMUS Element Plus stent length 32 or 28 mm (excluding sizes 2.25 x 32 mm) in routine practice. Patients were consecutively enrolled, and the target enrollment of 200 patients was exceeded. The follow-up rate achieved through 5- years was 84%. Weakness: Compared to non-platinum like patient population, the sample size of platinum-like patient population (n=13) was too small to make any meaningful comparison of the safety and effectiveness outcomes between the two subgroups.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P110010 S001/ PAS002
Date Original Protocol Accepted	06/01/2012
Date Current Protocol Accepted	08/23/2012
Study Name	Continued F/U of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket study, which is a concurrent, non-randomized, single-arm long lesion (LL) subtrial.
Study Population	Patients who met the inclusion/exclusion criteria for the PLATINUM Long Lesion (LL) sub-study, evaluating the PROMUS Element¿ Everolimus-Eluting Platinum Chromium Coronary Stent System for the treatment of coronary artery disease.
Sample Size	Cohort of 102 patients at 35 sites in the U.S., Europe, IC region and Japan.
Key Study Endpoints	Target lesion revascularization (TLR) rate, target lesion failure (TLF) rate, target vessel revascularization (TVR) rate, target vessel failure (TVF) rate, myocardial infarction [ MI (Q-wave and non¿Q-wave)] rate, cardiac death rate, non-cardiac death rate, all death rate, cardiac death or MI rate, all death or MI rate, all death/MI/TVR rate, and stent thrombosis rate (definite or probable by ARC definitions)
Follow-up Visits and Length of Follow-up	5 years 18-Month, and 2, 3, 4, 5-Year Follow-Up
Interim or Final Data Summary
Actual Number of Patients Enrolled	102
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	86.7% at 5years
Final Safety Findings	12 months The 12 month primary effectiveness was met. For ITT patients, the 12 month TLF rate was 3.1% (3/96) with upper 1-sided upper confidence bound 7.88% which is significantly less than the performance goal (PG) of 19.4% (p<0.001), and for per protocol patients the 12-month TLF rate was 3.2% (3/95) with 1- sided upper confidence bound of 7.96%, significantly less than the PG, 19.4% (P<0.001).
Final Effect Findings	The main safety and effectiveness endpoint rates through 5 years in the Platinum LL sub-study are: Target lesion revascularization (TLR) 7.5%, target lesion failure (TLF) 13.6%, target vessel revascularization (TVR) 11.6%, target vessel failure (TVF) 17.7%, myocardial infarction (Q and non-Q wave) 1.3%, cardiac death 8.6%, Non cardiac death 2.2%, all death 10.6%, all death or MI 11.7%, All death, MI, TVR 20.7% and Academic Research Consortium (ARC)-defined Stent Thrombosis 1%.
Study Strengths & Weaknesses	The Long lesion study met the primary endpoint and provided long term data. However the sample size was small and subgroup analyses were not conducted.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P110010 / PAS001
Date Original Protocol Accepted	11/22/2011
Date Current Protocol Accepted	05/10/2012
Study Name	PROMUS Element Plus US PAS
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, open-label, multi-center registry study
Study Population	PLATINUM-like patients
Sample Size	Approximately 2,689 patients will be enrolled consecutively from up to 65 sites in order to attain 906 PLATINUM-like patients (33.7% of the enrolled patients). Each site may enroll up to a maximum of 200 patients. A minimum of 200 subjects will be treated with the stent lengths 32/38 mm (diameters 2.5-4.00 mm) and 288 PLATINUM-like medically treated diabetic subjects. Approximately 1,706 and 345 PLATINUM-like subjects are required to provide 80% power to test the hypotheses for the primary and medically treated diabetic subset endpoints, respectively. A minimum of 1,660 PLATINUM-like patients at 5-years will be required to provide 90% power to test the secondary endpoint for the annual increase in the ST rates starting at 12 months.
Key Study Endpoints	Primary Endpoint The primary endpoint is the cardiac death or myocardial infarction (CD/MI) rate through 12 months post stent implantation expressed as the proportion of PLATINUM-like patients who experience CD/MI within 365 days among all PLATINUM-like patients who either experience 12-month CD/MI or survive free of CD/MI for at least 335 days. Secondary Endpoints Stent thrombosis (ST) rate, using ARC definition (definite/probable) in the following populations: overall patient population, the PLATINUM-like patient population (from this post-approval study) and the non-PLATINUM-like patient population (from this post-approval study). Rate of longitudinal stent deformation. Angiograms from reported cases of longitudinal stent deformation will be sent to the angiographic core lab for review. Overall and PROMUS Element Plus-related major adverse cardiac event (MACE) rates (cardiac death, MI, target vessel revascularization-TVR). Overall and PROMUS Element Plus-related cardiac death or MI rates. Overall and PROMUS Element Plus-related target vessel failure (TVF) rates. Overall and PROMUS Element Plus-related TVR rates. Overall and PROMUS Element Plus-related cardiac death rates. Overall and PROMUS Element Plus-related MI rates. All death rates Non-cardiac death rates All death or MI rates The secondary endpoints will be assessed for all patients at less than or equal to 24 hours, 30 days, 180 days, and annually through 5 years post-index stent implantation. Endpoint for PLATINUM-like Medically Treated Diabetic Subset The pre-specified endpoint for the PLATINUM-like medically treated diabetic subset is the TVF rate for PLATINUM-like medically treated diabetics through 12-month follow- up expressed as the proportion of PLATINUM-like medically treated diabetic patients who experience TVF within 365 days among all PLATINUM-like medically treated diabetic patients who either experience 12-month TVF or survive free of TVF for at least 335 days.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 2683 subjects were enrolled. The analysis data set included 2681 subjects (777 PLATINUM-like, 1851 non PLATINUM-like subjects plus 53 unclassified subjects). PLATINUM-like medically treated diabetic population was 293 subjects.
Actual Number of Sites Enrolled	Fifty-three (53) sites were recruited for the study.
Patient Follow-up Rate	86.0% (2012/2340) at 5 years
Final Safety Findings	All Subjects Primary Endpoint Results at 12 months The study met the primary endpoint of cardiac death or myocardial infarction (CD/MI) rate at 12-month for all PLATINUM-like subjects with a rate of 1.78% (33/1855), 1-sided upper 95% Confidence limit (CL) of 2.28% compared to 3.2% performance goal (P<0.0001). For the PLATINUM-like medically treated diabetic subset, target vessel failure (TVF) rate at 12 months was 4.22% (14/332), with a 1-sided upper 95% CL of 6.03% compared to 12.6% PG (P<0.0001), which also met the primary endpoint. Secondary Endpoint Results through 5 years The annual increase in stent thrombosis (ST) rates after the first year in PLATINUM-like subjects was less than the PG of 1.0%, for all annual follow-up time points. At 1-2 year, ST rate was 0.23% (4/1754), upper 1-sided 95% CL 0.42% (p<0.0001); at 2-3 year, ST rate was 0.18% (3/1660), upper 1 sided 95% CL 0.37% (p<0.0001); at 3-4 year, ST rate was 0.12% (2/1710), upper 1-sided 95% CL 0.25% (p<0.0001); at 4-5 year, ST rate was 0.12% (2/1672), upper 1-sided 95% CL 0.25% (p<0.0001). The overall stent thrombosis (ARC, definite/probable) rate through 5 years was 2.5% (59/2388). PROMUS Element Plus-related stent thrombosis rate was 2.3% (54/2388). The overall rate of longitudinal stent deformation was 0.05% (2/4020). The overall major adverse cardiac event (MACE, composite of cardiac death, myocardial infarction or MI, and target vessel revascularization or TVR) rate was 24.9% (595/2388). PROMUS Element Plus-related MACE rate was 17.1% (408/2388). The overall cardiac death or MI rate was 11.0% (263/2388). PROMUS Element Plus-related cardiac death or MI rate was 8.7% (208/2388). The overall target vessel failure TVF) rate was 23.8% (568/2388). PROMUS Element Plus-related TVF rate was 17.0% (407/2388). The overall TVR rate was 18.2% (435/2388). PROMUS Element Plus-related TVR rate was 11.1% (265/2388). The overall cardiac death rate was 7.2% (172/2388). PROMUS Element Plus-related cardiac death rate was 6.7% (159/2388). The overall MI rate was 4.9% (117/2388). PROMUS Element Plus-related MI rate was .8% (68/2388). All death rate was 14.3% (341/2388). Non-cardiac death rate was 7.1% (169/2388) All death or MI rate was 17.7% (423/2388).
Final Effect Findings	Safety findings continued; Subgroup Outcomes: Platinum-like and Non-Platinum like Patient Populations Stent thrombosis (ARC, Definite/Probable), binary rate in PLATINUM-like subjects was 1.3% (9/701) and in non-PLATINUM-like subjects was 3.1% (50/1639). Stent thrombosis (ARC, Definite/Probable), Kaplan Meier rate in PLATINUM-like subjects 1.3% versus non-PLATINUM-like patients 3.0% (log- Rank test, p= 0.01). No longitudinal stent deformation 0.0% (0/972) was reported in PLATINUM-like subjects. Longitudinal stent deformation was reported in two (2) in non PLATINUM-like subjects, 0.07% (2/2974). MACE, binary rate in PLATINUM-like subjects was 19.8% (139/701) and in non-PLATINUM-like subjects was 27.3% (447/1639). MACE, Kaplan Meier rate in PLATINUM like -subjects 19.4% versus non PLATINUM-like subjects 26.6% (log- Rank test, p < .0001). Cardiac death or MI, binary rate in PLATINUM-like subjects was 8.3% (58/701) and in non-PLATINUM-like subjects was 12.2% (200/1639). Cardiac death or MI, Kaplan Meier rate in PLATINUM like subjects 8.2% versus non PLATINUM-like subjects 12.1% (log- Rank test, p = 0.0031). TVF, binary rate in PLATINUM-like subjects was 18.7% (131/701) and in non-PLATINUM-like subjects was 26.2% (429/1639). TVF, Kaplan Meier rate in PLATINUM like subjects 18.4% versus non PLATINUM-like subjects 25.6% (log- Rank test, p<0.0001). TVR, binary rate in PLATINUM-like subjects was 14.8% (104/701) and in non-PLATINUM-like subjects was 19.9% (326/1639). Cardiac death, binary rate in PLATINUM-like subjects was 5.1% (36/701) and in non-PLATINUM-like subjects was 8.1% (132/1639). Cardiac death, Kaplan Meier rate in PLATINUM like subjects 5.1% versus non PLATINUM-like subjects 7.9% (log- Rank test, p = .0098). Myocardial infarction, binary rate in PLATINUM-like subjects was 3.9% (27/701) and in non-PLATINUM-like patients 5.4% (89/1639). All death, binary rate in PLATINUM-like patients was 10.6% (74/701) and in non-PLATINUM-like patients was 15.9% (261/1639). All death or MI, binary rate in PLATINUM-like patients was 13.4% (94/701) and in non PLATINUM-like patients was 19.6% (322/1639). The event rates analyzed for male and female subgroups using Kaplan Meier analysis did not show statistical significant results between the subgroups.
Study Strengths & Weaknesses	Strength: The PROMUS Element Plus US post-approval study was a prospective, open-label, multi-center study that evaluated outcomes in patients receiving PROMUS Element Plus Everolimus-Eluting Platinum Chromium Coronary Stent System in routine practice. Patients were consecutively enrolled. Subjects were followed through 5 years, with a 5-year follow-up rate of 86%. The study met the primary endpoint of cardiac death or MI for the PLATINUM-like subjects and target vessel failure for the subset of PLATINUM-like medically treated diabetics at 12-month follow-up. The study also met the secondary endpoint of annually increase in stent thrombosis rate after the first year, for all annual follow-up time points. Weakness: This was a single- arm observational study and therefore lacks the inherent advantages of a randomized control trial.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow-up visits etc.), final results, strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P110010 / PAS002
Date Original Protocol Accepted	11/22/2011
Date Current Protocol Accepted	05/11/2012
Study Name	Continued F/u of Premarket Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Workhorse (WH) Trial is a prospective, randomized, controlled, single blind, multicenter, non-inferiority trial Small Vessel (SV) is a prospective, single-arm, multi-center sub-study Human Pharmacokinetics (PK) is a prospective, single-arm, multi-center, international, observational sub-study
Study Population	Continued follow-up of the premarket cohorts: WH - Subjects with a maximum of 2 de novo lesions ≤ 24 mm in length in native coronary arteries ≥2.50 mm to ≤4.25 mm. PROMUS Element (test) vs. PROMUS (control) SV - Subjects with a single target lesion ≤28 mm in length in a native coronary artery ≥2.25 mm to <2.50 mm. PROMUS Element (test) vs. TAXUS Express (historical control) PK - Subjects with a maximum of 2 de novo lesions ≤24 mm in length in native coronary arteries ≥2.50 mm to ≤4.25 mm
Sample Size	WH 1,532 SV 94 PK 20-30 Approximately 85 sites in the US, 50 in Europe, 15 in the IC region, and 10 in Japan
Key Study Endpoints	WH target lesion failure (TLF), MI, or death at 12 months SV - TLF at 12 months PK - whole blood everolimus levels as delivered by the PROMUS Element stent.
Follow-up Visits and Length of Follow-up	Through 5 years post-procedure 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after the index procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	-WH Randomized Clinical Trial: 1530 -SV Subtrial: 94 -PK Subtrial: 22
Actual Number of Sites Enrolled	Actual number of study sites enrolled -Workhorse (WH) Randomized Clinical Trial: 132 -Small Vessel (SV) Subtrial: 23 -Pharmacokinetics (PK) Subtrial: 5
Patient Follow-up Rate	-WH Randomized Clinical Trial: 94% -SV Subtrial: 93.3% -PK Subtrial: 100%
Final Safety Findings	-WH Randomized Clinical Trial: At the 5 year follow-up both the PROMUS Element and PROMUS/Xience V stent had good safety rates with no significant difference between the groups in long term clinical outcomes. The PROMUS Element continued to trend toward numerically lower event rates for cardiac death (2.6% and 3.5% respectively). The cardiac death or myocardial infarction (MI) rate at five years for the PROMUS Element and the PROMUS Xience V were 6.2% and 5.7%, respectively. Academic Research Consortium (ARC)-defined (definite/probable) stent thrombosis (ST) at five years was similar among both groups (0.8% and 0.7% respectively). -SV Subtrial: The cardiac death or MI rate at five years for the PROMUS Element small vessel was 7.0%. No ST events were observed in the study. -PK Subtrial: There was no death, MI or ST observed during the length of the study.
Final Effect Findings	-WH Randomized Clinical Trial: the 12-month target lesion failure (TLF) primary endpoint was met, indicating non-inferiority of the PROMUS Element stent (3.4% [25/731]) versus the PROMUS/XIENCE V stent 2.9% [21/714], p=0.0013). At the 5 year follow-up, both the PROMUS Element and PROMUS/Xience V stent had low rates of revascularization with no significant difference between the groups in long term clinical outcomes. -SV Subtrial: The 12-month TLF primary endpoint was met. The TLF rate at 12 months was 2.4% (2/84) with an upper 1-sided 95% confidence interval of 7.31% which is less than the pre-specified performance goal of 21.1% (p<0.0001). -PK Subtrial: There were no target vessel revascularizations reported.
Study Strengths & Weaknesses	-WH Randomized Clinical Trial: This was a large (>1,500 subjects) randomized clinical trial with a low rate of attrition; therefore, confounding and selection bias were minimized. This study met its primary endpoint and provides longer-term (5-year) performance data for the PROMUS Element Everolimus-Eluting Coronary Stent System. -Both SV and PK subtrials provide longer-term (5-year) performance for the device although they have small sample sizes.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term (5-year) performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P040046 / PAS005
Date Original Protocol Accepted	02/20/2013
Date Current Protocol Accepted
Study Name	Focus Group Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 45 subjects. (18 in the augmentation group, 17 in the reconstruction group and 10 in the revision group)
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	In general, both indication specific brochures were well received. Overall, participants found the booklet easy to comprehend, saying it was organized in a logical way and written in language that was appropriate for the lay reader. As with the indication-specific brochure, the mini brochure was generally rated highly by focus group participants. The reconstruction groups rated it slightly lower than the augmentation groups, because they felt that it was aimed more to augmentation patients
Study Strengths & Weaknesses	The focus group study is useful in exploring ideas and concepts through group interaction. However, the analysis is qualitative, it is difficult to generalize results from a small number of participants, and data analysis can be time consuming due to the open-ended nature of questions proposed for the focus group discussion
Recommendations for Labeling Changes	No labeling change is recommended. The Focus Group Study was conducted to evaluate Patient Educational Brochures. No safety/effectiveness data of the sponsor¿s approved device were collected in the study. Allergan is considering the aesthetic comments related to photos, colors and font sizes for future labeling updates.
General
Study Status	Completed
Application Number / Requirement Number	P110013 S005/ PAS001
Date Original Protocol Accepted	02/22/2013
Date Current Protocol Accepted	10/16/2014
Study Name	Resolute Integrity PAS Newly Enrolled
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a sub-study of the ongoing Resolute Integrity PAS, ordered for P110013, which is a prospective, multi-center, non- randomized, single-arm, open-label study. To assess the safety and efficacy of the Resolute Integrity Stent for the treatment of de novo lesions in native coronary arteries with a reference vessel diameter (RVD) of 2.25 mm to 4.2 mm in two groups of patients, specifically those patients receiving stents ¡Ü 30 mm in length, referred to as the Primary Enrollment Group (PEG) and those patients who receive extended length stents (34 mm or 38 mm) referred to as the Extended Length Sub-study (XL Sub-study).
Study Population	Patients who met the inclusion/exclusion criteria for the RESOLUTE INTEGRITY US (RI-US) - XL, evaluating the Resolute Integrity Stent for the treatment of de novo lesions in native coronary arteries (Overall Study and Sub-study). The subjects enrolled with the 34mm or 38mm length stents will comprise the ¡°Extended Length Sub-study (XL) - New Enrollment Cohort¡±.
Sample Size	The observed event rate for the primary endpoints is assumed to be 3.5% so a sample size of 50 subjects will provide a 95% confidence interval [0.3%, 13.0%]. It is expected that the lost to follow-up rate at 12 months is less than 10%; however, a total of 56 patients will be conservatively enrolled in this trial to ensure that at least 50 patients will be evaluable at 12 months. Centers are allowed to enroll a maximum of sixteen (16) XL Sub-study patients per center or until study enrollment has been completed, whichever comes first.
Key Study Endpoints	Primary Endpoint The primary endpoint for all patients enrolled in this study (overall and sub-study) is the composite rate of cardiac death and target vessel myocardial infarction (MI) at 12 months Secondary Endpoints Composite endpoints: Major Adverse Cardiac Events (MACE) Target Lesion Failure (TLF) Target Vessel Failure (TVF) Cardiac Death and Target Vessel MI Clinical endpoints: Death Myocardial Infarction Target Lesion Revascularization (TLR) Target Vessel Revascularization (TVR) Stent Thrombosis Stroke Bleeding complications in general Dual antiplatelet therapy (DAPT) compliance In addition, the following will be assessed: Procedural success Device success Lesion success
Follow-up Visits and Length of Follow-up	The length of follow-up is 5 years. Frequency of Follow-up Assessments: 30 days, 6 months, 24 months and annually at 3, 4, and 5 years post procedure. The patient must return to the site where the procedure was performed for a clinic visit and 12-lead ECG at 12 months. The expected length of time for enrollment is approximately 24 months. The total time for the duration from first-subject enrolled to last-subject follow-up complete is approximately 7 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	56 subjects
Actual Number of Sites Enrolled	14 sites
Patient Follow-up Rate	96.3% (54/56) at 3-years
Final Safety Findings	The primary endpoint of the Resolute Integrity US Extended Length (XL) Sub-Study was the composite rate of cardiac death and target vessel myocardial infarction (TVMI) at 12-months. The primary endpoint was observed in 7.4% (4/54, 95% CI:2.1%, 17.9%) of the population. The key secondary endpoints based on the ITT population through three (3) years are as follows: MACE (Death, Myocardial Infarction, emergent coronary bypass surgery, or repeat TLR): 17.9% (10/56) Target Lesion Failure (Cardiac Death, TVMI, Clinically Driven TLR): 10.7% (6/56) Target Vessel Failure (Cardiac Death, TVMI, Clinically Driven TVR): 12.5% (7/56) All Death: 3.6% (2/56) TVMI: 5.4% (3/56) Clinically Driven Target Lesion Revascularization: 5.4% (3/56) Clinically Driven Target Vessel Revascularization: 7.1% (4/56) Stent Thrombosis (ARC Definite/Probable): 2.0% (1/51)
Final Effect Findings	Lesion Success, defined as the attainment of <50% residual stenosis of the target lesion using any percutaneous method, was obtained in 100.0% (67/67) of lesions. Device Success, defined as the attainment of <50% residual stenosis of the target lesion using only the assigned device, was achieved in 97.0% (65/67) of lesions. Procedural Success, defined as <50% residual stenosis and no in-hospital MACE, was achieved in 98.2% (55/56) subjects.
Study Strengths & Weaknesses	Strengthes: The RESOLUTE INTEGRITY US Extended Length (XL) Sub-Study was a prospective, open-label, multicenter study. The study achieved a follow-up rate greater than 90% at 3 years. An independent clinical event committee performed adjudication of the safety endpoints including all cases of death, Q-wave myocardial infarction (QMI), non-Q-wave MI (NQMI), stent thrombosis, target lesion revascularization and target vessel revascularization. Weakness: The sub-study is limited by the small sample size such that any further subgroup analysis can, at best, be considered exploratory.
Recommendations for Labeling Changes	The sponsor will be requested to add the complete 36-month follow-up data to the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P110013 S005/ PAS002
Date Original Protocol Accepted	02/22/2013
Date Current Protocol Accepted	02/22/2013
Study Name	Continued F/u of Premarket and OUS Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The 38 mm Length Group is designed as a prospective analysis of the pooled data from patients treated with a 38 mm stent from two multi-center, non-randomized studies, RESOLUTE US (R-US) and RESOLUTE Asia (R-Asia).
Study Population	Subjects enrolled in the Global Resolute Clinical Program
Sample Size	223 subjects (Consists of patients from 38 mm sub studies of R-US (N=114) and R-Asia (N=109))
Key Study Endpoints	Primary Endpoints Stent Thrombosis rates from 12-24, 24-36, 36-48 and 48-60 months Cardiac Death/TV MI annual rates up to 5 years post procedure.
Follow-up Visits and Length of Follow-up	Patient Contact (assessed by telephone, email and/or office visit): Annually 2, 3 years (R-Asia)* Annually 2, 3, 4, 5 years (R-US) Note: R-Asia patients were consented for 5 years. At 3 years if the event rates are demonstrated to plateau or decrease as compared to the rates in the prior years the Steering Committee and Sponsor may consider stopping further follow-ups.
Interim or Final Data Summary
Actual Number of Patients Enrolled	3004 subjects (including 223 subjects with de novo lesions treated with Resolute 38 mm length and 2781 subjects other than 38mm length in the Global Resolute Clinical Trial Program). There were 2240 on-label, which were followed for five years. All of the 223 subjects in the 38 mm Length Group were on-label.
Actual Number of Sites Enrolled	The Global Resolute Clinical Trial Program includes the following studies: Resolute FIM, Resolute All-Comers, Resolute International, Resolute US, Resolute Asia, and Resolute Japan. Patients of the 38 mm Length group were enrolled at 46 sites in the United States (US) and throughout Asia (Bangladesh, India, Hong Kong, Malaysia, Singapore, and Thailand) . Patients were enrolled at 29 sites in the 38mm Length Sub-study of the Resolute-US Clinical Study. Patients of the 38 mm group were enrolled at 17 sites in the Resolute-Asia Clinical Study.
Patient Follow-up Rate	Pooled (Global Resolute Clinical Trial Program): 96.70% (2905/3004)at 5 years 38mm: 92.82% (207/223) at 5 years
Final Safety Findings	The annual incidence rate for ARC definite/probable ST (48-60 months) for the on label population in the Global RESOLUTE Clinical Trial Program was 0.1% (3/2154) and the upper bound of the one-sided 95 percent confidence interval was 0.4%. The incidence rate for ARC definite/probable ST in Pooled populations at five years was 0.8% (18/2154) for on-label subjects. The 60-month rate of ARC definite/probable ST for the 38 mm length group was 1.4% (3/217). The rate of ARC definite/probable ST for the 38 mm length group was 0.9% (2/221) at 30 days, 12 months, 24 months, and 36 months, and 1.4% (3/220) at 48 months. The rate of Cardiac Death / Target Vessel Myocardial Infarction at five years of follow-up for the pooled results of the Global RESOLUTE Clinical Trial Program was 7.6% (164/2154) for on-label subjects. It was 8.8% (19/217) for the 38 mm length group. At 5 years the TLF rate of 13.8% is still numerically less than the performance goal of 19% proposed for 1 year. The study met the primary safety endpoint.
Final Effect Findings	The acute success rates for on-label subjects at five years of follow-up (R-FIM, R-AC, R-US, R-J, and R- Asia) are as follows: Procedural success 97.7% (2171/2221), Device success: 98.2% (2508/2554) and Lesion success 99.9% (2546/2548). The acute success rates of 38 mm length group at five years of follow-up are as follows: Procedural success 96.3% (210/218), Device success 97.0% (257/265) and Lesion success 100.0% (263/263). The study met the primary effectiveness endpoint.
Study Strengths & Weaknesses	The Resolute Integrity Zotarolimus-Eluting Coronary Stent System Extended Length (Resolute Integrity XL) study met the primary endpoint and provided long term data. However, the study experienced difficulty with recruiting eligible subjects.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P110013 S088/ PAS001
Date Original Protocol Accepted	03/08/2019
Date Current Protocol Accepted
Study Name	RESOLUTE ONYX CTO Post-approval study
General Study Protocol Parameters
Study Design	Meta Analysis
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Meta-analyis of CTO patients enrolled in on-going studies. The objective of the RESOLUTE ONYX CTO Post-Approval Study (PAS) is to demonstrate the generalizability of the performance the Resolute family of drug-eluting stents for the treatment of chronic total occlusions (CTOs) in a real-world setting..
Study Population	The RESOLUTE ONYX CTO PAS will consist of pooled lesion- and patient-level meta-analyses of subjects with CTOs treated with the Resolute Onyx stent system that are enrolled in the Primary, XLV and Bifurcation Cohorts of the RESOLUTE ONYX Post-Approval Study and the ONYX ONE outside of the US randomized controlled trial. Subjects will be followed according to the procedures in each respective study.
Sample Size	Approximately 100 subjects between all three studies. No formal hypothesis will be conducted.
Key Study Endpoints	The primary safety and effectiveness endpoint will be freedom from MACE (death, myocardial infarction, and clinically-driven target lesion revascularization) at 30-days. Secondary endpoints will include acute success (device, lesion, and procedure), cardiac death, target vessel MI, TLR, TLF, TVF, and stent thrombosis.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	78
Actual Number of Sites Enrolled	28
Patient Follow-up Rate	92.3% (72/78)
Final Safety Findings	Target lesion revascularization (TLR) rate and contributing to an overall 33.3% (10/30) TLF, TVF, and MACE rate. Lesion success defined as attainment of <50% residual stenosis of the target lesion using any percutaneous method was 100% (47/47) and device success defined as attainment of <50% residual stenosis of the target lesion using only Resolute Onyx was reported at 97.9% (46/47). Procedure success defined as attainment of <50% residual stenosis of the target lesion and no in-hospital MACE was reported at 70.0% (21/30) where failures were solely driven by the nine (9) peri-procedural ARC MIs reported for this cohort.
Final Effect Findings	The study used a primary composite endpoint of Freedom from Major Adverse Cardiac Events (MACE) defined as any death, myocardial infarction (per ARC definition), or clinically-driven target lesion revascularization (TLR) at 30-days was established as the primary endpoint for these cohorts. In total the MACE rate was 79.5% (62/78). Primary Endpoint Onyx PAS CTO (N=30 subjects) Onyx ONE CTO (N=35 Subjects) Onyx ONE Clear CTO (N=13 Subjects) Freedom from MACE at 30 days 70.0% 88.6% 76.9% The freedom from MACE rate is a cumulative probability of event-free estimate based on the Kaplan-Meier Method. MACE (death, myocardial infarction (per ARC MI definition), and clinically-driven target lesion revascularization)
Study Strengths & Weaknesses	The strength of this study is that I captures a close approximation of a real world population. The data included a large number of investigators at multiple sites providing a wide range of patients. This data helps to reflect how the device will perform in the clinical community. However, this trial was a single arm investigation which is a limitation. While this is not noted as a major weakness of the trial, it should be noted as a limitation.
Recommendations for Labeling Changes	We have recommended that the sponsor submit a labeling amendment to include this information in their future DFU.
General
Study Status	Completed
Application Number / Requirement Number	P110013 / PAS001
Date Original Protocol Accepted	02/17/2012
Date Current Protocol Accepted	02/17/2012
Study Name	Resolute Integrity
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, non- randomized, single-arm, open-label study.
Study Population	Patients with de novo lesions in native coronary arteries that meet the eligibility criteria and sign the informed consent form will participate in this study.
Sample Size	The observed event rate for the primary endpoints is assumed to be 2% at 12 months so a sample size of 200 subjects will provide a 95% confidence interval [0.5%, 5%]. It is expected that the lost to follow-up rate at 12 months is less than 10%; however, a total of 230 patients will be conservatively enrolled in this trial to ensure that at least 200 patients will be evaluable at 12 months. Centers (n≈30) are allowed to enroll a maximum of 40 subjects per center or until study enrollment has been completed, whichever comes first.
Key Study Endpoints	Primary Endpoint The primary endpoint for all patients enrolled in this study is the composite rate of cardiac death and TV MI at 12 months Secondary Endpoints Composite endpoints (hospital discharge, 30 days, 6 months, 12 months, and 24 months post-procedure): ¿ Major Adverse Cardiac Events (MACE) ¿ Target Lesion Failure (TLF) ¿ Target Vessel Failure (TVF) ¿ Cardiac Death and TV MI Clinical endpoints: ¿ Death ¿ Myocardial Infarction ¿ Target Lesion Revascularization (TLR) ¿ Target Vessel Revascularization (TVR) ¿ Stent Thrombosis ¿ Stroke ¿ Bleeding complications in general ¿ Dual antiplatelet therapy (DAPT) compliance In addition, the following will be assessed: ¿ Procedural success ¿ Device success ¿ Lesion success
Follow-up Visits and Length of Follow-up	The length of follow-up is 2 years. Frequency of Follow-up Assessments: 30 days, 6 months, 12 months, and 24 months post-procedure. The patient must return to the site where the procedure was performed for a clinic visit and 12-lead ECG at 12 months. The expected length of time for enrollment is approximately 12 months. The study will be conducted for a minimum of two (2) years from enrollment of the final subject.
Interim or Final Data Summary
Actual Number of Patients Enrolled	230 subjects
Actual Number of Sites Enrolled	Thirty sites enrolled in the study; however, one site did not enroll any study subjects and was subsequently closed.
Patient Follow-up Rate	94.8% (218/230)
Final Safety Findings	Primary endpoint: Cardiac death (CD) and target vessel myocardial infarction (TVMI) at 12 months: 3.5% (8/226, 95% CI: 1.5%-6.9%). It was expected that the composite rate of CD/TVMI will be consistent with the rate observed in the Resolute-US pre-approval trial (2% [95% CI: 0.5% - 5%]). The rate in this PAS does not seem to be much different. However, this PAS was designed to provide certain precision around the primary endpoint rate and not to test for differences in the studies¿ rates. Secondary endpoints at 24 months: Cardiac Death and Target Vessel Myocardial Infarction: 5.9% (13/219) Target Lesion: 9.1% 9.1% (20/219) Target Vessel Failure: 12. 3% (27/219) Major Adverse Cardiac Events: 11.0% (24/219) Death: 2. 7% (6/219) Cardiac Death: 1.9% (4/209) Target Vessel Myocardial Infarction: 4.1% (9/219) Clinically Driven Target Lesion Revascularization: 5.0% (11/219) Clinically Driven Target Vessel Revascularization: 8. 2% (18/219) Academic Research Consortium- definite/probable stent thrombosis: 1.9% (4/209) Stroke: 0.9% (2/219) Bleeding Complications in General: 12. 8% (28/219) Dual antiplatelet therapy compliance: 65.1% (136/209)
Final Effect Findings	Lesion Success1: 99.2% (243/245) Device Success2: 99.2% (243/245) Procedure Success3: 97.4% (221/227) 1 The attainment of < 30% residual stenosis by QCA (or < 20% by visual assessment) AND TIMI flow 3 after the procedure, using any percutaneous method. 2 The attainment of < 30% residual stenosis by QCA (or < 20% by visual assessment) AND TIMI flow 3 after the procedure, using the assigned device only. 7 The attainment of < 30% residual stenosis by QCA (or < 20% by visual assessment) AND TIMI flow 3 after the procedure, using any percutaneous method without the occurrence of MACE during the hospital stay.
Study Strengths & Weaknesses	This study provides longer term (2 years) safety and effectiveness results of the Resolute Zotarolimus- Eluting Coronary Stent System. This post-approval study was conducted in the United States and had a very low lost to follow-up rate. This study confirmed the safety and effectiveness results of the premarket data on the Resolute Zotarolimus-Eluting Coronary Stent System.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term (2-years) postmarket performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P110013 / PAS002
Date Original Protocol Accepted	02/17/2012
Date Current Protocol Accepted	02/17/2012
Study Name	Cont Followup of Premarket and OUS Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	These analyses will utilize the pooled data from the Global RESOLUTE Clinical Trial Program on-label usage patients (RESOLUTE All Comers (R-AC) and RESOLUTE International (R-Int), RESOLUTE initial feasibility trial (R-FIM), the pre-approval trial for Japan, RESOLUTE Japan (R-J), and the RESOLUTE US (R-US)). Objectives: 1) Demonstrate the safety in terms of stent thrombosis (ST) when the drug-eluting stent is used in accordance with the labeled indications from 12-24, 24-36, 36-48, and 48-60 months post implant. (36-60 months excludes R-Int) 2) Demonstrate the safety in terms of cardiac death (CD) and target vessel myocardial infarction (TVMI) when the drug-eluting stent is used in accordance with the labeled indications.
Study Population	The study population consists of four studies (R-FIM, R-AC, R-US, and R-J) with a five-year follow-up and one study with a three year follow-up (R-Int). The Global RESOLUTE Clinical Trial Program has currently amassed a dataset with a combined total of 5,130 subjects with follow-up at or greater than one year. This dataset consists of 2,349 Subjects considered to be ¿off-label¿ and 2,781 ¿on-label¿ subjects (Table 1).
Sample Size	Within the on-label subjects, a sample size of 1,312 will have 80% power to demonstrate the rate of ARC definite probable ST to be significantly less than 1% year-to-year. The Resolute program will have 2,781 on-label subjects scheduled for three years of follow-up and 2,017 on-label subjects scheduled for four and five years of follow up. Therefore, the Pooled Resolute program will have a large enough sample size with or without the RESOLUTE International Registry subjects.
Key Study Endpoints	Primary Endpoint ARC definite or probable ST rates from 12-24, 24-36, 36-48 and 48-60 months. CD/TVMI annual rates up to 5 years post procedure.
Follow-up Visits and Length of Follow-up	Data collection will be annually up to 5 years of follow-up, except for R-Int (36 months)
Interim or Final Data Summary
Actual Number of Patients Enrolled	2,017 on-label subjects 764 complex subjects
Actual Number of Sites Enrolled	RESOLUTE All Comers (R-AC): 17 sites RESOLUTE initial feasibility trial (R-FIM): 12 sites RESOLUTE Japan (R-J): 14 sites RESOLUTE United States (R-US): 116 sites
Patient Follow-up Rate	On-label: 96% (1937/2017) Complex: 98% (751/764)
Final Safety Findings	Objective 1: The annual rate of Academic Research Consortium (ARC)-defined definite and probable stent thrombosis (ST) at 5 years for on-label patients pooled from four studies (R-FIM, R-AC, R-US, and R-J) part of the Global RESOLUTE Clinical Trial Program was 0.02% (3/1937, upper 95% CI: 0.4%). The 5-year cumulative rate of ARC- definite/probable ST through five years was 0.8% (15/1937) for on- label subjects and 2.5% (19/751) for complex subjects. Objective 2: The 5-year cumulative rate of cardiac death or myocardial infarction for on-label and complex subjects pooled from four studies (R-FIM, R-AC, R-US, and R-J) part of the Global RESOLUTE Clinical Trial Program was 7.5% (145/1937) and 11.9% (89/751), respectively.
Final Effect Findings	Procedural success: 97.9% (1961/2003) Device success: 98.3% (2251/2289) Lesion success: 99.9% (2283/2285)
Study Strengths & Weaknesses	This study provides longer term (5 years) safety and effectiveness results of the Resolute Zotarolimus- Eluting Coronary Stent System. This study followed up the premarket cohorts through five years post- procedure. The study had a very low rate of attrition, thus minimizing selection bias. It demonstrated that the Resolute Zotarolimus-Eluting Coronary Stent System had a rate of ARC-definite/probable ST to be significantly less than 1% year-to-year. Although three of the four trials were conducted outside the US, 70% of the on-label subjects (1402/2017) were enrolled in the US. There were no complex subjects enrolled in US sites.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term (5-years) postmarket performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P110014 / PAS001
Date Original Protocol Accepted	12/27/2012
Date Current Protocol Accepted	09/02/2019
Study Name	MarginProbe System US PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, newly enrolled, multicenter, randomized, double arm, controlled study of adjunctive use of the MarginProbe System (Standard of Care (SOC)+Device) versus standard of care, including additional inspection (SOC+Additional Inspection). The study objective is to determine the MarginProbe Systems diagnostic accuracy at the margin level and impact on Positive Margin Presence originating from the main ex-vivo lumpectomy specimen after the initial lumpectomy surgery.
Study Population	Women histologically diagnosed with carcinoma of the breast and women with non-palpable malignant lesions, requiring image guided localization who undergo lumpectomy (partial mastectomy) procedure.
Sample Size	A total of 440 subjects with 220 in each arm.
Key Study Endpoints	Co - Primary effectiveness endpoints are: a. Sensitivity at the margin level b. Specificity at the margin level c. Incomplete Surgical Resection (ISR) - Positive Margin on the Main ex-vivo lumpectomy specimen after the initial lumpectomy surgery that was not addressed by taking a shaving(s) corresponding to the positive margin(s). Secondary effectiveness endpoints are: a. Proportion of patients with Positive Margin presence on the Outermost Shaving after the initial lumpectomy surgery (PMO) b. Cosmesis evaluation: - Objective evaluation by an evaluator blinded to arm assignment - Subject's self-reported evaluation. c. Repeat lumpectomy rate - Proportion of patients who underwent a repeat lumpectomy procedure d. Repeat lumpectomy and mastectomy rate - Proportion of patients who underwent a repeat lumpectomy procedure or a mastectomy e. Diagnostic Accuracy at the Patient Level (ignoring location) - Proportion of patients from whom shavings were taken
Follow-up Visits and Length of Follow-up	Patients will be followed until evaluation of cosmetic status, performed at 6 +/- 1 month following the end of surgical treatment (either conversion to mastectomy, or the latest ipsilateral repeat lumpectomy procedure).
Interim or Final Data Summary
Actual Number of Patients Enrolled	438 subjects
Actual Number of Sites Enrolled	12 Enrolled Study Sites
Patient Follow-up Rate	276/438 completed follow up visit in window = 63.01% 13/438 completed follow up visit < 30 out of window = 2.97% 52/438 completed follow up 1-3 months out of window = 11.87% 70/438 completed follow up > 3 months out of window = 15.98% 411/438 completed study follow up = 93.83%
Final Safety Findings	A total of 190 AEs (not including SAEs) were reported in the study, 98 (51%) within Device+SOP group and 92 (48.4%) within SOC+Additional Inspection Group. For 90 subjects AEs were reported, 48 (53%) subjects within Device+SOC group and 42 (46.7%) within SOC+Additional Inspection Group. From the 98 AEs within the Device+SOC group, 1 was classified as possible related to the device. 2 deaths occurred during this study; both unrelated to the device. Use of the MarginProbe proven safe and not associated with increased risk over Control Group.
Final Effect Findings	All components of the primary endpoint met predetermined study success criteria. The Sensitivity and Specificity at Margin Level co-primary endpoints were met at 70.2% and between 47.6% (worst case) and 48.7% (best case) respectively. These results are comparable to the 73.8% sensitivity and 45.1% specificity reported in the MarginProbe Pivotal trial. Device demonstrated decreased rates of incomplete surgical resection (ISR) compared to control arm. Secondary endpoints: Rate of positive margin presence on the outermost shaving after initial lumpectomy surgery (PMO), Cosmesis Blinded Evaluation, repeat lumpectomy/mastectomy rate, sensitivity, sensitivity, and Cosmesis Self Assessment. PMO endpoint met established success criteria. All other secondary endpoints demonstrated that the Device group may have qualitative non-inferiority compared to the Control group; however, these observations were not statistically significant.
Study Strengths & Weaknesses	Strength: Randomized Controlled Study with comprehensive endpoints. Inclusion of evaluator and self-reported evaluation of cosmesis. Weaknesses: Missing Data for Secondary Effectiveness Endpoints due to incomplete evaluations due to COVID19
Recommendations for Labeling Changes	We recommend labelling changes to reflect the results from the primary effectiveness endpoints (i.e. sensitivity, specificity, ISR) and PMO/Cosmesis secondary endpoints.
General
Study Status	Delayed
Application Number / Requirement Number	P040002 S070/ PAS001
Date Original Protocol Accepted	05/08/2023
Date Current Protocol Accepted
Study Name	VQI and VISION EVAR Registry Analysis
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The AFX2 LEAF Study is an observational, retrospective and prospective, multicenter study to evaluate the performance of the AFX2 System using real world evidence from VQI-VISION. Further information on the study design is included in the VQI LEAF System Protocol. The primary objective of this study is to valuate the clinical performance of the AFX2 System patients against other commercially available EVAR devices and evaluate the Type III endoleak occurrence in AFX2 System patients through 5 years
Study Population	The AFX2 System population includes patients who underwent EVAR as their first abdominal aortic aneurysm repair within the VQI EVAR registry
Sample Size	Clinical Endpoint Number of subjects: Minimum 2,000 AFX2 subjects and 18,000 comparator graft subjects Imaging Endpoint Number of subjects: Minimum 315 AFX2 subjects evaluable at 5 years
Key Study Endpoints	Co Primary Endpoints The primary clinical endpoint is the rate of the composite of AAA rupture, aortic-related reintervention, and mortality through 5 years. - The primary imaging-driven endpoint is the cumulative incidence of Type III endoleaks at 5 years. Secondary study endpoints: Secondary endpoints through 10 years include: • AAA rupture • Aortic-related reintervention (including indication for and type of reintervention) • Mortality • Aneurysm-related mortality • Rate of imaging with CT • Presence of untreated asymptomatic Type III endoleaks* • Occurrence of sac shrinkage, stability, and expansion >5mm in diameter • Limb occlusion *If a patient has not had a reintervention after a Type III endoleak is detected on imaging, additional clinical information will be gathered from the site to determine the reason that the image-only detected Type III endoleak has not been treated or if treatment is now planned.
Follow-up Visits and Length of Follow-up	Follow-up data of enrolled patients will be analyzed for the relevant cohorts through 5 years (primary endpoints) and 10 years (secondary endpoints). As this is an observational study using real world evidence, follow-up will be based on standard of care.
Interim or Final Data Summary
Actual Number of Patients Enrolled	24,020 in VQI-VISION EVAR Registry
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	Follow-up data was provided through 3 years. There were 773 AFX2 subjects that reached 3 year follow-up.
General
Study Status	Hold
Application Number / Requirement Number	P160053 S002/ PAS001
Date Original Protocol Accepted	06/29/2023
Date Current Protocol Accepted
Study Name	Post-Approval Study (2ml)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Purpose: The purpose of this study is to provide prospective evidence in the US population of the frequency of skin discoloration in patients who have received Magtrace for sentinel lymph node biopsy (SLNB) and to evaluate the impact that skin discoloration has on patients when it does occur using patient reported outcome measures. Design: A prospective, open label study will be conducted to characterize the post-operative skin discoloration that may arise following the use of Magtrace for sentinel lymph node biopsy in breast cancer patients undergoing lumpectomy. Patient perception will be assessed using patient reported outcome measures.
Study Population	Subjects considered for enrollment will be at least 18 years old at the time of consent, and: a) due to undergo planned breast conserving surgery (for example lumpectomy or partial mastectomy) and SLNB with Magtrace, b) meet all other inclusion and no exclusion criteria.
Sample Size	Number of subjects: 158 Assumptions for sample size estimation: A sample of 158 is expected to provide a sample of approximately 60 patients with discoloration (based on a 38% discoloration frequency from previous data). This would provide a 95% confidence interval of ±15.65% in this scenario. With 0% at 2 years (out of approximately 126 with follow up) the exact 95% confidence interval would be 0% to 2.9%. Number of sites: 3
Key Study Endpoints	Safety Endpoints Primary: Frequency of Magtrace-related skin discoloration as a proportion of patients receiving Magtrace Secondary: A. Change in BREAST-Q score from post-operative visit through to resolution of skin discoloration or through 24 months, whichever is earlier, in the subgroup of patients with discoloration. The following core scales will be used: 1) Psychosocial well-being; 2) Sexual well-being; 3) Cancer worry; 4) Fatigue; 5) Impact on work; 6) Physical well-being: Chest; and 7) Satisfaction with breasts. B. Change in Breast-Q score from pre-operative visit to post-operative visit in patients with and without skin discoloration at the postoperative follow up visit. C. Duration of discoloration over time post-op to resolution of discoloration or 24 month follow up D. Intensity of discoloration (absolute color and contrast to normal breast color) over time post-op to resolution of discoloration or 24mnth follow up E. Severity of discoloration over time post-op to resolution of discoloration or 24mnth follow up as assessed by height and width measurement F. Rates of device-related adverse events and serious device-related adverse events
Follow-up Visits and Length of Follow-up	Length of Follow up: Up to resolution or up to 2 years, whichever is sooner
General
Study Status	Ongoing
Application Number / Requirement Number	P110016 S080/ PAS002
Date Original Protocol Accepted	02/24/2023
Date Current Protocol Accepted
Study Name	LESS VT NICM Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The goal of this post approval study is to confirm the safety and effectiveness of the study catheter for the treatment of MMVT in the post-market space.
Study Population	This clinical investigation will enroll subjects of all sexes who have recurrent, drug-refractory, sustained MMVT from non-ischemic origin. Patients must meet all general eligibility criteria and provide written informed consent prior to sites conducting any investigation-specific procedures not considered standard of care.
Sample Size	56 subjects were enrolled at 10 sites
Key Study Endpoints	The primary safety endpoint will be the rate of study device and/or Study Ablation Procedure-related SAEs through 12 months post Index Ablation Procedure. This endpoint will be descriptively evaluated at 12 months. Only study device (FlexAbility SE)-related adverse events related to use during Study Ablation Procedures will be collected. The primary effectiveness endpoint is a composite of 12-month freedom from VT recurrence, death, and cardiac transplantation. This endpoint will be descriptively evaluated at 12 months. VT recurrence is defined as: Continuous VT for >30 seconds o If the subject has continuous VT throughout a 12-lead ECG recording, this will be considered sufficient documentation of recurrence unless there is evidence that the recorded arrhythmia is short-lived and less than 30 seconds. VT requiring intervention for termination regardless of its duration Repeat Ablation Procedure Use of a non-study device for ablation to the ventricles or cardiac ablation by any method other than RF energy during a Study Ablation Procedure will be considered an effectiveness failure. There are several descriptive endpoints. These endpoints will be summarized descriptively and no hypothesis tests will be performed. The primary safety endpoint and primary effectiveness endpoint will be summarized separately for subjects <65 years of age and subjects greater than or equal to 65 years of age 12-month all-cause mortality 12-month freedom from VT 12-month freedom from cardiac transplantation Study device- or Study Ablation Procedure- related SAEs through 7 days Rate of Repeat Ablation Procedures
Follow-up Visits and Length of Follow-up	Subjects will be followed for up to 12-months post-procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	7
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	Insufficient enrollment and duration of follow-up to determine follow-up rate.
Final Safety Findings	Insufficient enrollment and duration of follow-up to draw safety conclusions.
Final Effect Findings	Insufficient enrollment and duration of follow-up to draw effectiveness conclusions.
General
Study Status	Ongoing
Application Number / Requirement Number	P210027 / PAS001
Date Original Protocol Accepted	07/20/2023
Date Current Protocol Accepted	04/08/2025
Study Name	QDOT MICRO System PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Observational, multi-center, non-randomized, post-market study. This is a nested sub-study of the REAL AF Registry. Consecutive of symptomatic drug refractory paroxysmal atrial fibrillation (PAF) patients from the registry will be screened for enrollment to this sub-study per inclusion and exclusion criteria. Enrolled QDOT PAS subjects are defined as consented patients with symptomatic PAF enrolled in the REAL AF registry treated with the QDOT MICRO™ system (QDOT MICRO™ catheter and nGEN™ generator) in conjunction with VISITAG SURPOINT™ Module. Subjects are required to complete scheduled assessments within 12 months of the index procedure, and additional two assessments at 24 and 36-month post procedure. All subjects will undergo ablation procedures using the commercially approved QDOT MICRO™ catheter and nGen™ generator using QMODE+ and/or QMODE in conjunction with recommended VISITAG SURPOINT™ tag index values. All consecutive patients who are considered for an RF ablation procedure at study institutes would be screened by the investigator or designated member of the research team for sub-study eligibility. Eligible subjects will be consented for the participation of this sub-study. For the purpose of this sub-study, the first five (5) enrolled subjects will be treated using QMODE with the recommend VISITAG SURPOINT™ tag index values. This will also allow the operators to acclimate to the use of QDOT MICRO™ catheter manipulation using conventional RF catheter ablation. The primary objective of this study is to evaluate the safety and effectiveness of the QDOT MICRO™ System use in conjunction with VISITAG SURPOINT™ Module in the treatment of symptomatic drug refractory PAF.
Study Population	Study population will consist of patients in the REAL AF registry who have symptomatic PAF and undergo ablation procedures using the QDOT MICRO™ System with VISITAG SURPOINT™ Module
Sample Size	A total of 250 subjects will be enrolled, with at least 50% subjects from the US sites. Each site will contribute to no more than 20% of the target enrollment to allow for generalizable study results. Number of subjects: 250 Assumptions for sample size estimation: performance goal (PG) of 12% for the primary safety endpoint and a PG of 50% for the primary effectiveness endpoint, a sample size of 250 subjects will provide greater than 80% power of this study, controlling the overall type-I error rate at a one-sided 2.5% level under the null hypotheses
Key Study Endpoints	Safety Endpoints Primary: The primary safety endpoint is the occurrence of early onset Primary Adverse Events (PAE) within seven (7) days of an initial ablation procedure using the QDOT MICRO™ System with VISITAG SURPOINT™ Module Secondary: please see study protocol Effectiveness Endpoints Primary: The primary effectiveness endpoint is the freedom from documented (Symptomatic and asymptomatic) atrial arrhythmia (atrial fibrillation (AF), atrial tachycardia (AT) or atrial flutter (AFL)) episodes during the effectiveness evaluation period (Day 91-365)
Follow-up Visits and Length of Follow-up	All subjects will be followed for 36 months. Follow up clinical data will be collected at 10-12 weeks, 6, 12, 24, and 36 months post the ablation procedure.
Interim or Final Data Summary
Interim Results	Safety Results There were no reported primary safety events at the time of the report. Effectiveness Results There is insufficient follow-up at the time of the report to calculate effectiveness.
Actual Number of Patients Enrolled	74
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	83.9% at 10-12 week follow-up
General
Study Status	Completed
Application Number / Requirement Number	P110019 S066/ PAS001
Date Original Protocol Accepted	10/03/2014
Date Current Protocol Accepted	03/03/2017
Study Name	Extended Followup of the EXPERT CTO Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is the continued follow-up of the premarket cohort. It is a prospective, multi-center, single-arm study.
Study Population	All patients in whom recanalization and predilatation of CTO are completed and the study stent(s) (XIENCE V and/or XIENCE PRIME) is inserted into the coronary guiding catheter.
Sample Size	A total of 250 patients were enrolled at 20 sites in the United States, with the intention-to-treat population consisting of 222 patients. There are 205 patients available with 1-year follow-up.
Key Study Endpoints	The following outcomes will be reported annually through 5 years: XRate of Major Adverse Cardiac Events (MACE), defined as a composite of death, Myocardial Infarction (MI), or clinically- driven Target Lesion Revascularization (TLR), and individual MACE components ¿XTarget Lesion Failure (TLF), defined as a composite of cardiac death, target vessel-related MI, and clinically-driven TLR and individual TLF components ¿XTarget Vessel Revascularization (TVR) and clinically-driven TVR ¿XTarget Vessel Failure (TVF), defined as a composite of cardiac death, target vessel-related MI, and clinically-driven TVR ¿XOccurrence of stent fracture at target lesion, as assessed by fluoroscopy in patients undergoing clinically-driven angiographic follow-up at any time during the 5-year study period (the same angiographic core lab will continue to be utilized throughout the five-year follow-up period) ¿XStent thrombosis according to Academic Research Consortium (ARC) criteria (all, definite, definite/probable, probable, possible): acute, subacute, late, very late and accumulative rates
Follow-up Visits and Length of Follow-up	3 years post-procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	202 subjects available at 1 year for long term follow- up
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	84.7% (171/202) at 4 years
Final Safety Findings	The EXPERT CTO clinical trial met its primary endpoint. The stent related endpoint result of 1- year MACE [composite of death, myocardial infarction (MI) or clinically driven target lesion revascularization (CD-TLR)] rate was significantly lower than the pre-specified performance goal (PG) of 24.4% in both the intent-to-treat (ITT) population (18.5%, 1 sided UCL= 23.4%, p =0.0248) and the per protocol (PP) population (8.2%, 1 sided UCL = 12.3%, <.0001). The key secondary endpoints based on the ITT population through four (4) years are as follows: MACE (death, MI or CD-TLR) per ARC 31.6% (62/196) per protocol 22.4% (44/196) Target Lesion Failure (cardiac death, Target vessel-MI or CD-TLR) per ARC 24.1% (45/187) per protocol 17.2% (32/186) Target Vessel Failure (Cardiac death, Target vessel MI or CD-TVR) per ARC 26.2% (49/187) per protocol 19.4% (36/186) Death 10.5% (20/191) Cardiac Death 5.5% (10/181) All MI per ARC 20.3% (37/182) Target Vessel MI (TV-MI) per ARC 15.5% (28/181) All TLR (target Lesion revascularization) 11.9% (21/177) CD-TLR 11.3% (20/177) All TVR (target vessel revascularization), inclusive of target lesion) 13.6% (24/177) All TVR (non-target lesion) 2.9% (5/172) Stent Thrombosis (Definite/probable) 1.7% (3/174)
Study Strengths & Weaknesses	Strength: The EXPERT CTO study was a prospective, open-label, multicenter study. The study achieved a follow-up rate greater than 80% at 4 years. An independent clinical event committee performed adjudication of the safety endpoints including all cases of death, Q-wave myocardial infarction (QMI), non Qwave MI (NQMI), stent thrombosis, target lesion revascularization and target vessel revascularization. Weakness: There is no formal hypothesis testing for the long term (4 year) study outcomes. The study is limited by the small sample size. Study Strengths and Limitations: The EXPERT CTO study was a prospective, open-label, multicenter study. All event adjudications were performed by an independent Clinical Event Committee (CEC) with 100% site-reported adjudicable events being source-verified. This study provides important information on clinical outcomes in patients with chronic total occlusions treated with the XIENCE family of stents. The study is limited by being a small study with no head-to-head comparison with other DES platforms. In addition, due to the small population size, subgroup analysis can at best be considered exploratory.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post Approval mstudy methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), results and study strengths and limitations.
General
Study Status	Ongoing
Application Number / Requirement Number	P110019 S118/ PAS001
Date Original Protocol Accepted	05/06/2022
Date Current Protocol Accepted	07/20/2023
Study Name	SPIRIT XLV PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The XIENCE Skypoint Large Vessel PAS, SPIRIT XLV, is a prospective, single arm, open-label, multi-center global clinical study to evaluate the continued safety and effectiveness of the XIENCE Skypoint large vessel coronary stent system. This study will require new enrollment.
Study Population	The device group patients will be implanted with the XIENCE Skypoint LV stent system. There is no control group.
Sample Size	100 patients, 30 sites in the US or OUS
Key Study Endpoints	Main Endpoint Target Lesion Failure (TLF) at 1 year TLF is defined as the composite of cardiac death, myocardial infarction related to the target vessel (TV-MI), or ischemic driven target lesion revascularization (ID-TLR) For the assessment of periprocedural MI, modified Academic Research Consortium (ARC) II definition will be used. In the case when both cardiac Troponin and creatine kinase-MB (CK-MB) are available, cardiac Troponin will be used for the primary cardiac biomarker for MI assessment. For the assessment of spontaneous MI, the 4th universal MI definition will be used. Secondary Endpoint 1. Target lesion failure (TLFsp-MI) at 1 year TLFsp-MI is defined as the composite of CD, TV-MI including spontaneous MI and excluding periprocedural MI and, or ID-TLR In the case when both cardiac Troponin and CK-MB are available, cardiac Troponin will be used for the primary cardiac biomarker for MI assessment. For the assessment of spontaneous MI, the 4th universal MI definition will be used. 2. Target Lesion Failure (TLFSCAI) at 1 year TLFSCAI is defined as the composite of CD, TV- MI including both periprocedural MI and spontaneous MI, or ID-TLR For the assessment of periprocedural MI, Society for Cardiovascular Angiography and Intervention (SCAI) definition8 will be used. In the case when both cardiac Troponin and creatine kinase-MB (CKMB) are available, cardiac Troponin will be used for the primary cardiac biomarker for MI assessment. For the assessment of spontaneous MI, the 4th universal MI definition will be used.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Interim Results	Safety Results Target Lesion Failure (TLF) at 1 year 8.9% (9/101, 95% CI [4.16, 16.24). TLF is defined as the composite of cardiac death, myocardial infarction related to the target vessel (TVMI), or ischemic driven target lesion revascularization. Results for each component are: Cardiac death at 4.0% (4/101, 95% CI [1.09, 9.83]) TV-MI at 5.0% (5/101, 95% CI [1.63, 11.18]) PPMI assessment by modified ARC 2 at 3.0% (3/101) Spontaneous MI at 2.0% (2/101) ID-TLR at 1.0% (1/101) Effectiveness Results Secondary endpoints: 1. Target lesion failure (TLFsp-MI) at 1 year: 5.9% (6/101, 95% CI [2.21, 12.48)]). Results for each component are: Cardiac death at 4.0% (4/101, 95% CI [1.09, 9.83]) MI related to the TV (including spontaneous MI assessed by 4th universal and excluding PPMI) at 2.0% (2/101) ID-TLR at 1.0% (1/101) 2. Target Lesion Failure (TLFSCAI) at 1 year: 9.9% (10/101, 95% CI [4.85, 17.46]). Results for each component are: Cardiac death at 4.0% (4/101, 95% CI [1.09, 9.83]) MI related to the TV, including both PPMI (SCAI) and spontaneous MI at 5.9% (6/101, 95% CI [2.21, 12.48]) PPMI (SCAI) at 4.0% (4/101, 95% CI [1.09, 9.83]) Spontaneous MI (4th universal) at 2.0% (2/101, 95% CI [0.24, 6.97]) ID-TLR at 1.0% (1/101)
Actual Number of Patients Enrolled	101
Actual Number of Sites Enrolled	18 (US: 13; OUS: 5)
Patient Follow-up Rate	83.2%
General
Study Status	Ongoing
Application Number / Requirement Number	P210006 / PAS001
Date Original Protocol Accepted	08/08/2022
Date Current Protocol Accepted	08/01/2024
Study Name	EXTEND Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, non-randomized, single arm, post-market study. To evaluate the Thoraflex Hybrid device alone and in combination with the RelayPro NBS stent-graft in the treatment of aortic disease affecting the aortic arch and descending aorta with or without involvement of the ascending aorta.
Study Population	Patients who undergo treatment with the Thoraflex Hybrid device, with or without extension with a RelayPro NBS stent-graft (all-comers population).
Sample Size	200 subjects, with a minimum of 65 subjects with RelayPro NBS distal extension. Upto 55 sites will be included in Europe and North America.
Key Study Endpoints	The primary safety endpoint is a composite of the following: 1) Permanent disabling stroke (mRS >2 and an increase in at least one mRS category from the individual’s pre-stroke baseline, occurring within 30 days of either index procedure or extension and present at 1-year follow-up) 2) Grade 3 spinal cord ischemia occurring within 30 days of either index procedure or extension 3) All-cause mortality (within 1 year of either index procedure or extension) The primary effectiveness endpoint is Treatment Success, which is defined as device technical success (of either procedure) with the absence of the following at 1-year: Lesion-related mortality Aortic rupture in the treated segment Lesion expansion (greater than or equal to 5mm increase from measurement at discharge/within 30 days) Secondary intervention to address the following: Stent graft-induced aortic wall injury (SAWI) Fistula Type I or III endoleak (see definitions) Migration Loss of Patency Thromboembolic events Failure of integrity Additional secondary safety and effectiveness endpoints will be collected and reported at each follow-up point through 10 years post-procedure. Secondary Safety Endpoints All-cause mortality Lesion-related mortality All/any paraplegia/paraparesis defined as SCI (SVS grades 1 to 3) Any stroke (excluding TIA) Incidence of Myocardial Infarction Incidence of Respiratory Failure Incidence of Renal Failure Incidence of Bowel Ischemia Secondary Effectiveness Endpoints Any aortic rupture (treated and untreated segments) Aortic remodeling in the treated segment(s) New dissections Proximal and distal extension of dissections Any false lumen perfusion (specifying location and if intentional or not) Fistula formation All endoleaks Device migration Device integrity issues (e.g., stent fracture) All thromboembolic events Pseudoaneurysms (device-related) Secondary Interventions Graft patency (loss of patency will be defined as an opening of <50% due to, for example, occlusion, stenosis, kinking)
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	352
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	94% (329/349) of eligible subjects have completed the discharge/30 day follow-up visit. 47% (99/211) of eligible subjects have completed the 1 year follow-up visit. 49% (103/211) of eligible 1 year subjects are still in window for their visit. 1 subject has been lost to follow-up.
Final Safety Findings	NA
Final Effect Findings	NA
General
Study Status	Completed
Application Number / Requirement Number	P100042 / PAS001
Date Original Protocol Accepted	10/28/2011
Date Current Protocol Accepted	10/28/2011
Study Name	APTIMA HPV Assay
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	10,545
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	96.76%
Final Safety Findings	No issues concerning the safety of the APTIMA HPV Assay on either TIGRIS or PANTHER platform were reported by the sponsor or identified by the reviewer.
Final Effect Findings	The absolute risk of cervical disease is greater in subjects with positive APTIMA HPV Assay results than in subjects with negative APTIMA HPV Assay results.
Study Strengths & Weaknesses	This study was able to demonstrate that the APTIMA HPV assay¿s postmarket performance is characterized by relatively high sensitivity and specificity, especially for identifying women who have higher risk of developing high-grade and invasive cervical cancer. However, this study had a limited ability to stratify women with the low-grade lesions. In addition, the study did not address the relevance of HPV positivity in the absence of cytological abnormalities which would require de novo data collection with a longer follow-up.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P110019 / PAS001
Date Original Protocol Accepted	10/27/2011
Date Current Protocol Accepted	10/27/2011
Study Name	XIENCE PRIME and XIENCE PRIME LL Everolimus Elut
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	Core Size Registry (CSR) FAS: 401 subjects, ITT: 403 subjects Long Lesion Registry (LLR) FAS: 104 subjects, ITT: 106 subjects
Actual Number of Sites Enrolled	62
Patient Follow-up Rate	CSR FAS: 94% (377/401), ITT: 93.8% (378/403) at 3 years LLR FAS: 95.2% 99 (104), ITT: 95.3% (101/106) at 3 years
Final Safety Findings	Core Size Registry (FAS population) endpoint rates observed through 3 years All Death (Cardiac, vascular, non-cardiovascular) 3.1% (12/390) TV-MI - Q-wave and non Q-wave per protocol 2.6% (10/390) per ARC 6.2% (24/390) Non-target vessel MI (Q-wave, Non Q-wave) per protocol 0.8% (3/390) per ARC 0.8% (3/390) Clinically indicated-TLR 5.4% (21/390) Clinically indicated Target Vessel Revascularization 9.5% (37/390) All TLR (Clinically indicated and non-Clinically indicated) 5.6% (22/390) All TVR (Clinically indicated and non-Clinically indicated) 10.0% (39/390) All Coronary Revascularization (TVR and non-TVR) 14.9% (58/390) Target Lesion failure (cardiac death, target vessel MI and CI-TLR) per protocol 8.5% (33/390) per ARC 10.8% (42/390) DMR (All death, all MI and all revascularization) per protocol 19.0% (74/390 per ARC 20.5% (80/390) MACE (Cardiac death, all MI and CI-TLR) per protocol 9.0% (35/390) per ARC 12.6% (49/390) Cardiac death or All MI per protocol 3.8% (15/390) per ARC 8.7% (34/390) Stent thrombosis, Overall per protocol 1.0% (4/390) per ARC 0.8% (3/380) Long Lesion Registry (FAS) endpoint rates observed through 3 years All Death (Cardiac, vascular, non-cardiovascular) 2.9% (3/104) TV-MI - Q-wave and non Q-wave per protocol 4.8% (5/104) per ARC 10.6% (11/104) Non-target vessel MI (Q-wave, Non Q-wave) per protocol 1.9% (2/104) per ARC 1.9% (2/104) Clinically indicated-TLR 4.8% (5/104) Clinically indicated Target Vessel Revascularization 7.7% (8/104) All TLR (Clinically indicated and non-Clinically indicated) 4.8% (5/104) All TVR (Clinically indicated and non-Clinically indicated) 7.7% (8/104) All Coronary Revascularization (TVR and non-TVR) 14.4% (15/104) Target Lesion failure (cardiac death, target vessel MI and CI-TLR) per protocol 9.6% (10/104) per ARC 14.4% (15/104) DMR (All death, all MI and all revascularization) per protocol 20.2% (21/104) per ARC 25.0% (26/104) MACE (Cardiac death, all MI and CI-TLR) per protocol 10.6% (11/104) per ARC 15.4% (16/104) Cardiac death or All MI- per protocol 5.8% (6/104) per ARC 11.5% (12/104) Stent thrombosis, Overall per protocol 0.0% (0/99) per ARC 0.0% (0/99)
Final Effect Findings	No separate effectiveness findings were reported.
Study Strengths & Weaknesses	Strength: The study achieved a follow-up rate greater than 90% at 3 years. Weakness: No formal statistics were performed to compare the clinical outcomes in SPIRIT PRIME Core Size Registry versus pooled SPIRIT II, III and IV or SPIRIT PRIME Long lesion Registry versus SPIRIT IV overlapping cohort analyses.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post- approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow ¿up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P110021 / PAS001
Date Original Protocol Accepted	10/19/2012
Date Current Protocol Accepted	10/19/2012
Study Name	Continue F/u of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	115
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	94.8%
Final Safety Findings	At 5 year follow-up, the rates for major adverse events (in descending order) are all-cause mortality 65.8%, cardiovascular mortality 18.4%, reshospitalization 30.7%, bleeding (25.6%), major bleeding 21.0%, arterial vascular procedure 17.2%, major vascular complication 11.8%.
Final Effect Findings	At 5 year follow-up, the mean values ± standard deviation for quality of life measures are: KCCQ summary 69.1 ± 22.1, SF-12 Physical 34.9 ± 10.6, SF12 mental 52.2 ± 10.3, EQ-5D 0.7403 ± 0.2074.
Study Strengths & Weaknesses	Strength: Longer-term (5-year) safety and effectiveness results are obtained and the device benefits over risks are sustained up to 5 years. Weakness: smaller sample size, i.e. only 109 of the 115 eligible patients have completed the study follow-up. QoL follow-up rates at 3-5 years are low.
Recommendations for Labeling Changes	Labeling update is not needed because Edwards Lifesciences LLC ceased US market distribution of the Edwards SAPIEN Transcatheter Heart Valve.
General
Study Status	Completed
Application Number / Requirement Number	P110021 / PAS002
Date Original Protocol Accepted	10/19/2012
Date Current Protocol Accepted	09/13/2013
Study Name	Newly Enrolled Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Retrospective/Prospective Cohort Study
Study Population	High risk patients undergoing transcatheter heart valve replacement therapy with severe symptomatic native aortic stenosis.
Sample Size	A total of 5000 subjects combined for P110021 & P100041 patients enrolled into the STS/ACC TVT Registry in all US sites.
Key Study Endpoints	Two primary endpoints: stroke at 30 days and 1 year
Follow-up Visits and Length of Follow-up	5 years Discharge, 30 days and 1 year as well follow-up at 2 years, 3 years, 4 years and 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	4994
Actual Number of Sites Enrolled	209
Patient Follow-up Rate	year 1: >80%; year 2-5: <80%
Final Safety Findings	All-cause mortality at 5 years: 64.2% Stroke at 5 years: 13.9% TIA at 5 years: 4.2% Aortic Valve Re-intervention at 5 years: 3.1% Re-intervention on Unspecified Valve at 5 years: 0.5% New Requirement for Dialysis at 5 years: 4.8%
Final Effect Findings	Survival at 5 years: 35.8%
Study Strengths & Weaknesses	Strength: Large number of real-world patients enrolled in a relatively short period of time (about 10 months). Weakness: Drop in follow-up rate post 1 year due to the inherent limitations in linking the TVT Registry with the CMS claims database.
Recommendations for Labeling Changes	No. Device has been discontinued due to obsolescence.
General
Study Status	Completed
Application Number / Requirement Number	P120002 / PAS001
Date Original Protocol Accepted	11/07/2012
Date Current Protocol Accepted	11/07/2012
Study Name	STROLL Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A non-randomized, multicenter, prospective, single- arm study.
Study Population	Patients enrolled in the pivotal STROLL study who received the S.M.A.R.T. Nitinol Self-Expandable Stent. There is no pre-specified control group.
Sample Size	39 sites in the United States. A total of evaluable subjects at 3 year follow-up.
Key Study Endpoints	Primary safety endpoint: A composite of all-cause death, amputation and target lesion revascularization (TLR) at 3 years. Secondary Endpoints to be assessed at 2 and 3 years: (1) individual components of the composite safety endpoint including death, amputation and TLR, (2) Major adverse events (MAE) defined as: death, limb ischemia/amputation of target limb, TLR, or significant embolic events causing organ damage, (3) Stent fracture rate assessed by x-ray, (4) Clinically driven TLR, and target vessel revascularization (TVR), (5) Patency of the target vessel assessed by duplex ultrasound, (6) Limb ischemia assessed by Rutherford/Becker classification, and (7) Ankle brachial index.
Follow-up Visits and Length of Follow-up	No new enrollments are planned for the post-approval study. 3 years following index procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	250
Actual Number of Sites Enrolled	39
Patient Follow-up Rate	90.9% (190/209) [209 = number of patients eligible for 3 year visit]
Final Safety Findings	At 3 years the composite endpoint death, index limb amputation, or clinically driven TLR was 31.5% (70/222, 1-sided upper bound 97.5% CI: 38.1), which is lower than the PG of 57% [the denominator 222 = number of patients with a major complication within 1080 days or patients with sufficient follow-up (i.e. at least 1020 days for 1080-day visit)]. Thus the primary endpoint was met. KM estimate for the composite endpoint (secondary Analysis) was 30.3%. MAE rate (overall) at 3 years: 31.5% (70/222) Death = 9.9% (22/222) Index limb amputation rate = 0.9% (2/222) Clinically-driven TLR rate = 22.5% (50/222) Significant embolic event rate = 0.0% (0/222) Clinically-driven TVR rate (Overall) = 25.2% (56/222)
Final Effect Findings	At 3 years the composite endpoint death, index limb amputation, or clinically driven TLR was 31.5% (70/222, 1-sided upper bound 97.5% CI: 38.1), which is lower than the PG of 57% [the denominator 222 = number of patients with a major complication within 1080 days or patients with sufficient follow-up (i.e. at least 1020 days for 1080-day visit)]. Thus the primary endpoint was met. KM estimate for the composite endpoint (secondary Analysis) was 30.3%. MAE rate (overall) at 3 years: 31.5% (70/222) Death = 9.9% (22/222) Index limb amputation rate = 0.9% (2/222) Clinically-driven TLR rate = 22.5% (50/222) Significant embolic event rate = 0.0% (0/222) Clinically-driven TVR rate (Overall) = 25.2% (56/222
Study Strengths & Weaknesses	The study achieved a high follow-up rate of about 91% at 3 year, with enough patients with 3 year data for endpoint analysis. The primary safety endpoint was evaluated by a formal statistic and compared to a performance goal. Weaknesses The PAS population was the premarket cohort that was required to meet certain eligibility criteria. Thus, the study results may not reflect the device performance in routine clinical device.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow ¿up visits etc.), results and study strengths and limitations.
General
Study Status	Completed
Application Number / Requirement Number	P100049 / PAS001
Date Original Protocol Accepted	03/22/2012
Date Current Protocol Accepted	06/22/2012
Study Name	Extended f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, multi-center, single arm clinical study that will be conducted in the United States and Europe.
Study Population	Subjects ages > 18 or Age of Majority according to Law in states or countries where 18 is considered a minor and < 75 years seeking intervention for GERD who meet the study inclusion / exclusion criteria are eligible for this study. The study will consist of all IDE patients (100 subjects at the beginning of the IDE) available at the end of the IDE study (90 by time of the panel) that may be implanted with the device. Subjects entering study will be at least partially responsive to medical therapy (proton pump inhibitors) for their GERD symptoms and have tested positive (abnormal) in esophageal pH testing.
Sample Size	The study will continue to follow the 100 patients available in the IDE pivotal study. There were 90 patients available at time of panel discussion.
Key Study Endpoints	Primary safety endpoint: The primary safety endpoint is the rate of occurrence for serious device and procedure related adverse events. The primary safety end-point will be assessed by reporting all adverse events and by estimating the rate of serious device and procedure related adverse events through 12 months post implantation. Safety will also be evaluated by endoscopy to assess the mucosa and abdominal/chest X-ray evaluations to verify device location at 12 months post implantation. Primary effectiveness endpoints: Reduction in total distal esophageal acid exposure time defined by esophageal pH testing. Testing will be performed with subjects off PPIs. The subject¡¯s baseline pH acid exposure time will serve as the control and be compared to the subject¡¯s pH acid exposure time 12 months post implantation. Success criteria ¨C At least 60% of subjects will have normalized or improved by at least 50% in total distal acid exposure. Secondary effectiveness endpoints: Subjects GERD-HRQL (Health Related Quality of Life) scores will be assessed off all GERD medications. The subject¡¯s baseline GERD-HRQL score will serve as the control and be compared to the subject¡¯s GERD-HRQL 12 months post implantation. Success criteria - At least of subjects will have a reduction in total GERD-HRQL scores. Subject¡¯s average daily dose of PPI will be evaluated. The subject¡¯s baseline average daily dosage will serve as the control and be compared to the subject¡¯s average daily dosage 12 months post-procedure. Success criteria - At least of subjects will reduce their average daily PPI dosage .
Follow-up Visits and Length of Follow-up	The length of follow up will be 60 months post-implantation. The follow up assessments will take place at yearly intervals up to the end of the study at 60 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	85/100 (85%)
Final Safety Findings	10 serious adverse events were reported in 7 subjects. The serious SAE rate was 7.0% with an upper confidence limit of 15.2% at 60 months.
Final Effect Findings	83.3% of subjects had at least a 50% reduction in their 60 month total GERD-HRQL score when compared to baseline (95% confidence interval with lower confidence limit = 68.7%).
Study Strengths & Weaknesses	Strengths: This study had a high five year follow-up rate of 85 out of 100 subjects or 85%, which met the requirement of 80% specified in the condition of approval. It is important for a longitudinal study to have a high follow-up rate, in order to avoid potential bias and generate valid conclusions. Weaknesses: There was no comparator group in this study. The mean subject body mass index was 27.9 kg/m2 (range 19.8, 34.7). Therefore, the effectiveness of this device for patients with BMI over 35 is unknown.
Recommendations for Labeling Changes	None. There are no new safety or effectiveness concerns since the approval of the current labeling
General
Study Status	Completed
Application Number / Requirement Number	P110033 / PAS001
Date Original Protocol Accepted	10/22/2013
Date Current Protocol Accepted	10/22/2013
Study Name	VOLUMA-003 Repeat Treatment Study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Statistical analysis of data collected in the premarket study
Study Population	Subjects who enrolled in the premarket study and received repeat treatment
Sample Size	At least 167 modified intent-to-treat (mITT) subjects.
Key Study Endpoints	Safety Endpoints include: presence, severity, location (zygomaticomalar region, anteromedial cheek, and/or submalar region), and duration of common treatment site responses (CTRs) and any adverse events (AEs) after repeat treatment. There are no effectiveness endpoints.
Follow-up Visits and Length of Follow-up	12 months after repeat treatment 1, 3, 6, 9, and 12 months after repeat treatment
Interim or Final Data Summary
Actual Number of Patients Enrolled	167
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	121/167 (72.5%)
Final Safety Findings	Primary endpoint was met because the safety profile of VOLUMA XC after repeat treatment was not inferior (or worse) to the safety profile after initial/touch-up treatment. The incidence of early device/injection-related AEs after repeat treatment [8.4% (14/167)] was not significantly greater than the incidence rate for early device/injection-related AEs [33.5% (56/167)]. In fact, the incidence after repeat treatment was statistically significantly lower (25.1%) than the incidence after initial/touch-up treatment. No new safety concerns were identified after repeat treatment. The types of case reports and adverse events observed after repeat treatment were similar to those after initial/touch-up treatment, but were generally less severe after repeat treatment. Repeat treatment requires smaller doses and it is known that larger injection volumes lead to significantly higher adverse event rates. Therefore, it was expected that the number of adverse events in the repeat treatment post-approval study would decrease. A multivariate analysis of the data showed that the rate of device/injection-related adverse events increased with injection volume, was higher in females as compared to males and varied from site to site.
Final Effect Findings	This PAS study did not evaluate effectiveness
Study Strengths & Weaknesses	Strengths: Multi-center, single-blind, randomized, “no-treatment” control group, adequate sample size. Weaknesses: Low overall follow-up rate (72.5%).
Recommendations for Labeling Changes	The PAS study design, methods and results must be included in the labeling. Additionally, it should be indicated that multivariate analysis showed that the rate of device/injection-related adverse events was different among clinical sites, increased with larger injection volumes, and was higher in females as compared to males.
General
Study Status	Completed
Application Number / Requirement Number	P110038 / PAS001
Date Original Protocol Accepted	09/21/2012
Date Current Protocol Accepted	02/06/2018
Study Name	Relay Thoracic Stent-Graft w Plus Del Sys
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center observational prospective cohort study.
Study Population	This population will consist of 120 Relay Phase II subjects and 13 Relay Continued Access study subjects plus 45 subjects treated post-approval with the Relay Thoracic Stent-Graft at centers which did not participate in the premarket studies.
Sample Size	A sample size of 178 patients is based on the desire to have adequate follow up at 5-years to assess the primary endpoint assuming 20% attrition through thevfollow-up period. The sample size will include: 120 from Phase II study, 13 continued access subjects, and 45 subjects enrolled post-approval at a maximum of 30 sites which did not participate in the pre-marekt Relay studies, including Phase I feasiblity.
Key Study Endpoints	The primary endpoint is measured as freedom from ARM at 5 years post- procedure. Aneurysm-related mortality is defined as death from rupture of the descending thoracic aortic aneurysm (DTAA) or penetrating aortic ulcer (PAU), or from any procedure intended to treat the DTAA or PAU. If a death occurred within 30 days of any procedure intended to treat the DTAA or PAU, or within the hospital stay if the patient was not discharged within 30 days, then it is presumed to be aneurysm-related. Two secondary endpoints for this trial are the assessment of training effectiveness and the evaluation of major device-related events and major morbidity. Training effectiveness will be assessed by comparing the following: Delivery and deployment results of subjects treated by novice implanters of the Relay Thoracic Stent-Graft with Plus Delivery System (subjects enrolled in this study) to delivery and deployment results from the Relay Clinical Trial IP-0004-06 Survival, freedom from rupture, freedom from conversion, and number of endoleaks (Type I, III, and IV only) at 30 days post-implantation for the novice implanters’ first three implantations to those of the first three implantations of experienced implanters. Major device-related events include the following: aneurysm rupture, increase in aneurysm sac size, conversion to open surgery, endoleak (Type I, III and IV only), stent migration (migration greater than or equal to 10 mm as compared to the 1-month visit), wireform fracture, and lumen occlusion. Major morbidity is a composite of the following major adverse events. These events are considered by definition to be serious in nature. Stroke (defined as a sudden, non-convulsive loss of neurological function due to an ischemic or hemorrhagic intracranial vascular event); Paralysis / Paraplegia (defined as loss of power or voluntary movement in a muscle through injury to or disease of its nerve supply within 30 days of the procedure. Paraplegia is paralysis of both lower extremities, and generally lower trunk, within 30 days of the procedure); Myocardial Infarction (defined as an acute episode in which circulation to a region of the heart is obstructed and necrosis is occurring; it is usually characterized by severe pain, frequently associated with pallor, perspiration, nausea, dyspnea, and dizziness; electrographic abnormalities may include Q wave ST segment, and T wave alterations); Respiratory Failure (defined as a need for mechanical ventilation beyond the first 48 hours after the procedure or the need for reintubation or ventilator support any time between 48 hours and 30 days postoperative); Renal Failure (defined as rise in creatinine greater than 50% above the pre- procedure level resulting in a creatinine level above high normal that does not spontaneously resolve and requires dialysis treatment); and All-Cause Mortality.
Follow-up Visits and Length of Follow-up	5 years 1 month, 1 year, and annually thereafter
Interim or Final Data Summary
Actual Number of Patients Enrolled	45 subjects
Actual Number of Sites Enrolled	23 sites were initiated in the study
Patient Follow-up Rate	Clinical Follow-up rates: 30 day: 42/45 (93.3%) 1-year: 36/42 (85.8%) 2-year: 29/36 (80.6%) 3-year: 25/29 (86.2%) 4-year: 21/26 (80.8%) 5-year: 13/19 (68.4%)
Final Safety Findings	Death Twelve (12) subjects have expired. Aneurysm-Related Mortality Two (2) deaths were categorized as aneurysm-related mortality. The deaths occurred within 30 days of the initial procedure. Rupture There have been no treated aneursym ruptures. Major Adverse Events A total of four (4) subjects have experienced MAEs; events for two (2) of the subjects occurring within 2 days of the implant procedure. One (1) subject experienced a bilateral hemispheric stroke on the date of the procedure, and another (1) subject developed respiratory failure and paraplegia following the procedure. One (1) subject experienced a stroke at 128 days post implant, but subsequently recovered one day later following hospitalization and medical management. One (1) subject reported myocardial infarction at 1 year.
Final Effect Findings	Conversions to Open Surgery There have been no conversions to open repair Secondary Interventions There was one (1) secondary intervention at 1 year post-implant due to possible Type III endoleak. The subject was treated with an additional RelayPlus. Endoleaks Core Lab analysis of imaging data confirmed one (1) Type Ib endoleak and one (1) Type Ia endoleak at 3 years and one (1) Type III endoleak at 4 years. Interventions were not performed on the Type I endoleaks due to the investigators not agreeing with the findings. There were no Type IV endoleaks. Device Integrity There were no reports of device integrity events. Aneurysm Sac Enlargement ( > 5 mm) Two (2) subjects had onset of aneurysm sac increase of > 5mm at 1 year. One (1) subject with sac enlargement at 3 years. In total, three subjects experienced aneurysm sac enlargement. Patency There were no losses of patency in any subject through any follow-up visit. Migration Two (2) events of migration were reported by the Core Lab; however, for one (1) of these, the repositioning is thought to be likely related to aortic lengthening and not true distal migration.
Study Strengths & Weaknesses	Strengths: This was a multi-center prospective cohort study that enrolled sites and subjects that did not participate in the Relay Pivotal Study. Core Lab analyzed the imaging, and an independent clinical events committee adjudicated event relatedness to the procedure, technique, and/or device. Weaknesses: Due to difficulties with enrollment, the enrollment in the de novo cohort was capped at 45 subjects rather than the originally agreed upon target of 100 subjects. Therefore, the originally planned statistical analysis as defined in the original protocol could not be performed. As such, the results were presented in descriptive statistics. The study is a non-randomized study with inherent biases. The study had high attrition; only 19 of 45 initial subjects were eligible for the 5-year visit, of which 13 subjects completed the 5-year visit.
Recommendations for Labeling Changes	Labeling Supplement will not be recommended. However, the team will recommend to the sponsor to provide a labeling update to point to the Clinical Update for updated results on the study
General
Study Status	Completed
Application Number / Requirement Number	P110008 / PAS001
Date Original Protocol Accepted	10/17/2012
Date Current Protocol Accepted	04/23/2013
Study Name	Coflex Long-Term PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Randomized clinical trial
Study Population	The study population is comprised of patients who received the device during the IDE or controls that underwent Anterior Cervical Decompression and Fusion (ACDF) during the IDE
Sample Size	A total of 191 coflex and 104 fusion patients comprise the sample size.
Key Study Endpoints	The following criteria will be used to evaluate CCS at each post year 2 follow-up point including at year 5. These are the same as used for the two year study only modified to accommodate the longer-term follow-up. For the year 5 endpoint, these are: Improvement of at least 15 points in the Oswestry Low Back Pain Disability Index (ODI) at 5 years compared to baseline; No reoperations, revisions, removals, or supplemental fixation; No major device-related complications, including but not limited to permanent new or increasing sensory or motor deficit at 5 years; and No epidural steroid injections in the lumbar spine. In addition to the principal endpoint of survivorship, information on the following efficacy outcomes will be assessed: Oswestry Disability Index (ODI) Zurich Claudication Questionnaire (ZCQ) Leg (right, left) Pain Visual Analog Scale (VAS) (100mm scale) Back Pain Visual Analog Scale (VAS) (100mm scale) Quality of Life (SF-12) Neurological Status In addition, each component of the composite clinical success will be used to evaluate coflex® device performance in absolute terms and relative to fusion control, including overall device survival. The anterior/posterior and lateral radiographs will be assessed for evidence of: Radiolucency Migration Range of motion and translation in flexion/extension, at the implanted and adjacent level(s) as measured on lateral standing flexion/extension films. Adjacent level breakdown Radiographic Observations: Fractures, Heterotopic Ossification, etc. Patients with an unresolved spinous process fracture at 24 months, observed via independent radiographic assessment, will be subjected to a CT scan at 5 years to determine if the spinous process has healed, pending patient and IRB approval.
Follow-up Visits and Length of Follow-up	5 years. Patients in the long-term follow-up study will be asked to return for follow-up evaluations annually (± 4month) at 36, 48 months, and 60 60 months post-surgery. The follow-up evaluations will include assessment of complications, administration of the Oswestry Disability Index (ODI), Leg (right, left, max) and Back Pain VAS, Zurich Claudication Questionnaire (ZCQ), and SF-12, and radiographic evaluation.
Interim or Final Data Summary
Actual Number of Patients Enrolled	207 in investigation device group and 107 controls
Actual Number of Sites Enrolled	21
Patient Follow-up Rate	Investigational device group: 90.7% Control group: 86.0%
Final Safety Findings	No evidence raising serious concerns was found. The 60-month device failure rates are 3.6% and 2.4% for the investigational device group and controls (fusion), respectively. The results are similar when comparing one level procedure and two level procedures.
Final Effect Findings	Overall success outcomes including the FDA-defined criteria were met at the end of 60 months. The composite clinical success (CCS) at 60 months were 49.5% and 44.0% (p=0.385) for the investigational device group and the controls, respectively. The results were similar when comparing one level procedure and two level procedures. Other outcomes, including Improvement of at least 15 points in ODI at Month 60 compared to baseline, No reoperation or epidural, No reoperations, revisions, removals, or supplemental fixation, No epidural injection at any lumbar level up to and including the Month 60 visit, No persistent2 new or increasing sensory or motor deficit at 60 months, No persistent new or increasing sensory deficit at 60 months, and No persistent new or increasing motor deficit at 60 months, were all comparable between coflex and the fusion controls.
Study Strengths & Weaknesses	This Extended Follow-Up study was capable of demonstrating comparable outcomes between coflex and fusion, as well as between one level and two level coflex procedures. However, the data are only so far available from the subjects in the IDE study, which may not be necessarily repetitive of the real world evidence.
Recommendations for Labeling Changes	No labeling change is recommended, since all of the observed complications have already been listed in the product labeling and no unusually higher rates of AEs and complications have been observed in the PAS.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P110008 / PAS002
Date Original Protocol Accepted	10/17/2012
Date Current Protocol Accepted	04/23/2013
Study Name	Coflex Actual Practice PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Randomized clinical trial
Study Population	The study population is comprised of patients with radiographic confirmation of at least moderate degenerative spinal stenosis with constriction of the central spinal canal of one or two adjacent segments in the region L1 to L5.
Sample Size	The sample size is 230 patients. There will be 115 patients in each group. There will be 115 patients with decompression surgery and without Coflex, and 115 patients with decompression surgery and the Coflex.
Key Study Endpoints	The primary endpoint is improvement of Oswestry Low Back Pain Disability Index (ODI) after 24 months compared to control group. Secondary endpoints encompass: -Superior improvement of the Visual Analog Scale (VAS) for low back pain (on the 100 mm scale) within 24 months compared to control, group. -Leg pain (Measurement via a 100 mm VAS) -Zurich Claudication Questionnaire (ZCQ). This is a self rating questionnaire designed to assess symptom severity, physical functional status and patient satisfaction -Assessment of significant migration of the implant or the complete expulsion (significant is defined > 5 mm) -Neurological status (assessment of the maintenance of the improvement after surgery throughout the study duration) - Walking distance test on a treadmill (assessment of improvement in walking distance)
Follow-up Visits and Length of Follow-up	Patients will be followed for 2 years. Patients will be evaluated pre-operatively, and at 3, 12 and 24 postoperative months.
General
Study Status	Completed
Application Number / Requirement Number	P110039 / PAS001
Date Original Protocol Accepted	10/18/2012
Date Current Protocol Accepted	03/15/2013
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is multi-center prospective cohort. .
Study Population	The sample size is 70 patients. Sample size and power calculations are provided in the protocol. The study population will be comprised of patients inside the United States who sign an informed consent and receive the device in the post-market environment.
Sample Size	The sample size is 70 patients. Sample size and power calculations are provided in the protocol. The study population will be comprised of patients inside the United States who sign an informed consent and receive the device in the post-market environment.
Key Study Endpoints	Study endpoints include pain response, medication use and quality of life.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical examination at the time of enrollment and one month and 3 months post-treatment. The total length of follow-up is three months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	32
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	97% at 1 week, 90% at 1 month, 79% at 2 month, 81% at 3 month
Final Safety Findings	Out of 32 subjects treated, seven adverse events have been reported (five mild, one moderate and one severe). All adverse events are expected procedure finding. The safety profile is the same as previously reported in the PMA #P110039 as expected. Most events were mild and can be managed with adequate anesthesia (sonication pain) or treatment technique (e.g., skin burn). No new safety or subject protection concerns are raised by the reported information.
Final Effect Findings	The proportion of responders, NRS and BPI pain scores and percent change from baseline are presented and compared to the pivotal trial US Cohort. The findings are as expected and consistent with the pivotal trial.
Study Strengths & Weaknesses	Strength: The goal of the PAS study has been met to show that the results from pivotal trial have been duplicated in a separate study. No new safety or subject protection concerns are raised. Weakness: Small sample size due to difficulty in patient enrollment.
Recommendations for Labeling Changes	No Labeling change recommended
General
Study Status	Completed
Application Number / Requirement Number	P110039 / PAS002
Date Original Protocol Accepted	10/18/2012
Date Current Protocol Accepted	03/15/2013
Study Name	Enhanced Surveillance Registry Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	17
Actual Number of Sites Enrolled	7 sites were enrolled; 4 sites enrolled patients
Patient Follow-up Rate	N/A
Final Safety Findings	There were two adverse events reported that were possibly or probably relatedto the device: post procedural pain (moderate severity, not serious), and erythema (mild, not serious).
Final Effect Findings	This study did not have a primary effectiveness endpoint.
Study Strengths & Weaknesses	This enhanced surveillance requirement was designed to collect data for two years of commercial experience, in order to characterize adverse events from a real world setting. There was no pre-specified sample size, and only 17 patients were enrolled out of 47 patients who received commercial treatments at the participating study sites.
Recommendations for Labeling Changes	Due to the low sample size and study limitations, no labeling change is recommended.
General
Study Status	Completed
Application Number / Requirement Number	P120006 / PAS002
Date Original Protocol Accepted	10/05/2012
Date Current Protocol Accepted	08/28/2013
Study Name	Training Program
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, consecutively enrolling, single-arm, non-randomized, multi- center study
Study Population	Patients with abdominal aortic aneurysm with vascular morphology suitable for endovascular repair with the Ovation/Ovation Prime Abdominal Stent Graft System. Eligible patients must have met or must meet all of the inclusion criteria and none of the exclusion criteria. Patients will be categorized into those treated by physicians ¿ who completed fewer than 20 endovascular repairs of AAA with any endovascular graft in the 2 years preceding participation in the Ovation physician training program, and those ¿ who completed 20 or more cases in the preceding 2 years.
Sample Size	A total 320 subjects comprises of 161 pivotal cohort subjects, all continued access subjects, all subjects from the HDE PAS and at least 59 de novo subjects enrolled from a minimum of 15 U.S. sites.
Key Study Endpoints	At Implant Technical failure Type 1 endoleak Use of Accessory device Through 30 days Serious Adverse Events (SAEs) Mortality (AAA-related and all-cause) Device Patency Conversion to open surgical repair Endoleak AAA enlargement Stent Graft Migration Device integrity Secondary endovascular procedures Aneurysm rupture
Follow-up Visits and Length of Follow-up	30 days At implant and 30 days
Interim or Final Data Summary
Actual Number of Patients Enrolled	320
Actual Number of Sites Enrolled	49
Patient Follow-up Rate	100% at 30 days
Final Safety Findings	N/A
Final Effect Findings	At Implant Endpoint results for physicians with fewer than 20 prior endovascular repairs and physicians with 20 or more prior endovascular repair in 2 years preceding participation in Ovation/Ovation Prime Training Program were as follows: Technical failure 0% for both physician groups, Type 1 endoleak 0% vs. 0.7% (95% CI for difference 0.7%: -2.9%, 4.2%), and Use of Accessory devices 5.0% vs.8.7% (95% CI for difference 3.7%: -8.9%, 16.3%), respectively. Through 30 days post Implant The adverse events rates for physician with fewer than 20 endovascular repairs and physicians with 20 or more endovascular repair in 2 years preceding participation in Ovation/Ovation Prime Training Program were as follows: AAA-related secondary endovascular procedures 0% vs. 1.0%, device-related SAEs 0% vs. 1.3%, and renal events (including acute kidney injury, renal insufficiency, renal failure) 0% vs. 1.7%, respectively. No statistically significant differences were observed between the 2 groups for any adverse event. The rates for thromboembolic events, paralysis/paraparesis, stroke, claudication and ischemic colitis were 0% in both physician groups.
Study Strengths & Weaknesses	The study achieved the target enrollment of 320 patients with 100% follow-up at 30days and a high technical success. Patient enrollment in the physicians with fewer than 20 prior endovascular experience group was low.
Recommendations for Labeling Changes	Labeling change NOT Recommended
General
Study Status	Completed
Application Number / Requirement Number	P110042 S058/ PAS001
Study Name	EMBLEM MRI S-ICD Pt Mgmt System Surv PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Non-randomized, observational surveillance effort using a remote data collection database to identify spontaneous episodes of VF following possible clinical MRI exposure. Identified episodes will be used to assess sensing and detection via time-to-therapy. All data will be collected via Boston Scientific’s Latitude NXT Patient Management System and de-identified for analysis.
Study Population	All Boston Scientific S-ICD systems that have been placed into MRI Protection Mode and transmit data to the Latitude NXT Patient Management System. Subjects to be included will meet two criteria: Possible MRI exposure (as indicated by MRI Protection Mode having been enabled), and At least one documented spontaneous treated episode of VF subsequent to possible MRI exposure
Sample Size	25 subjects will contribute to this data analysis. Assuming a time to therapy of 20.0 seconds (S),1 a sample size of 25 episodes will produce a 95% confidence interval of [18.0, 22.0] S. The following assumptions were used to define the scope and duration: US sales projections indicate that an estimated 8,600 BSC SICD Systems will be implanted annually for the next 5 years. An estimated 70% of S-ICDs in the US will enroll and regularly transmit device data through the Latitude NXT Patient Management System. The annual incidence MRI scans in ICD patients is approximately 10% Based on episode data from the S-ICD Clinical Investigation, the annual incidence of VF is approximately 1-2% of patients per year. Per the above assumptions, it will take approximately 5 years to complete the project.
Key Study Endpoints	Primary Endpoints: The mean, median and standard deviation of time to therapy will be assessed for the first appropriately treated spontaneous episode of VF following placement into MRI Protection Mode. The time to therapy is defined as the interval starting when the rate of the VF is greater or equal to the lowest programmed zone (Conditional Zone) and measured until the start of the shock marker. Additional Observational Endpoints: Number of devices programmed to MRI Protection Mode Number / type of spontaneous episodes of VT/VF following placement in MRI Protection Mode Last shock impedance for episodes of VT/VF that occur subsequent to placement in MRI Protection Mode In the event that the calculated time to therapy exceeds 30 seconds, additional treated episodes from the same device prior to the MRI will be identified. This will allow within-patient time-to-therapy comparisons before and after the device is programmed into MRI Protection Mode. Additionally, the clinic and enrolling physician will be queried in order to identify the patient and provide an opportunity to consent to providing additional data, including: Details around the programming of MRI Protection Mode Details of the MRI Other pertinent medical history information that might explain the long time to therapy
Follow-up Visits and Length of Follow-up	5 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	34 subjects included in the endpoint analysis
Actual Number of Sites Enrolled	0 sites – study was performed using data collected from Latitude NXT Patient Management Systems transmissions
Patient Follow-up Rate	No patient follow-up required by study design due to data collection method using home monitor data.
Final Safety Findings	The time to therapy was assessed for the first appropriately treated spontaneous episode of ventricular fibrillation (VF) following placement into MRI Protection Mode.
Final Effect Findings	N/A study just had the endpoint listed above
Study Strengths & Weaknesses	Study used real-world evidence sources which eliminated the need for the use of sites for data collection. The study design allowed the study to be conducted faster and with more patients than planned (25 planned). The weakness of the study is that it was reliant on home monitor data and did not have the full follow-up with in-person patient visits to identify potential other signals unrelated to the time to therapy endpoint.
Recommendations for Labeling Changes	No labeling change is recommended as the performance is in line with the performance observed during the premarket study.
General
Study Status	Completed
Application Number / Requirement Number	P110042 / PAS001
Date Original Protocol Accepted	09/28/2012
Date Current Protocol Accepted	09/28/2012
Study Name	S-ICD PAS Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort study
Study Population	Any patient, who meets the inclusion criteria, does not meet the exclusion criterion and provides informed consent will be enrolled in the registry. Inclusion Criteria X Patients eligible for implantation with an S-ICD System, OR patients previously implanted with an S-ICD System Clinical Investigation (IDE G090013) X Willing and able to provide written informed consent or have informed consent a provided by a legal representative Exclusion Criterion X Remaining life expectancy of less than 360 days
Sample Size	1616 patients from approximately 50 investigational centers (up to 150) in the US
Key Study Endpoints	The primary safety endpoint of the study is the Type I Complication Free Rate at 60 months, which will be compared to a performance criterion The primary effectiveness endpoint is the Overall Shock Effectiveness in Converting Spontaneous Discrete Episodes of VT/VF through 60 months, which will be compared to a performance criterion. The secondary safety endpoint of the study is the Electrode-Related Complication Free Rate at 60 months, which will be compared to a performance criterion. The secondary effectiveness endpoint is First Shock Effectiveness in Converting Induced (Acute) and Spontaneous Discrete Episodes of VT/VF through 60 months, which will be compared to a performance criterion.
Follow-up Visits and Length of Follow-up	Data will be collected through the 60th month (1800 days) post implant. Data will be collected from each patient at enrollment, implant, annual follow-up visits and from unscheduled follow up visits associated with system/procedure-related complications or spontaneous episodes.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1766
Actual Number of Sites Enrolled	86
Patient Follow-up Rate	The mean follow-up duration was 40.4 months 43.6% of the subjects completed the study. 11.0% of the subjects were lost to follow-up
Final Safety Findings	PRIMARY SAFETY: Type I Complication Free Rate at 60 months passed the complication free rate at lower one-sided 95% confidence bound of 91.4%. This was above the performance criteria set at 85% SECONDARY SAFETY: The Electrode-Related Complication Free Rate at 60 months (1800 days) passed the performance goal of 92.5% with a lower one-sided 95% confidence bound of 98.8%.
Final Effect Findings	PRIMARY EFFECTIVENESS: The Overall Shock Effectiveness in Converting Spontaneous Discrete Episodes of VT/VF through 60 months passed the performance goal of 94% with a lower one-sided 95% confidence bound of 97.4%. SECONDARY EFFECTIVENESS: First Shock Effectiveness in Converting Induced (Acute) and Spontaneous Discrete Episodes of VT/VF through 60 months passed the performance goal of 84% with lower one-sided 95% confidence bound of 94.1% for induced episodes and 89.8% for spontaneous discrete episodes.
Study Strengths & Weaknesses	The safety and effectiveness primary and secondary endpoints were all acceptable. The additional pre-specified endpoints were favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling
General
Study Status	Completed
Application Number / Requirement Number	P120005 S041/ PAS001
Date Original Protocol Accepted	12/20/2016
Date Current Protocol Accepted	01/09/2024
Study Name	Dexcom G5 Mobile Cont Glucose Monitoring Sys -PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, observational, non-inferiority, adaptive design study intended to evaluate the safety of non-adjunctive CGM use in CGM-naïve adult and pediatric subjects, by assessing the number of hypoglycemic and diabetic ketoacidosis (DKA) events with use of CGM. The sponsor has defined hypoglycemia as (1) severe hypoglycemia resulting in a seizure or loss of consciousness or (2) moderate hypoglycemia defined as the inability to self-treat due to weakness or confusion to take carbohydrates, requiring assistance by a third party. The sponsor defined DKA as requiring an emergency room (ER) visit or hospitalization. The study has two cohorts: (1) Cohort A, enrolling adults and pediatric subjects, includes a baseline period of 6 months using a blood glucose meter (BGM) as a comparator. Subjects will perform self-monitored blood glucose (SMBG) testing using their personal BGM. Each subject will serve as their own control defined as the subject’s first 6 months in the study with diabetes management using SMBG. The second six months comprise the intervention period during which subjects will use CGM to manage their diabetes. Cohort A subjects will be in the study period for approximately 12 months and will have approximately 3 clinic visits and 10 monthly telephone calls. (2) Cohort B, enrolling pediatric subjects, includes only an intervention period of 6 months of study participation, using a CGM. Cohort B participants cannot serve as their own controls because they will not participate in a BGM period. These subjects will be included in all analyses that do not require a control. In order to ensure the safety results are the same for pediatric subjects in Cohort A and those in Cohort B subjects, additional sensitivity analyses will be performed to compare the safety outcomes during the CGM phase for Cohort A and Cohort B to ensure they are similar. Cohort B subjects will be in the study period for approximately 6 months and will have approximately 2 clinic visits and 5 monthly telephone calls.
Study Population	Adult and pediatric subjects, less than or equal to 2 years of age, with type 1 diabetes (T1D) or insulin-requiring type 2 diabetes (T2D), naïve to CGM (either naïve to real-time CGM or may have used professional CGM). Subpopulation enrollment is targeted for 1/3 pediatric (2/3 in Cohort A and 1/3 in Cohort B) and 2/3 adult subjects (all in Cohort A), with approximately 10% of adult participants greater than or equal to 65 years of age.
Sample Size	1110 participants are required to demonstrate non-inferiority of CGM to SMBG. Target enrollment specified up to 1,388 subjects (or more depending on the sample size re-estimation procedure) to allow for an assumed 20% lost to follow-up.
Key Study Endpoints	Primary Endpoint: The primary endpoint for this clinical study is to assess change in the average number of hypoglycemic events per participant after 6-months of CGM use compared to 6-months of BGM use in Cohort A. Secondary endpoints: The secondary endpoints for this clinical study will be to assess patient reported outcomes, clinical measurements, and CGM metrics after 6-months of CGM use compared with 6-months of baseline data with BGM use in Cohort A. For Cohort B, secondary analyses will assess outcomes after 6-months of CGM use compared with the baseline status collected at the initial visit. Additional analyses include, but are not limited to the following: Clinical Measurements 1. A1C change, overall and across the A1C range 2. Change in percentage of participants with at least one (1) hypoglycemia event 3. Change in the percentage of participants with at least one (1) diabetic ketoacidosis event 4. Percentage of participants with increased and decreased number of hypoglycemia events 5. Change in the number & proportion of hypoglycemia events stratified by day versus night Patient Reported Outcomes 1. Glucose Monitoring Satisfaction Survey (GMSS) 2. CGM Satisfaction 3. Diabetes Distress Scale (DDS) 4. Hypoglycemia Fear Survey-Worry subscale (HFS-W) 5. Hypoglycemia Confidence CGM Metrics-comparing Month 7 (after CGM initiated) with Month 12: 1. Average of CGM Glucose 2. Standard Deviation (SD) of CGM glucose 3. Percentage of CGM glucose within range: 70-180 mg/dL 4. Percent Time-in-Hypoglycemia (<70 mg/dL) 5. Percentage of CGM glucose in Hypoglycemia: (<55 mg/dL) 6. Percent Time-in-Hyperglycemia (>250 mg/dL) 7. Percentage of CGM glucose in Hyperglycemia (>300 mg/dL) Other Metrics 1. CGM adherence: frequency of CGM use at month 12 compared to month 7 of CGM use 2. Change in SMBG frequency after initiation of CGM compared to baseline period, defined aa time point when BGM or CGM is established (months 3-6 for BGM and months 9-12 for CGM) 3. Change in the numbers & proportions of hypoglycemic events stratified by sensor location (used in approved wear locations or off-label) 4. A subpopulation analyses will be conducted at the end of the study, including but not limited to: Type 1 diabetes, Type 2 diabetes, adult, pediatric, and elderly. In addition, the safety outcomes for the additional outcomes listed above will be repeated to compare the outcomes for pediatric subjects in Cohort A and those in Cohort B.
Follow-up Visits and Length of Follow-up	Follow-up Visits and Length of Follow-up Subjects in Cohort A will be in the study period for approximately 12 months and will have approximately 3 clinic visits and monthly telephone calls (total of 10). Subjects in Cohort B will be in the study period for approximately 6 months and will have approximately 2 clinic visits and monthly telephone calls (total of 5).
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,092 subjects were enrolled, of which 1,088 met all inclusion/exclusion criteria and were included in the Intent-to-Treat (ITT) population.
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	A total of 1,092 subjects were enrolled across the two cohorts of the study. The sponsor had an overall enrollment goal of 1,388 participants (allowing an assumed 20% loss to follow-up), targeted for 1/3 pediatrics (2/3 in Study Cohort A and 1/3 in Study Cohort B) and 2/3 adults (all in Study Cohort A), with approximately 10% of participants targeted to be 65 years of age or older. The study's overall follow-up rate was 83.2%. Across all cohorts, there were 184 subject withdrawals, the most common reasons being lost to follow-up (n=42, 3.8%), non-compliance (n=40, 3.7%), and other (n=68, 6.2%). Follow-up is summarized by study cohort below. Cohort A: A total of 911 subjects enrolled in the study and met all inclusion criteria and none of the exclusion criteria. Of these subjects, a total of 743 completed the 12-month final follow-up visit (519 adults and 224 pediatric participants). The follow-up rate was 83.8% for adults and 78.0% for pediatric participants. Cohort B: A total of 181 subjects were enrolled in the study and met all inclusion criteria and none of the exclusion criteria. Of these subjects, a total of 161 completed the 6-month final follow-up visit. The follow-up rate was 89.0%.
Final Safety Findings	Adults: There was a total of 975 adverse events (AEs) in the ITT adult population (446 in the SMBG period and 529 in the CGM period), of which 17 were device-related. For adults, the majority of AEs (399/446 = 89.5% in the SMBG period and 489/529 = 92.4% in the CGM period) were disease-related hypoglycemia. The majority of AEs were mild in the SMBG period (360/446 = 80.7%) and in the CGM period (488/529 = 92.2%). The percentage of participants with hypoglycemia (of any severity) was relatively stable across the two periods (26.8% in the SMBG period and 28.6% in the CGM period). The percentage of participants with DKA was very small in each period (0.7% in the SMBG period and 0.2% in the CGM period). Across the two periods, there were 5 DKA events (4 in the SMBG period and 1 in the CGM period) and 888 hypoglycemia events (399 in the SMBG period and 489 in the CGM period). Of the 17 device related AEs in the CGM period, most were insertion site AEs (13/17=76.5%). There were 2 deaths, both of which were determined not to be device-related. Pediatrics (COHORT A): There were 511 AEs in the ITT pediatric Cohort A population (262 in the SMBG period and 249 in the CGM period), of which 8 were device-related. The majority of AEs were mild in the SMBG period (204/262 = 77.9%) and in the CGM period (205/249 = 82.3%). The percentage of patients with hypoglycemia (of any severity) was 23.5% in the SMBG period and 30.5% in the CGM period. The percentage of patients with DKA was 5.7% in the SMBG period and 6.6% in the CGM period. Across the two periods, there were 43 DKA events (22 in the SMBG period and 21 in the CGM period) and 406 hypoglycemia events (210 in the SMBG period and 196 in the CGM period). Of the 8 device related AEs in the CGM period, 4 were insertion site AEs, 3 were hypoglycemia, and 1 was a sensor/catheter or introducer needle fracture and retained in situ (characterized as other). Pediatrics (COHORT B): There were 110 AEs in the ITT pediatric Cohort B population. There was a similar amount of mild and moderate AEs (53 mild, 52 moderate, and 5 severe). There were 4 DKA events and 3 hypoglycemia events reported. There were 15 device-related AEs, the majority of which were insertion site AEs, with the remaining categorized as "other". There were no reports of serious unanticipated adverse device effects in any cohort and no reports of deaths in any pediatric cohort.
Final Effect Findings	The primary endpoint was based on Cohort A and met. A modified statistical methodology from the approved protocol was used for this evaluation. All secondary endpoint analyses were exploratory and not adjusted for multiple hypothesis tests. Cohort A Adults: The Hypo event rate over a 6-month period decreased by 62% (95% CI: 22%, 81%) from 0.081 in the SMBG period to 0.031 in the CGM period. CGM was shown to be noninferior to SMBG (p-value = 0.0018). The percentage of adult participants with at least one Hypo event decreased from 5.6% in the SMBG period to 2.3% in the CGM period, and the percentage of participants with at least one DKA event decreased from 0.4% in the SMBG period to 0.0% in the CGM period. Cohort A Pediatrics: The Hypo event rate decreased by 53% (95% CI: 12%, 75%) from 0.076 in the 6-month SMBG period to 0.036 in the 6 month CGM period. CGM was shown to be non-inferior to SMBG (p value = 0.004). The percentage of Cohort A pediatric participants with at least one Hypo event decreased from 5.4% in the SMBG period to 3.1% in the CGM period, though the percentage of participants with at least one DKA event increased from 4.5% in the SMBG period to 5.4% in the CGM period. Cohort B Pediatrics: There was no 6-month SMBG wear period, so the comparison of the CGM period to the Initial visit may not be representative of the difference between SMBG and CGM use. The change in rates (CGM period minus Initial visit) is reported. The Hypo event rates were similar in the two periods (Initial visit = 0.000 and CGM = 0.006), with just one additional Hypo event in the CGM period. The percentages of participants with at least one Hypo event based on recall and in the CGM period were similar as well (Initial visit = 0.0% and CGM = 0.6%). However, the DKA rate decreased by 95% from 0.342 at the Initial visit to 0.019 with CGM. Further, the percentage of participants with at least one DKA event decreased from 34.2% to 1.9%.
Study Strengths & Weaknesses	Strengths: This post-approval study to evaluate the non-adjunctive use of Dexcom G5, G6, or G7 continuous glucose monitoring systems (CGM) included CGM-naïve pediatric and adult users and had a control phase (Cohort A with SMBG for diabetes management). The average number of hypoglycemia events per participant over a 6-month period was decreased in the CGM period compared to the preceding SMBG control period, and noninferiority of CGM to SMBG was demonstrated in adults and pediatric subjects in Cohort A. The post-approval study confirms that the Dexcom G5 CGM is safe for non-adjunctive use in CGM-naïve users. Weaknesses: The study did not meet its sample size requirement for the primary endpoint evaluation despite multiple efforts from the sponsor to increase enrollment. This was due to, at least in part, the protocol changes to remove the SMBG phase in Cohort B to address the pediatric enrollment challenges. However, available data from this post-approval study support safety of the Dexcom G5 CGM when used as intended.
Recommendations for Labeling Changes	Results of the post-approval study do not change the benefits and risks conclusions of the original PMA approval. Additionally, the PMA device (Dexcom G5 CGM) is no longer being marketed. Therefore, labeling changes are not recommended.
General
Study Status	Completed
Application Number / Requirement Number	P050006 S071/ PAS001
Date Original Protocol Accepted	05/28/2019
Date Current Protocol Accepted	12/18/2020
Study Name	Continued F/u of the ASSURED Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To characterize the clinical outcomes annually through 3 years post-procedure of all living subjects who were enrolled during the IDE pivotal and continued-access phases of the ASSURED study.
Study Population	All living subjects who were enrolled during the pivotal and continued-access phases of the ASSURED study.
Sample Size	All living subjects who were enrolled during the pivotal and continued-access phases of the ASSURED study.
Key Study Endpoints	Closure Success Composite Clinical Success, including: 1) Technical Success, 2) Safety Success 3) Closure Success Freedom from serious adverse events Freedom from device events (embolization, device removal, or other device intervention) • Clinically Significant New Arrhythmia
Follow-up Visits and Length of Follow-up	Total of 3 years post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	613
Actual Number of Sites Enrolled	22
Patient Follow-up Rate	1m – 98.4% 6m – 96.4% 12m – 94.6% 24m – 90.4% 36m – 77.7%
Final Safety Findings	379 subjects (61.8%) reported 1 MedDRA-coded AE; a total 52 subjects reported 82 SAEs; 31 SAEs were device-related, 7 SAEs were procedure-related; 26 subjects reported SAE within 30 days of index procedure.
Final Effect Findings	516 of the 566 subjects with technical success completed 6-month clinical residual defect check, and 1000% (516/516) achieved 6-month clinical closure success. 503 of the 577 subjects evaluated for 6-month composite clinical success achieved composited clinical success (87.2%); 74 (12.8%) experienced clinical failure at 6-month post procedure. Technical and procedure success rates were both 92.3%.
Study Strengths & Weaknesses	Study strengths: Additional enrollment into the Continued Access cohort and long-term follow-up through 3 years post-procedure. Weaknesses: The rate for the 36-month fluoroscopy follow-up was low at only 33.4%
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P150033 S061/ PAS001
Date Original Protocol Accepted	01/15/2020
Date Current Protocol Accepted	07/30/2020
Study Name	Micra AV Post Approval Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Micra AV PAS is a non-interventional observational study conducted within Medtronic’s Product Surveillance Registry (PSR) platform. Following consent and implant, patients will be followed per their center’s standard of care for a minimum of three years. As this study is designed to capture the real-world performance of the Micra AV system there are no device programming requirements. Primary Objective: To characterize the rate of pacemaker syndrome resulting in a system revision at 3- years post-implant. Secondary Objective #1: To estimate the acute major complication rate related to the Micra AV system and/or procedure. Secondary Objective #2: To estimate the 3-year major complication rate related to the Micra AV system and/or procedure. Ancillary Objectives: To characterize the rate and severity of adverse events potentially related to AV synchrony loss Summarize Micra AV system or procedure related adverse events Characterize the implant procedure Characterize electrical performance over time Characterize A4 amplitude over time Summarize quality of life as measured by the SF-36 v2 Standard and EQ-5D-5L questionnaires.
Study Population	All patients who have successful implant of the Micra AV System will be included in the analysis of the primary objective and secondary objective #2. All patients who have an implant attempt will be included in the analysis of secondary objective #1. Any patient with a qualifying adverse event related to the Micra AV will be included in the analysis of the AV synchrony loss ancillary objective.
Sample Size	Primary Objective: For the primary objective, the goal is to size the study to estimate the pacemaker syndrome rate meeting the primary endpoint within a desired precision of at least 1.5% (distance from point estimate to the upper two-sided 95% confidence interval less than or equal to 1.5%). Table 1 displays the relationship between the assumed pacemaker syndrome rate requiring system revision and the estimated rate of precision for a sample size of 750 patients. As an example, if the true rate of pacemaker syndrome events requiring a pacing system upgrade is 2.0% at 3-years then a sample size of 750 patients will estimate the rate of this event within 1.5% with near certainty based on the following assumptions: At least 750 patients will undergo an implant attempt with a Micra AV system. Two thirds of pacemaker syndrome events requiring a pacemaker system upgrade will occur within 12-months of the implant attempt Mortality rate not associated with major complications is 12% at 3-years (based on the mortality rate observed in 2667 dual chamber pacemaker patients from 6 prior Medtronic studies). Premature exit rate for reasons other than death is 3% per year. Premature exit and mortality not associated with pacemaker syndrome status are independent. Event rate at 3-years computed using Kaplan-Meier methods Table 1: Relationship Between Confidence Interval Width and Pacemaker Syndrome Requiring System Revision Rate at 3-Years Post-Implant for Sample Size of 750 Assumed Endpoint Rate at 3 Years Subjects Followed for 36-Months (95% MCCI) Observed Event Rate at 36-Months (95% MCCI) Median Upper Confidence Boundary Percentage of Simulations where Distance to Upper CI <1.5% 0.5% 602 (584 – 619) 0.5% (0.1% - 0.9%) 1.0% >99.9% 1% 601 (582 – 618) 1.0% (0.4% - 1.7%) 1.8% >99.9% 2% 601 (584 – 619) 1.9% (1.2% - 2.9%) 3.0% >99.9% 3% 602 (583 – 620) 3.0% (1.9% - 4.0%) 4.2% 98.3% Notes: Results based on 1000 simulated studies using based on assumptions described above. R Program: H:\DocumentReviews\MicraAV\PostMarketScenarios\PAS\simulationMicraAVsingleArmStudy.R Secondary Objective #1 For secondary objective #1, a final sample size of N = 750 patients with a Micra AV system implant attempt allows for an estimated 3% overall acute major complication rate with an expected precision (distance from upper two-sided 95% confidence interval to point estimate) of approximately 1.6%. Individual acute major complication rate occurring at a rate of 1.0% will be estimated with a precision of approximately 1.1%. Secondary Objective #2 For secondary objective #2, a sample size of N = 750 will enable estimation of the 3-year post-implant complication rate within 2.0%, with a probability around 99%, based on assumptions identical to those of the primary objective (listed above). It is known that the Micra AV system has the same implant procedure and form factor as the predicate VR system, so it is assumed the long-term safety profile of the Micra AV system will be similar. It is also assumed that most Micra AV patients will have atrioventricular (AV) block with normal sinus function and may be more susceptible to pacemaker syndrome during periods of low AV synchrony. The MARVEL 2 clinical study (IDE #G180277) shows Micra AV may have an elevated risk for major complications through 3-year post implant, relative to Micra-VR, due to pacing intolerance. The risk for major complications through 3-year post-implant associated with the Micra VR system suggests the rate of major complications at 3-year post implant for the Micra AV system may be 6.0%. Ancillary Objectives For the ancillary objectives, a sample size of 750 enrolled patients with an attempted Micra AV system implant provides sufficient precision in which to estimate the event rates associated with the primary and secondary objectives. For the quality of life assessment, it is anticipated 350 patients wil par
Key Study Endpoints	Main Effectiveness and Safety Endpoints: The primary objective is to characterize the rate of pacemaker syndrome resulting in a system revision at 3-years post-implant. Pacemaker syndrome resulting in system revision is defined as a Micra AV system revision where the investigator indicates the reason for system revision is pacemaker syndrome and the Micra AV system is replaced with a new or upgraded dual chamber pacemaker system. This includes revisions where the Micra AV device is abandoned electrically (i.e. programmed to OOO on a permanent basis) and replaced with a new or upgraded dual chamber pacemaker. Additionally, for a pacemaker syndrome event to meet the primary endpoint it must occur within 3-years (1095 days) of the Micra AV implant procedure. Secondary Endpoint #1: Secondary objective #1 is to estimate the acute major complication rate related to the Micra AV system and/or procedure. For an adverse event to meet the endpoint, the event must have occurred within 30 days (inclusive) of a Micra AV system implant attempt and be adjudicated by the Clinical Events Committee (CEC) as being a major complication related to the Micra AV system and/or procedure. Major complications are complications that result in one or more of the following: Death Permanent loss of device function due to mechanical or electrical dysfunction of the device (e.g. pacing function disabled, leaving device abandoned electrically) Hospitalization Prolonged hospitalization by at least 48 hours System revision (reposition, replacement [including replacement with any transvenous pacing system], or explant) Secondary Endpoint #2: Secondary objective #2 is to estimate the 3-year major complication rate related to the Micra AV system and/or procedure. For an adverse event to meet the endpoint, the event must have occurred within 3-years (1095 days) of a Micra AV system implant attempt and be adjudicated by the Clinical Events Committee (CEC) as being a major complication related to the Micra AV system and/or procedure.
Follow-up Visits and Length of Follow-up	3 years (1095 days).
Interim or Final Data Summary
Interim Results	Safety Results As of the visit cutoff date, 123 adverse events have been reported which occurred on or after a Micra AV implant attempt in 107 patients. There were 123 events requiring CEC adjudication of which 119 (96.7%) had been adjudicated by the CEC. Of the 119 adjudicated events, 105 were considered related to the Micra system or procedure and 14 were considered not related. Of the 105 related events, 40 (in 38 patients) were classified as Micra System-related and/or procedure-related complications by the CEC (Table 28). Most common were cardiac tamponade (6) and post procedural hematoma (3). Of the 40 Micra AV system or procedure related complications, 28 in 26 patients occurred within 30 days of the implant procedure. There have been 115 study exits, none of which were due to system explants. As of the visit cutoff, there have been 154 patient deaths reported. Of these 154 deaths, 89 did not require CEC adjudication, 63 have been adjudicated by the CEC and 2 are pending CEC adjudication. The CEC classified 1 of the 63 adjudicated deaths as being related to the Micra AV system or procedure and 0 deaths as having an unknown relatedness. The related death occurred in an 83-year-old female with a prior CRT-P. The death was associated with cardiogenic shock 6 days post implant attempt which followed a surgical intervention to repair an RV laceration which occurred during the procedure. This death was reported previously and there have been no new deaths related to the Micra AV system or procedure. Effectiveness Results: Of the 796 patients with a successful Micra AV implant, 756 pacing capture threshold data available at implant.
Actual Number of Patients Enrolled	There are 801 patients enrolled (796 patients successfully implanted)
Actual Number of Sites Enrolled	There are 97 study centers enrolled as of the cutoff date.
Patient Follow-up Rate	Year 1 (6-18 months): 644/694 = 92.8% Year 2 (18-30 months): 549/612 = 89.7% Year 3 (30-42 months): 257/272 = 94.5% Year 4 (42-54 months): 39/39 = 100%
Final Effect Findings	The pacing capture thresholds for patients were reported.
General
Study Status	Completed
Application Number / Requirement Number	P120007 / PAS001
Date Original Protocol Accepted	10/12/2012
Date Current Protocol Accepted	10/12/2012
Study Name	HPVGTS-US-10-002
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	10,545
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	96.76%
Final Safety Findings	No issues concerning the safety of the APTIMA HPV GT Assay on either TIGRIS or PANTHER platform were reported by the sponsor or identified by the reviewer.
Final Effect Findings	The absolute risk of cervical disease is greater in subjects with positive APTIMA HPV GT Assay results than in subjects with negative APTIMA HPV GT Assay results.
Study Strengths & Weaknesses	This study was able to demonstrate that the APTIMA HPV GT assay¿s postmarket performance is characterized by relatively high sensitivity and specificity, especially for identifying women who have higher risk of developing high-grade and invasive cervical cancer. However, this study had a limited ability to stratify women with low-grade lesions. In addition, the study did not address the relevance of HPV positivity in the absence of cytological abnormalities which would require de novo data collection with a longer follow-up
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P120009 / PAS001
Date Original Protocol Accepted	08/16/2013
Date Current Protocol Accepted	12/16/2016
Study Name	Nit-Occlud PDA PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a controlled, prospective, single-arm, multi-center (up to 20 sites) study. Enrolled subjects will be followed at 2, 12, and 24 months (2 years) post implant.
Study Population	Patients age 6 months to 21 years weighing > 5kg with an angiographically confirmed PDA with a minimum diameter < 4 mm.
Sample Size	A total of 180 subjects will be enrolled to ensure 150 subjects treated with the device will be available at 24 months post-procedure.
Key Study Endpoints	The primary safety endpoint is the serious device and/or procedure related adverse event rate at 60 months post-procedure. The primary effectiveness endpoint is the rate of complete closure of the ductus arteriosus as assessed by absence of residual flow at 5 years follow-up by by transthoracic echocardiogram with 2-D color of color flow mapping and pulse wave Doppler (ECHO).
Follow-up Visits and Length of Follow-up	5 years Clinical assessments at 2, 12, 24, 36, 48, and 60 months Echocardiography at 2, 12, 36, and 60 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	The study enrolled a total of 184 subjects from 11 study sites, 180 subjects were implanted with the device.
Actual Number of Sites Enrolled	The study enrolled a total of 184 subjects from 11 study sites, 180 subjects were implanted with the device.
Patient Follow-up Rate	155/163 (95.1%) completed the 24-month visit 9/9 (100%) completed the 36-month visit per protocol 8/8 (100%) completed the 48-month visit per protocol 6/6 (100%) completed the 60-month visit per protocol
Final Safety Findings	The primary safety endpoint was to demonstrate the 24-month serious device-related adverse event rate was no worse than the objective performance criterion (OPC) of 1%. The secondary safety endpoint was to demonstrate that the rate of device-related adverse events reported through 24 months post procedure was no worse than 6% (OPC rate of 3% plus an added 3% margin). A total of 130 adverse events were reported. Of those, 18 were either adjudicated as serious by the CEC (n=17) or categorized as serious by the investigator (n=1). Of the 18 SAEs, 2 were adjudicated as device-related. Additionally, six (6) device-related AEs were reported. Two (2) late-onset AEs were reported to occur >12 months post-procedure and adjudicated as device-related by the CEC. All other device- or procedure-related events occurred within one day of the implant procedure. For the primary safety endpoint, there were 2 serious device related adverse events reported through 24 months post implant attempt such events, yielding an event rate of 1.1%. The 2-sided 95% CI is 0.13% to 3.9% and the one-sided CI upper bound = 3.4%. For the secondary safety endpoint, there were 6 device related AEs in leass than 1 year post-procedure, yielding an event rate of 3.3% and a one-sided CI upper bound of 6.5%.
Final Effect Findings	The primary effectiveness endpoint was to demonstrate the 12-month complete closure rate for the device was no worse than the OPC of 85%. The primary effectiveness endpoint was calculated as the proportion of subjects with complete closure of the PDA as assessed by absence of residual flow at the Month 12 follow-up visit. The core lab reports 97.5% (157/161) of subjects had no (n=152) or trivial (n=5) residual leak at Month 12. The binomial confidence interval around this rate is 93.8% to 99.3%.
Study Strengths & Weaknesses	A strength of this study is that it evaluates the continued safety and effectiveness of the device in the post-approval phase. A weakness of this study is that it is a single-arm (non-randomized) study.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and effectiveness results from these studies.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P120010 / PAS001
Date Original Protocol Accepted	09/26/2013
Date Current Protocol Accepted	10/11/2017
Study Name	PAS of TS Feat. w Sensor-Augment Pump Sys
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A longitudinal, multi-center study to observe the Threshold Suspend (TS) feature with a sensor-augmented insulin pump in patients 16 and older with insulin-requiring diabetes. The study will measure the change in A1C from baseline over a period of one year while subjects are wearing the Medtronic MiniMed® 530G insulin pump.
Study Population	Adult (16 years and older) US subjects that meet the inclusion/exclusion criteria. Subjects will be grouped by baseline demographics: age, ethnicity, race, body mass index (BMI), gender, diabetes classification, duration of diabetes, and hypoglycemia awareness. Inclusion Criteria: 1. Subject is aged 16 or older at time of screening. 2. Subject has been diagnosed with diabetes mellitus for at least one year prior to screening. 3. Subject is currently on pump therapy. 4. Subject is transitioning to the 530G insulin pump system with the TS feature turned ON. 4. Subject is willing to complete all study related activities. 5. Subject is willing to upload data every 21 days from the study pump. 6. Subject must have Internet access and access to a computer system that meets the requirements for uploading the pumps. This may include use of family or friend¿s computer system with Internet access. 7. Subject is able (by insurance or financial means) to cover the initial investment and ongoing cost of the 530G insulin pump and consumables, CGM, Bayer CONTOUR Next Link RF enabled meter and supplies for the length of the study- 1 year. Exclusion Criteria: 1. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study devices in the last 2 weeks. 2. Subject is a woman of child-bearing potential who has a positive pregnancy test at screening or plans to become pregnant during the course of the study 3. Subject is being treated for hyperthyroidism at time of screening 4. Subject has an abnormality (>1.8mg/dL) in creatinine at time of screening visit 5. Subject has an abnormality (out of reference range) in thyroid- stimulating hormone (TSH) at time of screening visit. If TSH is out of range, Free T3 and Free T4 will be tested. Subject may be included with TSH out of range as long as Free T3 and Free T4 are in normal reference range. 6. Subject has taken any oral, injectable, or IV steroids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV steroids during the course of the study 7. Subject is currently abusing illicit drugs 8. Subject is currently abusing prescription drugs 9. Subject is currently abusing alcohol 10. Subject has sickle cell disease or hemoglobinopathy 11. Subject has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening or plans to receive red blood cell transfusion or erythropoietin over the course of study participation 12. Subject diagnosed with current eating disorder such as anorexia or bulimia 13. Subject has been diagnosed with chronic kidney disease that results in chronic anemia 14. Subject is on dialysis
Sample Size	Investigational centers (50 sites) will be activated across the United States. Up to 1,200 subjects will be enrolled so that there will be 1,000 subjects who are eligible to participate in the study . The 1000 subject sample size was calculated based on an overall consideration of the primary hypothesis, drop-out rate (20%), compliant rate (65%), and ability to detect serious adverse events (14.5%).
Key Study Endpoints	Primary endpoint: The overall mean change in A1C from baseline will be estimated and compared by a non-inferiority test with an A1C margin of 0.4% and a significance level of 0.025 (one-sided). Secondary endpoint: The mean change in A1C from baseline to end of study for each individual A1C cohort (i.e. less than 7.0%, 7.0-9.0%, greater than 9.0%). Safety endpoints: Serious Adverse Events (SAE), Unanticipated Device Effects (UADE), Incidence of Severe Hypoglycemia, Incidence of Severe Hyperglycemia, Incidence of Diabetic Ketoacidosis (DKA), Adverse Events will be stratified by age, ethnicity, race, baseline BMI, gender, diabetes classification, duration of diabetes, hypoglycemiac unawareness, questionnaire, frequency and average duration of hypoglycemic event (based on two weeks prior to the adverse event) Descriptive endpoints: Descriptive summary statistics will be provided for A1C Change, Hypo/Hyperglycemia Events and TS Metrics, Device Utilization, CGM Metric, Device Performance, Effectiveness of educational materials, Descriptive subgroup analysis of A1C data will be performed on demographic cohorts.
Follow-up Visits and Length of Follow-up	12 months There will be a total of 6 visits (Enrollment visit 0, Baseline visit 1 ¿ screening, visit 2 ¿ Day 90, visit 3 ¿ day 180, visit 4 ¿ day 270, visit 5 ¿ day 365).
General
Study Status	Completed
Application Number / Requirement Number	P120010 / PAS002
Date Original Protocol Accepted	10/11/2017
Date Current Protocol Accepted
Study Name	PAS of TS Feat w/sensor-aug w/comm data
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to demonstrate that home use of the Medtronic MiniMed 530G System with utilization of the Threshold Suspend feature is not associated with glycemic deterioration. The objective will be demonstrated using two substudies. Substudy 1: Multi Center Trial This prospective, multi center, new enrollment study will compare measured baseline HbA1c to end of study (12 months) HbA1c, and will also summarize adverse events and provide results broken down by patient characteristics of interest. Substudy 2: Commercial Data Evaluation This retrospective cohort study of a real world data set will evaluate data from a subcohort of the CareLink commercial database of MiniMed 530G users to verify that use of the MiniMed 530G System is not associated with glycemic deterioration over time.
Study Population	Substudy 1: Subjects aged 16 or older currently diagnosed with diabetes mellitus and having required insulin for over a period of one year. Substudy 2: Subjects from the CareLink data set who have all of the following: demographic information, been followed through the Outreach program for at least one year, have two self reported HbA1c values at least 30 days apart, have uploaded device data via CareLink, and do not overlap with the new enrollment study cohort.
Sample Size	Substudy 1: A total of 426 subjects have been enrolled. A total of 100 subjects is needed to test the hypothesis for this substudy. Substudy 2: A total of 1402 subjects fit the inclusion criteria for the CareLink commercial analysis cohort. A sample size of 200 subjects is needed to test each prespecified hypothesis for this substudy.
Key Study Endpoints	Substudy 1: Primary Endpoint: Overall mean change in HbA1c from baseline to 12 month follow-up. Secondary Endpoint: Overall mean change in HbA1c from baseline to 12 month follow-up stratified by baseline HbA1c measurement (less than 7 percent, 7 to 9 percent, greater than 9 percent). Safety Endpoints: Serious Adverse events, Unanticipated Adverse Device Effects, Incidence of Severe Hypoglycemia, Incidence of Severe Hyperglycemia, Incidence of Diabetic Ketoacidosis. Substudy 2: Primary Endpoint: The difference between self reported first HbA1c and subsequent HbA1c. Effectiveness Endpoints: 1. The difference in time spent with sensor glucose level less than 70 mg per dL with the Threshold Suspend Feature ON versus with the Threshold Suspend Feature OFF. 2. The difference in time spent with sensor glucose level greater than 180 mg per dL with the Threshold Suspend Feature ON versus with the Threshold Suspend Feature OFF. Secondary Endpoints will include: reporting of adverse events collected through Medtronic’s Outreach program, stratifications of the primary and effectiveness endpoints by baseline patient characteristics, and other descriptive endpoints related to subjects’ utilization of the Threshold Suspend Feature and subjects’ adherence to CGM and adjunctive fingerstick glucose readings.
Follow-up Visits and Length of Follow-up	Substudy 1: Follow-up will be 12 months. Substudy 2: Follow-up was up to one year.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Multi-Center Study (Sub-study 1) – Approximately 82 percent of subjects who enrolled and were eligible to participate in this study completed the study. Commercial Data Study (Sub-study 2) – 1316 device users were identified in the CareLink database that fit the criteria for analysis.
Actual Number of Sites Enrolled	Multi-Center Study (Sub-study 1) – Approximately 82 percent of subjects who enrolled and were eligible to participate in this study completed the study. Commercial Data Study (Sub-study 2) – Not Applicable.
Patient Follow-up Rate	Multi-Center Study (Sub-study 1) – Approximately 82 percent of subjects who enrolled and were eligible to participate in this study completed the study. Commercial Data Study (Sub-study 2) – Not applicable.
Final Safety Findings	Multi-Center Study (Sub-study 1) – Three subjects died during the study, but their deaths were not attributable to the device. There were 79 Adverse Events or Serious Adverse Events reported during this study, four of the 27 Serious Adverse Events were device related. There were no Serious Unanticipated Adverse Events. Seven occurrences of severe hypoglycemia were reported. Fourteen severe hyperglycemia events were reported, and six diabetic ketoacidosis events were reported. Commercial Data Study (Sub-study 2)—Not applicable.
Final Effect Findings	Multi-Center Study (Sub-study 1) – The use of the MiniMed 530G System with the Threshold Suspend Feature was not associated with glycemic deterioration greater than 0.4 percent over a 12 month period in this study group. When stratified by baseline HbA1c, only the group of subjects who had HbA1c’s less than seven percent had a mean increase in HbA1c at 12 months. Commercial Data Study (Sub-study 2) – The difference between (self-reported) HbA1c before MiniMed 530G use and follow-up (measured at least 30 days after start of first HbA1c) was reported as a decrease of 1.36 percent. Time spent in hypoglycemia or hyperglycemia (as determined by number of sensor readings) was lower with the Threshold Suspend feature On compared to Off in this cohort.
Study Strengths & Weaknesses	This multi-part study provided evidence from a variety of sources (new enrollment and long-term follow-up, retrospective analysis of a commercial data set, and systematic literature review) that overall the use of the MiniMed 530G system with the Threshold Suspend feature activated is not associated with deterioration in glycemic control. Multi-Center Study (Sub-study 1) – This study provided the first long-term (one year) safety and effectiveness results for a cohort of subjects utilizing a sensor augmented pump for management of diabetes. The follow-up rate in this analytical study was high enough to allow the hypothesis to be assessed without worry of substantial bias. The hypothesis-driven primary endpoint of the study was met and provided evidence that use of the Threshold Suspend feature does not result in glycemic deterioration. Additionally, the sponsor collected and reported detailed information on adverse events and device issues during the study duration. Lower than expected enrollment numbers forced a reduction in some of the aims of this study. Therefore, not all of the initially intended descriptive subgroup analyses were possible or meaningful. Commercial Data Study (Sub-study 2) – This real world data set allowed for analyses to be conducted on a relatively large sample (n=1316) of MiniMed 530G users. The basic patient demographics (age and gender) were similar between this data set and the multi-center study. While the initial HbA1c entered by the user into the CareLink database was self-reported, all the users in this analysis had a subsequent HbA1c collected and reported through CareLink through Medtronic’s “StartRight” program. This data set was not designed to address the safety and effectiveness questions outlined in the conditions of approval for this device. Follow-up of users through CareLink was not mandated by a study protocol prior to the collection of this commercial data, and detailed information on adverse events was not conducted through this database. Therefore, this data was not used to address questions regarding adverse events.
Recommendations for Labeling Changes	Yes, the sponsor should update the labeling to reflect Final Post Approval Study Results.
General
Study Status	Ongoing
Application Number / Requirement Number	P090029 S006/ PAS001
Date Original Protocol Accepted	12/15/2016
Date Current Protocol Accepted
Study Name	Device Failure and Complaint Analysis
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Surveillance study
Study Population	Patients diagnosed with degenerative disc disease at one or two levels in the cervical spine from C3 to C7 and implanted with Prestige LP
Key Study Endpoints	The main study end-point is assessment of device retrievals from collected explants. Additional Study endpoints are as follows: Complaint and MDR review Collection of surgeon notes/descriptions of revision surgery Analysis and histology of any adjacent or periprosthetic tissue collected
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Wear patterns consistent across retrievals conducted
Actual Number of Sites Enrolled	Explants collected from all investigational and commercial sites.
Study Strengths & Weaknesses	Study is limited by voluntary participation. Relatively few tissue collected due to consent issues. Direct analysis offers clear long term analysis of failed devices.
General
Study Status	Ongoing
Application Number / Requirement Number	P120021 / PAS001
Date Original Protocol Accepted	09/22/2017
Date Current Protocol Accepted	05/23/2019
Study Name	Amplatzer PFO Occluder New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single arm, multi-center, prospective, new enrollment study. The objectives of this study are the following: (1) To demonstrate safety of the AMPLATZER PFO Occluder by assessing the short-term (30-day) rate of device- or procedure-related serious adverse events (including those that led to death) (2) To demonstrate that the AMPLATZER PFO Occluder is effective by assessing the rate of recurrent ischemic stroke through 5 years (3) To demonstrate effectiveness of the training program for new operators
Study Population	Patients over the age of 18 years and less than 60 years who have experienced a cryptogenic stroke diagnosed by a neurologist in the 547 days prior to consent and have a patent foramen ovale diagnosed by transesophageal echocardiogram.
Sample Size	The overall sample size for this trial is 1214 subjects, which is driven by the primary effectiveness endpoint. The overall sample size accounts for 25% attrition over 5 years. To ensure that enrollment is balanced across sites, no investigational site will be allowed to enroll more than 20% of the maximum sample size (242 subjects). The sample size is estimated to have adequate power to test the primary effectiveness endpoint. The assumed primary effectiveness endpoint event rate is 2.2% and the performance goal is 3.9%. Using a one-sided 2.5% significance level, 910 subjects are required to have 80% power to reject the null hypothesis with the exact binomial method. Assuming 25% attrition over 5 years, a total of 1214 subjects is required. The sample size is estimated to have adequate power to test the primary safety endpoint. The assumed primary safety endpoint event rate is 2.07% and the performance goal is 4.14%. Using a one- sided 2.5% significance level, 653 subjects are required to obtain 80% power to reject the null hypothesis with the exact binomial method. Due to the acute nature of this endpoint, no attrition is assumed.
Key Study Endpoints	Primary Safety: Device- or procedure-related serious adverse events (as adjudicated by a Clinical Events Committee) through 30 days, including: Atrial Fibrillation Pulmonary Embolism Deep Vein Thrombosis Device Thrombus Device Erosion Device Embolization Ischemic stroke if subject was not successfully implanted with a device Hemorrhagic Stroke Major Bleeding requiring transfusion, or surgical or endovascular intervention Vascular Access Site Complication requiring surgical intervention Device- or Procedure-Related Serious Adverse Event leading to death Primary Effectiveness: 5-year rate of recurrent ischemic stroke Ischemic stroke is defined as acute focal neurological deficit presumed to be due to focal ischemia, and either 1) symptoms persisting 24 hours or greater, or 2) symptoms persisting less than 24 hours but associated with MR or CT findings of a new, neuroanatomically relevant, cerebral infarct. Descriptive Endpoints: Rate of stroke of unknown cause (determined by ASCOD adjudication) through each annual follow-up Rate of Transient Ischemic Attack (TIA)1 through each annual follow-up Rate of atrial fibrillation through each annual follow-up Rate of pulmonary embolism through each annual follow-up – the rate will be descriptively compared to the rates observed in the randomized groups in the RESPECT investigational device exemption (IDE) trial Rate of deep vein thrombosis through each annual follow-up – the rate will be descriptively compared to the rate observed in the randomized groups in the RESPECT IDE trial Rate of venous thromboembolism events (DVT or PE) through each annual follow-up – the rate will be descriptively compared to the rate observed in the randomized groups in the RESPECT IDE trial Rate of device thrombus through each annual follow-up Rate of device erosion through each annual follow-up Rate of device embolization through each annual follow-up Rate of ischemic stroke through each annual follow-up Rate of hemorrhagic stroke through each annual follow-up Rate of atrial flutter through each annual follow-up Rate of paroxysmal supraventricular tachycardia requiring treatment through each annual follow-up Antithrombotic medication (single antiplatelet, dual antiplatelet, warfarin, novel oral anticoagulant, other) use at each follow-up SF-12 quality of life physical and mental component score at baseline, 1 month, 6 months and 1 year Health state utility values from EQ-5D at baseline, 1 month, 6 months and 1 year Effective closure – Grade 0 or 1 maximal shunt through the PFO at rest and/or Valsalva as assessed by transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE) at 1 year Complete closure – Grade 0 maximal shunt through the PFO at rest and/or Valsalva as assessed by TTE or TEE at 1 year Technical success – Successful delivery and release of the AMPLATZER PFO Occluder for subjects in whom the delivery system entered the body Procedural success – Successful implantation of the AMPLATZER PFO Occluder with no reported in-hospital serious adverse events (SAEs) for subjects in whom the delivery system entered the body Training effectiveness - will be summarized by reporting the procedure-related SAE rate for new operators
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years post implant.
Interim or Final Data Summary
Interim Results	Primary Safety Endpoint: The Safety hypothesis will be assessed once all eligible subjects have met 30-day follow-up. As of this report, 34 subjects have had 35 Serious Adverse Events (29 atrial fibrillation, 3 deep vein thrombosis, 1 vascular hematoma, 1 vascular access site complication and 1 device thrombosis) that counts towards the primary safety endpoint. Serious Adverse Events: 185 events have been reported as Serious Adverse Events, 67 of these were adjudicated as device related. The device-related events were arrhythmia (n=2), atrial fibrillation (n=30), atrial flutter (n=5), chest pain – non cardiac (n=1), endocarditis (n=1), chest pain/discomfort (n=1), device embolization (n=1), ischemic stroke (n=3), migraine (n=2), paroxysmal supraventricular tachycardia (n=1), pulmonary embolism (n=3), Reintervention for Residual Shunt/device Removal (n=2), thrombus on device (n=3), and transient ischemic attack (n=5) and one sepsis event. Primary Effectiveness Endpoint: The Effectiveness hypothesis will be assessed once all eligible subjects have completed 5-year follow-up. As of this report, 19 events have been adjudicated as an Ischemic Stroke. These events will count towards the primary effectiveness. endpoint.
Actual Number of Patients Enrolled	1159
Actual Number of Sites Enrolled	96
Patient Follow-up Rate	Subject follow-up is ongoing. The reported follow-up rate is currently 96% at the 1-month study visit, 86% at the 6-month study visit, 84% at the 12-month study visit, 80% at the 24-month visit, 75% at the 36-month visit, and 67% at the 48-month visit and 55% at the 60 month visit.
General
Study Status	Completed
Application Number / Requirement Number	P050052 S049/ PAS001
Date Original Protocol Accepted	09/02/2015
Date Current Protocol Accepted	04/26/2017
Study Name	Radiesse Radiological Evaluation Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a 2-year, prospective, open-label, new enrollment PAS evaluating the radiographic appearance of Radiesse implantation in the dorsum of the hands.
Study Population	Adults who are at least 22 years old with hands rated as MHGS 2, 3, or 4 at baseline. There is no comparison group in this study.
Sample Size	Twenty subjects (10 subjects with MHGS 4 and 10 subjects with MHGS 2 or 3) will be enrolled at 1 site in the U.S. The sample size is not based on power calculations for a formal statistical hypothesis test, but rather is based on a clinically relevant sample of subjects that will provide a degree of characterization regarding the ability to perform radiologic evaluations after treatment with Radiesse.
Key Study Endpoints	The main study endpoint is the incidence of obscuration of the bones of the hand at 1-, 6-, 12-, and 24-months following injection of Radiesse in the dorsum of the hand. Other safety endpoints include: hand function testing and MHQ; incidence of device/injection-related severe AEs; and incidence of all AEs. Secondary effectiveness endpoints include MHGS ratings by a masked evaluator and subject-reported GAIS score.
Follow-up Visits and Length of Follow-up	2 years Follow-up in-clinic visits at months 1, 6, 12, 18, and 24. If repeat injections are administered at any of the 6-, 12-, or 18-month visits, subjects will receive a 72-hour phone call following each injection and return for follow-up visits 1 month post-injection at months 7, 13, and/or 19 respectively.
Interim or Final Data Summary
Actual Number of Patients Enrolled	20 subjects (40 hands)
Actual Number of Sites Enrolled	One
Patient Follow-up Rate	Over the course of the postoperative follow-up, 90% - 100% accountability was achieved at all scheduled visits through Month 24. Time Point Subjects Seen – Total [n (%)] Baseline X-Ray 20 (100%) Baseline Treatment 20 (100%) Month 1 X-Ray 20 (100%) Month 1 Visit 20 (100%) Month 6 X-Ray 20 (100%) Month 6 Follow-Up 20 (100%) Month 12 Follow-Up 20 (100%) Month 24 X-Ray* 6 (100.0%) Month 24 Follow-Up 20 (100.0%) (* Visit required only if subjects receive four treatments).
Final Safety Findings	As expected, over 80% of the subjects had foreign material (the Radiesse implant) present throughout 24 months of study period. Regarding the primary endpoint, no X-ray obscuring of bones were found at any of the evaluated time points. The most common treatment related AEs were “General disorders and administration site conditions” (the majority is swelling) and “Injury, poisoning and procedural complications”. Reported AEs are mostly mild or moderate in severity and did not last more than 30 days. Over the course of the study, 30% of the AEs were considered as possibly/definitely related to the treatment/device. There were two physician-reported severe AEs (administration site condition – swelling in both hands of one subject) to be related to the treatment. No death or serious AEs were reported and no subject withdrew due to an AE.
Final Effect Findings	Majority of subjects (80%) showed some improvements on GAIS from baseline to postoperative up to 24mon. The proportion of subjects with improvements is higher in group B (90%) than in group A (70%). The observed difference may be attributed to the age, and severity of loss of fatty tissue. Majority of subjects (65%) showed sustained improvements (>= 1point) on the scores MHGS from baseline to postoperative 24m. The proportion of subjects with improvements in group A is 80%, and in group B is 50%.
Study Strengths & Weaknesses	Strengths: The study findings provide information on the long-term safety and effectiveness (i.e. 24 months) of the device stratified by MHGS. The study is completed on time with an overall follow- up rate greater that 90%. Weakness: The study only enrolled one study site with 20 subjects (40 hands) by protocol. All enrolled subjects are females, with 95% of subjects being White Caucasian. Therefore, the study findings may not represent a diverse group of surgeons and diverse patient populations.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the 24-months long term results from the post-approval study. In addition, labeling change is recommended to report the adverse event profile by severity loss of fatty tissue (i.e. MHGS 2&3 vs. MHGS 4). The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow up visits etc.), results and study strengths and limitations.
General
Study Status	Terminated
Application Number / Requirement Number	P120023 / PAS002
Date Original Protocol Accepted	05/12/2016
Date Current Protocol Accepted	05/16/2017
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Post Approval Study (PAS) is comprised of 3 main elements: 1. Under KAMR-201-PRO1, the primary objective is to develop/adapt a patient reported outcomes (PRO) instrument that will assess KAMRA inlay-related visual symptoms and establish the content validity of that PRO instrument. This part of the study is a non-interventional, qualitative research, concept elicitation, cognitive debriefing interview study. 2. Under KAMR-202-PRO2, the primary objective is to assess the draft KAMRA Inlay Patient Questionnaire (KIPQ) for its ability to measure visual symptoms and its impact on subjects implanted with the KAMRA inlay. This part of the study is a psychometric validation of the draft KIPQ developed under the PRO1 study. 3. Under KAMR-203-PASQ the objectives are as follows: a. Evaluate the long-term performance (effectiveness) and safety of the device b. Evaluate the real-world performance of the device in subjects treated by refractive surgeons with a range of experience levels c. Evaluate the performance of the device in racial/ethnic subgroups representative of the population for which the device is indicated. This study is designed as an open-label, multicenter, prospective clinical study of at least 529 subjects from 20 to US sites implanted with the KAMRA inlay in the non-dominant eye.
Study Population	Phakic, presbyopic patients between 45 and 60 years of age with cycloplegic refractive spherical equivalent of +0.50 diopters to -0.75 diopters with less than or equal to 0.75 diopters of refractive cylinder, who do not require glasses or contact lenses for clear distance vision, and who require near correction of +1.00 to +2.50 diopters of reading add.
Sample Size	1. Under KAMR-201-PRO1, a total of 20-50 subjects implanted with the KAMRA inlay will be recruited from up to 5 sites for the study. Subjects will have a range of post-operative experience, satisfaction, visual symptoms, ages and educations. Non-Caucasian subjects will also be included. 2. Under KAMR-202-PRO2, a minimum of 105 subjects that have been enrolled under PASQ (new enrollment PAS) will be enrolled into this nested study, with approximately 15 subjects for each targeted population including Caucasian (Hispanic and Non- Hispanic), African American (Hispanic and Non-Hispanic), and Asian. 3. The second hypothesis (primary safety endpoint) would require 423 eyes. Considering a 20% dropout rate, a total of 529 eyes must be enrolled (from 30 to 50 US clinical sites). This sample size will be adequate to test the first hypothesis (only requiring 142 eyes) and assess the other endpoints.
Key Study Endpoints	The study endpoints are defined under KAMR -203-PASQ as follows: 1. Primary effectiveness endpoint: percentage of implanted eyes with monocular UCNVA of 20/40 or better at 5 years is ?75%. 2. Primary safety endpoint: fewer than 5% of eyes have persistent loss of two or more lines of BCDVA at 5 years after inlay implantation or 2 years after removal (whichever is longer). 3. Additional safety endpoints: a.Less than 1% of eyes that had BCDVA of 20/20 preoperatively may have BCDVA worse than 20/40 at 5 years. b.Cumulative incidence of ocular adverse events related to the device and associated with a functional vision loss of BCDVA worse than 20/40 at the time of adverse event should occur in no more than 10% of eyes; cumulative incidence of any single ocular adverse event related to the device and associated with a functional vision loss of BCDVA worse than 20/40 at the time of adverse event should occur in no more than 2.5% of eyes
Follow-up Visits and Length of Follow-up	KAMR-201-PRO1: 1 single visit, one 90-minute interview. KAMR-202-PRO2: follow-up is approximately 3.5 months, with total study duration of 9-12 months. KAMR-203-PASQ: five years (or 2 years after removal, whichever is longer).
General
Study Status	Completed
Application Number / Requirement Number	P120024 / PAS001
Date Original Protocol Accepted	06/11/2015
Date Current Protocol Accepted
Study Name	Post-Approval Clinical Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS is a continuation of the completed pivotal IDE study which was a prospective, randomized (2:1), single-masked, controlled, multi-center, non-inferiority clinical trial to evaluate the safety and effectiveness of the activL® Disc (investigational device) as compared to two different lumbar total disc replacement devices as a combined control group (Charité or ProDisc-L according to investigator preference) in treating single-level DDD of the lumbar spine (L4/L5, or L5/S1) that has been unresponsive to at least six months of conservative treatment.
Study Population	The IDE study population consisted of subjects with Degenerative Disc Disease (DDD) of the lumbar spine (L4-L5, or L5-S1) from the investigator?s practice who had failed to improve with conservative treatment for at least six months prior to enrollment. Subjects who presented for evaluation or treatment of lower back pain or leg pain were potential candidates for the study and were to be evaluated for inclusion based on the following inclusion/exclusion criteria. A screening form was completed for subjects evaluated. A subject was considered to be enrolled after signing the consent form and meeting all eligibility criteria. The PAS study population consists of the subjects treated during the IDE study. No new patients will be treated as part of this PAS.
Sample Size	The PAS sample size was calculated based on the formula of Farrington and Manning (Statistics in Medicine, 1990, 1447-1454). Calculations were performed in ADDPLAN, version 6. The following assumptions were used for the sample size calculations: ?s= 62% ??= 70% ? = 0.05 (one-sided type 1 error of 0.05) ? = 0.20 (80% power) ? = 15% 2:1 randomization ratio Note: Success rates were estimated for both treatment groups, based upon the observed 4 year data to date for the post-approval composite endpoint of individual subject success. Design Characteristic Solution Sample Size at 7 Years Total: 111 (activL®: 74; Control: 37) p-value required to pass NI at end of trial 0.05 Utilizing a delta of 10% as required by FDA, the sample size is as follows: ?s= 62% ??= 70% ? = 0.05 (one-sided type 1 error of 0.05) ? = 0.20 (80% power) ? = 10% 2:1 randomization ratio Note: Success rates are estimated for both treatment groups, based upon the observed 4 year data to date for the post-approval composite endpoint. Design Characteristic Solution Sample Size at 7 Years Total: 184 (activL®: 123; Control: 61) p-value required to pass NI at end of trial 0.05
Key Study Endpoints	PAS Primary Endpoint The primary study endpoint for the PAS is the same composite of effectiveness and safety measures for an individual subject (individual subject success) as was used in the IDE. Primary endpoint data will be evaluated annually; however the primary evaluation time point will be 7 years post-surgery: ?Improvement of at least 15 points in the ODI score at 7 years compared to baseline; ?Maintenance or improvement in neurological status at 7 years compared to baseline as measured by motor and sensory evaluations. A decrease of one grade in either evaluation will be considered a failure. ?Maintenance or improvement in motion at the index level, defined as: 7 year ROM ? preoperative ROM > 0 (with +2º measurement error applied) in a patient who does not meet the definition of fusion. ?No device failures requiring Subsequent Surgical Intervention (SSI) (e.g., revision, re-operation, removal, or supplemental fixation at the level of the original implant). ?Absence of serious device-related adverse events as adjudicated by the CEC. In addition, because the ROM success component of the primary endpoint was such a notable driver of the difference in overall success rates in favor of activL when comparing the two randomized treatment groups during the IDE, FDA will request an additional analysis of overall success without the ROM success component for the PAS as was done during the IDE. PAS Powered Secondary Endpoints ?Back Pain, measured at rest using a visual analog scale (VAS). A patient will be considered a responder if, at the 7 year visit, they achieve at least a 20 mm VAS improvement compared to baseline on a 100 mm VAS scale. ?Leg Pain, measured at rest using a visual analog scale (VAS). A patient will be considered a responder if, at the 7 year visit, they achieve at least a 20 mm VAS improvement compared to baseline in the leg with the maximum pain at baseline on a 100 mm VAS scale, with no worsening in the other leg. PAS Unpowered Secondary Endpoints ?The mean Oswestry Disability Index score, as well as the mean improvement, will be compared between groups across all study visits. The incidence of both 15% and 15 point improvements will be compared. ?Quality of Life, measured using the Short Form-36 Questionnaire (SF-36) will be compared between groups across all study visits; improvement of 15% in the overall score at each visit compared to baseline will be considered clinically significant. ?Disc height (incidence of 3mm change), as measured by standard lateral radiographs, will be compared between groups across all study visits. ?Incidence of subsidence of the device (>3 mm) at all study visits. ?Neurological status at all study visits compared to baseline. ?Safety: The individual incidence rates of all adverse events at all study visits through 7-years follow-up.
Follow-up Visits and Length of Follow-up	7 years Annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	29 non-randomized investigational subjects, 129 randomized investigational subjects, 6 non-randomized control subjects, 67 randomized control subjects. Overall 231 patients continued participation from the IDE study.
Actual Number of Sites Enrolled	15 sites were enrolled for the Post-Approval Study
Patient Follow-up Rate	200/231 (90%) presented for Year 7 follow up. 208/231 (87%) presented for Year 7 follow up. 67/151 (44%) of randomized investigational patients from the original IDE study returned for Year 7 follow up with complete data for the primary endpoint
Final Safety Findings	During the post-approval study time period (Years 2-7), a total of 630 adverse events (activL = 387; control = 243) were reported in 199 patients (activL = 129; control = 70), for a rate of 3.2 events per patient. The most common event reported was Musculoskeletal-Non-Lumbar (activL = 19.38%; control = 16.46%), followed by Pain-Lumbar and Lower Extremity (activL = 13.95%; control = 13.99%), Trauma (activL = 14.21%; control = 7.00%) and Gastrointestinal (activL = 11.37%; control = 9.88%). While the overall rate of adverse events in the PAS phase (199 per year) appears to be less than during the IDE phase (498 per year), there are several adverse events that occur at a higher rate in the activL group compared to the control group, which persists through the PAS period (e.g, lumbar pain).
Final Effect Findings	At Year 7 non-inferiority was demonstrated for Overall Success in the ITT population both with the ROM component (p=0.0447) and without the ROM component (p=0.0131).
Study Strengths & Weaknesses	The main strength of the study is the randomized design. The main weakness of the study is the low follow up rate, especially for patients with all data within window. This low follow up rate makes multiple sensitivity analyses, especially in the Per Protocol population, inconclusive and introduces significant uncertainty at later follow up timepoints.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P120024 / PAS002
Date Original Protocol Accepted	06/11/2015
Date Current Protocol Accepted	01/31/2020
Study Name	Enhanced Safety Surveillance Study
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ESS is an unmasked, uncontrolled surveillance system of the activL for 10 years following PMA approval. Data will be collected through surgeon surveys, reporting of adverse events, and Medical Device Reports (MDRs) that may result from complaints received at Aesculap or may be filed with FDAs adverse event reporting database (Manufacturers and User Facility Device Experience, MAUDE) by a hospital or surgeon, and literature review.
Study Population	Surgeons that use the device will be asked about their experience when treating patients with the activL device.
Sample Size	N/A
Key Study Endpoints	Information related to outcomes, subsequent surgical interventions (SSIs), additional pain management procedures, device ease of use, device satisfaction, device malfunction, device removal, and/or other serious device-related adverse events. Explant analysis (will be reported separately) Supporting documentation for all complaints and MDRs reported for the activL implants and instruments
Follow-up Visits and Length of Follow-up	There is no patient follow-up. The surveillance system survey will be conducted annually for 10 years .
Interim or Final Data Summary
Interim Results	N/A
Actual Number of Patients Enrolled	N/A There is no enrollment of patients. All patients who have received this device in the post-market environment, i.e. all patients who are implanted with the device. The intended patient population under general conditions of use in the United States and in the rest of the world.
Actual Number of Sites Enrolled	N/A Annual surgeon survey: active collection of surgeon feedback annually to elicit information related to HO, device malfunction, device removal, or other serious device related complications.
Patient Follow-up Rate	Numbers of sites, IRB approvals and study participants are not available, since this ESS does not include enrollment of sites/patients. There is no enrollment of patients.
Final Safety Findings	Not evaluated, this is a surveillance study.
Final Effect Findings	Not evaluated, this is a surveillance study.
Study Strengths & Weaknesses	The strength of this study is that the data is collected from real world usage of this device and used by practitioners with a variety of experience and familiarity with the device. The weakness is that this study is highly dependent on surgeon feedback, so the response rate may be low.
Recommendations for Labeling Changes	N/A Labeling was updated with 7-year follow-up data, and no new issues or concerns have been found since that time.
General
Study Status	Completed
Application Number / Requirement Number	P140031 / PAS001
Date Original Protocol Accepted	06/17/2015
Date Current Protocol Accepted	07/23/2018
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the PIIS3HR cohort and Nested Registry #7 under the IDE. The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the PIIS3HR cohort and Nested Registry #7 under the IDE
Sample Size	All living subjects
Key Study Endpoints	The safety and effectiveness endpoints include all-cause mortality, all stroke, total days alive and out of hospital (from date of index procedure), improvement per New York Heart Association (NYHA) Class (from baseline), improvement in 6 Minute Walk Test (at one year only), improvement per Kansas City Cardiomyopathy Questionnaire (KCCQ) and Euro Health Related Quality of Life (EQ5D), valve performance, major vascular complications, myocardial infarction, new permanent pacemaker, new onset atrial fibrillation, and bleeding.
Follow-up Visits and Length of Follow-up	5 years All subjects are followed at 30 days, 6 months, 12 months, and annually thereafter through 5 years post procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 664 subjects were implanted with a valve (valve implant population) and consisted 572 subjects enrolled in the PIIS3HR cohort (valve sizes 23-, 26-, 29-mm), and 92 subjects enrolled in the Nested Registry #7 cohort (valve size 20-mm).
Actual Number of Sites Enrolled	40 (39 US and 1 Canada)
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 85%. Compliance with visit assessments (e.g., NYHA Classification, KCCQ, EQ-5D, echocardiographic imaging) ranged from 72% to 85% of subjects who attended the final 5-year visit.
Final Safety Findings	The composite rate of death, all-stroke, and moderate or greater aortic insufficiency at 5 years was 75.2%. The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: All-cause death: 61.9% (42.3% cardiac death) All stroke: 15.0% (10.8% major stroke) Rehospitalization for symptoms of aortic stenosis or complications of the valve procedure: 36.3% Bleeding: 48.6% Vascular complications: 11.8% Myocardial infarction: 9.0% New permanent pacemaker: 21.8% New onset atrial fibrillation: 12.8% At 1 year, the mean number of days a subject spent alive and out of the hospital was 324.1 +/- 86.92 (n=664)
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit (unless otherwise noted): NYHA Classification: improvement compared to baseline was demonstrated in 82.8% (120/145) of subjects at 5 years, and 88.3% of subjects were Class I/II at 5 years. KCCQ: Clinically significant improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 16.6 +/- 2.21 (n=154) EQ-5D: clinically significant improvement was observed in EQ-5D visual analog scale score at all timepoints. The change from baseline at 5 years was 5.7 +/- 2.15 (n=149). 6-minute walk test (at 1 year only): the was an improvement in 6MWT distance of 27.5 +/- 127.13 (n=446) meters from baseline to 1 year. Valve Performance Outcomes: Mean effective orifice area at 5 years was 1.54 +/- 0.035 (n=134), representing a mean change from baseline of 0.88 +/- 0.035 (n=125) Overall, mean gradient decreased from 45.8 mmHg at baseline to 11.6 mmHg at 30 days. At 5 years, the overall mean gradient was 11.8 mmHg (n=143). Peak gradient decreased from 76.4 mmHg at baseline to 22.2 mmHg at 30 days. At 5 years, the peak gradient was 21.4 mmHg (n=143). At 5 years, 92.5% of subjects with available echocardiographic data (n=146) had mild or less total AR. No subjects had severe total AR. At 5 years, 94.5% of subjects with available echocardiographic data (n=145) had mild or less paravalvular AR. No subjects had severe paravalvular AR. o Structural valve deterioration at 5 years was 1.2% (5 events in 5 subjects)
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the SAPIEN 3 valve in patients with severe symptomatic aortic stenosis at high or greater surgical risk. Overall, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvement in quality of life outcomes and good hemodynamic performance. The lack of completion of some assessments of interest including NYHA Classification, KCCQ, and echocardiographic imaging at the 5-year study visit presents some challenges to the interpretability of longer-term effectiveness outcomes. Additionally, it should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results.
Recommendations for Labeling Changes	Complete longer-term follow-up data warrants inclusion into the labeling for the device and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status	Hold
Application Number / Requirement Number	P130001 / PAS001
Date Original Protocol Accepted	10/18/2016
Date Current Protocol Accepted
Study Name	Epi proColon PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single arm, prospective, multi-center, longitudinal, new enrollment study designed to evaluate the performance of the Epi proColon test by the following measures: test accuracy, longitudinal adherence to Epi proColon screening, adherence to follow-up colonoscopy, diagnostic yield, and assay failure. These are to be assessed in a population of patients at average risk for colorectal cancer, who after appropriate counseling from their healthcare provider, have been offered and declined screening by fecal occult blood testing and colonoscopy. The primary objectives are: a) To demonstrate that the proportion of subjects with a positive test (EPC+) result at Time 1 (T1), but without colorectal cancer as assessed by colonoscopy (D-), i.e., PrT1 (D-, EPC +), is significantly less than the proportion of subjects at baseline/Time zero (T0) with a positive test result but without colorectal cancer, PrT0 (D-, EPC +). b) To demonstrate the Epi proColon detects colorectal cancer at T1 in patients that tested negative at T0.
Study Population	Adults of either sex, 50 years or older (but younger than 75), defined as average risk for CRC, who have been offered and have a history of not completing CRC screening.
Sample Size	The sample size was determined based on a probability between 85 and 94% of being able to detect a colorectal cancer positive patient at T1 (assuming that patient tested negative at T0) using the Epi proColon test. It was determined that 4500 subjects would need to be enrolled. Additional assumptions included the estimated prevalence of colorectal cancer at T0 (0.6%), the estimated sensitivity (0.68) and specificity (0.82) at T0, a T1 return rate (between 66% and 80%), the estimated sensitivity (0.50) and specificity (0.88) at T1, and an estimated adherence to follow-up colonoscopy (between 66% and 80%).
Key Study Endpoints	The primary endpoints are the proportion of participants at T1 with a positive test result, but without colorectal cancer the proportion of subjects at the first screening (T0) with a positive test result, but without colorectal cancer colorectal cancer detection via Epi proColon test at T1 in patients tested negative via Epi proColon at T0. The secondary endpoints are the cumulative probability of cancer detection the cumulative probability of a false referral the probability of testing negative at both time points the adherence to Epi proColon at both screenings (i.e., T0, T1) the diagnostic yield the adherence to follow-up diagnostic colonoscopy after a positive Epi proColon test the assay failure rate adverse events related to blood draw adverse events related to diagnostic colonoscopy
Follow-up Visits and Length of Follow-up	Subjects will be followed for up to 21 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	2956
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	As of March 31, 2023, 2956 subjects have been enrolled since the study start, with the testing of the samples performed at four designated laboratories. Out of 2956 Subjects enrolled, 49 subjects have been excluded from analysis.
General
Study Status	Terminated
Application Number / Requirement Number	P100040 S012/ PAS001
Date Original Protocol Accepted	01/22/2014
Date Current Protocol Accepted
Study Name	Valiant Dissection PAS
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P980035 S277/ PAS001
Date Original Protocol Accepted	12/19/2012
Date Current Protocol Accepted	12/19/2012
Study Name	SureScan Pacing System
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	Total number of patients enrolled is 2483. This number comprised of 2323 patients in the Chronic Performance cohort and 160 patients in the Multiple Scan Characterization cohort. Of the Chronic Performance cohort patients, 407 patients had at least one MRI and 71 of the 407 patients were implanted with Advisa MRI IPG. Of the Multiple Scan Characterization cohort patients, 146 patients had at least one MRI and 15 of the 146 were implanted with Advisa MRI IPG.
Actual Number of Sites Enrolled	Seventy-five (75) sites were enrolled including 3 sites from Canada and 5 sites from India.
Patient Follow-up Rate	Of 827 eligible Chronic Performance Subjects at 5 years, 702 completed the expected visit for a follow- up rate of 84.9% (702/827) at 5 years
Final Safety Findings	Primary Objective no. 1 Primary objective no. 1, which was defined as ”the MRI complication rate is less than 2% at 5 years” was met. The 5-year MRI complication free rate was 0.0% with 95% confidence interval (CI) of 0.00% - 0.73%. The upper bound of the 95% CI of 0.73% was below the pre-specified performance goal of 2%. Primary Objective no.2 Primary objective no. 2, which was defined as “the complication free survival probability for Model 5086MRI lead in the right ventricle (RV) is greater than 92.5% at 5 years post-implant” was met. The 5- year complication-free estimate for Model 5086MRI leads in the RV was 99.3% (95% CI: 98.7%, 99.6%). The lower bound of the 95% CI of 98.7% was above the performance goal of 92.5%. Twelve (12) RV lead related complications contributed to the study primary endpoint. Chronic performance of the Model 5086 MRI RV lead stratified by MRI scan exposure (i.e. whether or not the lead had MRI exposure during follow-up) in a survival analysis yielded a log rank p-value of 0.71, indicating that RV lead survival times were not significantly different by lead MRI scan exposure. Primary Objective no. 3 Primary objective no. 3, which was defined as “complication free survival probability for Model 5086MRI leads placed in the right atrium (RA) is greater than 92.5% at 5 years” was also met. The 5-year complication-free estimate for Model 5086MRI leads placed in the RA was 99.0% (95%CI: 98.3%, 99.4%). The lower bound of the 95% CI of 98.3% was above the performance goal of 92.5%. Sixteen (16) of the 17 RA lead related complications contributed to the study primary endpoint. Chronic performance of the Model 5086 MRI RA lead stratified by MRI scan exposure in a survival analysis yielded a log rank p-value of 0.39, indicating that RA lead survival times were not significantly different by lead MRI scan exposure.
Study Strengths & Weaknesses	The Chronic Lead Performance Multiple MRI study was a large (n= 2483), prospective, global, multicenter study with 5-year long term follow-up. The follow up rate at nearly all timepoints exceeded 80%. All events adjudication was performed by the Clinical Event Committee (CEC). The primary study endpoints were formally evaluated with hypothesis testing and all primary endpoints objectives were met. This study provides important information on clinical outcomes in patients implanted with the Medtronic’s Revo/Advisa MRI SureScan Systems. The absence of MRI-related complications, and the high complication-free rate from RA lead-related complications at 5 years (lower bound of 95% CI: 98.3%), and from RV lead-related complications at 5 years (lower bound of 95% CI: 98.7%) support the safety of the Medtronic SureScan pacing system. The study limitations/weaknesses include visit non- compliance 47.4% (1178/2483), incomplete data collection/testing 36.0% (895/2483), and missing source document 2.0% (50/2483). The percentages were calculated based on number of subjects with the specified deviation as the numerator and total number of subjects enrolled as the denominator.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post Approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), results and study strengths and limitations.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P130004 / PAS001
Date Original Protocol Accepted	01/08/2014
Date Current Protocol Accepted	05/05/2020
Study Name	Device Exposure Registry Study
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to collect post-approval data relative to the incidence of endophthalmitis (within 30 days) for cataract surgery patients treated with the ReSure Sealant when used by a broad group of physicians under commercial use conditions. This study is designed as a retrospective, multicenter, observational, single- arm post-approval registry study that will include up to 100 US centers and will enroll at least 4857 patients treated with ReSure Sealant.
Study Population	The study population is defined as all patients who receive at least one application of the ReSure Sealant on the operative eye in 2014 or 2015 (up to October 2015).
Sample Size	A sample of 4857 patients provides approximately 82% power (alpha = 0.05) to detect a difference (P1 – P0) of -0.0020, using a one-sided binomial test, where P0 is the proportion of endophthalmitis within 30 days under the null hypothesis (0.0040) and P1 is the proportion of endophthalmitis within 30 days under the alternative hypothesis (0.0020). The results assume that the population proportion under the null hypothesis is 0.0040.
Key Study Endpoints	The primary endpoint will be the occurrence of endophthalmitis (based on the ‘specific’ definition) within 30 days (±10 days) of the cataract procedure. Endophthalmitis is defined (i.e., sensitive definition) to have occurred if at least one of the ICD-9-CM or ICD-10-CM codes listed belowhas been reported. Endophthalmitis is defined (i.e., specific definition) to have occurred if at least one of the ICD-9-CM or ICD-10-CM codes listed below has been reported and at least one of the CPT-4/HCPCS procedure codes listed below has been reported. ICD-9-CM Codes: 360.0 – purulent endophthalmitis 360.00 – unspecified purulent endophthalmitis 360.01 – acute endophthalmitis 360.02 – panophthalmitis 360.03 – chronic endophthalmitis 360.04 – vitreous abscess 364.03 – secondary iridocycitis, infectious CPT-4 / HCPCS Procedure Codes: CPT-4: 66030 – injection of medication in anterior chamber CPT-4: 67005/67010 – anterior vitrectomy CPT-4: 67028 – intravitreal injection of pharmacologic agent CPT-4: 67036 – pars plana vitrectomy
Follow-up Visits and Length of Follow-up	As a retrospective study, there is technically no follow-up. The study is designed primarily to ascertain if Medicare patients treated with ReSure Sealant were diagnosed with endophthalmitis within 30 days of cataract surgery. Patients from the Clinical PAS will be pooled into this study with the outcome reported through site/investigator record review.
General
Study Status	Completed
Application Number / Requirement Number	P130004 / PAS002
Date Original Protocol Accepted	01/08/2014
Date Current Protocol Accepted	10/02/2014
Study Name	Clinical PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To collect post-approval data relative to the incidence of pre-specified Adverse Ocular Events for cataract surgery patients treated with ReSure Sealant when used by a broad group of physicians under commercial use conditions. Prospective multicenter observational post-approval study that will be conducted at a minimum of 20 centers and up to 40 centers in the United States with enrollment of at least 598 sequentially-enrolled patients treated with ReSure Sealant. An expected minimum of 10 patients and a maximum of 60 patients may be enrolled at any one site.
Study Population	Adult patients undergoing cataract surgery using the surgeon¿s standard techniqu treated with ReSure Sealant.
Sample Size	A sample size of 598 achieves an alpha of 0.05 and 80% power to detect a difference (P1-P0) of -0.025 using a one-sided binomial test, where P0 is the proportion of individual primary endpoint adverse ocular events in the postoperative follow-up period under the null hypothesis (0.075) and P1 is the proportion of individual primary endpoint adverse ocular events under the alternative hypothesis (0.050). These results assume that the population proportion under the null hypothesis is 0.075.
Key Study Endpoints	The primary endpoints will be the following Adverse Ocular Events occurring in the postoperative follow-up period: ¿Anterior chamber cells greater than level 1+ persisting at Visit 2 (≥ Day 20) ¿Hypotony (≤ 5 mmHg) ¿Ocular discomfort (an OCI score greater than 51.7 or a within-person increase from baseline of greater than 37.8) ¿Surgical reintervention
Follow-up Visits and Length of Follow-up	4 weeks post-procedure Subjects will be evaluated in the immediate postoperative period (Visit 1: Day 1 to Day 3) and again at approximately 4 weeks post-procedure (Visit 2: Day 20 to Day 40).
Interim or Final Data Summary
Actual Number of Patients Enrolled	626 subjects
Actual Number of Sites Enrolled	22 sites
Patient Follow-up Rate	98.9%
Final Safety Findings	Event rates for each primary endpoint are as follows: anterior chamber cells greater than level 1+ persisting at visit 2 (greater than or equal to Day 20) 0.8%; hypotony 0%; ocular discomfort 0.6%; surgical reintervention 0.5%. For each of the individual primary endpoints, the upper confidence bound was well below the threshold of 7.5%. Therefore, the null hypothesis is rejected and it can be concluded that the true proportion for each individual primary endpoint is less than 7.5%.
Final Effect Findings	Effectiveness was not evaluated in the PAS.
Study Strengths & Weaknesses	Study strengths include this study being a large-scale prospective study of 626 patients from 22 U.S. sites. The large sample size from varied regions of the U.S. increases the generalizeability of the study results to patients at large undergoing cataract surgery in the U.S.
Recommendations for Labeling Changes	No
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P130021 / PAS001
Date Original Protocol Accepted	01/17/2014
Date Current Protocol Accepted	02/17/2014
Study Name	Contined f/u of IDE pivotal cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A longitudinal observational clinical trial following subjects that were enrolled in the Medtronic CoreValve® U.S. Pivotal Trial and received the Medtronic CoreValve® System (MCS).
Study Population	Extreme risk subjects currently consented to and enrolled in the Medtronic U.S. Pivotal Trial, and implanted with the MCS.
Sample Size	All subjects enrolled in the US Pivotal Trial, 656 iliofemoral and non-ilifemoral and 63 roll-in subjects in all sites (41).
Key Study Endpoints	The investigational 12-month primary and secondary endpoints have been met and is the basis for FDA approval of the MCS. The following safety/effectiveness endpoints will characterize clinical outcomes annually through 5 years: 1. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) event rates via Kaplan-Meier. MACCE is defined as a composite of: ¿ all-cause death ¿ myocardial infarction (MI) ¿ all stroke, and ¿ reintervention (defined as any cardiac surgery or percutaneousadjusts, or replaces a previously implanted valve) 2. The occurrence of individual MACCE components event rates via Kaplan-Meier 3. Major Adverse Events (MAE) event rates via Kaplan-Meier 4. Conduction disturbance requiring permanent pacemaker implantation event rates via Kaplan-Meier 5. Change in NYHA class 6. Quality of Life (QoL) change using the following measures: ¿ Kansas City Cardiomyopathy Questionnaire (KCCQ) ¿ SF 12, and ¿ EuroQoL7. Echocardiographic assessment of valve performance using the following measures: ¿ transvalvular mean gradient ¿ effective orifice area ¿ degree of aortic valve regurgitation (transvalvular and paravalvular) 8. Aortic valve disease hospitalization event rates via Kaplan-Meier 9. Cardiovascular deaths and valve-related deaths event rates via Kaplan-Meier 10.Strokes (of any severity) and TIAs event rates via Kaplan-Meier 11.Evidence of prosthetic valve dysfunction
Follow-up Visits and Length of Follow-up	annually through 5 years
General
Study Status	Completed
Application Number / Requirement Number	P130004 / PAS003
Date Original Protocol Accepted	05/05/2020
Date Current Protocol Accepted
Study Name	Retrospective Analysis Study for Endophthalmitis
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to compare the incidence of endophthalmitis within 30 days of any cataract surgery between sites with and without access to ReSure Sealant using the IRIS registry. The study will also compare the incidence of endophthalmitis within 30 days of cataract surgery between sites with and without access to ReSure Sealant, stratified by type of cataract surgery (i.e., routine and complex). The study is designed as a retrospective, multicenter, ecologic, post-approval registry study .
Study Population	The study size will be based on eyes who meet the following inclusion/exclusion criteria: Inclusion criteria include the following: 1. Presence of either CPT code 66982 or CPT code 66984 code for an extracapsular cataract removal with insertion of intraocular lens prosthesis between January 01, 2016 and December 01, 2019 2. At least one visit in the IRIS database within 30 days after the cataract procedure 3. Practices, with and without access to ReSure, where the cataract procedure with implantation of an IOL was conducted contributing data to the IRIS registry for at least 30 days following the date of the procedure 4. Age 22 and over on the date of the cataract surgery 1. Unspecified laterality of the procedure for cataract removal 2. Unknown demographic information (e.g., age, sex, race and region of the country)
Sample Size	The minimum sample size needed to detect an increase in the incidence of endophthalmitis in the cohort with access to ReSure Sealant, with a power of 90% and an alpha of 0.05, stratified by estimated incidence of endophthalmitis, versus the cohort without access to ReSure Sealant is 12,806
Key Study Endpoints	The pre-specified level for clincal significance for the incidence of endophthalmitis in sites with access to ReSure Sealant will be considered to be a doubling of the observed incidence of endophthalmitis in sites without access to ReSure Sealant.
Follow-up Visits and Length of Follow-up	30 days
Interim or Final Data Summary
Actual Number of Patients Enrolled	In the initial cohort selection, sponsor identified 5,231,758 unique patients and 8,317,635 eyes who had cataract surgery documented in IRIS. After applying inclusion and exclusion criteria, the master cohort contained 4,167,618 unique patients and 6,724,998 eyes from 2,481 practices in the IRIS Registry.
Actual Number of Sites Enrolled	In this study, 883 practices were considered to have access to ReSure Sealant while 1,598 practices were not for a total of 2,481 study sites.
Patient Follow-up Rate	30 days post- cataract surgery. Follow-up rate is not applicable because of the study did not involve follow-up of subjects.
Final Safety Findings	Primary Outcome: “Incidence of endophthalmitis between sites with and without access to ReSure Sealant”: No clinically significant difference (i.e., doubling) in incidence between eyes treated at practices with ReSure Sealant access (0.609 [95% CI: 0.583, 0.635]) vs. without ReSure Sealant access (0.660 [95% CI: 0.632, 0.688] per 1,000 cataract surgeries (P = 0.01)). Thus, incidence of endophthalmitis within 30 days of cataract surgery is not clinically significantly higher among sites with access to ReSure Sealant as compared to sites without access. Secondary Outcomes: o “Incidence of endophthalmitis stratified by cataract surgery type”: No clinically significant difference in endophthalmitis rate between ReSure access cohort vs. No Access cohort, among eyes that had routine cataract surgeries or complex cataract surgeries: ¿ incidence of endophthalmitis for routine cataract surgeries among ReSure access cohort was 0.572 cases per 1,000 surgeries (95% CI: 0.546, 0.598) and among No Access cohort was 0.614 cases per 1,000 surgeries (95% CI: 0.586, 0.642). incidence of endophthalmitis for complex cataract surgeries among ReSure access cohort was 1.082 cases per 1,000 surgeries (95% CI: 0.955, 1.209) and among No Access cohort was 1.219 cases per 1,000 surgeries (95% CI: 1.08, 1.357). o “Incidence of individual endophthalmitis types”: Incidence of secondary infectious iridocyclitis was statistically significantly lower in the cohort with ReSure Sealant access compared with the cohort without access (P < 0.0001). No statistical or clinical significance for unspecified purulent endophthalmitis, panophthalmitis acute or parasitic endophthalmitis . o “Incidence stratified by covariates”: No clinically or statistically significant difference in endophthalmitis incidence was found between cohorts with and without ReSure access, stratifying by cataract condition, age group, gender, race, urban/rural, season of surgery, history of diabetes, or concurrent glaucoma and vitreous procedures. Among eyes in West Region, endophthalmitis incidence was 0.490 per 1,000 cataract surgeries (95% CI: 0.441 - 0.540) among cohort with ReSure access, lower than those without access (). • Other Results: “Risk factors for endophthalmitis” ReSure Sealant access was not associated with significantly higher risk for endophthalmitis (OR = 0.94, 95% CI = 0.89 - 1.01). Note: Very large sample sizes may result in statistically significant results that are not clinically meaningful. Therefore, a pre-specified level for clinically meaningful threshold for the observed difference in endophthalmitis rate between sites with and without access to ReSure Sealant was agreed upon with FDA prior to study initiation. This was defined as a doubling of the observed incidence for sites with access compared to sites without access to ReSure Sealant.
Final Effect Findings	Not applicable for this DER PAS study
Study Strengths & Weaknesses	Strengths: The IRIS Registry is the largest electronic health record (EHR)-based comprehensive eye disease and condition registry in the US, a longitudinal dataset that aggregates de-identified patient data from over 232 million patient encounters (53 million unique patients) integrated from more than 55 EHR systems covering 14,945 ophthalmologists and affiliated optometrists (Chang 2019). IRIS Registry extracts data automatically from a participating practice’s EHR system and places in a clinical data repository. In contrast to prospective epidemiological studies using structured protocols, EHR data accrue in an unscheduled, real-world manner. Weaknesses: The primary limitation of the research method was the use of the ecologic study design. With this study design, there is no data at the patient level on the exposure to ReSure. The use of ReSure Sealant in the cohort of sites with access to ReSure Sealant was assumed and cannot be verified for a given cataract surgery as use is not routinely coded in EHR medication tables. Since the objective of the research was to identify whether or not use of ReSure Sealant causes an increase risk in endophthalmitis, this design can only be used to identify if the cohort with access to ReSure Sealant has any clinically significant increased risk of endophthalmitis; it cannot predict the impact of access to ReSure Sealant at a patient level. The second limitation is that study only matched the cohort at the physician level, not the practice level. It was assumed if a physician was matched to the list of NPIs provided by Ocular Therapeutix, then all practices to which that physician belonged were deemed to have access to ReSure Sealant. Patients may not have been exposed to ReSure Sealant if the physician did not use ReSure Sealant at all associated practices, or if the physician did not use ReSure Sealant in all cataract procedures that were performed at the practice. Thus, results cannot show a direct, causal link between endophthalmitis rate and ReSure Sealant use. Another limitation of the study is the retrospective reliance on the EHR and the physician’s documentation in the EHR. Although this is a legal record, omissions or errors in the documentation may occur and documentation behavior among physicians may differ. Endophthalmitis reports can also vary over time with spikes in reporting due to various factors including the prevalence of predisposing comorbid conditions, geographic factors in organism incidence, urban versus rural settings, ethnicity, outpatient versus inpatient populations especially those in tertiary care centers. With large sample sizes, these potential variations should be balanced across cohorts, however, it is possible that one or few sites can experience spikes in endophthalmitis thereby impacting the reported incidence for the entire cohort and potentially skewing the study interpretation. Another concern is the misidentification of toxic anterior segment syndrome (TASS), a complication of cataract surgery as endophthalmitis as the two diseases can present with similar symptoms. Incorrect coding of TASS as endophthalmitis might present as several cases in a given site which could skew the results.
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P150026 S008/ PAS001
Date Original Protocol Accepted	07/01/2020
Date Current Protocol Accepted
Study Name	HeartLight X3 PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to evaluate the long-term safety and effectiveness of the device in a commercial population and to clarify the safety profile of the device among females. This will be accomplished through a new enrollment prospective single-armed study.
Study Population	The study population will be subjects clinically eligible for the treatment of paroxysmal atrial fibrillation with the HeartLight Endoscopic Ablation System.
Sample Size	250 subjects will be enrolled at up to 25 sites in the US, and a minimum 135 of those subjects will be female, will accommodate the hypothesis testing with 80% power and an alpha of 0.025 for each of the hypotheses.
Key Study Endpoints	The primary effectiveness endpoint will be freedom from symptomatic Atrial Fibrillation at one-year, and will be compared to a performance goal of 55% of subjects free from symptomatic AF at one year. The primary safety outcome for the entire cohort will be the percentage of subjects experiencing a Primary Adverse Event by one-year of follow-up, and will be compared to a performance goal of PAE rate of 14% at one year. The same safety outcome will be assessed for females with the same performance goal. Longer term (three year) safety and effectiveness will be assessed as secondary outcomes. The long-term effect of operator experience will also be assessed as a secondary outcome. If there are gender differences in safety outcomes, the factors contributing to these differences will be evaluated as secondary outcomes.
Follow-up Visits and Length of Follow-up	Three years All subjects will undergo clinical follow-up pre-discharge, at 30 days, 90 days, 12 months, 24 months, and 36 months
Interim or Final Data Summary
Interim Results	Safety Results: There have been no unanticipated adverse events. The number of participants with at least one AE is 46 (40.0%), with 14 having a serious event. There have been 2 deaths. Effectiveness Results Overall, acute success is 94.2%.
Actual Number of Patients Enrolled	124
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	1 month: 98.1%; 3 months: 100%; 12 months: 97.8%; 24 months: 97.4%; 36 months: 98.3%
Final Effect Findings	Overall, acute success is 94.8%.
General
Study Status	Ongoing
Application Number / Requirement Number	P120006 S031/ PAS002
Date Original Protocol Accepted	10/09/2020
Date Current Protocol Accepted
Study Name	Alto US and OUS Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective of this post-approval study is to collect safety, effectiveness, and neck dilatation data on Alto Abdominal Stent Graft System for the endovascular treatment of infrarenal abdominal aortic aneurysms and evaluate real-world outcomes in comparison to commercially available comparator devices.
Study Population	The study population is patients with an infrarenal abdominal aortic aneurysm who met the anatomic criteria for implantation with the Alto device according to clinical guidelines and the treating physician’s judgement. Notably, treating physiscians will be making the determination regarding whether a subject should be enrolled and treated; they may request input from the Endologix Imaging Services.
Sample Size	A minimum of 450 consented patients diagnosed with AAA who are considered candidates for endovascular repair and meet the study eligibility criteria. At least 300 will be allocated to the Alto cohort, and 150 to the comparator group.
Key Study Endpoints	There are two primary endpoints: a clinical endpoint and a surrogate. The clinical endpoint is a composite of aneurysm-related complications (ARC), and consists of freedom from device-related interventions (for Type I & III endoleaks, stenosis/occlusion, migration, or other device-related cause), conversion to open surgery, Type I and III endoleaks, device migration (>10 mm), aneurysm sac enlargement (>5 mm), occlusion, aneurysm rupture, and aneurysm-related death. The surrogate is the hypothesized physiologic mechanism that leads to failure of several components within the clinical endpoint: proximal neck dilation over time. The surrogate allows for an early insight into eventual clinical sequelae. All individual components of the primary endpoint will be evaluated as separate outcomes using the Kaplan-Meier approach. Results will be stratified by device cohort.
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years.
General
Study Status	Completed
Application Number / Requirement Number	P970051 S172/ PAS001
Date Original Protocol Accepted	05/15/2020
Date Current Protocol Accepted
Study Name	Nucleus 24 Pediatric Post-Approval Study
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs
Detailed Study Protocol Parameters
Study Objectives	The Nucleus 24 Cochlear Implant Pediatric Post Approval Study (PAS) combines an extended follow-up study (Cohort 1) and a new, prospectively-designed, retrospective study (Cohort 2) to assess long-term safety and effectiveness of cochlear implantation up to a minimum of 2 years post-implantation in children aged 9-12 months. It is a retrospective, non-controlled, non-randomized, multicenter study.
Study Population	All available 84 subjects who were enrolled in the pre-market, prospectively-designed, retrospective study for the extended follow-up study (Cohort 1) and a minimum of 50 subjects implanted at age of 9-12 months for the new, prospectively-designed, retrospective study (Cohort 2).
Sample Size	Cohort 1 will consist of 84 subjects from the original study. Cohort 2 will include at least 50 new subjects.
Key Study Endpoints	Primary effectiveness endpoint: To evaluate the performance of the cochlear implant on parental questionnaires. Formal hypothesis tests are planned to establish superiority of the 24-month post-operative condition over the pre-operative condition. A within-subject analysis will be conducted on a minimum of 80% of subjects who have the same pre- to post-operative parental questionnaire available for comparison. Additional statistical hypothesis tests will be based on t-tests with a one-sided 0.025 alpha level. The formal statistical analysis plan will include a non-parametric test to be used in the event the conditions of normality are not met. Results will be compared to the existing body of literature regarding the administration of these metrics in both typical-hearing and hearing-impaired populations. Secondary Effectiveness endpoint: To evaluate the performance of the implant on audiometric thresholds. A descriptive analysis of change in audiometric thresholds pre- to post-operatively will be conducted to demonstrate the effectiveness of the device in providing access to sound. Primary safety endpoint: To demonstrate the rate of adverse events gathered in Cohort 2 and in the extension of Cohort 1 is qualitatively similar to the events reported in the original RWE dataset. At a minimum, adverse events will be sorted into the following categories: temperature regulation issues and/or instances of arrhythmia during surgery post-operative complications facial nerve injuries swelling/irritation related to the device(s) ear-related infections/conditions CSF leak device migration/extrusion due to skull growth (in young children) readmissions to the hospital within 30 days of surgery skin flap breakdown extrusions Rate of device-/procedure-/otologic-related events will be classified using the criteria outlined in Cohen and Hoffman (1991) and compared to the published literature.
Follow-up Visits and Length of Follow-up	2 years post-implantation for each subject.
Interim or Final Data Summary
Actual Number of Patients Enrolled	84 (Cohort 1); 51 (Cohort 2)
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	N/A
Final Safety Findings	Sites were asked to collect any untoward medical occurrences documented in the EHR for the specified time frame. The sponsor reports that a total of 16 events (ear-related infections/conditions) in 13 subjects (13/134 = 9.7%) were reported in the combined dataset. Four (4) events were reported for Cohort 1 (data collected between 6 months and 2 years post-operatively), and 12 events were reported for Cohort 2 (data collected out to two years post-operatively). Out of the 16 separate events that were reported, 8 were device/procedure-related (“definitely related”) or “possibly related”) (2 for Cohort 1 and 6 for Cohort 2) and 5 (1 for Cohort 1 and 4 for Cohort 2) met Medical Device Reporting (MDR) criteria due to their relationship to the device/procedure and requirement of surgical or antibiotic intervention. All resolved.
Final Effect Findings	Primary Effectiveness Endpoint: The primary effectiveness endpoint of this amendment (PAS) was to evaluate the performance of the cochlear implant on parental questionnaires. The sponsor concludes that the results of Cohort 1 and Cohort 2 compared to the existing body of literature regarding the administration of these metrics in both typical-hearing and hearing-impaired populations show that this data are qualitatively similar to the available published data for both the IT-MAIS (Robbins et al., 2004; Waltzman & Roland, 2005; Zimmerman-Phillips, Robbins, & Osberger, 2000) and LittlEARS (Connix et al., 2019; May-Mederake et al., 2010) questionnaires. Overall, the sponsor concludes that subjects within this data set demonstrated significant improvement in auditory skill development as demonstrated through administration of parental questionnaires pre- versus post-operatively. See below for assessment. Secondary Effectiveness Endpoint: The secondary effectiveness endpoint of this was to evaluate the performance of the implant on aided audiometric thresholds. The sponsor reports that data collected through this amendment demonstrate a significant improvement in audiometric threshold following cochlear implantation, demonstrating that the use of the device provides improved access to auditory information.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P100018 S034/ PAS001
Date Original Protocol Accepted	06/06/2024
Date Current Protocol Accepted	08/14/2025
Study Name	INSPIRE Pipeline Vantage Embolization Device PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: The purpose of the Pipeline Vantage Embolization Device with Shield Technology Post Approval Study (PAS) (“Pipeline Vantage PAS”) is to collect safety and effectiveness data in patients undergoing treatment for intracranial aneurysms (IA) using the Pipeline™ Vantage Embolization Device with Shield Technology (“Pipeline Vantage Device”) in a post approval setting.
Study Population	Adult patients that will be treated for intracranial aneurysms using the Pipeline Vantage device.
Sample Size	The PAS will enroll a minimum of 118 patients with expected 15% dropout. It is expected that there will be 100 evaluable subjects with a power of 0.82.
Key Study Endpoints	Key safety outcomes: Assessment of all intracranial ischemic and hemorrhagic events Composite of the incidence of major stroke in the territory supplied by the treated artery or neurological death evaluated within 1-, 3-, and 5-years of the index procedure. Incidence of patients with disabling strokes that have a mRS decline to a score of 3 or more (mRS greater than or equal to 3) due to a stroke-related cause assessed at a minimum of 90 days post-stroke event within 1-, 3-, and 5-years of the index procedure. Incidence of target aneurysm rupture through 5-years of the index procedure All serious adverse events Key effectiveness outcomes: 1) Composite of complete occlusion of the target intracranial aneurysm (Raymond-Roy I) without significant parent artery stenosis (= 50%) nor retreatment of the target intracranial aneurysm at 1-, 3-, and 5-years of the index procedure o Each component of the composite outcome (occlusion status, incidence of parent artery stenosis and incidence of retreatment and braid deformation) will also be presented separately at all three follow-ups (at 1, 3 and 5 years of the index procedure) 2) Rate of braid deformation at procedure and follow-up visits - Site-reported - Core-lab assessed 3) Implant success rate at the target site Implant success rate (device level) Implant success rate (patient level) 4) Number of devices implanted 5) Pipeline™ Vantage Device usability evaluation with objective scoring criteria (during the procedure) Assessment of braid deformation at procedure and follow-up visits will be carried out by neurointerventionalists. Device level analysis providing the rate of successful Pipeline™ Vantage Device implantations at the target site with the total number of Pipeline Vantage Devices attempted to be deployed. Percentage of patients with successful device implant(s). Usability will be evaluated by neurointerventionalists based on the following assessment factors with objective scoring criteria (per the definitions in the Device Usability section of the Procedure CRF): successful implantation, implantation time, device delivery, deployment, resheathing, visibility and overall performance. Objective scoring criteria Each factor will be evaluated based on whether the neurointerventionalist in a clinical setting found the device usability acceptable or unacceptable.Objective scoring criteria
Follow-up Visits and Length of Follow-up	Patients will be followed for a minimum of 5 years.
General
Study Status	Ongoing
Application Number / Requirement Number	P220012 / PAS001
Date Original Protocol Accepted	10/20/2023
Date Current Protocol Accepted	04/24/2024
Study Name	Enlighten PAS
General Study Protocol Parameters
Study Design	Enhanced Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	Safety Results Out of 805 subjects enrolled, 786 underwent an implant attempt, with 756 of them successfully implanted. Of those 756 patients, 285 (27.0%) required lead repositioning. Among those, 104 were due to atrial oversensing, 108 were due to suboptimal R-wave sensing, 59 implant attempts had both atrial oversensing and suboptimal R-wave sensing, and 4 had an unknown reason. Additionally, 124 (16.1%) implant attempts required re-tunneling and of those, 22 were due to atrial oversensing, 61 due to suboptimal R-wave sensing, 36 related to both, and 1 was unknown relation. 210 adverse events were reported in 163 patients, 193 were fully adjudicated by the CEC. Among the adjudicated events, 187 were deemed to be related to the EV-ICD system and/or EV-ICD procedure. Of the 193 fully adjudicated events for the 805 patients enrolled 58 were classified as major complications, 64 are serious, 142 are system related, and 93 are procedure related. None were unanticipated. 79 patients had 277 fully adjudicated episodes, of which 64 were inappropriate shocks, 16 were inappropriate ATP events, and 1 was inappropriate ATP and shock. Effectiveness Results: Regarding electrical performance, the most common pacing vector testing was Ring 1 to Coil 2 with a mean of 5.4V. Pacing capture threshold (PCT) at implant was consistent as enrollment increased. PCT was not measured at 6 or 12 months. Sensing at 12 months was similar to pivotal study. The average impedance remains consistent. Among the 786 patients with an implant attempt, 710 had defibrillation testing at the time of the implant with 701 patients having a reported minimum energy where defibrillation was successful.
Actual Number of Patients Enrolled	805
Actual Number of Sites Enrolled	133
Patient Follow-up Rate	At the time of the visit cutoff date, 358 out of the expected 484 patient contacts were completed for the 6-month visit window, 117 out of the expected 169 patient contacts were completed for the 12-month visit window, and 34 out of the expected 34 patient contacts were completed for the 18-month visit window. The mean follow-up time for the 756 patients with a successful implant enrolled by the visit cutoff date of June 13, 2025, was 4.5 months.
Final Effect Findings	N/A
General
Study Status	Completed
Application Number / Requirement Number	P130008 / PAS001
Date Original Protocol Accepted	04/30/2014
Date Current Protocol Accepted	04/30/2014
Study Name	Ext FU Premkt Cohort Inspire 4 STAR Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	to demonstrate long-term safety - Prospective, single arm cohort study
Study Population	Subjects implanted with the Inspire UAS System under the premarket study.
Sample Size	Approximately 124 STAR trial subjects are available for the extended follow-up
Key Study Endpoints	Long term safety of the Inspire system will be assessed via the description of all reported adverse events. Adverse events captured in the premarket study will be summarized by seriousness, severity, relatedness to the device and temporal relationship to the procedure, annually.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	126 patients were enrolled in the study. Of those, 97 patients were followed-up for a maximum duration of 60 months post-procedure.
Actual Number of Sites Enrolled	25 clinical sites (15 U.S. and 10 Europe)
Patient Follow-up Rate	60 months follow-up rate was 97 out of 126 or 76.3%.
Final Safety Findings	Serious adverse events: During the 60-months follow-up, 9 device, procedure- or therapy-related serious adverse events (SAEs) occurred in 8 out of 126 (6.3%) patients. All SAEs involved revision/repositioning (n=5) or replacement (n=4) of the device. Revisions and replacements surgeries did not incur complications or significant sequalae. In addition, there were 5 deaths, all of which were unrelated to device, procedure or therapy. Non-serious adverse events: 122 out of 126 patients experienced a total of 1,014 non-serious AEs, with 520 (51.3%) of these AEs in 108 patients being unrelated to the device, therapy or procedure and 494 (48.7%) of these AEs being related to the device / therapy (318 AEs in 104 patients) or procedure (176 AEs in 76 patients). The sponsor considered an AE to be procedure-related if it occurred within 30 days post-procedure and device- or therapy-related if it occurred after 30 days post-procedure. As patients completed their final follow-up visit and exited the study, there were 15 open events (‘Discomfort due to electrical stimulation’ (n=5); ‘Tongue abrasion’(n=3); ‘Mouth dryness’(n=4); ‘Intermittent discomfort from the IPG’ (n=1); ‘Other acute symptoms’ (n=1)) in 12 subjects that had not yet resolved. According to the sponsor, some remained open due to late onset of the event that required time to manage and monitor to closure, however others had been monitored throughout the study, but without resolution.
Final Effect Findings	Key effectiveness findings were based on a subset of the original 126 patients, depending on data availability, ranging between 113 patients and 90 patients. For the most part, effectiveness findings were not statistically significant, although there were some clinically meaningful findings. The mean FOSQ score at 60-months follow-up visit was 18.0 +/- 2.2, which is higher than the clinically meaningful value of 17.9. At other follow-up times, the mean FOSQ score was less than 17.9, making it not clinically meaningful. Furthermore, the mean change in FOSQ score from baseline was negative at each follow-up visit, suggesting no clinically meaningful improvement in FOSQ score from baseline, since a positive change in FOSQ score of 2.0 is considered clinically meaningful. The mean ESS score at each follow-up time was less than 10, making it clinically meaningful. although there is no minimum ESS change that can be considered clinically meaningful, the ESS change from baseline is expected to be negative if the patient was to improve over time. On average, ESS change from baseline at each follow-up vist was positive, suggesting no clinically significant improvement in ESS score over time. On average, AHI was 32.0 +/- 11.0 at baseline and 12.4 +/- 16.3 at 60 months follow-up. On average, ODI was 28.9 +/- 18.2 at baseline and 9.9 +/- 14.5 at 60 months of follow-up. These findings suggest improvement in AHI and ODI over time.
Study Strengths & Weaknesses	Study Strengths: Prospective cohort study is gold standard for epidemiologic studies. Long-term follow-up (up to 5 years) Safety and effectiveness were evaluated using multiple outcome measures. Study weaknesses: Descriptive study Follow-up rate is < 80% Not all patients with adverse events had known outcomes.
Recommendations for Labeling Changes	Labeling changes are recommended labeling based on safety and effectiveness data reported in the final report
General
Study Status	Completed
Application Number / Requirement Number	P130008 / PAS002
Date Original Protocol Accepted	04/30/2014
Date Current Protocol Accepted	09/11/2017
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to obtain additional long-term safety and effectiveness data on the use of Inspire therapy in a post-market setting. In addition, this study will evaluate physician training by collecting post-operative safety outcomes
Study Population	The study is being conducted in a post-market environment for the treatment of moderate to severe Obstructive Sleep Apnea (OSA) (15 less than or equal to AHI less than or equal to 65) in subjects who have been confirmed to fail or cannot tolerate positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BPAP] machines) and who do not have a complete concentric collapse at the soft palate level.
Sample Size	127 patients. 10 sites for now. Since study initiation efforts began in March of 2015, 15 sites have been activated for enrollment in the study. Activated sites have IRB approval, contract/clinical study agreement in place, study team training completed, and additional site regulatory documents in place. Of the 15 activated sites, five have closed due to logistical or resource challenges.
Key Study Endpoints	Safety: There are three safety endpoints included in this study. Long-term device-related serious adverse events (SAE): This safety endpoint will assess long-term (5 years) safety via comparison of device related SAEs with a performance goal. Device-related SAEs include device explants due to device-related infection, device malfunction, lead fracture, device or lead reposition that results in surgical intervention. Therapy-specific adverse events at 12 months: This safety endpoint will evaluate the safety of the Inspire system in the treatment of sleep apnea by evaluating procedure- and device-related AEs occurring immediately postimplant through 12 months. Long-term (5 years) therapy-related adverse events: This safety endpoint will assess long-term safety via the description of all reported AEs, including all therapy- and procedure-related events. Evaluation of Performance of Newly Trained Physicians: This endpoint will assess the performance of newly trained physician and will collect surgical times, post-operative pain recovery, procedure-related AEs and post-operation comments. Effectiveness: Effectiveness endpoints will use disease-specific quality of life measures and OSA severity measures of ODI and AHI. Therapy effectiveness will be measured by the Epworth Sleepiness Scale (ESS) and the Functional Outcome of Sleep Questionnaire (FOSQ) quality of life questionnaires annually out to 5 years. Therapy effectiveness as measured by the apnea hypopnea index (AHI) and the oxygen desaturation index (ODI) using a single in-lab PSG or two-night home sleep test at 3 years. Epworth Sleepiness Scale (ESS) at 12 months: The ESS is a validated quality of life instrument that rates a subject’s daytime sleepiness. The objective of this endpoint is to demonstrate an improvement at 12 months as compared to baseline Functional Outcomes of Sleep Questionnaire (FOSQ) at 12 months: The FOSQ is a validated quality of life instrument that assesses the effect of a subject’s daytime sleepiness on activities of ordinary living. The objective of this endpoint is to demonstrate an improvement at 12 months as compared to baseline. Oxygen Desaturation Index (ODI): Oxygen Desaturation Index (ODI) is a measure of OSA severity and is commonly used in the clinical evaluation of management of OSA. The ODI endpoint in this study will be determined by the ODI score at the 3-year follow up as compared to baseline. The objective is to demonstrate improvement at 3 years as compared to baseline. Apnea Hypopnea Index (AHI). Apnea Hypopnea Index (AHI) is a measure of OSA severity. The objective of this endpoint is to demonstrate an improvement of OSA severity at 3 years as compared to baseline.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	127
Actual Number of Sites Enrolled	15 sites
Patient Follow-up Rate	Follow up rate for AHI at 3 years: 57% Follow up rate of ODI at 3 years: 76%
Final Safety Findings	Long term device related adverse events <24 % at 5 years
Final Effect Findings	ESS-At 5 years is 6: FOSQ-not adequately powered at 5 years: Mean ODI-reduction at 3 years was 8: Mean AHI-reduction at 3 years is 16.7
Study Strengths & Weaknesses	Weaknesses: Missing data was significant Strengths: Long term data for AHI (3 years) and ODI (5 years)
Recommendations for Labeling Changes	None; Labeling updated to reflect results from study.
General
Study Status	Completed
Application Number / Requirement Number	P040003 S016/ PAS001
Date Original Protocol Accepted	11/04/2015
Date Current Protocol Accepted
Study Name	Study to Evaluate Safety of ExAblate
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Ongoing enrollment in multi-center, prospective, single arm study to evaluate safety of the ExAblate Model 2100 Type 1.1 System.
Study Population	Pre- or perimenopausal women with symptomatic uterine fibroids who desire a uterine sparing procedure and whose uterine size is less than 24 weeks. Patients should have completed child bearing.
Sample Size	Number of subjects enrolled: 106 Number of subjects required for the hypothesis test: 101 True rate of 0.03, 80% power, two-sided Type 1 error of 0.05 and 5% drop out rate.
Key Study Endpoints	Primary Endpoints: Incidence of any chronic leg pain or lower extremity neuropathy, persisting or occurring greater than 10 days following ExAblate treatment and Adverse events through 1-month post-treatment Secondary Endpoints: Fibroid ablation (number, location and volume); Average non-perfused volume; Average treatment rate; Number of executed sonications where the far field impinges on the sacral bone; and Physician qualitative assessment of new device features
Follow-up Visits and Length of Follow-up	1 month post-procedure 1 Week and 1 month post-procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	136
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	A total of 136 subjects were enrolled (i.e., consented). Of these, 30 subjects were reported to be screen failures. Of the 30 subjects that were reported to be screen failures, 2 subjects were screen failed because they only received < 10 sonications. These two subjects who received partial ExAblate treatment were included in the safety analysis. 60% of the total number of screen failures (n=18) were due to fibroid anatomy, 10% (n=3) were due to device accessibility, 13% (n=4) were subject declining treatment, and 17% (n=5) were “other” reasons. 106 patients were treated (received > 10 sonications). At the one month visit, 102 of the 106 completed their planned visit(s). Out of the remaining 4 subjects, two withdrew their consent prior to their 1-month follow-up and two were lost to follow up. A total of 108 subjects are in the ITT Safety Population (includes all treated patients plus the two patients who received < 10 sonications).
Final Safety Findings	94% of study participants experienced adverse events (AE), with most participants experiencing 1-3 AEs. The sponsor noted that the frequency of AEs is similar to prior studies and that there were no new AEs or unanticipated AEs. The most commonly reported event was sonication related pain (250/339). The majority of these events were classified as moderate/severe (59%) but transient, lasting approximately 20 seconds.
Final Effect Findings	Increase in the average non-perfused volume (per total fibroid volume) compared to the current ExAblate system
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	The labeling will be updated to include follow up outcomes.
General
Study Status	Completed
Application Number / Requirement Number	P130009 S037/ PAS002
Date Original Protocol Accepted	09/20/2016
Date Current Protocol Accepted	04/03/2017
Study Name	New Enrollment SAPIEN XT Pulmonic PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate longer-term safety and effectiveness of the SAPIEN XT Transcatheter Heart Valve (THV) in the pulmonic position for the intended patient population (especially pediatric) when used as indicated with all valve sizes (SAPIEN XT THV 23, 26, 29 mm). Single-arm, prospective, multicenter post-approval study using a performance goal based on the original COMPASSION trial.
Study Population	Pediatric and adult patients with a dysfunctional, non- compliant right ventricular outflow tract (RVOT) conduit with a clinical indication for intervention and: • pulmonary regurgitation = moderate and/or • mean RVOT gradient = 35 mmHg.
Sample Size	A total of 191 patients will be enrolled at up to 20 sites in the US.
Key Study Endpoints	Primary: Freedom from device- or procedure-related death or reintervention at 1 year Secondary: Improved valve hemodynamics at 30 days, 1 year, 2 years and annually through 5 years as demonstrated via transthoracic echocardiogram (TTE): a) Decrease in pulmonary regurgitation to mild or less for regurgitant lesions b) Decrease in RVOT mean gradient to less than 30mmHg for stenotic lesions c) Improvement in both a) and b) above for mixed lesions. Improvement of = 1 NYHA functional class from baseline for patients with NYHA functional class = 2 at baseline. Recurrent pulmonary stenosis, defined as RVOT peak gradient greater than or equal to 36 mmHg at 30 days, 1 year, 2 years and annually through 5 years as demonstrated via TTE for patients with stenosis at baseline (RVOT peak gradient = 36 mmHg at baseline). Device Success, defined as a composite of: a) Deployment of the valve to the target area, and b) Removal of the delivery catheter out of the body, and c) Improvement in pulmonary regurgitation to mild or less per the earliest evaluable TTE. Safety: MACCE at 30 days and 1 year, defined as a composite of death, myocardial infarction, reintervention, vascular injury resulting in the need for an unplanned vascular intervention, stroke and pulmonary embolism
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	52 enrolled; 47 implanted. Please note enrollment was stopped early due to the device no longer being sold or marketed.
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	At 5 years, 81.0% of eligible subjects had their visit completed.
Final Safety Findings	Overall Device Success: 97.8% Deployment of valve to target area and removal of the delivery catheter out of the body: 97.9% Improvement in PR of mild or less by TTE: 97.8% Freedom from device- or procedure related death and reintervention at 30-days: KM rate: 2% (one reintervention; no deaths) MACCE at 30-days: KM rate: 13.5% (7 vascular injuries; 1 reintervention)
Final Effect Findings	Pulmonary Regurgitation: Baseline: none/trace - 15.2% (7/46); mild - 28.3% (13/46); moderate - 26.1% (12/46); severe - 30.4% (14/46) 5-years: none/trace - 68.8% (22/32); mild - 25.0% (8/32); moderate - 6.3% (2/32); severe: - 0.0% (0/32) Mean RVOT gradient: Baseline: 29.7 mmHg 5-years: 14.1 mmHg Paravalvular Leak: Baseline: none/trace - 78.4% (29/37); mild - 10.8% (4/37); moderate - 5.4% (2/37); severe - 5.4% (2/37) 5-years: none/trace - 100.0% (31/31) NYHA Functional Class: Baseline: Class I/II - 82.2% (37/45); Class III/IV - 17.8% (8/45) 5-years: Class I/II - 93.9% (31/33); Class III/IV - 6.1% (2/33)
Study Strengths & Weaknesses	This new enrollment study provides longer-term data (through five years) on the safety and effectiveness of a transcatheter valve used for RVOT repair in the pulmonic position. It should be noted that enrollment was discontinued early due to the device no longer being sold or marketed in the US resulting in a small number of patients in the study.
Recommendations for Labeling Changes	No. The device is no longer sold or marketed
General
Study Status	Completed
Application Number / Requirement Number	P130009 S057/ PAS001
Date Original Protocol Accepted	11/04/2019
Date Current Protocol Accepted
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the PIIA cohort under the IDE (G090216). The objective of this PAS is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke, transient ischemic attack (TIA), myocardial infarction, new permanent pacemaker, new-onset atrial fibrillation, rehospitalization from symptoms of aortic stenosis and/or complications of the valve procedure, improvement per New York Heart Association (NYHA) Class, improvement per Kansas City Cardiomyopathy Questionnaire (KCCQ) and Euro Health Related Quality of Life (EQ-5D), valve performance and durability, and aortic valve re-intervention.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	2032 enrolled; 1938 attempted implanted (994 TAVR and 944 SAVR); 1910 valve implanted (974 TAVR and 936 SAVR)
Actual Number of Sites Enrolled	57
Patient Follow-up Rate	At 10 years subject status was known in 61.9% of TAVR subjects (59 Alive and on study; 544 dead) and 54.1% of SAVR subjects (61 alive and on study; 445 dead). Over 90% of subjects either did not reconsent to follow up past 5 years or had discontinued by Year 10, the majority due to death (mean age at the time of the procedure was 82). After conducting vital status check (VSC), subject status at 10 years was known in 90.5% of TAVR subjects (97 alive; 784 dead) and 89.5% of SAVR subjects (120 alive; 718 dead).
Final Safety Findings	Given the limited available data, a vital status check was conducted. The KM estimates for all-cause death through 10 years were 86.1% and 82.8% for the SAPIEN XT and SAVR cohorts, respectively, when data from a vital status check was included. Site-reported safety outcomes at 10 years: All stroke: XT: 23.7%; SAVR: 19.9% All reintervention: XT: 16.1%; SAVR: 2.7% Transient ischemic attack: XT: 7.4%; SAVR: 6.8% Myocardial infarction: XT: 21.5%; SAVR: 12.8% New permanent pacemaker: XT: 19.8%; SAVR: 16.8% New-onset atrial fibrillation: XT: 23.1%; SAVR: 34.8% Rehospitalization for symptoms of AS and/or complications of the valve procedure: XT: 25.9%; SAVR: 13.4%
Final Effect Findings	Site-reported efficacy outcomes at 10 years: Improvement from baseline in NYHA functional classification: XT: 72.5%; SAVR: 88.1% KCCQ Overall Summary Score change from baseline: XT: 11.1; SAVR: 12.0 EQ-5D VAS Overall Summary Score change from baseline: XT: 3.1; SAVR: 7.6 Effective Orifice Area: XT: 1.32 cm2; SAVR: 1.24 cm2 Mean Gradient: XT: 12.7 mmHg; SAVR; 12.7 mmHg Moderate or greater Total Aortic Regurgitation: XT: 9.1%; SAVR: 2.7% Moderate or greater Paravalvular Aortic Regurgitation XT: 7.1%; SAVR: 0.0% Structural Valve Deterioration per VARC-2: XT: 7.7%; SAVR: 2.3%
Study Strengths & Weaknesses	PARTNER II Cohort A was designed as a 5-year study. Improvements in quality of life, functional class, and valve hemodynamics were maintained through 5 years. After 5 years, there is a large bias due to informative censoring mostly related to the reconsent process both from the lack of reconsent and disproportionate lack of consent between the two arms. As the number of subjects censored increases, so does the imbalance between the two arms such that after five years the two cohorts are no longer comparable. Additionally, a large portion of subjects have died leading to a high risk of survivor bias (death as a competing risk) that is further exacerbated by the imbalance between the two arms. Although informative censoring was minimized for mortality rates by incorporating information obtained from the vital status sweep, this was not possible for other outcomes collected beyond 5 years. Statistical methods such as propensity-score adjustment and multiple imputation were unable to minimize the impact of these issues.
Recommendations for Labeling Changes	No. SAPIEN XT has been discontinued.
General
Study Status	Ongoing
Application Number / Requirement Number	P130009 S057/ PAS002
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry
Study Population	Patients with symptomatic heart disease due to either severe native aortic stenosis who are deemed to be at intermediate or greater surgical risk, defined as having predicted risk of surgical mortality of = 3% at 30 days based on the STS risk score and other clinical co-morbidities not included in the STS risk score assessment.
Sample Size	All implanted patients, with intermediate or greater risk for open surgical therapy, in the TVT-registry within five years of the device approval.
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological complications (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-5 years post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P130009 / PAS001
Date Original Protocol Accepted	06/16/2014
Date Current Protocol Accepted	08/02/2016
Study Name	Cont F/U of the IDE inop pts cohort(B)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To study the long term (5 year) device safety and effectiveness in continued follow-up of cohort B and six nested registries. Design: A continued follow-up of Cohort B and six nested registries in IDE pivotal study, a prospective randomized, multi-center trial with two population cohorts undergoing transcatheter heart valve replacement therapy with SAPIEN XT THV. Subjects will be all pivotal and CAP Patients enrolled in Cohort B and six nested registries (NR1, NR4, NR5, NR6) and who are not suitable for aortic valve surgery (i.e. inoperable patients).
Study Population	all pivotal and CAP Patients enrolled in Cohort B and four nested registries (NR1, NR4, NR5, NR6)
Sample Size	Currently, a total of 1790 patients from pivotal trials (560 from Cohort B and 1230 from the six registries) and 775 continued access (CAP) patients from the six nested registries (as of June 2, 2014) are available for continued follow-up.
Key Study Endpoints	Through TVT-Registry
Follow-up Visits and Length of Follow-up	Subjects will be followed annually through 5 years. Patients have been consented for up to 5 years follow-up, thus no re-consent is needed.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1042
Actual Number of Sites Enrolled	54
Patient Follow-up Rate	5-year follow-up rate of 94.7%
Final Safety Findings	The 5-year CEC adjudicated KM rate was 51.3% for all-cause death and stroke, 46.0% for all-cause death, 15.4% for all-stroke, and 33.4% for rehospitalization for symptoms of aortic stenosis and/or complications of the valve procedure.
Final Effect Findings	Patients showed persistent improvement from baseline in: 1. NYHA functional classification (80.7% of patients at 5 years) 2. KCCQ (change from baseline at 5 years was 15.9 +/- 1.3 for the overall summary score and 8.5 +/- 1.3 for the clinical summary score) 3. EQ-5D VAS score (change from baseline at 5 years: 6.5 +/- 1.4)
Study Strengths & Weaknesses	Good THV hemodynamic valve performance was demonstrated at each follow-up visit by an improvement from baseline in EOA, mean gradient and peak gradient. At 5 years, the proportion of patients with moderate or greater total aortic regurgitation and paravalvular regurgitation was 7.6% and 6.4%, respectively.
Recommendations for Labeling Changes	no need to update the labeling based on the results of the 5-year follow-up for the PIIB NR1, NR2, NR4, NR5, and NR6.
General
Study Status	Progress Adequate
Application Number / Requirement Number	P130009 / PAS002
Date Original Protocol Accepted	06/16/2014
Date Current Protocol Accepted	06/16/2014
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to severe native calcific aortic stenosis (aortic valve area < 1.0 cm2 or aortic valve area index < 0.6 cm2/m2, a mean aortic valve gradient of > 40 mmHg, or a peak aortic-jet velocity of > 4.0 m/s), and with native anatomy appropriate for the 23, 26, or 29 mm valve system, who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score > 8% or at a > 15% risk of mortality at 30 days).
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval.
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years 30 days, 12 months as per clinical practice; then annually up to 5 years through linking to CMS claims database.
General
Study Status	Ongoing
Application Number / Requirement Number	P100018 S026/ PAS001
Date Original Protocol Accepted	07/19/2021
Date Current Protocol Accepted
Study Name	Pipeline Flex Embolization w Shield Tech PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort. Will use sponsor’s “Product Surveillance Registry” platform.
Study Population	Adult patients receiving Pipeline Flex Embolization Device with Shield Technology for treatment of intracranial aneurysm.
Sample Size	203
Key Study Endpoints	Primary Endpoint: A patient will be considered a success if there is complete occlusion of the target aneurysm without significant parent artery stenosis (less than or equal to 50%), and the patient does not require retreatment of the target aneurysm. Secondary Endpoints: 1. Incidence of complete aneurysm occlusion (defined as Raymond-Roy Class 1) without significant parent artery stenosis (less than or equal to 50%) or retreatment of the target aneurysm through 1- and 3-years post-procedure. 2. Incidence of device deployment success rate at the target site. 3. Incidence of target aneurysm recurrence and retreatment through 1- and 3- year post-procedure. 4. Incidence of major stroke in the territory supplied by the treated artery or neurological death through 3-years post-procedure. 5. Incidence of major stroke in the territory supplied by the treated artery or neurological death through 30 days post-procedure due to procedural complications. 6. Incidence of delayed intracerebral hemorrhage > 30 days through 1- and 3- years post-procedure. 7. Incidence of patients with disabling strokes that have a mRS decline to a score of 3 or more (mRS = 3) due to a stroke-related cause assessed at a minimum of 90 days post-stroke event at 1- and 3-years post-procedure. 8. Incidence of all strokes, both hemorrhagic and ischemic, through 1- and 3-years post-procedure.
Follow-up Visits and Length of Follow-up	Patients will be followed for a minimum of 3 years.
Interim or Final Data Summary
Interim Results	Safety Results As of the data cut off date of 27-FEBRUARY-2025, there have been no unanticipated adverse events (AEs). One hundred seventy-five (175) AEs have been adjudicated by the CEC and a listing of the data is included in Annex B. A summary of CEC-Adjudicated Neurological Adverse Events of Interest Post-Procedure (up to 1 year, >1 year) is presented in Table 12. There has been one (1) reported neurological death (Annex E.5) and one (1) reported non-neurological death (Annex E.4). There has been one (1) death pending CEC adjudication (reported in Annex E.7). There have been ten (10) non-disabling strokes (nine (9) minor strokes and one (1) indeterminate stroke) and four (4) intra-cranial hemorrhage (ICH). Two (2) patient narratives describing endpoint-related adverse events (patients 6088010 and 2944017), one (1) patient narrative describing a patient (3242013) who experienced two (2) ICH events and one (1) patient narrative regarding non-neurological death (patient 2944006), are presented within Annex E. A listing of site-reported AE data is included in Annex B. Effectiveness Results As of the data cut off date of 27-FEBRUARY-2025, the following data was entered and available in the database: 1) implant and device deployment success of two hundred thirty-seven (237) patients, 2) Core Lab reported post-procedure imaging outcomes of two hundred thirty-five (235) patients, 3) Core Lab reported six (6) month follow-up imaging of one hundred seventy-seven (177) patients, 4) Core Lab reported one (1) year follow-up imaging of one hundred four (104) patients, 5) modified Rankin Scale (mRS) clinical outcome scores at baseline, 180-day follow-up, 1-year and 3-year follow-up for two hundred twenty-eight (228), one hundred fifty-seven (157), one hundred sixteen (116) and three (3) patients respectively, and 6) all available CEC (clinical events committee)-adjudicated adverse events (AEs).
Actual Number of Patients Enrolled	246
Actual Number of Sites Enrolled	16
Patient Follow-up Rate	Follow-up is on schedule.
General
Study Status	Ongoing
Application Number / Requirement Number	P130013 S057/ PAS001
Date Original Protocol Accepted	10/31/2023
Date Current Protocol Accepted	10/31/2023
Study Name	SURPASS Pro
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	SURPASS Pro is an observational, prospective, non-randomized, multicenter registry surveillance analysis plan for all patients entered into the LAAO Registry who had a WATCHMAN FLX Pro Device implant attempt. This surveillance is designed to monitor data including: . ischemic stroke and systemic embolism at hospital discharge, 45 days, 6 months, 12 months, and 24 months post-procedure. The surveillance should also monitor the rate of all-cause death, ischemic stroke, systemic embolism, or device or procedure related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair within seven days of the procedure or by hospital discharge, whichever is later.
Study Population	SURPASS Pro data will include all patients enrolled in the LAAO Registry who had a WATCHMAN FLX Pro Device implant attempt and were discharged between Q4 2023 to Q4 2025. As appropriate, subgroup analyses may be performed. These analyses may include (but are not limited to) endpoint evaluation for the following subgroups: • IFU/Indication compliant implants • Post-implant drug regimens • Sex/gender • Race/ethnicity
Sample Size	Data will be captured from all LAAO Registry participating sites in the United States The estimated number of subjects for this study is approximately 30,000
Key Study Endpoints	Safety Endpoints Primary: • The occurrence of one of the following events between the time of the first implant procedure and within seven days of the procedure or by hospital discharge, whichever is later: o All-cause death, o Ischemic stroke, o Systemic embolism, or o Device or procedure-related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair. Percutaneous catheter drainage of pericardial effusions, snaring of an embolized device, thrombin injection to treat femoral pseudoaneurysm and nonsurgical treatments of access site complications are excluded from this endpoint and will be reported separately. Secondary: Additional analyses will include occurrence of the following endpoints at each LAAO Registry follow-up time points (discharge, 45 days, 6 months, 12 months, and 24 months post-procedure): • All-cause death • All stroke • Ischemic stroke • Hemorrhagic stroke • Device-related thrombus (DRT) • Systemic thromboembolism • Major bleeding • Device embolism These endpoints will be analyzed descriptively. Effectiveness Endpoints Primary: The occurrence of ischemic stroke or systemic embolism at 24 months post-implant Secondary: Additional analyses will include occurrence of the following endpoints at each LAAO Registry follow-up time points (discharge, 45 days, 6 months, 12 months, and 24 months post-procedure): • Effective device closure o Note: Effective device closure is measured via LAAO Registry DCF field “Device Margin Residual Leak”. Effective device closure is defined as “Complete Seal” or 0 < Device Margin Residual leak (mm) less than or equal to 5mm. • Implant success (defined as device release and deployed) These endpoints will be analyzed descriptively.
Follow-up Visits and Length of Follow-up	The LAAO Registry will collect data at baseline, procedure, discharge, and at follow-up visits: 45 days, 6 months, 12 months, and 24 months post-procedure. Patients will be followed for 2 years.
General
Study Status	Study Pending
Application Number / Requirement Number	P040024 S142/ PAS001
Date Original Protocol Accepted	12/23/2025
Date Current Protocol Accepted	12/23/2025
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the safety of Restylane Lyft with Lidocaine for augmentation of the chin region 3 months after retreatment.
Study Population	A total of 100 adult male and female subjects aged 22 years or older with the intent to undergo treatment of the chin region to improve the chin profile is planned to be included in this study.
Sample Size	Number of subjects: 100 Assumptions for sample size estimation: No sample size calculation has been performed. Number of sites: approximately 8 Sites location: United states of America
Key Study Endpoints	Safety Endpoints Primary: Treatment-emergent adverse events (TEAEs) that are related to the device and/or injection procedure after the Month 12 optional retreatment. Secondary: To evaluate the safety of Restylane Lyft with Lidocaine for augmentation of the chin region to improve the chin profile up to 3 months after retreatment, for the defined endpoints: • To evaluate the incidence, intensity, time to onset, and duration of adverse events (AEs) collected throughout the study period. • To evaluate pre-defined, expected, post-treatment events reported for 28 days from each treatment as recorded in the subject diary. • Subject pain assessment before (prior to application of any anesthetic) and immediately after (before any post-injection therapy is provided, e.g., ice packs) treatment, using an 11-point Numeric Pain Scale (NPS). Effectiveness Endpoints Primary: Secondary: To evaluate the effectiveness of Restylane Lyft with Lidocaine for augmentation of the chin region to improve the chin profile, for the defined endpoints: • Binary responder status variables (Yes/No) indicating whether a subject has at least 1 grade improvement from Baseline based on the Treating Investigator’ live assessment of the Galderma Chin Retrusion Scale (GCRS) at 3, 6, 9, 12 and 15 months after initial treatment to optimal correction. • Binary responder status variables (Yes/No) indicating whether a subject has at least “Improved” (Improved, Much Improved or Very Much Improved) on the Global Aesthetic Improvement Scale (GAIS) as assessed by the Subject and Treating Investigator separately at 3, 6, 9, 12 and 15 months after initial treatment to optimal correction. • Subject satisfaction with chin projection and shape at 3, 6, 9, 12 and 15 months, using the Subject Satisfaction Questionnaire (SSQ).
Follow-up Visits and Length of Follow-up	72-hour telephone call after initial treatment/ visit 2 (+/-24 hours) 14 days after initial treatment /visit 2a (+7 days) 1 month after initial treatment (+7 days) – (Optional touch-up visit /visit 3 72-hour telephone call after touch-up / Visit 3a (+/-24 hours) 14 days after touch-up / Visit 3b (+7 days) Month 1 after optional touch-up / Visit 3c (+7 days) 3, 6, and 9 months after last treatment (+/-14 days) Visits 4-6 12 months after last treatment (+14 days) - Optional retreatment visit 72-hour telephone call/Visit 7a (+/-24 hours) 14 days after retreatment/Visit 7b (+7 days) Month 1 after optional retreatment / Visit 7c (+7 days) Month 15 (end of study, EOS visit) / Visit 8 (+/-14 days)
General
Study Status	Ongoing
Application Number / Requirement Number	P130013 S074/ PAS002
Date Original Protocol Accepted	12/15/2025
Date Current Protocol Accepted	12/15/2025
Study Name	WATCHMAN FLX Pro NOAC Alone PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational, prospective, non-randomized, multicenter registry surveillance analysis designed to characterize clinical outcomes and to assess the real-world use of the commercial WATCHMAN FLX Pro LAA Closure Device with Delivery System. The analysis is designed to assess safety outcomes associated with the use of non-vitamin K oral anticoagulant (NOAC) alone as an alternative to an oral anticoagulant (OAC) and aspirin as the post-implant medication regimen for the WATCHMAN FLX Pro Left Atrial Appendage (LAA) Closure Device with Delivery System in a routine clinical setting. Data will be captured from the Left Atrial Appendage Occlusion (LAAO) Registry within the American College of Cardiology Foundation’s (ACCF) National Cardiovascular Data Registry (NCDR) conducted in the United States.
Study Population	LAAO registry subjects who were successfully implanted with a WATCHMAN FLX Pro device, discharged 6 months prior to the NOAC alone labeling change implementation (16Jan2025 to 16Jul2025) or 6 months post labeling change implementation (17Jul2025 to 17Jan2026), and who meet inclusion/exclusion criteria.
Sample Size	Number of subjects: N/A. See above study population Assumptions for sample size estimation: N/A Number of sites: Data from all sites participating in the LAAO Registry in the United States will be used for the analysis. Sites location: US
Key Study Endpoints	Co-Primary Endpoint: Composite Endpoint The composite event rate is defined as all-cause death, stroke (ischemic and/or hemorrhagic), major bleeding, and systemic embolism. The composite event endpoint will be assessed in successfully implanted subjects between the date of hospital discharge and 45 days post-implant procedure and between hospital discharge and 6 months post-implant procedure. Co-Primary Endpoint: Safety Endpoint The occurrence of one of the following events between the time of the first implant attempt procedure and within seven days of that procedure or by hospital discharge, whichever is later: • All-cause death, • Ischemic stroke, • Systemic embolism, or • Device or procedure-related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair. Percutaneous catheter drainage of pericardial effusions, snaring of an embolized device, thrombin injection to treat femoral pseudoaneurysm and nonsurgical treatments of access site complications are excluded from this endpoint and will be reported separately. Co-Primary Endpoint: Effectiveness Endpoint The occurrence of ischemic stroke or systemic embolism at 24 months post-implant procedure. Additional Endpoints Additional analyses will include the evaluation of the following events prior to and after the NOAC alone labeling implementation. Clinical events will be assessed between hospital discharge and 45 days, 6 months, 12 months and 24 months post-implant procedure: • All-cause death • Cardiovascular death • All stroke • Ischemic stroke • Hemorrhagic stroke • Systemic thromboembolism • Major bleeding • Pericardial effusion • Device embolization • Device margin residual leak • Device-related thrombus
Follow-up Visits and Length of Follow-up	Subjects in all cohorts will be followed at hospital discharge, 45 days, 6 months, 12 months and 24 months post-implant procedure.
Interim or Final Data Summary
Interim Results	Safety Results: Co-Primary Endpoint: Composite Endpoint: Propensity score matching (1:1) was conducted to adjust for known differences in baseline characteristics across cohorts. The following results reflect the matched population outcomes. Subjects prior to NOAC alone labeling implementation, NOAC alone subjects had a lower rate of the composite event at both 45 days and 6 months compared to both NOAC + ASA and DAPT, primarily driven by a lower rate of major bleeding. Discharge to 45 days: - Matched NOAC Alone subjects: 1.14% - Matched NOAC + ASA: 2.33% - Matched NOAC Alone subjects: 1.18% - Matched DAPT: 2.53% Discharge to 6 months: - Matched NOAC Alone subjects: 4.65% - Matched NOAC + ASA: 6.93% - Matched NOAC Alone subjects: 5.57% - Matched DAPT: 7.87% Subjects Post NOAC alone labeling implementation, NOAC alone subjects had a lower rate of composite events at 45 days compared to both NOAC + ASA and DAPT. Discharge to 45 days: - Matched NOAC Alone subjects: 1.10% - Matched NOAC + ASA: 1.78% - Matched NOAC Alone subjects: 1.30% - Matched DAPT: 1.98% The rate of the key safety endpoint was low in both time periods. Given the large sample size in this analysis, the small differences in this endpoint between medication regimen cohorts do reach statistical significance but may not be clinically meaningful. Co-Primary Endpoint: Safety Endpoint (unmatched) Prior to NOAC alone labeling implementation: - NOAC alone: 0.29% - NOAC +ASA: 0.17% - DAPT: 0.34% Post NOAC alone labeling implementation: - NOAC alone: 0.15% - NOAC +ASA: 0.17% - DAPT: 0.25% Effectiveness Results: Currently no subjects have reached 24 months follow-up; the key effectiveness endpoint has not been analyzed.
Actual Number of Patients Enrolled	Prior to labeling implementation (enrollment is complete): NOAC Alone - 10581 subjects NOAC Alone + ASA - 11678 subjects DAPT - 16631 Subjects Post Labeling implementation (enrollment is NOT complete): NOAC Alone - 10388 subjects NOAC Alone + ASA - 10941 subjects DAPT - 14596 Subjects
Actual Number of Sites Enrolled	N/A - LAAO Registry
Patient Follow-up Rate	Prior to NOAC Alone Labeling Implementation Cohort: 45 Day Clinical Follow-up - NOAC Alone 90.9% - NOAC + ASA 94.4% - DAPT 92.2% 6 Month Clinical Follow-up - NOAC Alone 53.3% - NOAC + ASA 58.8% - DAPT 54.7% 12 Month Clinical Follow-up - NOAC Alone 4.5% - NOAC + ASA 5.2% - DAPT 4.9% Post NOAC Alone Labeling Implementation Cohort: 45 Day Clinical Follow-up - NOAC Alone 63.5% - NOAC + ASA 69.8% - DAPT 69.1% 6 Month Clinical Follow-up - NOAC Alone 3.6% - NOAC + ASA 4.2% - DAPT 4.6%
General
Study Status	Completed
Application Number / Requirement Number	P130013 / PAS001
Study Name	Continued f/u of IDE Cohorts
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohorts in one randomized controlled trial (PREVAIL) and two continued access single arm registries (CAP and CAP2). The objective of these studies is to characterize the safety and effectiveness of the WATCHMAN LAA Closure Technology annually through 5 years post-procedure.
Study Population	Patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism and are eligible for warfarin therapy. All patients in CAP and CAP2 were designated to receive the device. PREVAIL patients were randomized to either the device or long-term warfarin therapy.
Sample Size	Initial enrollment in the premarket studies was as follows: CAP: 566 PREVAIL: 407 (269 in device group, 138 in control group) CAP2: 579
Key Study Endpoints	Primary Endpoints (CAP): - stroke, systemic embolism, and cardiovascular or unexplained death - life threatening events as determined by the Clinical Events Committee (such as device embolization requiring retrieval, pericardial effusion requiring drainage, cranial bleeding, gastrointestinal bleeding requiring transfusion, and any bleeding related to the device/procedure that necessitates an operation) Primary Endpoints (PREVAIL and CAP2): - stroke, systemic embolism, and cardiovascular or unexplained death - ischemic stroke and systemic embolism occurring more than 7 days post-enrollment Secondary Endpoints: - complete and effective LAA closure rate - warfarin discontinuation rate - warfarin or other oral anticoagulation resumption rates and reasons - device thrombus rates and outcomes
Follow-up Visits and Length of Follow-up	Follow-up will continue through 5 years post-procedure PREVAIL/CAP2: post-enrollment intervals of 45 days, 6 months, 12 months, semi-annually through 3 years, and therafter annually through 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	CAP: A total of 566 subjects implanted with the WATCHMAN Left Atrial Appendage Closure Technology constituted the post-approval study population. PREVAIL: A total of 461 subjects were enrolled with 407 randomized and the remaining 54 participating in the WATCHMAN Roll-in group. Of the 407 randomized subjects, 269 were assigned to the WATCHMAN group and 138 assigned to the warfarin control group. Of the 269 subjects randomized to the WATCHMAN group, 252 subjects received a WATCHMAN device. CAP2: A total of 578 subjects implanted with the WATCHMAN Left Atrial Appendage Closure Technology constituted the post-approval study population.
Actual Number of Sites Enrolled	CAP: 26 sites PREVAIL: 41 sites CAP2: 48 sites
Patient Follow-up Rate	CAP: 86.0% (487/566) of subjects completed the 5 year visit. PREVAIL: 87.4% (235/269) of the device group and 81.8% (112/137) of the control group completed the 5 year visit. CAP2: 84.4% (488/578) of subjects completed the 5 year visit.
Final Safety Findings	CAP: The primary safety endpoint was defined as the occurrence of life-threatening events as determined by the Clinical Events Committee, which included the following events: device embolization requiring retrieval, bleeding events such as pericardial effusion requiring drainage, cranial bleeding events due to any source, gastrointestinal bleeds requiring transfusion, and any bleeding related to the device or procedure that necessitates an operation. Freedom from the primary safety endpoint was 87.4% at 5 years. PREVAIL: The occurrence of all-cause death, ischemic stroke, systemic embolism, or device or procedure related events requiring open cardiac surgery or major endovascular intervention between the time of randomization and within 7 days of the procedure or by hospital discharge, whichever is later, was 2.2% (6/269) (95% CI: 0.6%, 2.7%). This analysis was only performed for the device group. CAP2: The CAP2 safety endpoint was the same as PREVAIL. The rate of the safety endpoint was 1.4% (8/576) (95% CI: 0.6%, 2.7%).
Final Effect Findings	CAP: Freedom from stroke (ischemic and hemorrhagic), systemic embolism, and cardiovascular/unexplained death was 86.3% at 5 years. PREVAIL: Freedom from the first primary endpoint (hemorrhagic stroke, ischemic stroke, systemic embolism or cardiovascular/unexplained death) through 5 years was 83.5% (95% CI: 78.1, 87.7) in the intent-to-treat (ITT) device group and 86.2% (95% CI: 78.4, 91.4) in the control group. Freedom from the second primary endpoint (ischemic stroke or systemic embolism after 7 days following randomization) through 5 years was 92.1% (95% CI: 87.7, 94.9) in the device group and 96.3% (95% CI: 90.4, 98.6) in the control group. CAP2: Freedom from the first primary endpoint (same as PREVAIL) through 5 years was 78.2% (74.2%, 81.7%) in the ITT group. Freedom from the second primary endpoint (same as PREVAIL) in the ITT group was 90.2% (95% CI: 87.2, 92.5) at 5 years. Of subjects successfully implanted with WATCHMAN and followed for 5 years, 94.8% of CAP subjects, 98% of PREVAIL subjects, and 97.1% of CAP2 subjects discontinued warfarin therapy at 5 years.
Study Strengths & Weaknesses	A strength of all three studies (CAP, PREVAIL, and CAP2) is that they provided results on the long-term (5 years) safety and efficacy of the device. A weakness of CAP was that there was no pre-specified safety endpoint. A weakness of the CAP and CAP2 studies was that these studies are single-arm (non-randomized) studies.
Recommendations for Labeling Changes	A labeling change is recommended to add the long-term safety and efficacy results from the pre-market cohort
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P130013 / PAS002
Date Original Protocol Accepted	11/21/2016
Date Current Protocol Accepted	11/30/2016
Study Name	WATCHMAN New Enrollment (NESTed-PAS)
General Study Protocol Parameters
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P130013 / PAS003
Date Original Protocol Accepted	03/18/2016
Date Current Protocol Accepted	11/30/2016
Study Name	WATCHMAN Comprehensive/Linked-Registry
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This Novel Surveillance plan is designed to monitor registry collected data including the following: implant success rate, procedural safety, effective closure of the orifice of the left atrial appendage, and stroke through two years post implant and CMS identification of adverse events of interest and death from two through five years post implant. Patients from a subgroup analysis will have their outcomes compared to pre- specified performance goals for the following: occurrence of composite of stroke (including ischemic or hemorrhagic), systemic embolism, and all cause death at 24 months from the time of implant. The second endpoint is the occurrence of ischemic stroke or systemic embolism at 24 months from the time of implant. The third endpoint is the occurrence of any of the following events within seven days of the implant procedure or by hospital discharge, whichever is later: all cause death, ischemic stroke, systemic embolism, or device or procedure related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair.
Study Population	Patients with attempted implant of the WATCHMAN device enrolled at sites participating in the LAAO registry.
Sample Size	A minimum of 2000 patients implanted with the WATCHMAN device. At least 1000 of the patients will be match the Indications for Use for the WATCHMAN device. Another 1000 patients will be eligible for the WATCHMAN device, have CHADS score of two or greater or a CHA DS -VASc score of 2 2 2 three or greater, and do not have a concomitant cardiac or non-cardiac procedure.
Key Study Endpoints	Study Endpoints Overall surveillance will monitor implant success rate, procedural safety, effective closure of the orifice of the left atrial appendage, and stroke (ischemic or hemorrhagic) through two years post-implant and CMS claims identified occurrence of all stroke (ischemic or hemorrhagic). For the subgroup analysis the Primary Endpoints follow. Primary Endpoint 1. The occurrence of the composite stroke (ischemic or hemorrhagic), systemic embolism, and all cause death at 24 months from the time of implant. Primary Endpoint 2. The occurrence of ischemic stroke or systemic embolism at 24 months from the time of implant. Primary Endpoint 3. The occurrence of any of the following events within seven days of the procedure or by hospital discharge whichever is later: all cause death, ischemic stroke systemic embolism, or device or procedure realted events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair.
Follow-up Visits and Length of Follow-up	Patients will be followed through five years post implant.
Interim or Final Data Summary
Actual Number of Patients Enrolled	0-2 years: 2000 subjects (1000 subjects each in the LAAO registry primary and LAAO registry secondary cohorts) 3-5 years: 21,963 subjects* *Patient outcomes during years 3-5 were evaluated via Centers for Medicare and Medicaid Services (CMS) data. Includes all patients implanted with a Watchman device between April 1, 2016 to December 31, 2018 with available CMS claims data.
Actual Number of Sites Enrolled	All sites participating in LAAO registry
Patient Follow-up Rate	45 day: 14/992 (82.1%) 6 months: 700/938 (74.6%) 1 year: 711/891 (79.8%) 2 year: 593/822 (72.1%) 3-5 year: N/A - All available subjects from CMS data
Final Safety Findings	Primary Endpoint 3 (The occurrence of any of the following events within seven days of the procedure or by hospital discharge whichever is later: all cause death, ischemic stroke systemic embolism, or device or procedure related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair.) LAAO registry primary cohort at 24 months: 1.4% (14/1000).
Final Effect Findings	Primary Endpoint 1 (The occurrence of the composite stroke (ischemic or hemorrhagic), systemic embolism, and all cause death at 24 months from the time of implant): LAAO registry primary cohort rate at 24 months: 17.1% CMS FFS claims rate at 5 years: 44.89% Primary Endpoint 2 (The occurrence of ischemic stroke or systemic embolism at 24 months from the time of implant): LAAO registry primary cohort rate at 24 months: 1.24% (12/965). CMS FFS claim rate at 5 years: 4.77%
Study Strengths & Weaknesses	Strength: Large number of real-world patients enrolled in a relatively short period of time (2 years). Weakness: Medicare claims data does not characterize medications; thus, medication history as well as current medication regimen, or medication compliance cannot be assessed. Non-Medicare (Patients < 65 years old) and Medicare advantage patients are also excluded from outcomes assessment in years 3 – 5.
Recommendations for Labeling Changes	Update labeling to include long term outcomes
General
Study Status	Completed
Application Number / Requirement Number	P130016 / PAS001
Date Original Protocol Accepted	03/20/2014
Date Current Protocol Accepted	09/11/2014
Study Name	Extended f/u study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an extended follow-up of the premarket cohort. The purpose of the study is to evaluate the long term safety and effectiveness of the Nucleus Hybrid L24 Implant in implanted subjects out to 5 years post-activation. It is a prospective, multicenter, non-controlled, non-randomized study
Study Population	Subjects from the original pivotal study and associated Continued Access study who remain implanted with Hybrid L24 Implant, enrolled in the study, and have not met their 5 year post-activation interval.
Sample Size	Up to 35 subjects.
Key Study Endpoints	The primary safety endpoint will be the comparison of the type and frequency of adverse events and serious adverse events occurring over the course of this study up to the 5 year post- activation interval as compared to the pivotal clinical study for the Hybrid L24 implant. The co-primary efficacy endpoints for this study will be the assessment of statistical significance of the within-subject differences for two speech recognition tests (CNC test and AzBio test), measured in two conditions: the implant ear and both ears
Follow-up Visits and Length of Follow-up	5 years post-activation for each subject 2 years post-activation (if not yet completed), 3 years post- activation (if not yet completed), 4 years post-activation (if not yet completed), 5 years post-activation (if not yet completed)
Interim or Final Data Summary
Actual Number of Patients Enrolled	35
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	100% at 5 years* The primary endpoint for this investigation is 5 years post-activation of the Hybrid L24 device. As of March 18, 2019, all 35 enrolled subjects have reached this designated study phase.
Final Safety Findings	A total of eight (8) Adverse Events (AEs) occurred during this PAS. Serious AEs in three (3) subjects were reported during the PAS, but only one (1) was related to the study device. This included a significant decline in residual low frequency hearing thresholds that was accommodated by explantation of the study device and replacement with a traditional cochlear implant was accomplished electrode array. There were no unanticipated adverse device effects reported. In general, the type and frequency of adverse events and serious adverse events occurring over the course of this study up to 5 year post-activation interval as compared to the pivotal clinical study for the Hybrid L24 implant
Final Effect Findings	Through the 5-year post-activation follow-up, the Hybrid L24 improves overall mean CNC Word (words in quiet) and AzBio (sentences in noise at +5 dB SNR) scores compared with pre-implant baseline unilateral and bilateral conditions. The device benefit is sustainable over the five years of follow up.
Study Strengths & Weaknesses	This is a single arm study with no comparator; however, the subjects served as their own control. It is a long-term study (up to 5 years post-implantation) with a high followup rate.
Recommendations for Labeling Changes	Yes. A labeling update is recommended to reflect the findings of the study.
General
Study Status	Completed
Application Number / Requirement Number	P130016 / PAS002
Date Original Protocol Accepted	03/20/2014
Date Current Protocol Accepted	06/16/2022
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a new enrollment study. The Nucleus Hybrid L24 Implant System New Enrollment Study will be conducted as a repeated-measures single-subject experiment. Additional data will come from subjects in the Hybrid Extended Duration Study as well as real world evidence (RWE) from a retrospective study of patients at the University of Iowa. Data from the Hybrid Extended Duration study will be pooled with the New Enrollment study for analysis of effectiveness. Data from both the Hybrid Extended Duration study and the RWE study at the University of Iowa will be pooled with the New Enrollment study for analysis of safety.
Study Population	Subjects will include a minimum of 50 newly implanted individuals, 18 years of age and older, who will be implanted with the Hybrid L24 cochlear implant from up to 25 investigational centers. Data collected from two additional sources, including the Nucleus Hybrid Extended Duration post approval study and/or a retrospective review of standard of care clinical records will be included for a total population of up to 85 subjects for effectiveness analysis and 150 individuals for safety analysis.
Sample Size	A total of 150 subjects would provide a precision (defined as the halfwidth of a two-sided 95% confidence interval) of approximately 11.9% or smaller. The three sources of data include: 1) A minimum of 50 subjects from this New Enrollment post approval study 2) Up to 35 subjects in continued follow-up in the Hybrid Extended Duration post approval study 3) A minimum of 65 subjects who were implanted outside of this New Enrollment post approval study following device approval and commercial availability using standard of care techniques. This calculation is based on an exact binomial confidence interval. Additionally, speech performance will be characterized in a total of 85 target subjects (range: 50-100 subjects, precision 4.7% - 8.2%).
Key Study Endpoints	The primary effectiveness endpoint for this study will include the within- subject differences for a monosyllabic word recognition test, measured in two conditions: the implant ear alone and when using both ears together through 3 years post-activation • Word recognition in quiet as evaluated with the Consonant Nucleus- Consonant (CNC) test The secondary effectiveness endpoint for this study will include the within- subject differences for a sentence recognition test: • Sentence recognition in noise) best unilateral condition as evaluated with the AzBio test The primary and secondary safety endpoints are the same as previous protocol.
Follow-up Visits and Length of Follow-up	3 years post-activation for each subject. Preoperative candidacy assessment/ Baseline evaluation Surgery, Initial activation, 3 months post-activation, 6 months post-activation, 12 months post-activation, Annual evaluation thereafter to 3 years post-activation
Interim or Final Data Summary
Actual Number of Patients Enrolled	52 subjects were implanted in the New Enrollment Study. Forty-eight subjects completed the 1-year post-activation interval, and 38 subjects completed the 3-year post-activation interval.
Actual Number of Sites Enrolled	19 sites
Patient Follow-up Rate	At the 1-year timepoint, the rate was 92%. At the 3-year timepoint, the rate was 73%.
Final Safety Findings	A total of 223 Adverse Events (AEs) occurred during the New Enrollment Study, 99 of which were device and/or procedure-related. Twenty-five serious AEs were reported in 13 subjects during the PAS, but only one was related to the study device. These AEs included a significant decline in the residual low frequency pure-tone averages (PTA). When account for subject attrition, 36% of subjects at 3 years post-activation and 55% of subjects at 5 years post-activation had a total/profound ( > 90db HL) loss of residual hearing in the New Enrollment Study. The real-world data (RWD) safety data shows similar rates of decline in low-frequency PTAs. There were no unanticipated adverse device effects reported. In general, the type and frequency of adverse events and serious adverse events occurring over the course of this study up to 3-year post-activation interval is similar to that observed in the previous Extended Duration study.
Final Effect Findings	Through the 3-year post-activation follow-up, the Hybrid L24 improves overall mean CNC Word (in quiet) and AzBio (sentences in noise at +5 and/or +10 dB SNR) scores compared with pre-implant baseline unilateral and bilateral conditions. The device benefit is sustainable over the three years of follow up. Subjective hearing benefit improved over the baseline.
Study Strengths & Weaknesses	This is a single arm study with no comparator; however, the subjects served as their own control. It is a long-term study (up to 5 years post-implantation) with a high follow-up rate. The New Enrollment Study is supplemented with RWD, which provides an additional source of safety data.
Recommendations for Labeling Changes	Yes, labeling changes were recommended
General
Study Status	Ongoing
Application Number / Requirement Number	P080006 S129/ PAS001
Date Original Protocol Accepted	04/10/2019
Date Current Protocol Accepted
Study Name	Attain Stability Quad PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Medtronic Attain Stability Quad (ASQ) LV Lead Post-Approval Study (PAS) is a nonrandomized, multi-site, world-wide clinical study of implanted commercially available Model 4798 leads. The study is conducted in the US, Canada, Europe (and Asia). All enrolled patients were implanted with a Model 4798 LV Lead and all data is collected prospectively. Data will be collected through Medtronic’s Post Market Surveillance platform and through leveraging extant data including potential use of administrative claims, electronic health records, available registries, and remote monitoring. The study requires a minimum of 1000 leads enolled to satisfy both the primary objective analysis sample size requirement and to estimate individual failure modes at five year post implant for the general population. Attain Stability Quad ISE patients are eligible to continue in the PAS upon market approval is followed at a participating Product Surveillance Registry (PSR) study site and are consented.
Study Population	Patients included in the Model 4798 lead Post Approval Study, were consented and implanted with a Model 4798 LV Lead
Sample Size	The PAS plans to prospectively enroll 1000 subjects through the PSR Sample Size Justification Power 0.864 a 0.05 (two-sided) Success Rate, investigational 95.5% PG 92.5% Attrition 12% per year N 1000
Key Study Endpoints	Primary Objective To demonstrate that the complication-free probability is greater than 92.5% at five years post-implant for Attain Stability Quad LV leads Primary objective analysis includes all complications related to lead hardware or design failure as pre-specified in the Attain Stability Quad Post Approval Study, Analysis Plan (Version 1, 12 Oct 2018) and base protocol of the Product Surveillance Registry (PSR) (Version 6, 7 March 2016). Secondary Objective To summarize all lead related adverse events or Adverse Device Effects (ADEs) To summarize analysis results from explanted and returned Attain Stability Quad leads
Follow-up Visits and Length of Follow-up	All enrolled patients will be followed for 5 years
General
Study Status	Completed
Application Number / Requirement Number	P130017 / PAS001
Date Original Protocol Accepted	02/02/2015
Date Current Protocol Accepted	09/25/2015
Study Name	Cologuard PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The study objective is to collect longitudinal data on subjects for whom Cologuard is used over the course of 3 years. It is a prospective, longitudinal, multi-center study.
Study Population	The study population is defined with the following criteria: Subjects must meet the following criteria to be eligible for the study: 1. Subject has been prescribed Cologuard for colorectal cancer screening 2. Subject is at average risk for development of colorectal cancer 3. Subject is 50 years or older 4. Subject willing and able to sign informed consent. 5. Subjects not listed in the exclusion criteria, described in 6.2 of the protocol.
Sample Size	A total of 2,173 subjects will be enrolled to have 1,119 subjects at the year 3 visit (T3) for the Cologuard evaluation assuming 16.1% positivity rate at T0, with 15% annualized lost to follow up (LTFU). Further, it is assumed that 15% of the 1,119 subjects will refuse T3 colonoscopy to result in 951 being evaluable for T3 analyses.
Key Study Endpoints	The primary endpoint for this study is the difference between the positive predictive value (PPV) at T3 (PPV3) and 1 minus the negative predictive value (NPV) at T3 (NPV3). The secondary endpoint is the observed vs. the expected reduction in CRC incidence at T3. Other outcomes to be assessed include the following: -The predictive values of a positive Cologuard at T0 and T3 and of a negative Cologuard atT3; -The sensitivity and specificity of Cologuard at T3; -The positive (PLR) and negative (NLR) likelihood ratios at T3; -The cumulative risk of false positive result (cFPR) and cumulative risk of a true positive result -(cTPR); -The probability that a negative Cologuard result at baseline remains negative through 3 years; -The probability that a negative Cologuard result at baseline (T0) results in no CRC/AA through 3 years; -The distribution of colorectal epithelial lesions overall and among positive Cologuard subjects at T0 and -T3 will be reported with counts and proportions; -The rate of adherence to repeat Cologuard at T3 will be reported with counts and proportions; -The Cumulative compliance to Colonoscopy following a positive Cologuard result -The rate of crossover to alternative screening methodologies (e.g. FOBT, colonoscopy, other) at T1 and T2; -The rate of no Cologuard result (e.g. invalid result); and -The adverse event rate (events occurring between collection kit distribution and sample submission).
Follow-up Visits and Length of Follow-up	Study participants will be followed for 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	2,321
Actual Number of Sites Enrolled	40
Patient Follow-up Rate	Of the 2,321 subjects enrolled in the study, T0 Cologuard results were obtained for 2,073 (89.3%), with 284 subjects obtaining a positive result and 1,760 subjects obtaining a negative result. The study design required all subjects with a negative T0 Cologuard result to remain in the study and return for follow-ups. A total of 1,645 of the possible 1,760 eligible subjects (93.5%) completed the T1 office/phone visit, 1,510 (87.1%) subjects completed the T2 office/phone visit, and 1,223 (75.7%) provided some data at the T3 timepoint. The overall follow-up rate is 69.
Final Safety Findings	No adverse events were reported.
Final Effect Findings	The primary endpoint is the Predictive Summary Index (PSI), defined as (PPV3-[1-NPV3]), where PPV3 is the positive predictive value at T3 and NPV3 is the negative predictive value at T3. The primary endpoint was calculated for CRC alone and for CRC+AA combined. A PSI value of 0% reflects a test with no predictive value. No CRCs were detected at T3, the PSI for CRC alone was 0, and the PSI for CRC+AA combined was 9.29% (95% CI 1.83%, 17.63%, p-value = 0.0124). The secondary endpoint was the observed versus the expected reduction in colorectal cancer (CRC) incidence at T3. Only 1 case of CRC occurred after T0, giving an observed incidence after a negative T0 Cologuard of 0.001374, numerically less than expected (two-sided p=0.0729 or one-sided p = 0.0402.
Study Strengths & Weaknesses	Weakness: low procedure compliance rate for primary endpoints, only 37.1% patients (653 out of 1760) had colonoscopy at T3, only 33.5% patients (591) had both valid Cologuard and colonoscopy at T3 for study endpoint analyses. No statistical adjustment for multiplicity. Strength: 3-year long term data
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P130019 / PAS001
Date Original Protocol Accepted	06/02/2015
Date Current Protocol Accepted	02/15/2019
Study Name	Extended F/u of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Open label crossover study from premarket cohort for VBLOC therapy. All remaining subjects either received an implanted device at randomization, have crossed over from to active device after the 12 month visit, or will crossover to the active device.
Study Population	Transitional. Adolescent B (as adults) : 18-21 years, Adult: >21
Sample Size	203 patients will receive VBLOC therapy. The sponsor anticipates approximately 100 subjects will have complete follow-up data at the 5-year visit.
Key Study Endpoints	The primary safety objective is to show that the rate of serious adverse events (SAEs) related to the device, implant/revision procedure (including the explant procedure), general surgical procedure, or therapy algorithm is statistically lower than 25% at 5 years. Other Safety Objectives To evaluate the long-term (5-year) rate of therapy-related adverse events. To evaluate the long-term (5-year) rate of device (neuroregulator or lead) malfunction requiring a revision procedure. To specifically report events involving the lead over 5 years such as lead breakage/fracture, twisting/entanglement, replacement, lead erosion, and bowel/tissue obstruction. Efficacy Objectives To evaluate the mean percentage excess weight loss (%EWL) through 5 years To evaluate the percentage of subjects achieving at least 20% EWL and 25% EWL through 5 years To evaluate the mean percentage total body weight loss (%TBL) through 5 years To evaluate the percentage of subjects achieving at least 5% TBL and 10% TBL through 5 years Other Objectives To evaluate the long-term (5-year) rate of surgical revision To evaluate the long-term (5-year) rate of surgical removal of the device To evaluate the long-term (5-year) rate of surgical removal of the device to undergo magnetic resonance imaging (MRI) To evaluate change in cardiovascular and metabolic risk factors (blood pressure, lipid levels, triglycerides, blood glucose, HbA1c and waist circumference) To evaluate change in weight related quality of life (Impact of Weight on Quality of Life Questionnaire-Lite [IWQOL-Lite]) and eating behaviors (Three Factor Eating Questionnaire [TFEQ])
Follow-up Visits and Length of Follow-up	At least 5 years after receiving the active device until PAS closure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	The post-approval study enrolled 84 patients from the premarket cohort: 55 patients were active treatment subjects from the premarket study, and 29 subjects were sham control subjects from the premarket study who were to begin to receive therapy. However, 4 out of these 29 subjects chose to withdraw from the study before beginning therapy. Thus, 80 subjects were consented and received therapy as part of this PAS study.
Actual Number of Sites Enrolled	8 (6 U.S. sites)
Patient Follow-up Rate	78 subjects completed year 1; 71 subjects completed year 2 and year 3; 65 subjects completed year 4; and 53 subjects completed year 5 of the study.
Final Safety Findings	Final safety findings (key endpoints): Primary Safety Objective The device- and procedural-related serious adverse event (SAE) rate (Kaplan Meier estimate) at 5 years was 6.8% (upper 95% CI: 13.8%) As the upper bound of the 95% confidence interval (CI) is less than 25% at 5 years, the study met this primary safety endpoint. Other Safety Objectives Long-term (5-year) rate of therapy-related adverse events: A therapy related adverse event is defined as an adverse event related to the delivery of therapy which is the application of an electronic signal to a nerve in order to partially or completely block the propagation of naturally occurring nerve action potential. A total of 61 out of 80 subjects (76.3 %) experienced a total of 142 therapy-related adverse events. Long-term (5-year) rate of device (neuroregulator or lead) malfunction requiring a revision procedure: In the overall PAS population, 6 out of 80 (7.5%) subjects have undergone surgical revision due to device malfunction. Events involving the lead over 5 years such as lead breakage/fracture, twisting/entanglement, replacement, lead erosion, and bowel/tissue obstruction: 6 out of 80 (7.5%) subjects experienced seven (7) lead malfunctions which included five (5) events of impedance out of range and one (1) event of twisting/entanglement. There were zero (0) events of lead erosion, lead migration, lead breakage/fracture, or bowel/tissue obstruction.
Final Effect Findings	Final effectiveness findings (key endpoints): Efficacy Objectives Mean percentage excess weight loss (%EWL) through 5 years: The observed %EWL was 18.3% (95% CI: 12.8%, 23.9%) for the 55 subjects remaining in the study at 5 years. Percentage of subjects achieving at least 20% EWL and 25% EWL through 5 years: Of the 55 subjects in the study at the 5-year point, 25/55 (45.5%) achieved 20% EWL and 20/55 (36.4%) achieved 25% EWL. Mean percentage total body weight loss (%TBL) through 5 years: The observed %TBL was 6.6% (95% CI: 4.7%, 8.6%) for the 55 subjects remaining in the study at 5 years. Percentage of subjects achieving at least 5% TBL and 10% TBL through 5 years: Of the 55 subjects in the study at the 5-year point, 32/55 (58.2%) achieved 5% TBL and 18/55 (32.7%) achieved 10% TBL. Other Objectives Long-term (5-year) rate of surgical revision: 7 out of 80 (8.8%) subjects have undergone 8 surgical revisions. The Kaplan-Meier rate estimate of surgical revision at 5 years is 9.9% (95% CI: 4.8%, 19.8%). Long-term (5-year) rate of surgical removal of the device: The Kaplan-Meier rate estimate of surgical removal rate at 5 years is 33.1% (95% CI: 23.9%, 44.7%). Long-term (5-year) rate of surgical removal of the device to undergo magnetic resonance imaging (MRI): 3 out of 80 (3.8%) subjects had the device removed to undergo an MRI. Change in cardiovascular and metabolic risk factors (blood pressure, lipid levels, triglycerides, blood glucose, HbA1c and waist circumference): Results show nonsignificant changes in systolic, diastolic and mean arterial blood pressures; total cholesterol and HDL; LDL and triglycerides; and FPG and HbA1c compared to baseline through 60 months. Subjects maintained reductions in waist circumference. Change in weight related quality of life (Impact of Weight on Quality of Life Questionnaire-Lite [IWQOL-Lite]) and eating behaviors (Three Factor Eating Questionnaire [TFEQ]): Improvements in quality life from baseline were maintained through 60 months. Improvements in all three factors of the TFEQ were maintained compared to baseline through 60 months.
Study Strengths & Weaknesses	Study Strength and Weaknesses: • This was a prospective study of treated patients in the US. • There was no concurrent comparison group, which limits interpretation of the results. • Study enrollment was lower than anticipated. Only 53 subjects completed year 5 of the study. The subjects that remained in the study may be different than those that were lost to follow up, and therefore, the generalizability of results can be limited.
Recommendations for Labeling Changes	Need labeling supplement.
General
Study Status	Terminated
Application Number / Requirement Number	P130019 / PAS002
Date Original Protocol Accepted	07/24/2015
Date Current Protocol Accepted	01/24/2018
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this PAS is to evaluate the long-term safety and effectiveness of Maestro. This is a prospective, multi-center, new enrollment study. The study will include an observational arm and a randomized sub-study. Subjects in the observational arm will receive the device implant and use the vBloc Achieve weight management program. The randomized sub-study will randomly assign subjects (1:1) to either treatment or control. Subjects assigned to the treatment arm of the randomized sub-study will receive the device implant and use the vBloc Achieve weight management program. Subjects who are randomized to the control arm of the randomized sub-study will participate in a Control Weight Management (CWM) program during a 6-month control period prior to receiving the device implant and using the vBloc Achieve program. The vBloc Achieve weight management program consists of recommendations regarding diet, exercise, and behavior modification, and will be utilized be all subjects following their device implantation.
Study Population	Patients at least 18 years old who have a BMI of 40-45 kg/m2, or a BMI of 35-39.9 kg/m2 with 1 or more obesity related comorbidities and have failed at least 1 supervised weight management program in the past 5 years. There is no control group in this study.
Sample Size	200 total subjects with obesity will be implanted with the Maestro Rechargeable System at a minimum of 10 and a maximum of 15 sites. 100 of the subjects will be implanted in an observational portion of the study. 100 subjects will be implanted in a randomized sub-study. Subjects enrolled in the randomized substudy will be randomized 1:1 to either treatment or control arms as described in this protocol. It is anticipated that approximately 120 subjects will have complete follow-up data at the 5-year visit. 200 subjects with an approximate 8% of attrition per year will provide at least 90% statistical power for the powered 5-year safety objective.
Key Study Endpoints	The main study endpoint is the 5-year rate of SAEs related to the device, implant/revision procedure (including explant procedure), general surgical procedure, or therapy. Other study endpoints include: weight loss measured by %TBL and %EWL; change in obesity-related comorbidities (blood pressure, waist circumference and the number, type and dose of medications for treatment of diabetes, hypertension and dyslipidemia); surgical revision, surgical explant, device explants specifically to undergo MRI, therapy-related AEs, and device (neuroregulator or lead) malfunction requiring a revision procedure; and AEs involving lead breakage/fracture, twisting/entanglement, replacement, lead erosion, and bowel/tissue obstruction.
Follow-up Visits and Length of Follow-up	200 subjects enrolled at a minimum of 10 and a maximum of 15 sites 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	4 patients out of 200 that were expected to be enrolled
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	3 out of 4 enrolled patients
Final Safety Findings	There was one (1) unrelated SAE of breast cancer that occurred among the 3 patients that were followed. There were three (3) related AEs among two (2) subjects that included burning at the neuroregulator site, left shoulder soreness and bleeding.
Final Effect Findings	The mean % of total body weight loss (TBL) among the three (3) patients who reached 15 months, was 10.49%. Among these three (3) patients, 2 of them met a > 10%TBL. The mean change in systolic blood pressure among the three (3) patients being followed was -12.00 (SD: 7.535) at 12 months. At the same interval for the three (3) patients, the diastolic blood pressure increased by 4.44 (SD: 7.128). The pulse rate at 12 months decreased by - 11.33 (SD: 19.348). Although it was decrease in systolic BP at 12 months. At the same interval, the diastolic BP slightly increased. The pulse rate decreased at 9 and 12 months, as well as at trail exit, but not at 15 or 18 months of follow-up. The differences in the magnitude and direction from increase to decrease in these measurements make impossible to evaluate the impact of treatment on the pulse and blood pressure in these three (3) patients. The waist and hip circumference were reduced when assessed at 6 and 12 months. However, these reductions were assessed in two patients at 6 months and in three (3) patients at 12 months.
Study Strengths & Weaknesses	No strengths. The weaknesses include an inadequate progress including small sample size, poor follow-up, and early termination of the study. The study enrolled two (2) out of 20 sites that were expected and four (4) out of 200 expected patients as per approved protocol. From the four (4) enrolled study subjects one (1) of them was followed for 18 months, two (2) more for one year and the other patient dropped out.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P130021 S002/ PAS001
Date Original Protocol Accepted	06/12/2014
Date Current Protocol Accepted	05/09/2017
Study Name	Continued f/u of the premarket cohorts
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Extended follow-up study of all available subjects that were enrolled in the Medtronic CoreValve® U.S. Pivotal Trial and Continued Access Study who received the Medtronic CoreValve® System (MCS) or underwent surgical aortic valve replacement (SAVR).
Study Population	High risk and extreme risk subjects currently consented to and enrolled in the Medtronic U.S. Pivotal Trial and Continued Access Study who received the MCS or underwent SAVR.
Sample Size	All available subjects enrolled in the US Pivotal Trial, 394 subjects randomized to transcatheter aortic valve replacement (TAVR) and 401 subjects randomized to surgical aortic valve replacement (SAVR), and 76 roll-in subjects in all sites (up to 45) and approximately 2800 CAP subjects.
Key Study Endpoints	The primary endpoint of all-cause mortality at 12 months in High Risk subjects is non-inferior to surgical aortic valve replacement (SAVR), has been met. Clinical outcomes will be characterized annually through 5 years. The secondary endpoints through 12 months have been evaluated. The following secondary endpoints will characterize clinical outcomes annually through 5 years: A. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) event rates via Kaplan-Meier. MACCE is defined as a composite of: ¿ all-cause death ¿ myocardial infarction (MI) ¿ all stroke, and ¿ reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve) 2. The occurrence of individual MACCE components event rates via Kaplan-Meier 3. Major Adverse Events (MAE) event rates via Kaplan-Meier 4. Conduction disturbance requiring permanent pacemaker implantation event rates via Kaplan-Meier 5. Change in NYHA class 6. Quality of Life (QoL) change using the following measures: ¿ Kansas City Cardiomyopathy Questionnaire (KCCQ) ¿ SF 12, and ¿ EuroQoL 7. Echocardiographic assessment of valve performance using the following measures: ¿ transvalvular mean gradient ¿ effective orifice area ¿ degree of aortic valve regurgitation (transvalvular and paravalvular) 8. Aortic valve disease hospitalization event rates via Kaplan-Meier 9. Cardiovascular deaths and valve-related deaths event rates via Kaplan-Meier 10.Strokes (of any severity) and TIAs event rates via Kaplan-Meier 11.Evidence of prosthetic valve dysfunction
Follow-up Visits and Length of Follow-up	Annually through 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Pivotal Extreme Risk Cohort: 656 CAP Extreme Risk Cohort: 1,658 Pivotal High Risk Cohort: 797 CAP High Risk Cohort: 1,119
Actual Number of Sites Enrolled	Pivotal Extreme Risk Cohort: 41 study sites CAP Extreme Risk Cohort: 45 study sites Pivotal High Risk Cohort: 45 study sites CAP High Risk Cohort: 45 study sites
Patient Follow-up Rate	Pivotal Extreme Risk Cohort: 96.2% at 5 years (152/158) CAP Extreme Risk Cohort: 91.6% at 5 years (1488/1624) Pivotal High Risk Cohort: 92.9% at 5 years in TAVR ITT subjects (367/395); 77.9% at 5 years in SAVR ITT subjects (313/402) CAP High Risk Cohort: 89.6% at 5 years (993/1108)
Final Safety Findings	Pivotal Extreme Risk Cohort: The Kaplan Meier (K-M) rate of all-cause mortality or major stroke in the extreme risk (ER) Pivotal Cohort at 60 months was 71.7% in Iliofemoral subjects and 72.6% in combined group. The KM rate for all-cause mortality at 60 months was 70.9% in Iliofemoral subjects and 71.6% in combine group. The KM rate of cardiovascular mortality at 60 months was 55.0% in Iliofemoral group and 55.8% in combine group. CAP Extreme Risk Cohort: The Kaplan Meier (K-M) rate for all-cause mortality at 60 months was 69.1%. Pivotal High Risk Cohort: The Kaplan-Meier (K-M) rate for all-cause mortality was 55.1% and 55.3% at 60 months for TAVR subjects and SAVR subjects respectively. The K-M rate of all stroke (major and minor) at 60 months was 17.5% in the TAVR cohort and 21.0% in the SAVR cohort. CAP High Risk Cohort: The Kaplan Meier (K-M) rate for all-cause mortality at 60 months was 60.3%.
Final Effect Findings	Pivotal Extreme Risk Cohort: The mean change in NYHA class at 60 months compared to baseline remained statistically significant with a mean reduction of -1.5 + 0.8 in Iliofemoral subjects and -1.4+0.8 in combine group (p<0.0001). The change in KCCQ overall summary score at 60 months compared to baseline remained statistically significant with a mean change of 21.2 +/- 27.9 in Iliofemoral subjects and 21.2+27.0 in combine group (p<0.0001). The EOAs values remained stable throughout the follow-up visits and the EOA mean for all sizes was reported 1.83+0.64 cm2 at 60 months CAP Extreme Risk Cohort: The mean change in NYHA class at 60 months compared to baseline is statistically significant with a mean reduction of -1.3 + 0.8 (p<0.0001). The change in KCCQ overall summary score at 60 months compared to baseline is statistically significant with a mean change of 24.0 + 28.8 (p<0.0001). The low post-procedure mean gradients remained stable through the subsequent follow-up visits and mean gradient 7.03 +/- 4.02 mmHg (n=260) was observed for the Extreme Risk cohort at 60 months. EOA values remained stable throughout the follow-up visits and a mean EOA of 1.92 +/- 0.61 cm2 was reported for the ER group (n=285) at 60 months. Pivotal High Risk Cohort: The mean change in NYHA class at 60 months compared to baseline is statistically significant with a mean reduction of -1.3 + 0.9 (p<0.0001) for TAVR subjects and of -1.3 + 0.8 (p<0.0001) for SAVR. The change in KCCQ overall summary score at 60 months compared to baseline is statistically significant with a mean change of 15.2 + 28.3 (p<0.0001) for TAVR and 15.8 + 25.4 for SAVR (p<0.0001). A mean gradient of 7.07 +/- 3.55 mmHg was observed for the TAVR subjects at 60 months (N=114) and 10.93 + /- 5.71 mmHg (N=90) was observed in the SAVR group at the 60-month follow-up (p<0.0001 vs TAVR). EOA values remained stable throughout the follow-up visits and a mean EOA of 1.92 +/- 0.58 cm2 was reported for the TAVR group (N=101) and 1.66 +/- 0.61 cm2 for the SAVR group (N=86) at 60 months (p=0.003 vs TAVR). CAP High Risk Cohort: The mean change in NYHA class at 60 months compared to baseline is statistically significant with a mean reduction of -1.3 + 0.8 (p<0.0001). The change in KCCQ overall summary score at 60 months compared to baseline is statistically significant with a mean change of 21.0 + 26.1 (p<0.0001). The low post-procedure mean gradients remained stable through the subsequent follow-up visits and mean gradient 7.14 +/- 4.25 mmHg (n=260) was observed for the High Risk cohort at 60 months. EOA values remained stable throughout the follow-up visits and a mean EOA of 1.90 +/- 0.58 cm2 was reported for the HR group (n=240) at 60 months.
Study Strengths & Weaknesses	Pivotal Extreme Risk Cohort: The ER Pivotal trial compliance rate was high (i.e., 96.7%) at 5 years. The ER Pivotal trial met the primary 5 endpoints and provided long term data. However, the KM rate of all-cause mortality was high (i.e., 71.6%) in the combined group at 5 years. These patients tended to have a worse baseline health condition with high STS score of 10.4 +/- 5.6% (combined group) and this could have contributed to the high all-cause mortality. Given that all-cause mortality is an evaluable endpoint for the study, this data was captured. Thus, patient exit through death is likely to have less impact on the validity of the study results. Pivotal High Risk Cohort: For the HR Pivotal cohort, improvements in hemodynamic and functional performance were generally preserved through 5 years as evidenced by echocardiographic results, NYHA classification and overall KCCQ score. The 5 year follow-up was lower for SAVR than TAVR in both the ITT and AT cohorts. 77.9% of the SAVR ITT cohort had completed follow-up as compared to 92.9% of the TAVR ITT cohort. 85.8% of the SAVR AT cohort had completed follow-up as compared to 93.4% of the TAVR AT cohort. This raises the possibility of non-random missingness which could result in biased longer-term data. CAP Extreme Risk Cohort & CAP High Risk Cohort: The unadjusted mortality rates (i.e. mortality rates that do not take into account known risk factors for death such as subject’s age or comorbidities at baseline) for both the ER and HR cohorts, over the study duration, are in line with the unadjusted mortality rates previously reported for other studied CoreValve TAVR patient populations with multiple comorbidities and/or risk factors. The follow-up rate for potentially eligible subjects (not dead and in visit window) was lower than ideal at the five-year visits for both the ER and HR cohorts (75% for both). However, the overall follow-up rate for subjects with attempted procedures is high when known deaths are included as followed (91.6% for ER and 89.6% for HR). Also, data completion for key assessments such as echocardiograph are lower than ideal for the longer-term follow-up visits. Because there was loss to follow-up and missing assessments, the potential for selection bias due to systematic attrition or systematically missing assessments cannot be ruled out.
Recommendations for Labeling Changes	Pivotal Extreme Risk Cohort & CAP Extreme Risk Cohorts: The CoreValve System used for this study is no longer marketed – replaced by the EvolutR and then the EvolutPro. No labeling changes are recommended. Pivotal High Risk Cohort & CAP High Risk Cohorts: Complete longer-term follow-up data for the Pivotal High Risk and Continued Access Study High-Risk cohorts warrants inclusion into the labeling for the device and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S002/ PAS002
Date Original Protocol Accepted	06/12/2014
Date Current Protocol Accepted	06/12/2014
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score greater than or equal to 8% or at a greater than or equal to 15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure) (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological, vascular and quality of life outcomes at 30 days and 12 months; and (4) all-cause mortality, neurological and vascular outcomes annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P950022 S085/ PAS001
Date Original Protocol Accepted	02/21/2014
Date Current Protocol Accepted	05/20/2020
Study Name	OptiSure Lead Post Approval Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to collect long term safety data of Optisure family of high voltage leads. This study transitions the Optisure Post Approval Study from a traditional prospective study design to a real world evidence data method for post market monitoring of the Optisure lead. This method merges multiple real world datasets to assess the Optisure lead performance in a larger patient population. The proposed method matches patient population datasets from Abbott and Centers for Medicare and Medicaid Services (CMS) in order to generate data that can be used to evaluate safety of leads in a post market setting.
Study Population	All patients who had an implant of the Optisure Lead, meet inclusion/exclusion criteria, and link to Medicare FFS claims will be included in the analysis of this endpoint.
Sample Size	Assuming the time to first complication follows an exponential distribution and the complication-free survival at 5 years is 95%, a minimal sample size of 645 patients provides 80% power to reject the null hypothesis of 92.5% complication-free survival years at the 5% significance level. It is estimated that 4287 patients with Optisure lead implants will meet inclusion/exclusion criteria and link to Medicare FFS claims for this study, which greatly exceeds the minimal required sample size.
Key Study Endpoints	The primary outcome measure is the complication free survival rate at five years for complications related to the Otisure leads. The secondary outcome measure is a rate of cardiac tamponade or cardiac perforation events.
Follow-up Visits and Length of Follow-up	The study completion is 5 years after final implant, December 2020. The data retention period will be for 2 years after the submission of the final report.
Interim or Final Data Summary
Actual Number of Patients Enrolled	4,023 eligible subjects with 4,028 Optisure leads
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	The rate of freedom from Optisure lead related complications was 97.3% for the worst-case scenario
Final Effect Findings	The rate of all cardiac tamponade and cardiac perforation events during the study time period was 44 events in 28 patients (0.6960% of patients with event) and 7 events in 7 patients (0.1740% of patients with event), respectively
Study Strengths & Weaknesses	Overall, the results demonstrate the safety of the Optisure family of leads within a large patient population using a real-world data analysis approach. The rate of cardiac tamponade and cardiac perforation events in the Optisure RWE Study remains comparable to what was observed and reported in the Optisure PAS 72-month clinical study report for Optisure lead related cardiac tamponade and perforation complications. The benefit to risk ratio associated with the Optisure leads remains favorable as determined using RWE analysis. No new risks were identified in the course of the RWE Study.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P950022 S085/ PAS002
Date Original Protocol Accepted	02/21/2014
Date Current Protocol Accepted	02/21/2014
Study Name	Externalization and Abrasion Sub-Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	477 subjects from the main study were consented and enrolled in the sub study
Actual Number of Sites Enrolled	60 clinical sites
Patient Follow-up Rate	As of the cut-off date for this report, in the sub-study a total of 370 subjects have completed the 12 month visit, 335 subjects have completed the 24 month, 279 subjects have completed the 36 month, 233 have completed the 48 month follow-up visit, and 9 have completed the 60 month visit, which includes some of the initial cinefluoroscopy evaluations for the sub-study.
Final Safety Findings	There were a total of 5 adverse events (3 complications and 2 observations) reported post Optisure lead interventions. The complications were related to the following: Lead Dislodgement or Migration and Pericardial Effusion. The observations were related to the following: Bleeding and other.
Final Effect Findings	There are 10 cases of Optisure RV leads that were adjudicated by the Electrical Data Adjudication Committee (EDAC). Of the 10 cases, 1 was adjudicated as having electrical dysfunction. The others had reasons other than the integrity of the lead as the cause for electrical abnormalities. The sponsor states that as of the cutoff date of this report, zero externalized conductors, zero visual lead anomalies and zero other insulation anomalies have been identified by the CAC for the Optisure RV leads.
Study Strengths & Weaknesses	There has been no incidence of externalized conductors (EC) or visual lead anomalies (VLA) in Optisure leads as measured throughout >4 years of follow-up in the sub-study.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P120023 / PAS001
Study Name	Continuation Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to evaluate the safety of the AcuFocus¢â ACI 7000PDT corneal inlay implanted intrastromally in presbyopes and the effectiveness of the inlay for improvement of near vision.
Study Population	Presbyopic subjects needing a magnitude of 1.00D to 2.50D of reading add will be enrolled. Subjects must be natural emmetropes and have a preoperative spherical equivalent of plano defined as +0.50D to -0.75D with no more than 0.75D of refractive cylinder as determined by cycloplegic refraction. Eligible subjects must be greater than or equal to 45 years and less than or equal to 60 years of age.
Sample Size	This will be a prospective multicenter clinical trial in which 400 consecutive eyes of 400 patients will be implanted with the ACI 7000PDT and followed with post-operative visits over a 36 month period at a maximum of 20 clinical sites. Enrollment of the study population will be phased, such that 75 eyes will be enrolled initially. Following review of 3-month postoperative data from the first 75 eyes having undergone ACI implantation, an interim report will be submitted requesting expansion to the full study population- an additional 325 eyes.
Key Study Endpoints	Postoperatively, subjects will undergo complete ophthalmic examinations at regular intervals to evaluate safety and effectiveness of the ACI in improving near vision. -Improvement in uncorrected near visual acuity (40cm/16in.) at 12 months. 75% of eyes should achieve uncorrected near visual acuity of 20/40 or better. -Subjective improvement in near vision as measured by subject satisfaction questionnaire. Primary Effectiveness Endpoint The percentage of eyes with a UCNVA of 20/40 or better (success rate) will be calculated at each postoperative visit for near ETDRS visual acuity. The 95% confidence intervals of the success rates will be calculated based on the exact binomial distribution. The 95% confidence interval at 12-months will be used to compare with the target success rate of 75%. The lower limit of the confidence interval must be 75% or greater in order to claim effectiveness of the device. Logistic regression analyses will be used to examine the possible effects of investigator sites, age, flap thickness, and other clinical parameters identified by clinicians prior to the analyses. The success rates will be stratified by the significant factors identified by the logistic regression. Secondary Effectiveness Outcome The secondary effectiveness endpoint of subjective improvement in near vision as measured by subject satisfaction questionnaire will be assessed when the primary effectiveness endpoint has been achieved. Change in subject satisfaction from baseline, and the reduction in spectacle dependence for near tasks will be summarized by descriptive statistics such as mean and frequency. The corresponding 95% confidence intervals for mean and frequency will be calculated.
Follow-up Visits and Length of Follow-up	Postoperative follow-up through 36 months on all study patients will be completed.
Interim or Final Data Summary
Actual Number of Patients Enrolled	271
Actual Number of Sites Enrolled	19 (13 US, 6 OUS)
Patient Follow-up Rate	93.4% (253/271)
Final Safety Findings	The safety cohort consists of 269 subjects at 48 months and 253 subjects at 60 months. The primary safety outcome of persistent BCDVA loss of two or more lines at two or more consecutive visits was 0.7% (2/269) at 48 months and 0.8% (2/253) at 60 months, both of which were below the protocol-specified target of less than 5%. The two cases of persistent loss of BCDVA at Months 48 and 60 (61118 and 86120) were attributed to lenticular changes.
Final Effect Findings	The primary effectiveness parameter specified in the protocol was improvement in uncorrected near visual acuity (UCNVA) at Month 12, with a target of at least 75% attaining monocular 20/40 or better UCNVA. The effectiveness cohort consisted of 267 subjects at 48 months and 252 subjects at 60 months. For monocular UCNVA of implanted eyes, 89.1% (238/267) of eyes had UCNVA of 20/40 or better at Month 48 and 215/252 (85.3%) at Month 60. These results are consistent with the 87.1% (363/417) reported at Month 36. For changes from baseline UCNVA in the implanted eye, gains of greater than or equal to 2 lines were sustained in 75% or more of the eyes through 60 months; gains of greater than 3 lines were sustained in approximately half of the eyes. Looking specifically at gains in UCNVA of 2 lines or greater, the reported proportions are 78.2% (326/417) at Month 36, 75.7% (202/267) at Month 48 and 189/252 (75.0%) at Month 60.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P130021 S014/ PAS001
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled under the IDE (G140059). The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	351 subjects were enrolled, of which 241 received an attempted implant.
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 90%. Compliance with visit assessments (e.g., NYHA Classification, KCCQ) was approximately 67% of subjects who completed the 5Y follow-up visit, and compliance with echocardiographic imaging assessments ranged from 46% to 53% of subjects who attended the final 5-year visit.
Final Safety Findings	The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: All-cause mortality: 46.9% (27.3% cardiovascular mortality) All stroke: 14.4% (8.1% disabling stroke) Vascular complications: 14.5% Bleeding: 34.6% (15.7% life-threatening or disabling) Acute kidney injury: 0.8% Stage 2, 0.4% Stage 3 Myocardial infarction: 5.1% New permanent pacemaker: 27.4% Valve thrombosis: 0.6% Valve endocarditis: 1.0% Valve-related dysfunction requiring repeat procedure: 0.0% Coronary artery obstruction: 0.4%
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit (unless otherwise noted): NYHA Classification: Improvement in NYHA classification was maintained through 5 years. The mean change compared to baseline at 5 years was -1.3 +/-0.8 (n=90), and 76.1% of subjects were Class I/II. KCCQ: Clinically significant improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 23.6 +/- 28.0 (n=90) Valve Performance Outcomes: Mean effective orifice area (EOA) increased from 0.6 +/- 0.2 cm2 at baseline to 1.9 +/- 0.5 cm2 at 30 days. At 5 years, the EOA was 1.8 +/- 0.5 cm2 (n=54) Overall, mean gradient decreased from 48.2 +/- 13.0 mmHg at baseline to 7.8 +/- 3.1 mmHg at 30 days. At 5 years, the overall mean gradient was 10.0 +/- 8.0 mmHg (n=60). At 5 years, 100% of subjects with available echocardiographic data (n=60) had mild or less total aortic regurgitation (AR). At 5 years, 100% of subjects with available echocardiographic data (n=58) had mild or less paravalvular AR.
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the CoreValve Evolut R valve in patients with severe symptomatic aortic stenosis at high or greater surgical risk. Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvement in quality of life outcomes and hemodynamic performance. The lack of completion of some assessments of interest including NYHA Classification, KCCQ, and echocardiographic imaging at the 5-year study visit presents challenges to the interpretability of longer-term effectiveness outcomes. The missing data is in part related to challenges with in-person visits during the COVID-19 pandemic. Additionally, it should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results.
Recommendations for Labeling Changes	The labeling is recommended to be updated to reflect the 5 year findings of the study and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S014/ PAS002
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score =8% or at a =15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P010030 S056/ PAS001
Date Original Protocol Accepted	12/17/2015
Date Current Protocol Accepted
Study Name	PMA Post-Approval Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospectively collect and assess device data with the patients under 18 years of age using manufacturer owned registry
Study Population	The patient population will be all patients who have been prescribed the LifeVest under the proposed indication. There are no comparison groups.
Sample Size	For the purpose of this data collection proposal, ZOLL will collect data on 150 patients under 18 years of age.
Key Study Endpoints	The following data will be collected: a) Patient Demographics: i. Age ii. Gender iii. ICD-9 code(s) describing the patient’s condition b) Performance: i. Daily compliance with use ii. Duration of use iii. Appropriate therapy delivery, as determined by internal medically trained personnel iv. ECG recordings during appropriate therapy delivery and any available description of the circumstances found within the Call Report Database. c) Safety: i. Inappropriate defibrillation therapy delivery, as determined by internal medically trained personnel ii. ECG recordings during inappropriate therapy delivery and any available description of the circumstances found within the Call Report Database iii. Adverse events reported to ZOLL through the customer support or technical support departments
Follow-up Visits and Length of Follow-up	The device will be used temporarily (days) and the data will be obtained from returned device. No actual patient followup is needed.
Interim or Final Data Summary
Actual Number of Patients Enrolled	273
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	Adverse event rate reported as complaints: - 4 (1.47% of patients) - 0.1 AEs/patient years of wear time (4/39.5) Inappropriate Defibrillation Data: 1 shock/14,435 patient days = 0.002 inappropriate shocks/month
Final Effect Findings	Only 1 appropriate shock was observed in the current study. First shock success rate: 100%.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P130021 S016/ PAS001
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohorts. The objective of this study is to characterize the cumulative clinical outcomes of all subjects through 5 years post procedure.
Study Population	The study will consist of all living subjects who were enrolled in the ¿Low Flow Low Gradient¿ (LFLG) and ¿End-Stage Renal Disease¿ (ESRD) cohorts under the IDE.
Sample Size	All living subjects.
Key Study Endpoints	The safety and effectiveness endpoints include all-cause mortality or major stroke at 6 months, 12 months and annually through 5 years and the following at 30 days, 6 months, and annually through 5 years: major adverse cardiovascular and cerebrovascular event (MACCE) event rate; occurrence of individual MACCE components; major adverse events (MAE); conduction disturbance requiring permanent pacemaker implantation; change in New York Heart Association (NYHA) classification; quality of life (QoL) change as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ), SF-12, and EuroQoL; echocardiographic assessment of valve performance; aortic valve disease hospitalization; cardiovascular deaths and valve-related deaths; strokes (of any severity) and transient ischemic attacks (TIAs); and evidence of prosthetic valve dysfunction.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	133 subjects (ESRD) 215 subjects (LFLG)
Actual Number of Sites Enrolled	36 (ESRD) 28 (LFLG)
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 95% for the ESRD cohort and 97% for the LFLG cohort
Final Safety Findings	The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: ESRD Cohort All-cause mortality or major stroke: 89.9% All-cause mortality: 89.9% Cardiovascular mortality: 68.5% All stroke: 13.3% (9.9% major stroke) Bleed: 56.3% Valve-related death: 9.8% Aortic valve hospitalization: 36.3% Reintervention: 1.8% Major adverse cardiovascular and cerebrovascular event (MACCE): 90.9% New PPM: 50.8% LFLG Cohort All-cause mortality or major stroke: 74.4% All-cause mortality: 74% Cardiovascular mortality: 56.9% All stroke: 18.5% (13.8% major stroke) Bleed: 38.9% Valve-related death: 7.6% Aortic valve hospitalization: 50.4% Reintervention: 5% Major adverse cardiovascular and cerebrovascular event (MACCE): 78.1% New PPM: 45.9%
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit: ESRD Cohort NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. The mean change compared to baseline at 5 years was -1.2 +/- 0.8 (n=9). KCCQ: Improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 15.2 +/- 30.0 (n=9). Valve Performance Outcomes: Mean gradient decreased from 45.03 +/- 13.61 at baseline to 9.02 +/- 3.92 at 30 days. At 5-years, the overall mean gradient was 7.71 + 3.55 mmHg (n=8). Mean effective orifice area (EOA) increased from 0.72 +/- 0.20 cm2 at baseline to 1.77 +/- 0.47 cm2 at 30 days. At 5 years, the EOA was 1.70 + 0.84 cm2 (n=8). At 5 years, 100% of subjects with available echocardiographic data (n=8) had mild or less total aortic regurgitation (AR). LFLG Cohort NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. The mean change compared to baseline at 5 years was -1.2 +/- 0.7 (n=33). KCCQ: Improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 20.9 +/- 24.9 (n=35). Valve Performance Outcomes: Mean gradient decreased from 28.41 +/- 5.06 at baseline to 6.40 +/- 3.23 at 30 days. At 5-years, the overall mean gradient was 6.21 +/- 3.65 mmHg (n=32). Mean effective orifice area (EOA) increased from 0.77 +/- 0.19 cm2 at baseline to 1.83 +/- 0.55 cm2 at 30 days. At 5 years, the EOA was 1.96 +/- 0.77 cm2 (n=29). At 5 years, 93.6% of subjects with available echocardiographic data (n=32) had mild or less total aortic regurgitation (AR).
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the Medtronic CoreValve System in patients with symptomatic severe aortic stenosis with predicted operative mortality or serious, irreversible morbidity risk of > 50% at 30 days who have end stage renal disease or low gradient, low output aortic stenosis. Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvements shown for both cohorts from baseline to 5 years. However, Echocardiography Corelab and Quality of Life compliance rates at 5 years are low for both cohorts (44-65%). The incomplete data may impact the ability to interpret and draw conclusions from the results.
Recommendations for Labeling Changes	The labeling is recommended to be updated to reflect the 5 year findings of the study and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S016/ PAS002
Date Original Protocol Accepted	11/02/2015
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance of the Medtronic CoreValve and CoreValve Evolut R systems in the post-approval setting through the national TVT-registry (TVT-R).
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score ¡Ý8% or at a ¡Ý15% risk of mortality at 30 days) with either end stage renal disease (ESRD) or low gradient low output (LGLO) aortic stenosis
Sample Size	All implanted patients in the TVT-R within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P130021 S025/ PAS001
Date Original Protocol Accepted	10/26/2016
Date Current Protocol Accepted
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Interim or Final Data Summary
Actual Number of Patients Enrolled	72 enrolled; 60 received an attempted implant
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 75%. Compliance with visit assessments (e.g., NYHA Classification, KCCQ) ranged from 69% to 72% of subjects who completed the 5Y follow-up visit, and compliance with echocardiographic imaging assessments were approximately 63% of subjects who attended the final 5-year visit.
Final Safety Findings	The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: - All-cause mortality: 45.9% (29.8% cardiovascular mortality) - All stroke: 14.6% (6.3% disabling stroke) - Vascular Complications: 3.3% - Bleeding: 22.8% (13.2% life-threatening or disabling) - Acute kidney injury: 0.0% - Myocardial infarction: 13.9% - New permanent pacemaker: 35.7% - Valve thrombosis: 2.1% - Valve endocarditis: 2.8% - Valve-related dysfunction requiring repeat procedure: 2.8% - Coronary artery obstruction: 0.0%
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit (unless otherwise noted): • NYHA Classification: Improvement in NYHA classification was maintained through 5 years. The mean change compared to baseline at 5 years was -1.1 +/- 0.8 (n=23), and 91% of the remaining 23 subjects were Class I/II. • KCCQ: Clinically significant improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 17.0 +/- 22.9 (n=22) • Valve Performance Outcomes: o Mean effective orifice area (EOA) increased from 0.8 +/- 0.2 cm2 at baseline to 2.6 +/- 0.7 cm2 at 30 days. At 5 years, the EOA was 2.6 +/- 0.7 cm2 (n=20) o Overall, mean gradient decreased from 41.5 +/- 10.3 mmHg at baseline to 6.3 +/- 3.2 mmHg at 30 days. At 5 years, the overall mean gradient was 8.3 +/- 5.6 mmHg (n=20). o At 5 years, 100% of subjects with available echocardiographic data (n=20) had mild or less total aortic regurgitation (AR). o At 5 years, 100% of subjects with available echocardiographic data (n=20) had mild or less paravalvular AR.
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the CoreValve Evolut 34R valve in patients with severe symptomatic aortic stenosis at high or greater surgical risk. Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvement in quality of life outcomes and hemodynamic performance. The lack of completion of some assessments of interest including NYHA Classification, KCCQ, and echocardiographic imaging at the 5-year study visit presents challenges to the interpretability of longer-term effectiveness outcomes. The missing data is in part related to challenges with in-person visits during the COVID-19 pandemic. Additionally, it should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results.
Recommendations for Labeling Changes	Complete longer-term follow-up data warrants inclusion into the labeling for the device and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S025/ PAS002
Date Original Protocol Accepted	10/26/2016
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score greater than or equal to 8% or at a greater than or equal to 15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P130021 S029/ PAS001
Date Original Protocol Accepted	03/20/2017
Date Current Protocol Accepted
Study Name	Cont f/u of CoreValve Evolut PRO System
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the CoreValve Evolut PRO IDE (G160039). The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	93 subjects enrolled; 60 received an attempted implant
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 75%. Compliance with visit assessments (e.g., NYHA Classification, KCCQ) ranged from 62% to 68% of subjects who completed the 5Y follow-up visit, and compliance with echocardiographic imaging assessments ranged from 38% to 56% of subjects who attended the final 5-year visit.
Final Safety Findings	The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: - All-cause mortality: 46.2% (32% cardiovascular mortality) - All stroke: 17.4% (13.9% disabling stroke) - Vascular Complications: 11.7% - Bleeding: 42.6% (15.6% life-threatening or disabling) - Acute kidney injury: 5% - Myocardial infarction: 7.2% - New permanent pacemaker: 19.2% - Valve thrombosis: 4.6% - Valve endocarditis: 0.0% - Valve-related dysfunction requiring repeat procedure: 0.0% - Coronary artery obstruction: 0.0%
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit (unless otherwise noted): • NYHA Classification: Improvement in NYHA classification was maintained through 5 years. The mean change compared to baseline at 5 years was -1.2 +/- 0.7 (n=21), and 95% of the remaining 21 subjects were Class I/II. • KCCQ: Clinically significant improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 14.9 +/- 23.4 (n=22) • Valve Performance Outcomes: o Mean effective orifice area (EOA) increased from 0.7 +/- 0.2 cm2 at baseline to 2.0 +/- 0.5 cm2 at 30 days. At 5 years, the EOA was 2.3 +/- 0.8 cm2 (n=13) o Overall, mean gradient decreased from 44.9 +/- 13.0 mmHg at baseline to 6.4 +/- 2.1 mmHg at 30 days. At 5 years, the overall mean gradient was 6.2 +/- 2.9 mmHg (n=18). o At 5 years, 100% of subjects with available echocardiographic data (n=19) had mild or less total aortic regurgitation (AR). o At 5 years, 100% of subjects with available echocardiographic data (n=18) had mild or less paravalvular AR
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the CoreValve Evolut PRO valve in patients with severe symptomatic aortic stenosis at high or greater surgical risk. Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvement in quality of life outcomes and hemodynamic performance. The lack of completion of some assessments of interest including NYHA Classification, KCCQ, and echocardiographic imaging at the 5-year study visit presents challenges to the interpretability of longer-term effectiveness outcomes. The missing data is in part related to challenges with in-person visits during the COVID-19 pandemic. Additionally, it should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results
Recommendations for Labeling Changes	Complete longer-term follow-up data warrants inclusion into the labeling for the device and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S029/ PAS002
Date Original Protocol Accepted	03/20/2017
Date Current Protocol Accepted
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S033/ PAS002
Date Original Protocol Accepted	04/09/2018
Date Current Protocol Accepted
Study Name	Intermediate Risk Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive- Linked/Registry Based Surveillance. This is prospective, non-randomized study. The purpose of the surveillance plan is to utilize the TVT Registry to evaluate longer term the safety and device performance of the Medtronic TAVR for intermediate risk patients with symptomatic severe native aortic stenosis for 2 years following device approval. Annual clinical summaries will report long term follow-up and monitor adverse events (as collected through the TVT-R and CMS claims data) through 5 years post implant.
Study Population	Patients with symptomatic heart disease due to severe native calcific aortic stenosis who are judged by a heart team, including a cardiac surgeon, to be at intermediate or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality greater than or equal to 3% at 30 days, based on the Society of Thoracic Surgeons (STS) risk score and other clinical comorbidities unmeasured by the STS risk calculator).
Sample Size	Subjects with an attempted implant of Medtronic TAVR within 2 years of approval for intermediate surgical risk and entered in the TVT-R from participating sites.
Key Study Endpoints	Intra-procedure Device success At 30 days and 12 months: All-cause mortality All stroke Life threatening/Major bleeding New requirement for dialysis Peri-procedural myocardial infarction Repeat procedure for valve-related dysfunction (surgical or interventional therapy) Neurological (Non-stroke) Vascular complications Quality of life (KCCQ) outcomes At 2 – 5 years post-implantation: All-cause mortality All stroke Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
Follow-up Visits and Length of Follow-up	5 year post implantation.
Interim or Final Data Summary
Interim Results	Overall TVT-R/CMS Matched Population Event Rates at 3 Years: All-Cause Mortality: 24.7%, Any Stroke: 9.3%, Aortic Valve Reintervention: 1.0%
Actual Number of Patients Enrolled	12,627 TVT-R intermediate risk patients; 10,374 subjects were uniquely matched with the CMS claims and encounter data
Actual Number of Sites Enrolled	Registry based
Patient Follow-up Rate	Overall Study Compliance Rate: Of 12,627 TVT-R intermediate risk patients, 10,374 subjects were uniquely matched with the CMS data
General
Study Status	Completed
Application Number / Requirement Number	P160049 / PAS001
Date Original Protocol Accepted	07/26/2017
Date Current Protocol Accepted
Study Name	ILLUMINATE Continued Follow-Up Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will evaluate the long-term safety and effectiveness of the Stellarex 035 DCB in 300 subjects from the premarket study (ILLUMINATE trial).
Study Population	The test group is the Stellarex DCB and the control group is standard PTA.
Sample Size	A minimum of 236 subjects evaluable at 24 months are required for the sample size calculations.
Key Study Endpoints	The primary effectiveness endpoint is primary patency of the target lesion at 24 months. The primary safety endpoint is a composite of freedom from device- and procedure-related death at 30 days and freedom from target limb major amputation and clinically-driven target vessel revascularization (CD-TVR) at 24 months. Secondary endpoints include : (1) major adverse events (MAE), (2) clinically-driven target lesion revascularization (CD-TLR), (3) all TLR, (4) clinically-driven target vessel revascularization (CD-TVR), (5) target limb major amputation, (6) mortality, and (7) arterial thrombosis. The endpoints to be assessed at 2 and 3 years post-procedure are: (1) patency, (2) change in ankle-brachial index (ABI), (3) change in walking impairment questionnaire (WIQ), (4) change in walking distance, (5) change in Rutherford-Becker classification, and (6) change in quality of life assessment by EQ-5D questionnaire.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	300
Actual Number of Sites Enrolled	43
Patient Follow-up Rate	86.3% at 5 years
Final Safety Findings	Major adverse events, as well as all-cause mortality were similar between treatment arms through 5 years.
Final Effect Findings	Primary patency was assessed through 3 years, showing similar outcomes at this point. Similar outcomes were also demonstrated for clinically-driven target lesion revascularization through 5 years.
Study Strengths & Weaknesses	Strengths: The study was a prospectively designed randomized controlled trial with appropriate oversight. Weakness: A higher rate of missing data was present for 5 year follow up.
Recommendations for Labeling Changes	Labeling should be updated to include 5 year clinical data
General
Study Status	Completed
Application Number / Requirement Number	P170003 / PAS001
Date Original Protocol Accepted	08/25/2017
Date Current Protocol Accepted
Study Name	IDE Cohort Post Approval Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will evaluate the long-term safety and effectiveness of the Lutonix 035AV Drug Coated Balloon Catheter (Lutonix 035 DCB) in the remaining 265 subjects from the premarket study.
Study Population	The test group is the Lutonix 035 DCB and the control group is standard PTA.
Sample Size	265 subjects
Key Study Endpoints	The primary effectiveness endpoint is target lesion primary patency (TLPP) through 24 months. The primary safety endpoint is freedom from any serious adverse event(s) involving the AV access circuit through 24 months. Additional endpoints to be assessed through 24 months post-procedure are: (1) access circuit primary patency (ACPP), (2) device, procedural, and clinical success, (3) abandonment of permanent access in the index extremity, (4) number of interventions required to maintain access circuit patency, (5) number of interventions required to maintain target lesion patency, and (6) rate of device and procedure related adverse events.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	285
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	90.5% at 6 months
Final Safety Findings	The primary safety result was 94.9% (130/137) for DCB and 95.8% (138/144) for control PTA freedom from localized or systemic serious adverse events through 30 days.
Final Effect Findings	The primary effectiveness was 71.4% for DCB and 63.0% for control PTA Kaplan-Meier (KM) survival at Day 180.
Study Strengths & Weaknesses	The study had adequate follow-up. It did not meet its primary effectiveness endpoint, but safety was demonstrated to be similar to the control and there was a reduction in the number of reinterventions compared to control.
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S058/ PAS002
Date Original Protocol Accepted	08/16/2019
Date Current Protocol Accepted	03/20/2020
Study Name	Evolut R and PRO Sys Registry-Based Low Risk RWU
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objectives of the surveillance are to characterize the clinical outcomes of the Continued Access Protocol (CAP) cohort annually through 10 years post implantation and to assess the real-world use of the commercial Medtronic CoreValve Evolut R System and CoreValve Evolut PRO System to ensure that the device is used in appropriate circumstances.
Study Population	The surveillance of the CAP cohort will consist of all living CAP patients who were enrolled at participating institutions, and the surveillance of the real-world use will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All living CAP subjects and all consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry; and the follow-up data from year 2 through year 10 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database. The surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-10 year post implantation.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	TVT Registry at 30 days and 1 year: Real World Surveillance Low Risk Cohort K-M Adverse Event Rates: All-cause mortality: 1.2% at 30 days; 5.1% at 1 year Any Stroke: 2.7% at 30 days; 3.6% at 1 year Life-threatening/major bleeding: 3.9% at 30 days; 4.8% at 1 year Vascular Complication: 3.8% at 30 days; 4.0% at 1 year New requirement for dialysis: 0.2% at 30 days; 0.3% at 1 year Myocardial infarction: 0.3% at 30 days; 1.1% at 1 year Aortic Valve Re-intervention: 0.4% at 30 days; 0.7% at 1 year KCCQ: Change from Baseline to 1-Month at 30 days: 25.7 + 24.3; Change from Baseline to 1-Month at 1-Year: 27.5 + 23.9. Low Risk CAP Cohort K-M Adverse Event Rates: All-cause mortality: 0.7% at 30 days; 2.3% at 1 year Any Stroke: 2.7% at 30 days; 3.6% at 1 year Life-threatening/major bleeding: 3.4% at 30 days; 3.8% at 1 year Vascular Complication: 2.8% at 30 days; 3.1% at 1 year New requirement for dialysis: 0.0% at 30 days; 0.1% at 1 year Myocardial infarction: 0.1% at 30 days; 0.5% at 1 year Aortic Valve Re-intervention: 0.3% at 30 days; 0.8% at 1 year KCCQ: Change from Baseline to 1-Month at 30 days: 21.3 + 23.0; Change from Baseline to 1-Month at 1-Year: 24.7 + 22.8 TVT-R/CMS Linked Data: Real World Surveillance Low Risk Cohort: All-Cause Mortality: 5.9% at 1 year Any Stroke: 4.8% at 1 year Aortic Valve Re-intervention: 0.8% at 1 year. Low Risk CAP: All-Cause Mortality: 3.6% at 2 years Any Stroke: 5.9% at 2 years Aortic Valve Re-intervention: 1.0% at 2 years
Actual Number of Patients Enrolled	Real World Surveillance Low Risk Cohort: 7,440 Low Risk CAP Cohort: 745
Actual Number of Sites Enrolled	Registry based
Patient Follow-up Rate	Real World Surveillance Low Risk Cohort: TVT-R: 30 day: 89.3%; 12 months: 83.3% TVT-R/CMS Linked Data: 7,490; 5,338 (71%) were uniquely matched to CMS claims and encounter data. Low Risk CAP: TVT-R: 30 day: 99.6%; 12 month: 97.5% TVT-R/CMS Linked Data: Total Patients: 745; 616 (82%) were uniquely matched to CMS claims and encounter data.
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S076/ PAS001
Date Original Protocol Accepted	08/17/2020
Date Current Protocol Accepted
Study Name	Cont F/u Low Risk Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all 148 subjects who were enrolled in the Bicuspid Registry under IDE G160022. The objective of this study is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the Bicuspid Registry.
Sample Size	148
Key Study Endpoints	All-cause mortality, all stroke (disabling and nondisabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	10 years. All subjects are followed annually through 10 years post procedure.
Interim or Final Data Summary
Interim Results	Safety Results At 6 years: All-cause mortality: 11.8% All stroke (disabling and nondisabling): 10.5% Life-threatening bleeding: 6.4% Acute kidney injury at stage 2 or 3: 0% Coronary artery obstruction requiring intervention: 0.7% Major vascular complication: 2.9% Valve-related dysfunction requiring repeat procedure: 6.6% New permanent pacemaker implantation: 23.5% Prosthetic valve endocarditis: 4.6% Prosthetic valve thrombosis (clinical): 1.3% Effectiveness Results: At 5 years: NYHA classification (change from baseline): 81.1% improved KCCQ overall summary score (change from baseline): 18.9 Mean Gradient: 9.84 mmHg Mean Effective Orifice Area: 2.09 cm2 Total Aortic Regurgitation (greater than or equal to moderate): 0.0%
Actual Number of Patients Enrolled	150 attempted implants
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	87% at 6 years
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S076/ PAS002
Date Original Protocol Accepted	08/17/2020
Date Current Protocol Accepted
Study Name	Low Risk Real World Use Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objective of the surveillance is to assess the real-world use of the CoreValve Evolut R System, CoreValve Evolut PRO System, and Evolut PRO+ System to ensure that the devices are used in appropriate patient population.
Study Population	The surveillance of the real-world use will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period).
Sample Size	All consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry; and the follow-up data from year 2 through year 10 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database. The surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-10 year post implantation.
Follow-up Visits and Length of Follow-up	10 years. All subjects are followed annually through 10 years post procedure.
Interim or Final Data Summary
Interim Results	K-M Adverse Event Rates: All-cause mortality: 1.3% at 30 days; 3.3% at 1-year Any Stroke: 2.6% at 30 days; 3.6% at 1- year Aortic Valve Re-intervention: 1.0% at 30 days; 1.9% at 1-year
Actual Number of Patients Enrolled	Real World Surveillance Low Risk Bicuspid Cohort: 728
Actual Number of Sites Enrolled	278
Patient Follow-up Rate	registry based
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S107/ PAS001
Date Original Protocol Accepted	07/22/2020
Date Current Protocol Accepted
Study Name	Cont f/u of SAPIEN 3 Bicuspid Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all 71 subjects who were enrolled in the Bicuspid Registry under IDE G150278. The objective of this study is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the Bicuspid Registry.
Sample Size	71
Key Study Endpoints	All-cause mortality, all stroke (disabling and nondisabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	10 years - All subjects are followed annually through 10 years post procedure
Interim or Final Data Summary
Interim Results	At 7 years: All-cause mortality (including vital status check): 17.7% [10.4, 29.1]* - KM Stroke: 5.9% [2.2, 14.9]* - KM Aortic valve reintervention: 7.1% [2.6, 14.6]* - CIF Endocarditis: 3.0% [0.8, 11.6]* - KM Bioprosthetic valve failure: 7.1% [2.6, 14.6]* - CIF NYHA (% in class I/II): 93.6% KCCQ (Mean Change from Baseline): 19.4 Transvalvular mean gradient: 13.2 Effective orifice area: 2.0 Greater than or equal to Moderate Total Aortic Regurgitation: 2.3% Greater than or equal to Moderate PVL: 0.0% *Confidence Interval
Actual Number of Patients Enrolled	75 enrolled; 71 implanted
Actual Number of Sites Enrolled	28
Patient Follow-up Rate	At 7 years (patient status known): 94.4%
General
Study Status	Study Pending
Application Number / Requirement Number	P130021 S174/ PAS001
Date Original Protocol Accepted	08/27/2025
Date Current Protocol Accepted	08/27/2025
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Characterize long-term clinical outcomes for the Evolut PRO+, Evolut FX, and Evolut FX+ Systems in patients with a failing aortic transcatheter bioprosthetic valve after PMA approval through the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) registry-based surveillance.
Study Population	All patients entered into the TVT Registry database and treated with the Evolut PRO+, Evolut FX, or Evolut FX+ System for the first 2 years following device approval or a total of 500 consecutively treated such patients, whichever is greater, will be included as part of this registry-based post-approval surveillance.
Sample Size	All consecutive patients treated within the first 2 years following device approval or a total of 500 consecutively treated such patients, whichever is greater, that are entered into the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry (enrollment period).
Key Study Endpoints	Primary Endpoints • Device success (intra-procedure) collected as device implanted successfully in TVT-R • Clinical event outcomes at 30 days and 1 year (collected in TVT-R): o All-cause mortality o All stroke o Life-threatening / major bleeding o New requirement for dialysis o Myocardial infarction o Repeat procedure for valve-related dysfunction (surgical or interventional therapy), collected as aortic valve reintervention o Neurological (non-stroke) collected as transient ischemic attack o Vascular complications (major and minor) • Quality of life (as measured by KCCQ) outcomes at 30 days and 1 year (collected in TVT-R) • All-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2 – 10 years post implantation (collected through CMS claims and encounter data) Secondary Endpoints In-hospital coronary artery obstruction or compression, 30-day and 1-year echo measurements (including mean gradient, effective orifice area, and aortic regurgitation), and 30-day and 1-year NYHA classification scores collected in TVT-R will be summarized.
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P130021 / PAS002
Date Original Protocol Accepted	01/17/2014
Date Current Protocol Accepted	02/17/2014
Study Name	Continued f/u of continued access cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A longitudinal observational clinical trial following subjects that were enrolled in the Medtronic CoreValve® Continued Access Study (CAS) and received the Medtronic CoreValve® System (MCS). Not a hypothesis driven study.
Study Population	Extreme risk subjects currently consented to and enrolled in the Medtronic U.S. CAS Protocol, and implanted with the MCS.
Sample Size	All subjects enrolled in the CoreValve® Continued Access Study (approximately 2250, including both ilio-femoral and non-ilio-femoral implant access) at all sites (up to 45).
Key Study Endpoints	Primary endpoints: all-cause death or major stroke at 6 months and annually through 5 years. Secondary endpoints: The following endpoints will be assessed at 1 month, 6 months, and annually through 5 years: 1. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) event rates via Kaplan-Meier. MACCE is defined as a composite of: ¿ all-cause death ¿ myocardial infarction (MI) ¿ all stroke, and ¿ reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve) 2. The occurrence of individual MACCE components event rates via Kaplan-Meier 3. Major Adverse Events (MAE) event rates via Kaplan-Meier 4. Conduction disturbance requiring permanent pacemaker implantation event rates via Kaplan-Meier 5. Change in NYHA class 6. Quality of Life (QoL) change using the following measures: ¿ Kansas City Cardiomyopathy Questionnaire (KCCQ) ¿ SF 12, and ¿ EuroQoL7. Echocardiographic assessment of valve performance using the following measures: ¿ transvalvular mean gradient ¿ effective orifice area ¿ degree of aortic valve regurgitation (transvalvular and paravalvular) 8. Aortic valve disease hospitalization event rates via Kaplan-Meier 9. Cardiovascular deaths and valve-related deaths event rates viaKaplan-Meier 10. Strokes (of any severity) and TIAs event rates via Kaplan-Meier 11. Evidence of prosthetic valve dysfunction
Follow-up Visits and Length of Follow-up	Annually through 5 years
General
Study Status	Terminated
Application Number / Requirement Number	P130021 / PAS003
Date Original Protocol Accepted	01/17/2014
Date Current Protocol Accepted
Study Name	New Enrollment of extreme risk patients
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P120011 / PAS001
Date Original Protocol Accepted	11/14/2014
Date Current Protocol Accepted	11/14/2014
Study Name	Post-Approval PMA Cohort Study (PACS)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will continue to follow subjects from the premarket cohorts for 10 years. The data are to be collected via annual physician follow-up evaluations
Study Population	Women aged 18 or over who are undergoing primary breast augmentation or replacement of existing augmentation implants
Sample Size	502 subjects enrolled at 35 study sites
Key Study Endpoints	Safety endpoints: The incidence and timing of all adverse events that are collected throughout the study. Additionally, several distinct adverse events, including peri-prosthetic infection, seroma, capsule contracture (Baker class II-IV), explant, spontaneous failure of the inner shell, spontaneous failure of the outer shell and spontaneous deflation will be summarized separately Effectiveness endpoints: Increase in breast size; Patient satisfaction; Investigator satisfaction
Follow-up Visits and Length of Follow-up	10 years All subjects will be followed annually through 10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	503
Actual Number of Sites Enrolled	32
Patient Follow-up Rate	The follow-up rate was 92.7% for primary augmentation cohort and 96.6% for revision augmentation cohort at 10 years.
Final Safety Findings	pending final labeling review
Final Effect Findings	pending final labeling review
Study Strengths & Weaknesses	pending final labeling review
Recommendations for Labeling Changes	Yes, labeling to be updated with 10 year data.
General
Study Status	Completed
Application Number / Requirement Number	P130024 / PAS002
Date Original Protocol Accepted	10/09/2014
Date Current Protocol Accepted	11/09/2018
Study Name	(New Enroll of Female Pt Study)SAFE-DCB RW US Std
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the safety and effectiveness of the Lutonix Catheter for treatment of stenosis of the femoropopliteal arteries in the US female population. The originally designed study (CONFIRM) was a prospective, multicenter, randomized study. The sponsor had difficulty enrolling for numerous years since approval. The sponsor noted the following reasons regarding the difficulty in enrollment: “Enrollment as a randomized study is not feasible due to the following: • Ethically, IRB approval would be difficult as this study is requiring randomization of patients to POBA which is known to be inferior to a commercially available drug coated balloon... • Patient consent would be difficult given the commercial availability of DCBs, clinical outcomes of the DCBs, and the potential for randomization to POBA.” In order to help with enrollment, this study was later changed to a single-arm study with a performance goal prior to enrolling any patients. Yet, the study continued to have enrollment issues, enrolling only 4 subjects 4 years after approval. At this time, it was ultimately decided by FDA and Lutonix that retrospective analysis of the female patients in their SAFE-DCB real world US registry would be the only way to get results for this evaluation in a timely manner. The design and results from the SAFE-DCB registry are described below.
Study Population	US patients presenting with claudication or ischemic rest pain and an angiographically significant lesion in the superficial femoral or popliteal artery. Subjects are treated per IFU with the Lutonix Catheter.
Sample Size	Approximately 1005 patients were enrolled at 74 US sites.
Key Study Endpoints	The primary safety endpoint is the composite of freedom from device and/or procedure related peri-operative (less than or equal to 30 day) death and freedom at 1 year from the following: target limb major amputation (above the ankle), and target vessel revascularization (TVR). The primary effectiveness endpoint is target lesion revascularization (TLR) at 12 months.
Follow-up Visits and Length of Follow-up	36 months 1, 6, 12, 24 and 36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1005 (418 female)
Actual Number of Sites Enrolled	74
Patient Follow-up Rate	79.3%
Final Safety Findings	Freedom from Primary Safety Event DCB Overall Population - 98.2% (937/954) [97.2%,99.0%] DCB Female Subgroup - 97.8% (401/410) [95.9%,99.0%] Comparison to LEVANT 2 Pivotal Study DCB Overall Population - 99.4% (306/308) [98.5%, 100.0%] DCB Female Subgroup – Not analyzed
Final Effect Findings	Freedom from TLR DCB Overall population - 88.8% (763/859) [86.5%, 90.9%] DCB Female Subgroup - 86.4% (325/376) [82.6%, 89.7%] Comparison to LEVANT 2 Pivotal Study DCB Overall population - 87.7% (250/285) [83.9%, 91.5%] DCB Female Subgroup - 83.2% (119/143) [78.2%, 91.5%]
Study Strengths & Weaknesses	Strengths: Large sample size Real-world population Weaknesses: Single Arm Trial Lack of imaging Retrospective analysis
Recommendations for Labeling Changes	NONE
General
Study Status	Completed
Application Number / Requirement Number	P130024 / PAS001
Date Original Protocol Accepted	10/09/2014
Date Current Protocol Accepted	11/28/2017
Study Name	PAS 1 (Extended Follow-up Study)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort study, continued follow-up of premarket cohorts and LEVANT 2 Safety Registry subjects
Study Population	Patients treated with the Lutonix DCB for stenosis of the femoropopliteal artery
Sample Size	657 DCB subjects from the LEVANT 2 Safety Registry 372 DCB subjects from the LEVANT 2 Pivotal IDE study 160 PTA controls from the LEVANT 2 Pivotal IDE study The assumption is that results at 2 years will be proportionally similar in DCB subjects and controls to what they were in the pivotal IDE study. The PAS study will have a much larger sample size and therefor greater power than that of the pivotal IDE study.
Key Study Endpoints	Primary effectiveness: Primary patency of the target lesion at 24 months Primary safety: Composite freedom for all cause perioperative (within 30 days), index limb amputation (2 years), index limb re-intervention (2 years), and index limbrelated death (2 years) Secondary endpoints: Individual components of the primary safety endpoint, device- and drug-related adverse events, all-cause death, major vascular complications, target lesion revascularization, and Rutherford classification
Follow-up Visits and Length of Follow-up	5 years Clinical follow-up, including Duplex Ultrasound (DUS) will be done at 6 months, 12 months, and 24 months. Telephone f/u will be done at 1 month, 3, 4, and 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Actual number of subjects enrolled: DCB Subjects (1029) Control Subjects (160) This includes: LEVANT 2 Safety Registry patients (n=657), LEVANT 2 randomized DCB (n=316) and LEVANT 2 randomized roll-in (n=56) compared against the results from the LEVANT 2 randomized control PTA (n=160).
Actual Number of Sites Enrolled	74
Patient Follow-up Rate	DCB Subjects 86% (143/1029) Control Subjects 84% (26/160) Lost to follow up plus withdrew from study.
Final Safety Findings	The composite of freedom from all-cause perioperative death (= 30 days) and index limb amputation (including above or below the knee), index limb reintervention, or index limb related death through 24 months was 74.7% (674/902) for the DCB group and 67.1% (94/140) for the PTA group. The DCB group has a higher freedom from the composite safety endpoint rate of 6.4% through the 24 months follow-up.
Final Effect Findings	Primary patency of the target lesion at 24 months was 54.5% (458/841) for the DCB group and 47.2% (60/127) for the control group. The DCB group demonstrated a higher rate of primary patency, approximately 6.4%, over the PTA group throughout 24 months.
Study Strengths & Weaknesses	The strengths of the study include randomization against an appropriate control and adequate and extended follow up. Study weaknesses include increase mortality for the test device versus control after two years in the randomized patients
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P130026 / PAS001
Date Original Protocol Accepted	08/20/2014
Date Current Protocol Accepted	08/20/2014
Study Name	TactiCath Quartz PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, non-randomized, multicenter, cohort study which will combine new enrollments with patients currently enrolled in the TOCCASTAR supplemental IDE study (G100230/S014) and/or CAP study (G100230/S020) that are still active in the follow-up phase.
Sample Size	A target of approximately 175 patients will be enrolled from 35 sites in the United States. For the safety endpoint, a performance goal of 16.2% is proposed, equal to the rate of 8.1% plus a margin of 8.1%. Based on this performance goal, with a one-sided 0.05 alpha level, a total of 175 subjects would provide greater than 95% power for this endpoint on a one sample exact test of binomial proportions. For the efficacy endpoint, a performance goal of 54.9% is proposed, equal to the lower quartile 64.9% minus a 10% margin. Based on this performance goal, with a one-sided 0.05 alpha level, a total of 175 subjects would provide approximately 80% power for an assumed event rate of 64.9% on a one sample exact test of binomial proportions.
Key Study Endpoints	performance goal of 54.9%. Procedural failure is defined by the occurrence of any of the following events: 1. Documentation of recurrence of AF/AFL/AT episodes during the 9-month observational period lasting longer than 30 seconds 2. Repeat ablation following the blanking period 3. Use of a new antiarrhythmic drug (AAD) following the blanking period (use of a previously ineffective drug does not constitute treatment failure) Secondary endpoints 1. Recurrence of symptomatic AF at 5 years 2. Number of repeat ablations (incidence and time from index procedure) 3. Use of antiarrhythmic drugs Primary endpoints Safety The rate of device or procedure related serious adverse events occurring within 7 days of the index procedure or hospital discharge, whichever is later, is lower than a performance goal of 16.2%. Effectiveness The rate of subjects free from symptomatic paroxysmal atrial fibrillation (PAF), atrial flutter (AFL), and atrial tachycardia (AT) lasting longer than 30 seconds through 9 months of follow-up after a 3-month blanking period is higher than a 4. Long-term (5 year) occurrence of Serious Adverse Events (SAEs) 5. Device malfunction
Follow-up Visits and Length of Follow-up	Duration of Study Participation: Enrollment period: 18 months. Patients will be evaluated at pre discharge, at 7 days, at 3, 6 and 12 months post index procedure and then yearly thereafter through 60 months. After the index procedure, patients will be followed for a total of 60 months. Total Study Duration: Up to 78 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	178 subjects enrolled, 173 evaluable subjects
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	The overall follow-up rate is 43.8% (78/178) at 60-months. Follow-up rates were 69.7% (124/178) and 70.7% (126/178) at 48-month and 36-month follow-up, respectively. Out of the initial 178 enrolled subject, 56 subjects withdrew during the 60-month follow-up period. The final visit cut-off date was October 5, 2020. 78 out of the expected 93 subjects completed the 60-month follow-up visit. The remaining 15 subjects were not able to complete their 60-month follow-up due to the cut-off date. 33 out of 56 subjects voluntarily withdrew. 29 subjects were considered withdrawn from trial prior to 60-month follow-up given that visit windows were not open prior to early termination of the trial on October 5, 2020.
Final Safety Findings	8.7% (15/173) of subjects experienced a device or procedure related serious adverse event occurring within 7 days of the index procedure or hospital discharge (whichever is later), which met the primary safety endpoint performance goal (PG) of 16.2%. The most common primary serious adverse events (PSAE) were hospitalizations (3.5%, 6/173), vascular access complications (2.9%, 5/173) and cardiac perforation/tamponade (2.3%, 4/173). A total of 80 events that occurred in 45 subjects (26.0%, 45/173) were adjudicated as serious adverse events (SAEs) over the 5-year study period. 23 SAEs were reported as procedure related and 9 SAEs were device related. There were no deaths or unanticipated adverse events.
Final Effect Findings	The proportion of patients free symptomatic recurrence of atrial fibrillation, atrial flutter, or atrial tachycardia that lasted longer than 30 seconds through 12-months was 73.9% (122/165) [lower bound of 95% CI: 67.7%]. The proportion of patients free from symptomatic and asymptomatic AF/AFL/AT recurrence that lasted more than 30 seconds through 12-months was 66.1% (109/165) [lower bound of 95% CI: 59.5%]. The primary effectiveness endpoint PG of 54.9% at 12-months after exclusion of a 3-month blanking period was met.
Study Strengths & Weaknesses	Strengths: The TactiCath Quartz PAS evaluated 5-year long term safety and effectiveness of the device. The primary endpoints performance goals were met. Weakness: There was significant number of subjects lost to follow-up over the 60-month period. However, 33 subjects were withdrawal of consent and 29 were lost due to early termination of the study at the cut-off date of October 5, 2020.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the TactiCath Quartz PAS. The labeling should include a new section in the instructions for use for the TactiCath Contact Force, Sensor Enabled catheter, which provides a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow-up visits, etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P140003 S004/ PAS001
Date Original Protocol Accepted	08/09/2016
Date Current Protocol Accepted	07/13/2021
Study Name	Impella AMI CS PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to evaluate the safety and effectiveness of Impella devices in a real world representative population through the cVAD registry. The study design is an observation, prospective and retrospective, multicenter, and single cohort clinical investigation of patients supported with Impella devices for the indication of AMICS with revascularization and enrolled in the cVAD registry.
Study Population	Patients (> 18 years old) supported with Impella devices (Impella 2.5, CP, 5.0 or LD) for the indication of acute myocardial infarction (AMICS) with revascularization and enrolled in the cVAD registry at U.S. institutions after the PMA post market study approval will be considered eligible for the post-approval study. Patients will be enrolled consecutively without interruption at all participating sites without preselection.
Sample Size	A minimum of 276 participants will be evaluated to compare the survival rate at 30 days or discharge, whichever is longer, to a performance goal of 34%. It is estimated that 304 participants will be enrolled, assuming 10% loss to follow-up to 30 days post- procedure.
Key Study Endpoints	Primary endpoint: Survival rate at 30 days or discharge, whichever is longer Secondary endpoints: Adverse event rates to 30 days or discharge whichever is longer The technical success rate and device (implant) success rate at exit from catheterization laboratory or operation room.
Follow-up Visits and Length of Follow-up	1 year post implant 30 days, 90 days, 1 year post implant follow ups
Interim or Final Data Summary
Actual Number of Patients Enrolled	418
Actual Number of Sites Enrolled	41
Patient Follow-up Rate	68%
Final Safety Findings	The relatively more frequent site-reported adverse events at 30 days or discharge, whichever is longer, included: death (48.8%), anemia requiring transfusion (25.60%), acute renal dysfunction/failure (22.97%), hypotension during support (20.10%), cardiac arrest (17.94%), and ventricular arrhythmia (15.07%).
Final Effect Findings	In evaluable patients (i.e., those with a known status for the primary endpoint), the PAS’ primary endpoint of survival at 30 days or discharge, whichever is longer, met the prespecified performance goal of 34%. However, in the sensitivity analysis for the worst-case scenario where all patients without a known status for the primary endpoint were assumed to have died, the PAS missed the performance goal. The survival rates at 30 days and at discharge were generally consistent with the premarket results.
Study Strengths & Weaknesses	The study’s main strength was its representation of the real-world experience and its size in patient cohort, which was much bigger than the main clinical data set used to support the PMA approval. The study’s main weakness was its relatively low follow-up rate due to some participating sites not being able to obtain post-discharge follow-up consent from all enrolled subjects.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P140003 S005/ PAS001
Date Original Protocol Accepted	08/09/2016
Date Current Protocol Accepted	07/13/2021
Study Name	Impella PCCS PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the study is to evaluate the safety and effectiveness of Impella devices in a real world representative population through the cVAD registry. The study design is an observation, prospective and retrospective, multicenter, and single cohort clinical investigation of patients who suffered cardiogenic shock after open heart surgery and received an Impella device.
Study Population	Patients (>18 years old) supported with Impella devices (Impella 2.5, CP, 5.0 or LD) for the indication of post-cardiotomy cardiogenic shock (PCCS), enrolled in the cVAD registry at U.S. institutions, after the PMA post market study approval will be considered eligible for the post-approval study. Patients will be enrolled consecutively without interruption at all participating sites without preselection.
Sample Size	A minimum of 44 participants will be evaluated to compare the survival rate at 30 days or discharge, whichever is longer, to a performance goal of 30%. It is estimated that 48 participants will be enrolled, assuming 10% loss to follow-up to 30 days post- procedure.
Key Study Endpoints	Primary endpoint: Survival rate at 30 days or discharge, whichever is longer. Secondary endpoints: Adverse event rates at 30 days or discharge whichever is longer. The technical success rate and device (implant) success rate at exit from catheterization laboratory or operation room.
Follow-up Visits and Length of Follow-up	1 year post implant 30 days, 90 days, 1 year post implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	63
Actual Number of Sites Enrolled	46
Patient Follow-up Rate	83%
Final Safety Findings	Secondary endpoints for the study conducted covers both adverse event rates within the time frame of the primary endpoint and technical/ device success rates. The device and technical success rates exceeded 98% which demonstrates that the device can be safely implanted and positioned for hemodynamic support. A few adverse events such as bleeding, infection and thrombocytopenia, occurred at a higher incidence when compared to the rates of the same events specifically related to the Impella procedure and device.
Final Effect Findings	The primary endpoint of survival at 30 days post-implant or discharge, whichever is longer, was found to be 55.0 % (33/60). This fulfilled the PAS requirement for a 30% survival rate.
Study Strengths & Weaknesses	The study was able to effectively fill the requirements for the PAS with respect to the primary endpoint, patient outcomes at 30 days post-implant or discharge, whichever comes first. However, the contributory role of patient profile, comorbidities, and nature of surgery remains open as the study was not designed to answer such questions due to the limited subject population.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P140003 S008/ PAS001
Date Original Protocol Accepted	08/22/2017
Date Current Protocol Accepted	07/13/2021
Study Name	Impella PROTECTED PCI PAS cVAD Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is a prospective and retrospective, multicenter, single-arm post-approval study (PAS) of use of the percutaneous Impella devices in elective or urgent high-risk percutaneous coronary intervention (PCI). The study objective is to monitor post market safety and efficacy trends of the Impella 2.5 and CP devices in high-risk PCI patient population by assessing outcomes at discharge and outcomes at 90 days relative to a performance goal of 53%.
Study Population	The study population will consist of adult patients (age = 22 years old) supported with the Impella 2.5 or Impella CP for the approved indication of elective or urgent high-risk PCI, who are enrolled in the cVAD registry at U.S. institutions (both IDE and non-IDE sites) after the PMA post market study approval. Patients will be enrolled consecutively without interruption at all participating sites, without preselection.
Sample Size	Approximately 750 subjects at the cVAD registry sites will be treated to compare a composite rate of ten (10) major adverse events (MAE) at 90 days to the performance goal of 53%. This number was chosen to ensure enrollment of at least 369 subjects who are similar to the original PMA Impella 2.5 cohort in PROTECT II. The number of PROTECT II like patients needed (369) was chosen to provide a 90% power to reject the null hypothesis in favor of the alternative hypothesis with the assumption (from the PROTECT II data): The true proportion of MAE (pPAS) at 90 days is 45%*; Margin of 8%; The Performance Goal is 53%; The power of the study is 90%; and The one-sided alpha error is 5%. *Determined with the FDA based on the PROTECT II study results.
Key Study Endpoints	Primary Endpoints: A composite rate of the following intra-procedural and post-procedural major adverse events* (MAE) at 90 days post index procedure: 1. Death; 2. Myocardial infarction; 3. Stroke/TIA; 4. Repeat revascularization; 5. Need for cardiac operation or thoracic or abdominal vascular operation or vascular operation for limb ischemia; 6. Acute renal dysfunction; 7. Increase in aortic insufficiency by more than one grade; 8. Severe hypotension defined as systolic blood pressure <90 mmHg for greater than or equal to 5 minutes requiring inotropic/pressor medications or IV fluid; 9. Cardiopulmonary resuscitation or ventricular arrhythmia requiring cardioversion; and 10. Failure to achieve angiographic success defined as residual stenosis < 30% after stent implantation. *Complete definitions of the components of the primary endpoint along with other adverse events are provided in the Appendix A of the study protocol. Secondary Endpoints: 1. Improved hemodynamics post support initiation as compared to baseline, as measured by maximum increase in mean arterial pressure within 30 min of support initiation. 2. Improvement in LVEF at 90 days as compared to baseline. 3. Improvement in NYHA class at 90 days as compared to baseline.
Follow-up Visits and Length of Follow-up	1 year
Interim or Final Data Summary
Actual Number of Patients Enrolled	1237
Actual Number of Sites Enrolled	46
Patient Follow-up Rate	15.8% of patients missed 30 day follow up, 5.6% missed 90 day follow up, and 9.1% missed 1 year followed up.
Final Safety Findings	The composite major adverse event (MAE) for the Protect II like cohort at 90 days was 25.6%, with a two sided confidence interval of 22.1%, 29.2%. Worst case scenario at 90 days is 42.6%, with a 39.0% - 46.1% 95% confidence interval. The Kaplan-Meier estimates of cumulative MAE, Major adverse cardiac and cerebrovascular events (MACCE), and death reates are also below the 53% performance goal. At 90 days, the Impella 2.5 cohort had a composite MAE rate of 17.7% and a composite MACCE rate of 12.1%. The Impella CP cohort had a composite MAE rate of 25.2% and a composite MACCE rate of 16.2%. For the entire cohort, the rates were 23.6% and 15%, respectively.
Final Effect Findings	The total cohort saw an improved mean LVEF at 90 days of 7.3% +/- 12.33, the Impella 2.5 cohort saw an improved mean LVEF at 90 days of 13.3% +/- 15.13%, the Impella CP saw an improved mean LVEF of 6.3% +/- 11.68%. 4.5% decreased New York Heart Association class by 3 classes, 22.7% by 2 classes, 24.2% by 1 class, 40.9% saw no change, 6.1% increased by 1 class, 1.5% increased by 2 classes.
Study Strengths & Weaknesses	Strengths: The study’s primary endpoint was the composite MAE at 90 days for the Protect II cohort. The MAE composite rate for this cohort was 25.6%, with a two sided, 90% confidence interval of 22.1% and 29.2%. This meets the performance goal of 53%. Weakness: The sponsor had difficulty with enrollment and follow up data collection throughout the study and data collection was paused due to the COVID-19 Pandemic. The sponsor was able to complete enrollment with 90 day follow up data available through a waiver of informed consent.
Recommendations for Labeling Changes	A labeling change supplement will be requested.
General
Study Status	Completed
Application Number / Requirement Number	P160025 / PAS001
Date Original Protocol Accepted	03/23/2017
Date Current Protocol Accepted	08/07/2017
Study Name	BIOFLEX-I PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center follow-up of the BIOFLEX-I pivotal study (G100002)
Study Population	The study population included subjects greater than or equal to 18 years old with life-style limiting claudication or rest pain, with an ABI less than or equal to 0.9 (resting or exercise). Inclusion criteria included one de novo, restenotic or occluded femoropopliteal lesion, OR two de novo , restenotic or occluded lesions representing one femoropopliteal indication and one iliac indication on contralateral limbs (i.e., one lesion per limb). Lesion length was specified as less than or equal to 190 mm (if de novo or restenotic) or less than or equal to 100mm (if occluded), with target vessel reference diameter: 2.5 to 6 mm (SFA/PPA) by visual estimate and with angiographic evidence of atleast one distal vessel runoff to the foot.
Sample Size	A total of 280 subjects were active at the time of the 12-month primary endpoint assessment. The long-term post-market analysis of the Pulsar stent group will include a minimum of 202 subjects (238 subjects x 0.85) at 36 months and a minimum of 238 subjects (280 subjects x 0.85) at 24 months. This calculation accounts for a 15% annual attrition rate due to premature exits including subject withdrawal and lost to follow (LTF) and excluding deaths.
Key Study Endpoints	The primary endpoint to be assessed is freedom from a composite of clinically-driven target lesion revascularization (TLR) and index limb amputation at 36 months, as defined by the protocol. The secondary endpoints to be assessed include the following: Freedom from a composite of clinically-driven TLR and index limb amputation at 24 months. Major adverse events (MAE) rate (30-day mortality, clinically-driven TLR, and index limb amputation) and their components at 24 months. MAE rate (30-day mortality, clinically driven TLR, and index limb amputation) and their components at 36 months. Target lesion revascularization (TLR) rate at 24 months. Target lesion revascularization (TLR) rate at 36 months. Stent fracture rate at 24 months. Stent fracture rate at 36 months. Adverse events rates at 36 months.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	782
Actual Number of Sites Enrolled	43
Patient Follow-up Rate	1, 6, 12, 24, and 36 months
Final Safety Findings	Primary- Freedom from clinically-driven target lesion revascularization (TLR) and index limb amputation: 78.2% (201/257), 95% CI [72.7%, 83.1%] at 36 months
Final Effect Findings	Primary – primary patency of the Astron Pulsar stent at 12 months: 66.8% (179/268), 95% CI [60.8%, 72.5%]
Study Strengths & Weaknesses	NONE
Recommendations for Labeling Changes	Yes, update to include PAS data
General
Study Status	Completed
Application Number / Requirement Number	P140003 S088/ PAS001
Date Original Protocol Accepted	08/18/2022
Date Current Protocol Accepted	04/27/2023
Study Name	Impella RW Surveillance of Pts using Sodium Bicarb
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Detailed Study Protocol Parameters
Study Objectives	A multicenter, observational, records review study of routine clinical care. Subjects are from post-market cohorts and new enrollment.
Study Population	Device: The study will include up to 60 sites from the US. The population enrolled in this study are all subjects who received an Impella in which a bicarbonate-based purge solution was used. Comparator: The study will include up to 60 sites from the US. The population enrolled in this study are all subjects who received an Impella in which a heparin-based purge solution was used.
Sample Size	A sample size of 300 subjects is proposed for the study based on the following assumptions: Event rate 6% Target margin of error of +/- 3% (the width of 95% confidence interval of 6%) While the sample size with the above assumptions is 275, the additional subjects ensure the target 3% margin of error for a potentially higher event rate in the all-comers population enrolled in the study. For Impella RP, the sample size will be the number of subjects available at the time the left-sided device population completes enrollment, up to 30 subjects. As the use of Impella RP is an order of magnitude less than the left-sided devices, a target margin of error is not feasible for this population.
Key Study Endpoints	1. Left-sided devices (Impella 2.5, Impella CP, Impella LD, Impella 5.0 and Impella 5.5): Hierarchical composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus [Time Point: Discharge] 2. Impella RP: Hierarchical composite of pulmonary thromboemboli and deep vein thrombosis (DVT) [Time Point: Discharge] 1. Bleeding, BARC greater than or equal to 3 [Time Point: Discharge] 2. For left-sided devices: Thrombotic events excluding LV thrombus, stroke and TIA [Time Point: Discharge] 3. For Impella RP: Thrombotic events excluding pulmonary thromboemboli and DVT [Time Point: Discharge]
Follow-up Visits and Length of Follow-up	1. Left-sided devices (Impella 2.5, Impella CP, Impella LD, Impella 5.0 and Impella 5.5): Hierarchical composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus [Time Point: Discharge] 2. Impella RP: Hierarchical composite of pulmonary thromboemboli and deep vein thrombosis (DVT) [Time Point: Discharge] 1. Bleeding, BARC =3 [Time Point: Discharge] 2. For left-sided devices: Thrombotic events excluding LV thrombus, stroke and TIA [Time Point: Discharge] 3. For Impella RP: Thrombotic events excluding pulmonary thromboemboli and DVT [Time Point: Discharge]
Interim or Final Data Summary
Actual Number of Patients Enrolled	312
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	100%
Final Safety Findings	The primary endpoint for left-sided Impella devices (Impella 2.5 System, Impella CP System, Impella LD System, Impella 5.0 System and Impella 5.5 System) was a composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus evaluated at discharge. Event data included all events during index hospitalization, including prior to, during and after Impella support. The composite event rate of 7.7% during the entirety of the index hospitalization fell within the expected event rate of the Impella device usage for the studied patient population. Additional descriptive endpoints included 1) BARC greater than or equal to 3 bleeding events through hospital discharge; 2) For left-sided devices, thrombotic events excluding LV thrombus, stroke, and TIA through hospital discharge; and 3) For right-sided devices, thrombotic events excluding pulmonary thromboemboli and deep vein thrombosis (DVT) through hospital discharge. The key contributor to the composite endpoint was stroke, with 22 of the 23 composite endpoint events being stroke events (22/300; 7.33%). The remaining event was one event of left ventricular thrombus. The observed rate of stroke (7.33%) fell within with the expected stroke rate derived from literature reports. When patients were grouped by Impella-only patients and Impella patients with other MCS (Impella + MCS), the endpoint rates were considerably lower in the Impella-only group. Specifically, the composite endpoint rate of stroke/TIA/LV thrombus was 3.1% in the Impella-only group versus 13.5% in the Impella + MCS group. Fourteen (14) out of 23 primary endpoints were reported to be unlikely or not related to the device, only two primary endpoints were found to be probably related to the device, four possibly related to the device, and relatedness of two other primary endpoints was classified as unknown. Similar to the finding seen with the primary endpoints, there is an appreciable difference in descriptive endpoint rates between Impella only and Impella + MCS sub-groups, with lower BARC greater than or equal to 3 bleeding event rates (15.4% versus 29.4%) and thrombotic event rates (3.1% versus 4.8%) seen in Impella only sub-group, with majority of the endpoints reported to be unlikely or not related to the device. The primary endpoint for right-sided Impella devices was a composite of pulmonary thromboemboli and DVT evaluated at discharge. No patients met the primary endpoint in the right-sided cohort. No right-sided cohort patient experienced the descriptive endpoint of thrombotic events, while BARC greater than or equal to 3 bleeding was seen in 15.0% of the patients. None of the BARC greater than or equal to 3 bleeding in the right-sided cohort was reported to be definitely or probably related to the device.
Final Effect Findings	The primary and descriptive endpoints of the study are described above in the “Final safety findings” section above.
Study Strengths & Weaknesses	The study’s main strength was its representation of the real-world experience, representing physician preference for the use of sodium bicarbonate in the purge fluid during Impella support for a variety of challenging clinical scenarios, indications, and procedural characteristics. The study provided rigorous data on this real-world cohort. The study’s main weaknesses were its lack of data to identify timing of the purge administration with respect to the timing of the endpoints, and lack of data to directly compare outcomes between bicarbonate and other purge fluids.
Recommendations for Labeling Changes	The clinical information in the Instructions for Use should be updated to include the results of the post-approval study.
General
Study Status	Ongoing
Application Number / Requirement Number	P130013 S074/ PAS001
Date Original Protocol Accepted	12/15/2025
Date Current Protocol Accepted	12/15/2025
Study Name	WATCHMAN FLX Pro OPTION PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational, prospective, non-randomized, multicenter registry surveillance analysis designed to characterize clinical outcomes and to assess the real-world use of the commercial WATCHMAN FLX Pro LAA Closure Device with Delivery System. The analysis is designed to assess safety outcomes associated with the use of non-vitamin K oral anticoagulant (NOAC) alone as an alternative to an oral anticoagulant (OAC) and aspirin as the post-implant medication regimen for the WATCHMAN FLX Pro Left Atrial Appendage (LAA) Closure Device with Delivery System in a routine clinical setting. Data will be captured from the Left Atrial Appendage Occlusion (LAAO) Registry within the American College of Cardiology Foundation’s (ACCF) National Cardiovascular Data Registry (NCDR) conducted in the United States.
Study Population	LAAO registry subjects who were successfully implanted with a WATCHMAN FLX Pro device, discharged 6 months prior to the NOAC alone labeling change implementation (16Jan2025 to 16Jul2025) or 6 months post labeling change implementation (17Jul2025 to 17Jan2026), and who meet inclusion/exclusion criteria.
Sample Size	Number of subjects: N/A. See above study population Assumptions for sample size estimation: N/A Number of sites: Data from all sites participating in the LAAO Registry in the United States will be used for the analysis. Sites location: US
Key Study Endpoints	Co-Primary Endpoint: Composite Endpoint The composite event rate is defined as all-cause death, stroke (ischemic and/or hemorrhagic), major bleeding, and systemic embolism. The composite event endpoint will be assessed in successfully implanted subjects between the date of hospital discharge and 45 days post-implant procedure and between hospital discharge and 6 months post-implant procedure. Co-Primary Endpoint: Safety Endpoint The occurrence of one of the following events between the time of the first implant attempt procedure and within seven days of that procedure or by hospital discharge, whichever is later: • All-cause death, • Ischemic stroke, • Systemic embolism, or • Device or procedure-related events requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair. Percutaneous catheter drainage of pericardial effusions, snaring of an embolized device, thrombin injection to treat femoral pseudoaneurysm and nonsurgical treatments of access site complications are excluded from this endpoint and will be reported separately. Co-Primary Endpoint: Effectiveness Endpoint The occurrence of ischemic stroke or systemic embolism at 24 months post-implant procedure. Additional Endpoints Additional analyses will include the evaluation of the following events prior to and after the NOAC alone labeling implementation. Clinical events will be assessed between hospital discharge and 45 days, 6 months, 12 months and 24 months post-implant procedure: • All-cause death • Cardiovascular death • All stroke • Ischemic stroke • Hemorrhagic stroke • Systemic thromboembolism • Major bleeding • Pericardial effusion • Device embolization • Device margin residual leak • Device-related thrombus
Follow-up Visits and Length of Follow-up	Subjects in all cohorts will be followed at hospital discharge, 45 days, 6 months, 12 months and 24 months post-implant procedure.
Interim or Final Data Summary
Interim Results	Safety Results: Implanted subjects All-cause death: - Concomitant cohort 0.08% (6/7679) - Sequential cohort 0.00% (0/1490) Cardiovascular death: - Concomitant cohort 0.08% (6/7679) - Sequential cohort 0.00% (0/1490) Ischemic stroke: - Concomitant cohort 0.17% (13/7679) - Sequential cohort 0.00% (0/1490) Hemorrhagic stroke: - Concomitant cohort 0.01% (1/7679) - Sequential cohort 0.00% (0/1490) Systemic thromboembolism: - Concomitant cohort 0.08% (6/7679) - Sequential cohort 0.00% (0/1490) Major Bleeding: - Concomitant cohort 0.94% (72/7679) - Sequential cohort 0.40% (6/1490) Pericardial effusion: - Concomitant cohort 0.20% (15/7679) - Sequential cohort 0.01% (1/1490) Device embolization: - Concomitant cohort 0.00% (0/7679) - Sequential cohort 0.00% (0/1490) Device margin residual leak: Complete seal was 99.3% in the concomitant cohort and 99.5% in the sequential cohort after the procedure, leading to an effective device closure (device margin residual leak <5mm) rate of 100% after the procedure in ITT concomitant and sequential patients with available imaging data. In the Implanted data set, device related thrombus occurred in 0.02% (1/6519) of Concomitant Cohort subjects and 0.07% (1/1351) of Sequential Cohort subjects who had a TEE or CT at discharge. Effectiveness Results: Safety and effectiveness endpoints were reported as a composite endpoint; see the safety results section for study outcomes.
Actual Number of Patients Enrolled	9,169 Impanted subjects - 7,679 subjects who were successfully implanted with a WATCHMAN FLX Pro device during a concomitant ablation procedure - 1,490 subjects successfully implanted with a WATCHMAN FLX Pro device following a historical ablation procedure that occurred between 3-12 months prior to the WATCHMAN FLX Pro implant
Actual Number of Sites Enrolled	N/A -LAOO Registry
Patient Follow-up Rate	Subject follow-up is currently ongoing. Implanted 45-day follow-up rate for the Concomitant Cohort was 45.9% and the Sequential Cohort was 51.4%.
General
Study Status	Completed
Application Number / Requirement Number	P130021 S010/ PAS001
Study Name	Continued f/u of the premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled under the IDE in Registry 6: TAV-in-SAV. The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the ¿TAV-in-SAV¿ Registry
Sample Size	All living subjects.
Key Study Endpoints	The safety and effectiveness endpoints include all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE), change in functional status and quality of life, conduction disturbance requiring permanent pacemaker implantation, echocardiographic assessment, and valve dysfunction.
Follow-up Visits and Length of Follow-up	5 years All subjects are followed at 30 days, 6 months, 12 months, and annually thereafter through 5 years post procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	232
Actual Number of Sites Enrolled	38
Patient Follow-up Rate	The follow-up rate through 5 years was approximately 88%
Final Safety Findings	The Kaplan-Meier rates of CEC-adjudicated safety outcomes at 5 years are summarized as follows: All-cause mortality or major stroke: 47.2% All-cause mortality: 46.8% (29.8% cardiovascular mortality) Valve-related death: 4.7% All stroke: 9.8% (6.7% major stroke) Aortic valve rehospitalization: 31% Reintervention: 5.9% Major adverse cardiovascular and cerebrovascular event (MACCE): 51.7% Bleeding: 34.7% New permanent pacemaker: 24%
Final Effect Findings	Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit: NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. The mean change compared to baseline at 5 years was -1.4 +/- 0.9 (n=78). KCCQ: Improvement was observed in both overall and clinical summary scores through five years. The change in KCCQ overall summary score at 5 years compared to baseline was 27.6 +- 23.3 (n=80). Valve Performance Outcomes: Mean gradient decreased from 37.84 +/- 18.03 at baseline to 15.62 +/- 8.79 at 30 days. At 5-years, the overall mean gradient was 14.12 + 9.81 mmHg (n=72). Mean effective orifice area (EOA) increased from 1.02 +/- 0.61 cm2 at baseline to 1.45 +/- 0.63 cm2 at 30 days. At 5 years, the EOA was 1.57 0.70 cm2 (n=62). At 5 years, 93.2% of subjects with available echocardiographic data (n=74) had mild or less total aortic regurgitation (AR).
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the Medtronic CoreValve System in patients with symptomatic severe aortic stenosis with predicted operative mortality or serious, irreversible morbidity risk of greater than or equal to 50% at 30 days who received a transcatheter implantation of the CoreValve System in a failed surgical prosthetic aortic valve (TAV-in-SAV). Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvements shown for key effectiveness endpoints from baseline to 5 years. However, Echocardiography Corelab and Quality of Life compliance rates at 5 years are low (53-70%). The incomplete data may impact the ability to interpret and draw conclusions from the results.
Recommendations for Labeling Changes	The labeling is recommended to be updated to reflect the 5 year findings of the study and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status
Application Number / Requirement Number	P130021 S010/ PAS002
Study Name	Comprehensive/Linked-Registry
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score greater than or equal to 8% or at a greater than or equal to 15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure) (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological, vascular and quality of life outcomes at 30 days and 12 months; and (4) all-cause mortality, neurological and vascular outcomes annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P140004 / PAS001
Date Original Protocol Accepted	11/18/2015
Date Current Protocol Accepted
Study Name	SPACER
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To demonstrate that the success rate of the study group receiving the Superion Interspinous Spacer (investigational arm) is not inferior to the success rate observed in X-STOP IPD control group when the device is used in patients with moderately impaired degenerative lumbar stenosis at 5 years post-surgery.
Study Population	Subjects suffering from moderate symptoms of neurogenic claudication secondary to a confirmed diagnosis of moderate LSS at one or two contiguous levels from L1 to L5 who meet all inclusion/exclusion criteria. Study subjects were randomized to treatment with either the Superion ISS or X-STOP IPD interspinous devices.
Sample Size	The numbers of patients in the final primary analysis set for effectiveness and safety included 190 patients randomized to Superion® and 201 patients randomized to the X-STOP® IPD® Control group. Eight (8) Superion® patients and 12 X-STOP® IPD patients are from 2 sites that are not participating in the PAS. This reduces the analysis set to 182 and 189, respectively.
Key Study Endpoints	An individual will be considered a success if they meet all of the following conditions at the 60-month follow-up visit: Clinically significant improvement as compared to baseline as determined by meeting at least two of the three domains of ZCQ (as defined in the protocol); no re-operations, revisions, removals or supplemental fixation at the index level(s); no major implant or procedure-related complications; and no clinically significant confounding treatments. Data will be evaluated for safety endpoints by an independent Clinical Events Committee (CEC). Safety outcomes will be determined by evaluating the type, frequency, severity, and relationship to device of adverse events through the 60-month time point for all subjects. Adverse events will be categorized as implant-related or procedure-related. All device-related and major procedure-related failures reported by the site PIs will be adjudicated by the independent CEC. In addition, events reported as having unknown or undetermined relationship to the device by the PI will be adjudicated by the CEC.
Follow-up Visits and Length of Follow-up	length of follow-up: 60 months frequency of follow-up: yearly
Interim or Final Data Summary
Actual Number of Patients Enrolled	28 non-randomized training patients and 391 randomized patients (190 in Superion/treatment arm, 201 in X-STOP/control).
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	At 60 months, 85.8% for Superion IDS and 82.1% for X-STOP IPD
Final Safety Findings	The incidence of any adverse event, device-related adverse events, procedure-related adverse events, serious adverse events, and device- or procedure-related serious adverse events were similar between both groups at 60 months.
Final Effect Findings	The primary effectiveness endpoint was a composite endpoint comprised of four elements: 1. Clinically significant improvement in outcomes compared to baseline, as determined by meeting the following for at least two of three domains of the Zurich Claudication Questionnaire (ZCQ): 2. No re-operations, revisions, removals, or supplemental fixation at the index level(s) 3. No major implant or procedure-related complications 4. No clinically significant confounding treatments. The overall Composite Clinical Success demonstrates that the Superion is non-inferior to the X-STOP at all yearly time points through the 60-month follow-up.
Study Strengths & Weaknesses	Study strengths include comprehensive endpoints, a clinical control, and inclusion of a “patient preference” evaluation. The most notable study weakness is that it lacks a comparison to conservative (non-operative) treatment.
Recommendations for Labeling Changes	At the close of the report, we recommended that the sponsor update the labeling with the 60 month data. We are currently reviewing this data.
General
Study Status	Delayed
Application Number / Requirement Number	P140004 / PAS002
Date Original Protocol Accepted	12/15/2015
Date Current Protocol Accepted	09/10/2019
Study Name	Superion New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, observational post-approval (Conditions of Use) study through 60 months. The first and primary objective is to evaluate longer term (5 year) Superion® device performance in the ‘actual conditions of use’ population relative to the IDE investigational cohort. A composite clinical success (CCS) endpoint will be used to facilitate this comparison. A Month 24 composite clinical success (CCS) endpoint similar to that used in the IDE trial will be employed for this comparison. The third objective is to compare clinical status of patients implanted with the Superion® device relative to surgical decompression two years post operatively. A composite clinical success (CCS) endpoint will be used for this comparison.
Study Population	Subjects suffering from moderate symptoms of neurogenic claudication secondary to a confirmed diagnosis of moderate LSS at one or two contiguous levels from L1 to L5 who meet all inclusion/exclusion criteria. Subjects will be either randomized to the Vertiflex or ACDF.
Sample Size	214 subjects (174 Superion®) at up to 25 sites
Key Study Endpoints	Primary effectiveness endpoint is a composite of safety and effectiveness. Subjects will be evaluated for success at 24 months, compared to the success of Superion® IDS subjects in the IDE trial at 24 months. The study endpoint is the non-inferiority of overall subject success at the 24-month follow-up visit vs. the 24-month success in the IDE trial. An individual subject will be considered a success if they meet all of the following conditions at the 24-month follow-up visit: 1. Clinically significant improvement of neurogenic claudication symptoms as determined by meeting at least two of three domains of the ZCQ • = 0.5-point improvement in physical function • = 0.5-point improvement in symptom severity • = 2.5 point on patient satisfaction domain 2. No reoperations, removals, revisions, or supplemental fixation at the index level(s) 3. No major implant or procedure-related complications • no dislodgement, migration, or device deformation • no new or persistent worsened neurological deficit at the index level The following endpoints will be evaluated at 24 months and annually thereafter through end of study. • Proportion of subjects with VertiFlex® Patient Satisfaction Survey scoring =3 on a 4-point scale • Change in opioid medication use for Lumbar Spinal Stenosis (LSS) from baseline • Proportion of Subjects with improvement of 20mm in Visual Analog Scale (VAS) for low back and leg pain (on the 100 mm scale) compared to baseline • Proportion of Subjects with ODI improvement of at least a 15 points compared to baseline • Improvement in quality of life as defined by EQ-5D-5L • Proportion of subjects with epidural injections, nerve block procedures or rhizotomies at index level, or spinal cord stimulators • Characterization of spinous process fractures in terms of location, configuration, displacement, angulation and rate of healing. The following endpoint will be evaluated at 36 months through end of study: • Clinically significant improvement of neurogenic claudication symptoms as determined by meeting at least two of three domains of the ZCQ o = 0.5-point improvement in physical function o = 0.5-point improvement in symptom severity o = 2.5 point on patient satisfaction domain • No reoperations, removals, revisions, or supplemental fixation at the index level(s)
Follow-up Visits and Length of Follow-up	Study events occur at the following time points: • Screening/Baseline Visit • Surgical Treatment- Day 0 (up to 30 days after confirming Eligibility requirements) • Discharge (0-7 days post IDS implant) • 6-Week Visit (42 days ±14 days post IDS implant) • 6-Month visit (180 days ±60 days post IDS implant) • 12-Month Visit (365 days ±60 days post IDS implant) • 24-Month Visit (730 days ±60 days post IDS implant) • 36-Month Visit (1,090 days ±120 days post IDS implant) • 46-Month Visit (1,460 days ±120 days post IDS implant) • 60-Month Visit (1,825 days ±120 days post IDS implant)
General
Study Status	Completed
Application Number / Requirement Number	P140008 / PAS001
Date Original Protocol Accepted	02/26/2016
Date Current Protocol Accepted	11/28/2018
Study Name	ORBERA PAS (OPAS-001)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multicenter, open-label new enrollment post-approval study of the safety and effectiveness of ORBERA as an adjunct to weight reduction for obese adults (22 years of age and older) with a Body Mass Index (BMI) of greater than or equal to 30 kg/m2 and BMI of less than or equal to 40 kg/m2. Treatment includes behavioral modification program in conjunction with endoscopic placement of a single ORBERA Intragastric Balloon, filled with saline to an inflation volume between 400cc and 700cc, for 26 weeks followed by endoscopic ORBERA removal.
Study Population	Male and female subjects, 22 years of age and older, with a BMI of greater than or equal to 30 kg/m2 and less than or equal to 40 kg/m2 who have failed more conservative weight- reduction alternatives, such as supervised diet, exercise, and behavioral modification programs will be enrolled into this study.
Sample Size	Up to 284 subjects will be enrolled to yield approximately 255 subjects treated with the ORBERA. Sample size calculations were performed for the primary objective and the key secondary effectiveness objective, with the sample size being driven by the primary objective. Approximately 255 subjects will be treated with the device and will provide 80% power to demonstrate that the device and procedure-related serious adverse event rate is <15%, assuming the rate is no more than 5% than what was observed in the pivotal study. Assuming 255 subjects are treated with ORBERA with an attrition rate of 10% during treatment, there will be approximately 230 subjects completing 26 weeks of treatment. This will provide greater than 99% power to demonstrate that the observed mean %TBWL is more than 7.5% after 26 weeks of ORBERA treatment.
Key Study Endpoints	The primary endpoint is the incidence of device and procedure-related SAEs after 26 weeks of ORBERA treatment. Secondary Effectiveness Endpoints: Mean %TBWL at study week 26 %TBWL at each post-placement visit %EWL at each post-placement visit Change from baseline in BMI at each visit Response to ORBERA™ treatment Change in satiety using the SNAQ Subject Satisfaction
Follow-up Visits and Length of Follow-up	Evaluations while on treatment will be performed at baseline (pre-placement), Day 0 (ORBERA™ placement), Day 2 phone call, and eight (8) regularly scheduled clinic visits while on device treatment at study weeks 1, 2, 4, 8, 12, 16, 20, and 24. Device removal will occur at 26 study weeks. If device is removed earlier than 26 weeks, the visits will continue in accordance with the study week visits specified during treatment. Reasons for early removal may include, but are not limited to, an adverse event, subject dissatisfaction or achievement of weight loss goal. Seven (7) clinic visits will occur during the weight loss maintenance follow-up period at study weeks 28, 32, 36, 40, 44, 48, and 52 (study exit).
Interim or Final Data Summary
Actual Number of Patients Enrolled	284
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	> 90%
Final Safety Findings	Primary Endpoint: The incidence of device and procedure-related serious adverse events (SAEs) after balloon treatment among available subjects (hypothesis SAEs < 15%). SAEs incidence: 8.9% (23/257), upper limit of 1-sided 95% confidence interval: 12.4% (p-value = 0.0033). Body System / Preferred Term Incidence Rate % N = 257 Gastrointestinal Disorders 7.8 Abdominal Distension 0.4 Abdominal Pain 1.9 Diarrhea 0.8 Epigastric Discomfort 0.8 Gastroesophageal Reflux Disease 0.4 Impaired Gastric Emptying 1.9 Nausea 2.7 Vomiting 4.7 Metabolism and Nutrition Disorders 0.8 Dehydration 0.4 Hypokalemia 0.4 Device Malfunction 1.6 Hyperinflation of Balloon 1.6 Adverse Events: 62.8% subjects (162/258) 87% device related 10% procedure related 58% mild 9% severe 1% erosive gastritis 1% gastric ulcers 1 incidental partial deflation reported at the time of balloon removal 1 esophageal mucosal tear was repaired during the procedure with no additional sequelae No deaths, pancreatitis gastric perforation, esophageal perforation or esophageal ulcers Early removal: 47(18%) AEs related to symptoms associated with gastrointestinal intolerance were: abdominal pain, dyspepsia, epigastric discomfort, gastroesophageal reflux disease, impaired gastric emptying, nausea, retching and vomiting accounted for 71% of all device-related AEs (65% were mild, 80% moderate and 80% severe). Device related AEs were associated with gastrointestinal intolerance that resolved between 0 to 29 weeks, 90% resolved with no treatment or medication, and over 64% resolved within 2 weeks of onset. Device deficiencies: 16 (6%) 10 subjects had device malfunctions (9 device related and 1 due to trauma). Six subjects have technical issues with a feature of the balloon system during placement or removal. None resulted in injury or needed an aborted procedure. Device Removal: 210 subjects (81%) completed the 26-week treatment period prior to device removal, 9 of them had their initial removal aborted due to excess food found in the stomach without having AEs. The second removal attempts were completed with no issues. Additional Safety Data: 6 out of 258 patients (2%) had balloon hyperinflation with onset of symptoms from within 1 to 23 weeks after balloon placement. Symptoms include nausea, vomiting, and abdominal pain. In 4 of the 6 cases, symptoms prompted the early removal of the balloons, 1 patient had balloon removed emergently at week 24, and in the last one, balloon hyperinflation was found at removal time with no symptoms.
Final Effect Findings	%Total Body Weight Loss: %TBWL = 100(weight of post-placement visit – baseline weight) / baseline weight. %TBWL Mean Completers Population: -13 Efficacy Population: -13 Full Analysis Population: -12 Multiple Imputation: -13 %TBWL Week Mean by visit 1: -4 2: -4 4: -6 12: -9 24: -11 36: -10 52: -8 % Excess Weight Loss: %EWL = 100 (weight of post-placement visit – baseline weight) / excess weight %EWL Week Mean by visit 1: 14 2: 17 4: 23 12: 34 24: 41 36: 38 52: 31 Simplified Nutrition Assessment Questionnaire (SNAQ) by Visit as % of subjects with reduced appetite (score < 14) Week % Subjects with SNAQ < 14 (N =258) Baseline 10 1: 77 2: 65 4: 49 12: 25 24: 24 36: 14 52: 15 Subject Satisfaction A treatment experience was applied in the 8-week through the 24-week follow-up visits, and a satisfaction questionnaire was applied at the exit visit. Satisfaction Questionnaire Summary by Visit Type (Selected Response) N = 247 Response 24 Weeks Overall, how would you rate your experience with ORBERA®? Category % Excellent: 21 Very Good: 24 Good: 26 Fair: 19 Poor: 9 Exit Satisfaction Questionnaire Summary (Selected Responses) N = 245 Overall, how would you rate your experience with ORBERA? Category % Excellent: 24 Very Good: 24 Good: 22 Fair: 18 Poor: 11 Overall, given your recent experience with ORBERA®, if you had to do it all over again, would you choose ORBERA? Category % Definitely: 36 Probably: 20 Not sure: 11 Probably not: 16 Definitely not: 17
Study Strengths & Weaknesses	Strengths: Sample size adequate and power over 90% for the overall analysis. Follow up rate over 90% for all follow-up visits. Weaknesses: No comparator was included and not enough sample size for BMI safety subgroup analysis.
Recommendations for Labeling Changes	Yes, including the design, methods and results of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P140010 S015/ PAS001
Date Original Protocol Accepted	12/06/2016
Date Current Protocol Accepted
Study Name	Surveillance Post Market Registry
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To assess the long-term safety and performance of the IN.PACT Admiral DCB in a U.S. population for the treatment of in-stent restenosic (ISR) lesions in the superficial femoral and popliteal arteries. Prospective, non-randomized, multi-center, single-arm post-market registry
Study Population	Patients from the U.S. with ISR lesions in the superficial femoral and popliteal arteries who have symptoms of claudication and/or rest pain (Rutherford Class 2, 3, or 4) who were entered into the VQI PVI Registry and met all other inclusion and exclusion criteria.
Sample Size	300 patients from the SVS VQI Registry, treated with the IN.PACT Admiral DCB per the standard of care, will be extracted consecutively and analyzed to evaluate the safety and performance of the IN.PACT Admiral DCB in a U.S. population for the treatment of ISR lesions in the femoropopliteal artery. According to literature research on the performance of DCB in the treatment of ISR femoropopliteal lesions, the 12-month TLR rate for IN.PACT Admiral DCB treatment is expected to be 16%. Assuming 10% attrition at the 12-month follow-up, with 270 evaluable patients, the precision of the assumed 16% point estimate can be assessed by calculating the difference from the 1-sided 95% upper confidence limit. This difference, or margin of error, is calculated to be 4.1%.
Key Study Endpoints	Primary: Target lesion revascularization (TLR) within 12 months post-index procedure. Secondary: 1. All-cause mortality at 12 months and 24 months. 2. Target lesion revascularization (TLR) at 24 months. 3. Target vessel revascularization (TVR) at 12 months and 24 months. 4. Major target limb amputation at 12 months and 24 months.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	300
Actual Number of Sites Enrolled	50
Patient Follow-up Rate	78%
Final Safety Findings	Primary Safety Endpoint: Target lesion revascularization (TLR) within 12 months post-index procedure = 10.1% (28/276); Kaplan-Meier estimate of 10.2% with a 95% confidence interval of [7.1%, 14.5%]. Secondary Safety Endpoints: • All-cause mortality at 12, 24, and 36 months = 4.7% (14/299), 10.7% (32/298), and 15.5% (45/291), respectively • Target lesion revascularization at 24 and 36 months = 29.2% (71/243) and 45.9% (89/194) • Target vessel revascularization at 12, 24, and 36 months = 12.0% (33/276), 33.3% (82/246), and 49.5% (99/200), respectively • Major target limb amputation at 12, 24, and 36 months = 0.4% (1/275), 1.3% (3/237), and 1.7% (3/173), respectively
Final Effect Findings	Technical success, defined as successful deployment of the balloon without resulting in occlusion and having residual stenosis 30% and resting systolic pressure gradient < 10 mmHg (if measured), was achieved in 98.7% (296/300) of patients
Study Strengths & Weaknesses	Strengths: This PAS followed subjects through 3 years in a real-world, registry, setting. The trial met its study goals and results demonstrate long-term safety and effectiveness of the IN.PACT Admiral DCB in the treatment of in-stent restenosis lesions in the superficial femoral and popliteal arteries up to 36-months follow-up post-index procedure. Weaknesses: The study lacked a comparison group. There was less than 80% patient follow up rate at 3-years. The compliance data did not include "lost to follow-up" metrics.
Recommendations for Labeling Changes	A labeling update will be requested to include the 3 year data to support treatment of in-stent restenotic lesion
General
Study Status	Completed
Application Number / Requirement Number	P140010 / PAS001
Date Original Protocol Accepted	06/19/2015
Date Current Protocol Accepted	06/19/2015
Study Name	IN.PACT SFA Extended f/u study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is the continued the follow-up of the premarket trial. The IN.PACT Superficial Femoral Artery (SFA) trial is a two-phase, global, multicenter, single-blind, randomized (2:1 IN.PACT Admiral drug-coated balloon (DCB) to Percutaneous Transluminal Angioplasty (PTA)) trial. The SFA I and SFA II trials were conducted in Europe and in the United States, respectively.
Study Population	220 subjects treated with the IN.PACT Admiral DCB and 111 subjects treated with PTA in the SFA I and SFA II trials.
Sample Size	Total of 331 subjects: 220 DCB subjects and 111 PTA subjects It is estimated that from the randomized cohort of the IN.PACT SFA Trial approximately 248 subjects (165 DCB subjects and 83 PTA subjects) will have primary endpoint data at 24 months
Key Study Endpoints	Primary effectiveness endpoint Primary patency at 24 months Primary safety endpoint Freedom from device- and procedure-related death at 30 days and freedom from target limb major amputation and clinically- driven target vessel revascularization (CD-TVR) at 24 months Secondary study endpoints Through 60 months -Major Adverse Event Composite and its individual components (All-cause mortality, CD-TVR, major target limb amputation, and thrombosis at the target lesion site). - Clinically-driven target lesion revascularization (CD-TLR) - All TLR At 24 and 36 months -Primary sustained clinical improvement -Secondary sustained clinical improvement -Duplex-defined binary restenosis (peak systolic velocity ratio (PSVR) > 2.4) of the target lesion -Duplex-defined binary restenosis (PSVR > 3.4) of the target lesion -Quality of Life assessment -Walking capacity
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	IN.PACT Admiral drug-coated balloon (DCB) group: 220 subjects Percutaneous Transluminal Angioplasty (PTA) group: 111 subjects Follow-up rate: Through 60 months the follow-up rate for each of the study groups was: IN.PACT Admiral DCB group: 80% (176/220) PTA group: 85.6% (95/111)
Actual Number of Sites Enrolled	57 sites
Patient Follow-up Rate	Through 60 months the follow-up rate for each of the study groups was: IN.PACT Admiral DCB group: 80% (176/220) PTA group: 85.6% (95/111)
Final Safety Findings	Primary Safety Endpoint: Freedom from device- and procedure-related death at 30 days and freedom from target limb major amputation and clinically- driven target vessel revascularization (TVR) at 24 months. -IN.PACT Admiral DCB group: 87.4% (173/198) vs. PTA group: 69.8% (74/106) Difference: 17.6% (Lower bound of 95% CI: 8.5%, p-value: <0.001 (non-inferiority), 95% CI: 7.7%, 27.5%, p-value: <0.001 (superiority p-value)) Secondary safety endpoints through 60 months: -Major Adverse Event Composite (including death, major target limb amputation, clinically-driven TVR, and thrombosis): IN.PACT Admiral DCB group: 42.9% (79/184) vs. PTA group: 48.1% (50/104) -Death (all-cause): IN.PACT Admiral DCB group: 15.8% (29/184) vs. PTA group: 9.6% (10/104) -Clinically-driven TVR: IN.PACT Admiral DCB group: 29.3% (54/184) vs. PTA group: 40.4% (42/104) -Major Target Limb Amputation: IN.PACT Admiral DCB group: 0.5% (1/184) vs. PTA group: 0.0% (0/104) -Thrombosis: IN.PACT Admiral DCB group: 2.2% (4/184) vs. PTA group: 4.8% (5/104) -Clinically-driven target lesion revascularization (TLR): IN.PACT Admiral DCB group: 25.5% (47/184) vs. PTA group: 35.6% (37/104) -Any TVR: IN.PACT Admiral DCB group: 29.9% (55/184) vs. PTA group: 40.4% (42/104) -Any TLR: IN.PACT Admiral DCB group: 26.6% (49/184) vs. PTA group: 37.5% (39/104) It was noted that the difference in TLR rates between the two treatment groups decreased over time, from ~20% at 2 years to ~10% at 5 years
Final Effect Findings	Primary Effectiveness Endpoint: Primary patency at 24 months. IN.PACT Admiral DCB group: 69.2% (108/156) vs. PTA group: 50.5% (48/95) Difference (95% CI): Superiority test: 18.7% [6.3%, 31.1%], p-value =0.005. Primary Sustained Clinical Improvement at 36 months: IN.PACT Admiral DCB group: 68.7% (114/166) vs. PTA group: 52.6% (51/97) Difference (95% CI): Superiority test: 16.1% [3.9%, 28.3%], p-value= 0.012.
Study Strengths & Weaknesses	Strengths: This PAS followed through 5 years subjects in SFA trial, the premarket cohort. It met its study goals; the IN.PACT Admiral DCB group showed statistical superiority in the primary effectiveness endpoint against the PTA group. It also met the predefined 10% non-inferiority margin in the primary safety endpoint against the PTA group. In addition to meeting the study goals and the long-term follow-up of 5 years, strengths of this PAS include randomized treatment assignment and a low rate of attrition in both treatment groups, thus minimizing selection bias. Weakness: The generalizability of the study results to a broader group of patients may be limited since this randomized clinical trial comprised of a selected study population, as it generally occurs in this type of studies. In addition, 150 subjects (45%) included in the trial were from Europe when enrolled in the first phase of the IN.PACT SFA Trial.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results including study strengths and limitations. The updated label will reflect the long-term performance of the device from the pre-market randomized clinical trial.
General
Study Status	Completed
Application Number / Requirement Number	P140010 / PAS002
Date Original Protocol Accepted	06/19/2015
Date Current Protocol Accepted	06/19/2015
Study Name	Cont f/u of Sub in SFA Global Clin Prog
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective cohort study of the continued follow-up of patients enrolled in the IN.PACT superficial femoral artery (SFA) Global Clinical Program (premarket cohorts and the IN.PACT Global Study). The study population includes all IN.PACT Admiral drug-coated balloon (DCB) subjects enrolled in the IN.PACT SFA Trial, the IN.PACT SFA pharmacokinetic (PK) Sub-study, and the IN.PACT Global Study. The IN.PACT SFA Trial was designed as a two-phase, global, multicenter, single-blind, randomized (2:1 IN.PACT Admiral DCB to percutaneous transluminal angioplasty (PTA)) trial. The IN.PACT SFA PK Sub-study was designed to characterize the concentration level and pharmacokinetic parameters of paclitaxel in the systemic circulation over time. The sub-study was conducted concurrently with the IN.PACT SFA II phase of the IN.PACT SFA Trial in the United States. The IN.PACT SFA Global Study was designed as a prospective, multi- center, single-arm study of consecutively enrolled patients treated for atherosclerotic disease of the SFA and/or popliteal artery (PA) with the IN.PACT Admiral DCB.
Study Population	The study population includes all IN.PACT Admiral DCB subjects enrolled in the IN.PACT SFA Trial, the IN.PACT SFA PK Sub- study, and the IN.PACT Global Study.
Sample Size	There are at least 1,600 IN.PACT Admiral DCB subjects, including 220 DCB subjects from the IN.PACT SFA Trial, 25 DCB subjects from the IN.PACT SFA PK Sub-study, and 1,400 DCB subjects from the IN.PACT Global Study.
Key Study Endpoints	Key safety and effectiveness endpoints Through 60 months -Major Adverse Event Composite and its individual components (All-cause mortality, clinically-driven target vessel revascularization (CD-TVR), major target limb amputation, and thrombosis at the target lesion) -Clinically-driven target lesion revascularization (CD-TLR) -All TLR -All TVR -Serious Adverse Events At 24 and 36 months - Primary sustained clinical improvement - Secondary sustained clinical improvement - Quality of Life assessment - Walking capacity
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Cohort Subjects Enrolled On-Label 650 All-Subject 1651 Long Lesion 227
Actual Number of Sites Enrolled	On-Label - IN.PACT SFA I: The first phase of the IN.PACT Admiral DCB program completed enrollment in Europe with 13 participating clinical sites. - IN.PACT SFA II: The second phase of the IN.PACT Admiral DCB program completed enrollment in the US with 44 participating clinical sites. - IN.PACT SFA PK Sub-study: Completed enrollment in the US with nine participating clinical sites. On-Label and all subjects: IN.PACT Global Study: Completed enrollment globally with 64 participating clinical sites. Long Lesion 28 non-US investigational sites
Patient Follow-up Rate	Cohort Follow-up Time Overall Follow-up Compliance % On-Label 60 Months 86.3 All-Subject 60 Months 85.1 Long Lesion 36 Months 86.7
Final Safety Findings	Cohort Primary Safety Endpoint On-Label MAE composite and its individual components (all-cause All-Subject mortality, CD-TVR, major target limb amputation, and thrombosis at the target lesion site), CD-TLR, all TVR, all TLR, and serious adverse events. Long Lesion Freedom from device and procedure-related death through 30 days post-procedure and freedom from target limb major amputation and clinically-driven target vessel revascularization (CD-TVR) within 12 months post-index procedure.
Final Effect Findings	On-Label Primary sustained clinical improvement, secondary sustained All-subject clinical improvement, quality of life assessment by EQ-5D questionnaire, and walking capacity assessment by WIQ. Long Lesion Primary patency within 12 months post-index procedure, defined as freedom from clinically-driven target lesion revascularization (CD-TLR), and freedom from restenosis as determined by Doppler Ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) less than or equal to 2.4.
Study Strengths & Weaknesses	The study has a patient mortality rate of 16.1% for the Global Registry Patients at 5 years, and 6.4% for the Long Lesion Patients at 3 years. However, safety and functional results were as expected at these time points. Additionally, the follow-up period includes a very high number of patients not eligible for follow-up (e.g., death, withdrawal) in the on-label and all-subject cohorts. However, of those eligible for follow-up, the rate was 86.3% for on-label and 85.1% for the all-subject cohort.
Recommendations for Labeling Changes	No labeling changes recommended
General
Study Status	Terminated
Application Number / Requirement Number	P110008 / PAS003
Date Original Protocol Accepted	08/05/2015
Date Current Protocol Accepted	05/22/2026
Study Name	Coflex Actual Practice PAS USA
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective: To conduct 2 and 5 year comparative evaluation of clinical outcomes in the treatment of degenerative spinal stenosis with concomitant low back pain by decompression with and without additional stabilization using the Coflex® Interlaminar Technology. Study Design: multicenter, non-randomized but concurrently enrolled, propensity score controlled clinical study (new enrollment, patient-blinded)
Study Population	Patients suffering from a confirmed diagnosis of moderate spinal stenosis with concomitant low back pain at one or two contiguous levels from L1-L5 that require surgical decompression and who meet all of the inclusion/exclusion criteria. Group A: decompression surgery without any further stabilization by an implant (control group) Group B: decompression surgery with additional stabilization with the coflex® Interlaminar Technology (treatment group).
Sample Size	The total enrolled will be 186 coflex® patients and 220 decompression control patients at up to 20 investigational sites (up to 10 coflex and 10 control sites). This sample size is based on 150 per group (300 total) plus 15% to account for lost to follow-up in both groups, plus 20% in the control group and 5% in the study device group to account for trimming of control patients and possible trimming of study device patients during the propensity score design.
Key Study Endpoints	Primary endpoint is CCS: At least 15 point improvement relative to pretreatment in the Oswestry Disability Index (ODI). No reoperations, revisions, removals, or supplemental fixation at index level(s). No greater than or equal to 2 injections or series of injections for the treated level, or nerve block procedures performed to treat spinal stenosis for the index level(s); or a single injection within 12 months of the 5 year endpoint. As an exploratory analysis, primary hypothesis will be tested using: At least 15 point improvement relative to pretreatment in ODI. No reoperations, revisions, removals, or supplemental fixation at index level(s). No epidural injections or nerve block at any level at any time. Secondary Endpoints: ODI change compared to baseline at 24 and 60 months. Change in Visual Analog Scale (VAS) for low back pain after 24 and 60 months compared to baseline. Change in leg pain using VAS after 24 and 60 months compared to baseline. Change in worst leg pain using VAS after 24 and 60 months compared to baseline. Change of Zurich Claudication Questionnaire (ZCQ) after 24 and 60 months compared to baseline. Maintenance or improvement in EQ-5D compared to baseline. Change from baseline to Month 24 and Month 60 in maximum walking time from treadmill test. Neurological status. Radiography Endpoints: 1. Migration of the implant or the complete expulsion 2. Spinous process fracture 3. Maintenance of foraminal height 4. Adjacent level disease
Follow-up Visits and Length of Follow-up	60-months
General
Study Status	Completed
Application Number / Requirement Number	P140028 / PAS001
Study Name	SuperNOVA Continued f/u study
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a continued follow-up of premarket cohorts
Study Population	Patients implanted with the Innova¿ Vascular Self-Expanding Stent System. No comparator.
Sample Size	299 subjects were previously enrolled. All subjects in active follow-up will continue through their final required follow-up visit.
Key Study Endpoints	Primary Safety Endpoint - extended The safety endpoint assesses a composite major adverse event (MAE) rate and will be reported at 2 and 3 years post-procedure. The MAEs considered and adjudicated by the Clinical Events committee (CEC) are defined as: o All causes of death through 1 month post-index procedure o Target limb major amputation o Target Lesion Revascularization (TLR) Co-Primary Efficacy Endpoints - extended The efficacy endpoints assess vessel primary patency as determined by Duplex Ultrasound (DUS). Primary patency will be reported at 2 years post-procedure for the core stent matrix, the long stents and the entire matrix. o Vessel primary patency is defined as freedom from more than 50% stenosis based on DUS peak systolic velocity ratio (PSVR) comparing data within the target segment to the proximal normal arterial segment in the absence of Target Lesion Revascularization (TLR) or bypass. o The DUS will be conducted at each site per protocol requirements and sent to an independent core laboratory for analysis. o A systolic velocity ratio (SVR) >2.4 suggests >50% stenosis.
Follow-up Visits and Length of Follow-up	No new enrollment Follow-up is ongoing in this study with all subjects past the 12 month visit. Office visits will continue at 2 and 3 years post-index procedure for all subjects. Additional office visits will occur at 4 and 5 years for subjects enrolled in Japan only.
Interim or Final Data Summary
Actual Number of Patients Enrolled	299
Actual Number of Sites Enrolled	49
Patient Follow-up Rate	A total of 299 subjects enrolled in the study. As of September 29, 2016, 295 enrolled study subjects completed the 30-day post-procedure visit, 276 subjects the 6-month follow-up visit, 266 subjects the 12-month follow-up visit, 254 subjects the 24-month follow-up visit, and 238 subjects have completed the 36-month follow-up visit.
Final Safety Findings	The primary safety endpoint of the 12-month Major Adverse Event (MAE)-free rate was met at 85.8%, above the pre-established performance goal (PG) of 59.6%.
Final Effect Findings	The primary efficacy endpoint of primary patency (peak systolic velocity ratio {PSVR} less than or equal to 2.4 in the absence of TLR) at 12 months was 66.4% for the entire matrix. The established PG was 63%.
Study Strengths & Weaknesses	The study was completed with a reasonably high rate of follow-up compliance out to 36 months. The major weakness is the large number of protocol deviations. However, as noted by the clinical reviewer these were mostly a result of missed follow-up or incomplete protocol assessments.
Recommendations for Labeling Changes	No additional information is available from these results that contradicts the information already contained in the publicly available SSED and labeling. No labeling changes are therefore recommended.
General
Study Status	Terminated
Application Number / Requirement Number	P140012 / PAS001
Date Original Protocol Accepted	01/14/2016
Date Current Protocol Accepted	05/30/2018
Study Name	REDUCE PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary study objective is to demonstrate the safety of the ReShape Dual Balloon treatment using a composite endpoint consisting of all device- and/or procedure-related serious adverse events (SAEs) including those associated with early device explants or deflations, gastric ulcers and esophageal trauma. The study design is a prospective, new-enrollment, multicenter, single arm, open label clinical study.
Study Population	Patients intending to have the ReShape procedure will be recruited to include men and women 22 years of age and older with BMI = 30kg/m2 and = 40kg/m2 with one or more obesity-related comorbidities. The device group will act as its own comparator, with the device being removed after 24 weeks.
Sample Size	250 Intention to treat (ITT)/safety subjects will be enrolled at 10-15 sites in the US only (including ~4 from the pivotal trial sites) in order to have 223 weight-loss completed subjects at 24 weeks post device insertion and 182 weight-loss completed subjects at 48 weeks post- device insertion. Assumptions: CSE rate = 7.5% in REDUCE pivotal trial; With a 1-sided upper confidence bound (UCB) of 0.975 and performance goal of 13%, an 80% power and normal approximation CIs result in an estimated sample size of 217 subjects. Precision estimates/Confidence bounds for descriptive assessments: 1. % excess weight loss (%EWL) at 24 weeks: Assuming an ITT 25.0 ± 21.0%EWL at 24 Weeks, a sample size of 250 will provide a precision on the estimate of %EWL of 3.0 % with > 99% probability. For the Completer Cohort (n = 223) the precision will be 3.5% with > 99% probability. 2. % total body weight loss (%TBL) at 24 weeks: Assuming an ITT 7.5 ± 5.5%TBL at 24 Weeks, a sample size of 250 will provide a precision on the estimate of %TBL of 1.0% with > 99% probability. For the Completer Cohort (n = 223) the precision will be 1.0% with > 99% probability. 3. Rate of gastric ulceration through the date of device retrieval: Assuming a rate of any device-related gastric ulceration of 10.5% using the modified tip (commercialized) device based on the REDUCE Pivotal and Single Arm studies, a sample size of 250 will provide an exact binomial UCB of 14.9% 4. Rate of deflations through the date of device retrieval: Assuming a rate of any device deflation of 6.0% based on the REDUCE Pivotal Trial, a sample size of 250 will provide an exact binomial UCB of 9.7% 5. Rate of early retrievals: Assuming a rate of any retrieval occurring before 154 days of 15.0% based on the REDUCE Pivotal Trial, a sample size of 250 will provide an exact binomial UCB of 19.8% 6. Training and real world performance: for the comparison of safety rates between REDUCE Pivotal Trial (n=265) and ReShape PAS (n=250) a sample size of 250 subjects will achieve a precision of 6.5% or less with > 99% probability for the safety rates of interest (early retrievals and procedure- related SAEs). *Note: subgroup assessments will be performed for the following: Extended Treatment subjects, Subjects Older Than Sixty, Obesity Drug Treatment subjects, subjects dichotomized by received fill volume (900cc/750cc), subjects dichotomized by age (<45, =45 years), subjects dichotomized by baseline BMI (<35kg/m2, =35kg/m2) and sex, age and baseline BMI (<35kg/m2, = 35kg/m2)
Key Study Endpoints	The primary safety endpoint is a composite of certain device- or procedure-related SAEs – CSE to include: Any gastric ulcer SAE, any esophageal injury SAE, any device-related SAE (including those SAEs associated with deflations), any insertion/retrieval procedure-related SAE (including those SAEs associated with early retrievals). The secondary/additional safety endpoints include: 1. The rates of each individual CSE component 2. Rate of all device retrievals prior to day 154 3. Rate of device deflations 4. Rate of all device-related gastric ulcers, SAE and non-SAE 5. Analysis of accommodative symptoms of nausea, vomiting, and/or abdominal pain using the prospective Rhodes Index of Nausea, and Abdominal Pain Visual Scale instruments. There is no primary effectiveness endpoint The secondary/additional effectiveness endpoints include: 1. Intent-To-Treat (with multiple imputation – ‘MI’) as last- observation-carried-forward (LOCF) – (for missing data) and Completed Cases weight loss characterization at weeks 24 and 48 (%EWL, %TBL, pounds lost and BMI unit reduction using all available data, and for 48 week data, comparison to 24 week values) 2. Subject satisfaction survey, Impact of Weight on Quality of Life (IWQoL) and Three Factor Eating Questionnaire (TFEQ) at weeks 24, and 48.
Follow-up Visits and Length of Follow-up	Virtual visits may be allowed for Week 1, 4, 8, 12, 16, 20, 28, 32, 36, 40, and 44. During these visits, the subjects will submit their weight via the Patient Portal. A full assessment will be done over the phone by the Study Doctor or designee. Blood pressure measurement will be optional for these visits.
Interim or Final Data Summary
Actual Number of Patients Enrolled	The study was terminated early due to voluntary market withdrawal of the device by the sponsor for business reasons. 187 subjects were enrolled and 159 device implants were attempted, 152 subjects received the device.
Actual Number of Sites Enrolled	15
Patient Follow-up Rate	97.4% (148/152) at Week 1; 80.3% (122/152) at Week 12; 82.9% (126/152) at Week 24; 42.1% (64/152) at Week 36; 36.2% (55/152) at Week 48
Final Safety Findings	Primary Safety Endpoint Composite Safety Endpoint (CSE) The CSE includes any device- or procedure-related gastric ulcer SAE, any device- or procedure-related esophageal injury SAE, any other device-related SAE (including those SAEs associated with deflations), any other procedure-related insertion/retrieval SAE (including those SAEs associated with early retrievals). Of the 159 subjects who were enrolled and device implant was attempted, twelve (12) had missing removal data. Therefore, the CSE was considered for the subjects with data (N=147, “available cases”), a best-case scenario where no CSE adverse events occurred in the subjects for which there is missing data, and a worst-case scenario where CSE adverse events occurred in all subjects for which there is missing data. Available Cases: 8.8% (13/147) with one-sided 97.5% upper confidence bound of 13.4% Best-Case Scenario: 8.2% (13/159) with one-sided 97.5% upper confidence bound of 12.4% Worst-Case Scenario: 15.7% (25/159) with one-sided 97.5% upper confidence bound of 21.4% The hypothesis test for the primary endpoint was based on an estimated sample size of 217 subjects. Given the actual sample size of 159 subjects, the power is 61%. Secondary/Additional Safety Endpoints The rates of each individual CSE component Any gastric ulcer SAE rate: 0.6% (1/159), 95% CI: 0.0, 1.9% Any esophageal injury SAE rate: 0.6% (1/159), 95% CI: 0.0, 1.9% Any other device-related SAE rate: 6.9% (11/159) 95% CI: 3.0, 10.9% Any other procedure-related SAE rate: 1.3% (2/159), 95% CI: 0.0, 3.0% Additional Safety Data One event of procedure-related pancreatitis reported: 0.6% (1/159); and two events of device-related pancreatitis reported: 1.3% (2/159). One event of procedure-related pneumonia aspiration reported: 0.6% (1/159) No events of gastric or esophageal perforation reported No events of death reported No events of spontaneous hyperinflation reported Rate of all device retrievals prior to day 154 There were 23 early device retrievals (15.1%; 23/152), 95% CI: 9.4, 20.8% Rate of device deflations There were six (6) device deflations (3.9%; 6/152), 95% CI: 0.9, 7.0% Rate of all device-related gastric ulcers, SAE and non-SAE Device or procedure related gastric ulcer rate: 4.4% (7/159) with one-sided 95% upper confidence bound of 7.6%; one (1) was an SAE: 0.6% (1/159); and six (6) events were non-SAE. Analysis of accommodative symptoms of nausea, vomiting, and/or abdominal pain using the prospective Rhodes Index of Nausea, and Abdominal Pain Visual Scale instruments Rhodes Index of Nausea, Vomiting and Retching, as well as Abdominal Pain VAS, were evaluated in subjects at baseline, Week 1, Week 4, Week 12, and Week 24. The Rhodes overall score increased with severity of symptoms. Results showed increased overall score from baseline at Week 1, approximately 6.3 times that of baseline, and at Week 4, approximately 3 times that of baseline. Scores were comparable to baseline following Week 4. Abdominal Pain Visual Scale showed substantial increase from baseline through Week 1 for all subjects, approximately 10% increase in pain level. The overall pain level decreased by Week 4 to less than 3% (or 2% below baseline level).
Final Effect Findings	No Primary Effectiveness Endpoint Secondary/Additional Effectiveness Endpoints Intent-To-Treat (with multiple imputation – ‘MI’) as last- observation-carried-forward (LOCF) – (for missing data) and Completed Cases weight loss characterization at weeks 24 and 48 (%EWL, %TBL, pounds lost and BMI unit reduction using all available data, and for 48 week data, comparison to 24 week values) Week 24 Data Completed Case (N=126): Mean (SD) (Min, Max) %EWL: 36.22% (23.42%) (-4.8%, 112.7%) %TBL: 10.06% (6.06%) (-1.2%, 24.1%) Weight Loss (lbs): 22.04 (14.16) (-2.3, 62.9) BMI Loss (kg/m2): 3.58 (2.20) (-0.4, 9.3) LOCF (N=159): Mean (SD) (Min, Max) %EWL: 32.69% (23.49%) (-4.8%, 112.7%) %TBL: 8.90% (6.14%) (-1.2%, 24.1%) Weight Loss (lbs): 19.29 (14.17) (-2.3, 62.9) BMI Loss (kg/m2): 3.14 (2.22) (-0.4, 9.3) Worst Case (N=159) assumes no weight change for subject not evaluated at 24 weeks: Mean (SD) (Min, Max) %EWL: 28.71% (25.52%) (-4.8%, 112.7%) %TBL: 7.97% (6.77%) (-1.2%, 24.1%) Weight Loss (lbs): 17.46 (15.46) (-2.3, 62.9) BMI Loss (kg/m2): 2.83 (2.44) (-0.4, 9.3) The study was terminated prior to achieving full enrollment. Due to this, and subjects lost to follow-up, only 53 subjects completed the 48-week follow up and had weight data available for Week 24. Completed Case at Week 24 who also had Week 48 data (N=53): Mean (SD) (Min, Max) %EWL: 45.82% (25.06%) (-0.3%, 112.7%) %TBL: 12.60% (6.09%) (-0.1%, 24.1%) Weight Loss (lbs): 27.81 (14.93) (-0.3, 62.9) BMI Loss (kg/m2): 4.48 (2.24) (-0.1, 9.3) Completed Case at Week 48 who also had Week 24 data (N=53): Mean (SD) (Min, Max) %EWL: 40.80% (28.78%) (-16.5%, 109.7%) %TBL: 11.25% (7.76%) (-3.1%, 29.9%) Weight Loss (lbs): 24.77 (18.66) (-6.9, 81.1) BMI Loss (kg/m2): 4.02 (2.92) (-1.0, 12.0) Difference in Week 24 and Week 48 data (N=53): Mean (SD) (Min, Max) %EWL: -5.03% (20.81%) (-62.2%, 48.1%) %TBL: -1.35% (5.17%) (-13.3%, 8.6%) Weight Loss (lbs): -3.05 (11.25) (-6.2, 18.2) BMI Loss (kg/m2): -0.46 (1.80) (-4.2, 2.7) Subject satisfaction survey, Impact of Weight on Quality of Life (IWQoL) and Three Factor Eating Questionnaire (TFEQ) at weeks 24, and 48 Subject satisfaction surveys were provided to subjects at Week 24 and Week 48. The survey requested a response to three different questions. Over 60% of the subjects were satisfied with their experience with the ReShape balloon at Week 24 and would choose to repeat the process again. The percent satisfaction remained approximately the same at Week 48 based on the limited number of subjects who completed this study time point. Impact of weight on quality of life (IWQoL-Lite) was assessed by subjects at baseline, Week 24 and Week 48. Quality of life is assessed in five areas: physical function, self-esteem, sexual life, public distress and work. While all scales demonstrated positive changes from baseline, the largest changes were observed in the physical function and self-esteem scales. Three factor eating (TFEQ-R18v2) was assessed by subjects at baseline, Week 24 and Week 48. The questionnaire characterizes eating behavior in three different domains: cognitive restraint, uncontrolled eating, and emotional eating. All domains demonstrated positive changes from baseline.
Study Strengths & Weaknesses	This was a prospective study of newly enrolled and treated patients in the US. There was no concurrent comparison group, which limits interpretation of the results. The study did not complete enrollment resulting in a lower sample size than expected. 82.9% of treated subjects were evaluable at the 24 Week point when the device was removed. However, only 36.2% of the subjects were available at Week 48 which limits the interpretation of the study results. The subjects that remained in the study may be different than those that were lost to follow-up, and therefore, the generalizability of results can be limited.
Recommendations for Labeling Changes	Not applicable. As of January 1, 2019, the sponsor stopped selling and distributing the device.
General
Study Status	Completed
Application Number / Requirement Number	P140013 / PAS002
Date Original Protocol Accepted	07/25/2015
Date Current Protocol Accepted	07/25/2015
Study Name	Minerva Pivotal Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Minerva Pivotal Study is a randomized (2:1), controlled, multicenter study to evaluate the safety and effectiveness of the Minerva Endometrial Ablation System. The Post Approval study will collect extended effectiveness and safety data at 2-3 years post treatment.
Study Population	Pre-menopausal women with menorrhagia (excessive uterine bleeding) due to benign causes for whom childbearing is complete or who no longer wish to retain fertility. The premarket study included a rollerball control group.
Sample Size	Up to 162 women (108 treatment arm and 54 control arm)
Key Study Endpoints	Any treatments or hysterectomy for dysfunctional uterine bleeding Compliance with contraception Any pregnancies Menstrual status (questions assess bleeding, i.e., amenorrhea, spotting hypomenorrhea, eumenorrhea or menorrhagia) Any gynecological adverse events Completion of Quality of Life Questionnaire
Follow-up Visits and Length of Follow-up	Three years 30 days (data were provided premarket), one year, two year, and three year
Interim or Final Data Summary
Actual Number of Patients Enrolled	153 subjects were enrolled in the study
Actual Number of Sites Enrolled	13 sites were enrolled in the study
Patient Follow-up Rate	The 3-year follow-up rate was 125/153 total subjects (81.7%). This included 88/102 subjects (86.3%) in the Minerva treatment arm and 37/51 subjects (72.5%) in the Rollerball control arm.
Final Safety Findings	There were no unexpected device-related adverse events in the Minerva Pivotal study. There were five events classified as Serious Adverse Events (SAEs) in the Minerva Group. The SAEs were as follows: Four Hysterectomies were performed, two (2) for pelvic cramping, one (1) for fibroids and one (1) for chronic pelvic pain secondary to a diagnosis of hematometra. One pregnancy was reported between the 12- and 24-month reporting period. A Dilation and Curettage (D&C) was performed to terminate the pregnancy.
Final Effect Findings	Success Rate The following success rates were reported at 1, 2, and 3 years in the intent-to-treat (ITT) population: 1 year* Minerva (N=102): 95 (93.1%); 95% CI (86.4%, 97.2%) Rollerball (N=51): 41 (80.4%); 95% CI (66.9%, 90.2%) 2 years** Minerva (N=102): 89 (87.3%); 95% CI (79.2%, 93.0%) Rollerball (N=51): 35 (68.6%); 95% CI (54.1%, 80.9%) 3 years** Minerva (N=102): 87 (85.3%); 95% CI (76.9%, 91.5%) Rollerball (N=51): 35 (68.6%); 95% CI (54.1%, 80.9%) *Based on Alkaline Hematase lab value **Based on telephone questionnaires Amenorrhea Rate The following amenorrhea rates were reported at 1 and 3 years in the intent-to-treat (ITT) population: 1 year Minerva (N=102): 73 (71.6%); 95% CI (61.8%, 80.1%) Rollerball (N=51): 25 (49.0%); 95% CI (34.8%, 63.4%) 3 years* Minerva (N=102): 58 (56.9%); 95% CI (46.7%, 66.6%) Rollerball (N=51): 19 (37.3%); 95% CI (24.1%, 51.9%) *Mean follow-up time of 4.1 years Subject Satisfaction At 2- and 3-year follow-up, 93.4% and 95.5% of the Minerva subjects, respectively compared to 92.1% and 89.2% of the Rollerball subjects, respectively were “Satisfied” or “Very Satisfied” post-procedure. In addition, at the 2- and 3-year follow-up, 94.6% and 95.4% of the Minerva subjects, respectively compared to 94.8% and 91.9% of Rollerball subjects, respectively would “Maybe” or “Definitely” recommend the procedure to a friend or relative with a similar problem
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes, labeling change recommended to update the device labeling with the final study results.
General
Study Status	Completed
Application Number / Requirement Number	P140016 / PAS001
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To monitor longer-term (5 year) safety and effectiveness of the device. Design: Prospective, nonrandomized, single-arm, multicenter, multinational study. This is a continued follow-up of premarket cohorts, including pivotal study and continued access cohorts in accordance with the previously approved Investigational Device Exemption protocol.
Study Population	Subjects who are enrolled in the aneurysm/ulcer clinical study initiated prior to device approval and alive at the time of the device approval.
Sample Size	The total patients who are alive at the time of device approval
Key Study Endpoints	Primary safety endpoints: The 30 day freedom from major adverse event (MAE) rate Primary effectiveness endpoints: The 12-month device success rate.
Follow-up Visits and Length of Follow-up	5 years post-procedure (pre-discharge), 30 days, 6 months, 12 months, yearly thereafter through 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 110 patients were enrolled in the pivotal study and 18 patients in the Continued Access cohort.
Actual Number of Sites Enrolled	Twenty-three (23) sites including 14 sites in the U.S. and 9 sites outside of the United States.
Patient Follow-up Rate	Pivotal cohort, clinical Follow-up was 90.5% (57/63) at 5 years; CT scan was completed for 85.7% (54/63) of patients at 5 years. Continued Access cohort, clinical follow-up was 77.8% (7/9) at 5 years, CT scan was completed for 77.8% (7/9) of patients at 5 years.
Final Safety Findings	Aneurysm related Mortality Survival from aneurysm-related mortality by Kaplan Meier (KM) estimate at 5 years in the pivotal cohort was 99% for all patients, 98.8% for the aneurysm group and 100% for the ulcer group. Through 5 years there was one (1) CEC confirmed aneurysm-related death in the pivotal cohort, and two confirmed aneurysm related death in the continued access cohort. All-Cause Mortality Survival from all-cause mortality by KM estimate at 5 years for pivotal cohort was 75.9% for all patients. There were a total 23 deaths in the pivotal cohort and 10 deaths in the continued access cohort. Endoleak For pivotal cohort, there were 13 patients with Type I endoleak, 16 patients with Type II endoleak, 2 patients with Type III endoleak and 6 patients with unknown endoleak type. cohort. At 5 years, the percentage of pivotal patients with Type I endoleak was 13.6% (6/44), Type II endoleak rate was 6.8% (3/44), Type III endoleak rate was 0%. For continued access patients, there were 8 patients with core laboratory reported endoleak. Change in Aneurysm Size In the pivotal cohort, a total of 20 patients experienced aneurysm growth at one or more follow-up timepoints. At 5-year timepoint, the percentage of all patients with an increase (> 5 mm) in aneurysm size was 26.0% (13/50), decrease (> 5 mm) in aneurysm size was 24.0% (12/50) and no change (less than or equal to 5 mm) in aneurysm size was 50%. In the continued access cohort, core laboratory increases in aneurysm occurred in 5 patients. Rupture No rupture was reported for pivotal and continued access patients through 5 years post procedure. Two ruptures were reported for pivotal patients after 5 years. Graft Patency No pivotal patients experienced occlusion in the pivotal or continued access cohort. Device Integrity The percentage of pivotal patient that experienced at stent fracture at 2, 3, 4 and 5 years for all pivotal patients was 1.3% (1/80), 1.4% (1/72), 1.5% (1/68) and 0%. There were no reports of clinical sequelae from the stent fracture.
Final Effect Findings	(cont) There was one report of component separation reported by the core-lab in the continued access cohort. Migration There were three (3) reports of CEC confirmed migration, 3.8% (3/80) at 2 years in the pivotal patients. The percentage of pivotal patients that experienced stent migration from 3 through 5 years was 0% at each timepoint. One report of CEC confirmed migration occurred in the continued access cohort at 5 years. Secondary Intervention A total of 19 pivotal patients have undergone a secondary intervention. Eleven (11) of the secondary interventions occurred in patients with core-laboratory observed growth of the treated aneurysm. In total 4 patents in the continued access cohort have required secondary intervention for reasons of Type I and Type III endoleaks, Type I endoleak and device migration, device separation and Type III endoleak, and persistent Type I endoleak. Conversion There has been one (1) conversion to open surgical repair in the pivotal cohort which occurred at 1 year. KM estimate of freedom from conversion at 5 years was 99.0%. There have been no conversions to open repair in the continued access cohort. Major Adverse events A total of 46 patients in the pivotal cohort experienced a major adverse events (MAE) through 5 years. KM estimate of freedom from major adverse event at 5 years for all pivotal patients was 53.7%. There were 13 patients in the continued access cohort with MAEs. The MAEs include wound complication requiring return to operating room (n=1), death (n=6), stroke (n=1), re-intubation (n=1), aneurysm or vessel leak requiring re-operation (n=3), and persistent endoleak (n=1).
Study Strengths & Weaknesses	Study Strength: This study is a multicenter study involving 23 investigational sites, 14 in the US and 9 sites outside of the U.S. Clinical Follow-up and imaging out to 5 years were completed for at least 75 of patients in the pivotal and continued access cohorts. Weakness: This is a non-randomized study with inherent biases.
Recommendations for Labeling Changes	Labeling update is recommended to reflect the long-term results of the pivotal and continued Access study. The labeling change should include a new section on the label showing a summary of the study results (final endpoint results, clinical follow-up rate and available imaging), strengths and limitations of long-term Study.
General
Study Status	Terminated
Application Number / Requirement Number	H140001 / PAS002
Date Original Protocol Accepted	01/23/2015
Date Current Protocol Accepted	01/23/2015
Study Name	Impella RP Pediatric Study
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	A retrospective, single-arm multicenter study
Study Population	Pediatric patients with the right side heart failure supported with the Impella RP System. Patients that meet all eligibility criteria
Sample Size	15 consecutive pediatric patients or all pediatric patients supported with the Impella RP over a 5 year time period (whichever comes first) will be enrolled at a minimum of 5 participating clinical centers.
Key Study Endpoints	Data collected in the PAS will be based on institutional standard of care. Data will be retrospectively collected throughout the study. Data must be collected on the case report forms. Source documents include, but are not limited to, death certificate, autopsy report, laboratory reports, operative report, echocardiograms, ultrasound report, angiograms, cardiac catheterization logs and cardiac catheterization reports, patient discharge report. Primary: Survival at 30 days post device explant or hospital discharge (whichever is longer), or to induction of anesthesia to a longer term therapy, including a heart transplant or an implant of a surgical RVAD. Secondary: Safety Rates of the following major adverse events measured at hospital discharge or to induction of anesthesia to a longer term therapy (including a heart transplant or an implant of a surgical RVAD): Death (any cause of death and cardiac death) Major Bleeding Hemolysis Pulmonary Embolism Survival only will be assessed at 30 days (± 10 days) and 180 days (± 30 days). Other adverse events Device failures and malfunctions will be retrospectively documented Secondary Probable benefit Improvement in hemodynamic parameters Cardiac Index Central Venous Pressure LVAD flows after initiation of Impella RP support. Major adverse events will be reviewed adjudicated and categorized by the Clinical Events Committee.
Follow-up Visits and Length of Follow-up	180 days post explant Survival status will be assessed at 30 and 180 days post explant
General
Study Status	Completed
Application Number / Requirement Number	P140017 / PAS001
Date Original Protocol Accepted	01/27/2015
Date Current Protocol Accepted	01/27/2015
Study Name	Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center study, historically controlled clinical trial, designed to follow up subjects from the IDE trial up to five years
Study Population	150 subjects who were successfully implanted in the original 5 IDE centers.
Sample Size	150 subjects who were successfully implanted in the original 5 IDE centers. The five U.S. IDE centers are continuing their participation in the study for the required five-year follow- up period for enrolled subjects.. Using a power of 80%, a one-tailed alpha of 5%, and an estimated freedom from TPV dysfunction at 5 years of 47%, the calculated required sample size for the 5 year study comes to 133. The sponsor does not estimate the effect of subjects lost to follow-up on the final 5 year study population.
Key Study Endpoints	Primary Endpoints TPV dysfunction is the primary endpoint. It is defined as either: ¿Þ RVOT reoperation for conduit dysfunction or device- related reason OR ¿Þ Catheter re-intervention on the TPV OR ¿Þ Hemodynamic dysfunction of the TPV (moderate or greater pulmonary regurgitation, and/or a mean RVOT gradient greater than 40 mm Hg) Secondary Endpoints ¿Þ Percent patients with procedural success ¿Þ Percent subjects with serious procedural adverse events ¿Þ Percent subjects with serious device-related adverse events ¿Þ Stent fracture ¿Þ Re-intervention on the TPV ¿Þ Surgical replacement of the RVOT conduit ¿Þ Death o All-cause o Procedure-related o Device-related ¿Þ NYHA classification
Follow-up Visits and Length of Follow-up	5 years Annually until followed for 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	There is no new enrollment for this study, as it involves only follow-up of the premarket cohort. However, a total of 150 subjects who received the Melody Transcatheter Pulmonary Valve (TPV) device.
Actual Number of Sites Enrolled	There are no new study sites for this study, as it involves only study subjects from the premarket cohort. The study subjects were enrolled at five (5) sites in the premarket study.
Patient Follow-up Rate	The follow up rate for this study is 85% (128/150).
Final Safety Findings	21 subjects experienced 30 serious procedure related adverse events 47 subjects experienced 86 serious device related adverse events 23 stent fractures, with 13 occurring in years 2 or 3, and 3 or less in all other years 29 catheter related re-interventions 15 RVOT conduit reoperations 6 deaths
Final Effect Findings	Freedom from TPV dysfunction at 5 years after TPV implant was 74.2%, by K-M analysis, with a 95% confidence interval ranging from 65.5% to 81.0%
Study Strengths & Weaknesses	This study provides longer term (5 years) safety and effectiveness results of the Melody Transcatheter Pulmonary Valve (TPV) device. This study followed up the premarket cohort through five years post- procedure. Kaplan-Meier analysis of the primary endpoint, freedom from TPV dysfunction, estimates a rate of 72% at 5 years. This compares very favorably with the performance goal of 36%. The study had a low rate of attrition (7/150), thus minimizing selection bias. At the same time the study had 86 serious device related adverse events. Considering the fact that this device precludes the need for major surgery, this relatively high number of serious device related adverse events does not represent an unreasonable risk for the long term safety and effectiveness of the Melody TPV device.
Recommendations for Labeling Changes	Labeling changes are recommended to add a summary of the 5-year study results including the complete and updated Kaplan-Meier analysis. The updated labeling will reflect the long-term (5-years) performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P140017 / PAS002
Date Original Protocol Accepted	01/27/2015
Date Current Protocol Accepted	01/27/2015
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center study.
Study Population	100 subjects who were successfully implanted in this study will continue to be followed
Sample Size	100 subjects: Using a power of 80%, an alpha of 5%, a one- tailed test, and assuming an estimated rate of 86% (the rate found in the premarket study), the required sample size comes out to 81. Therefore, a sample size of 100 with only six months follow-up will ensure that a sufficient number of patients are followed for the entirety of the study.
Key Study Endpoints	Primary Endpoints As noted in the study hypothesis, above, the primary endpoint is the percentage of subjects with acceptable hemodynamic function at six months post-implant. Acceptable hemodynamic function is defined as: ¿Þ Mean RVOT gradient less than or equal to 30 mmHg AND ¿Þ Less than moderate severity of pulmonary regurgitation AND ¿Þ No RVOT conduit reoperation or catheter re-intervention since implant Secondary Endpoints ¿Þ Percent patients with procedural success ¿Þ Percent subjects with serious procedural adverse events ¿Þ Percent subjects with serious device-related adverse events at 6 months post-implant ¿Þ Incidence of serious device-related adverse events during full follow-up period ¿Þ Stent fracture ¿Þ Re-intervention on the TPV ¿Þ RVOT conduit reoperation ¿Þ Death ¿X All-cause ¿X Procedure-related ¿X Device-related ¿Þ NYHA classification
Follow-up Visits and Length of Follow-up	5 years Annually until followed for 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	One hundred thirty-one (131)
Actual Number of Sites Enrolled	Ten (10)
Patient Follow-up Rate	The follow-up rate at 5 years excluding deaths and withdrawals is 67% (=65/97)
Final Safety Findings	23 subjects (19%, 23/121) experienced 30 serious procedure related adverse events Of the 100-implanted subjects, 33 subjects (33%) experienced 78 serious device related adverse events. The most common serious adverse events classified as device-related were: endocarditis (n=17 subjects (13 pediatric + 4 adult)) valve dysfunction: recurrent stenosis (n=12) valve dysfunction: regurgitation (n=9) major stent fracture (n=6) 2 device unrelated deaths were reported in this study
Final Effect Findings	Procedural success was demonstrated in 91.1% of subjects. Kaplan-Meier (K-M) analyses were performed to assess freedom from stent fracture, catheter reintervention, reoperation, and mortality. At 5 years post-implant, freedom from major stent fracture was 93.0%, catheter reintervention was 92.8%, reoperation was 82.4%, and all-cause mortality was 97.5%. There were no procedure or device related deaths. The NYHA class improved significantly from baseline to 6 months post-implant and during the final follow up at 5 years, with 37.9% of subjects in class I at baseline, and 85.5% of subjects in class I at 6 months.
Study Strengths & Weaknesses	Study Strength: The primary objective of the study was to confirm that the short-term hemodynamic effectiveness of implantation of the Melody™ TPV at six months post-implant is equal to or greater than the Performance Goal (PG)of 75%, established based on the performance of this device in the IDE study.. The primary objective was met with 96.7% ()of subjects having acceptable hemodynamic function 6 months post-implant (p-value < 0.0001 and 95% lower confidence bound of 91.6%) which compares very favorably with the PG. Study Weaknesses: The study had a lower rate of follow up (67%) and a higher rate of attrition (33.7%), that may be subject to selection bias. Further, during the duration of this study the study protocol was modified to allow for the phone call visits from 2 to 5 years resulting in the number of subjects with echocardiographic data less than the total number of subjects for whom follow-up data were collected for years 2 through 5. Also, the study had 78 serious device related adverse events. Considering the fact that this device precludes the need for major surgery, this relatively high number of serious device related adverse events does not represent an unreasonable risk for the long term safety and effectiveness of the Melody TPV device.
Recommendations for Labeling Changes	Labeling changes are recommended to add a summary of the 5-year study results reflecting the long-term (5-years) performance of the device.
General
Study Status	Delayed
Application Number / Requirement Number	P130018 / PAS001
Date Original Protocol Accepted	11/02/2016
Date Current Protocol Accepted	10/03/2025
Study Name	ProAct Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ProACT PAS is a 5-year prospective, open-label, multi-center study designed to evaluate the long-term incidence of urethral stricture and device erosion after ProACT implantation. In addition, the study will evaluate whether treatment with ProACT affects clinical outcomes after subsequent SUI therapies.
Study Population	Inclusion Criteria 1. Subject is a male of at least 50 years of age. 2. Subject demonstrates stress urinary incontinence. 3. Subject has undergone a radical prostatectomy, transurethral resection of the prostate, or other prostate surgery. 4. Subject is willing and able to undergo surgical implantation of ProACT devices. 5. Subject is willing and able to comply with study-required follow-up activities, including annual telephonic follow –up interviews, for a period of 5 years from their date of initial implantation. This includes compliance even after possible explant of ProACT devices and/or possible implantation of subsequent therapies. 6. Subject is willing and able to sign the approved informed consent. 7. Subject has two positive 24-hour pad weight tests (greater than or equal to 8 gram pad weight increase demonstrated in two 24-hour pad weight tests). 8. Subject has a negative urine culture. 9. Subject has no known urogenital malignancy, other than previously treated prostate cancer. 10. Subject meets ONE of the following criteria: a. Baseline PSA less than or equal to 2.5ng/mL; b. Baseline PSA > 2.5ng/mL and less than or equal to 10 ng/mL AND free PSA greater than or equal to 25% of total PSA; 11. Physician determines subject to be a suitable surgical candidate. Exclusion Criteria 1. Subject has an existing urethral stricture, a history of any urethral strictures, or has ever had a urethrotomy. 2. Subject has undergone prostate surgery or any anti-incontinence surgery within the last 12 months. 3. Subject has an artificial urinary sphincter or any components of a previously implanted artificial urinary sphincter in vivo. 4. Subject has undergone radiation therapy in the prostatic area within the last 12 months. 5. Subject has untreated or unsuccessfully treated detrusor instability or over-activity. 6. Subject has an atonic bladder. 7. Subject had, presently has, or is suspected of having bladder cancer. 8. Subject has untreated or unsuccessfully treated bladder stones. 9. Subject has detrusor sphincter dyssynergia. 10. Subject has known hemophilia or a bleeding disorder. 11. Subject has a known severe contrast solution allergy (e.g., anaphylaxis, cardiac, or respiratory arrest). 12. Subject has insulin-dependent diabetes that is uncontrolled or not controllable, as indicated by an A1c test result of = 6.5%.
Sample Size	145 subjects will be enrolled at 5 to 7 clinical sites in the U.S.
Key Study Endpoints	1. Cumulative incidence of ProACT-related clinically relevant urethral strictures over 5 years of follow up. 2. Cumulative incidence of ProACT device erosions over 5 years of follow-up. 3. Incontinence Quality of Life Questionnaire (I-QoL) over 5 year of follow-up. 4. Choice of subsequent SUI therapy(ies) post ProACT treatment.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P140019 / PAS001
Date Original Protocol Accepted	03/17/2016
Date Current Protocol Accepted
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is designed to assess the long-term (out to 6 years post-op) performance of i-FACTOR compared to local autograft by continued follow-up of available subjects from the approved IDE study. NO new subjects will be enrolled. Subjects, radiologists and neuro evaluators will remain blinded. Subjects will be informed of their treatment after the last evaluation.
Study Population	study group: allograft ring filled with i-FACTOR and stabilized with metallic anterior plate system control group: allograft ring filled with local autograft bone and stabilized with metallic anterior plate system
Sample Size	218 subjects from the IDE study (106 investigational and 112 control) provided informed consent for long-term follow-up. The sponsor estimates attrition of 10 subjects per year due to lost-to-follow-up or withdrawal with a follow-up rate of at least 70% for each assessment period. Table 6 of the submission provides detailed power estimates for each primary endpoint, however each endpoint will have a minimum of 80% at each timepoint.
Key Study Endpoints	primary endpoints: radiographic assessment of fusion Neck Disability Index (NDI) for function neuro evaluations rate and type of AEs lack of secondary surgical interventions at the treated spinal level secondary endpoints: neck and arm/shoulder pain using VAS SF36v2 quality of life modified Odoms criteria for surgical success
Follow-up Visits and Length of Follow-up	Each subject will be followed for total of 6 years post-op.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 220 subjects (106 i-FACTOR [identified a P-15 below] and 114 autograft control) participated in the study.
Actual Number of Sites Enrolled	A total of 17 sites participated in the PAS.
Patient Follow-up Rate	The follow-up rates at 72 months post-op were the following: rate when counting only visits within windows and all primary endpoint data are available: P-15 group 75.8% control group 68.3% rates when any visit data are available: P-15 group 77.9% control group 77.2% While lower than the rates observed at 12 and 24 months post-op, these rates are reasonable for the extended follow-up time of the post-approval study.
Final Safety Findings	The proportion of subjects with any AEs was 96.2% in the P-15 group and 97.4% in the control group. The difference in the proportion of subjects with any AEs between the groups was not statistically significant. Secondary surgical interventions (SSI) at the treated level was better in the investigational group (16.7% P-15, 23.1% control). Need for SSI over time by study visit was comparable between study groups. There were no deaths reported. The PAS AE safety hypothesis was that complication rates at the follow-up visits should not differ between the P-15 group and the control group at 72 months post-op. The total number of unique events reported in the P-15 group was 847 compared with 892 events in the control group. Altogether, 102 subjects (96.2%) in the P-15 group had one or more AEs reported, compared to 111 subjects (97.4%) in the control group. The difference in the proportion of subjects with any AEs between the groups was not statistically significant. AE and SAE rates were comparable between study groups, as were the categories and times of occurrence. AEs and SAEs by Body System, and Preferred Term showed no statistically significant difference between the 2 study groups, nor differences in time of presentation. In both study groups, study-related AEs were primarily reported on the C5/C6 and C5/C7 cervical level; there was no statistically significant difference between study groups in any category and on any cervical level There are no significant differences in the AE rate between the two study arms besides the superficial infections which occurred at a significantly higher rate in the P-15 group (5 subjects, 4.7%) compared to the control group (0 subjects). Although this difference was statistically significant, the rate of superficial infection observed in the study was within the range of infection rates reported in literature for similar surgical procedures. Generally, these events resolved uneventfully and were short in duration. The number of occurrences did not raise any notable safety concerns. The rates of device- and procedure-related AEs by System Organ Class per DMC adjudication were comparable between study groups. A total of 33 (31%) of P-15 subjects and 29 (25.4%) of control subjects experienced a device-related AE according to the DSMB, which is slightly lower than the number of study-related AEs reported by the Investigator. The rate of incidence in all categories was similar between groups, and any observed numerical differences and between-group differences did not reach statistical significance.
Final Effect Findings	primary endpoints: radiographic assessment of fusion Neck Disability Index (NDI) for function neurologic evaluations rate and type of AEs lack of SSI at the treated spinal level Study success at 72 months was achieved if both the primary efficacy endpoints and the primary safety endpoint met the pre-defined success criteria for the composite endpoint: • non-inferiority (NI, margin defined as 10%) of the P-15 group compared to the control group in fusion, and • NI (defined as 11 points) of the P-15 group compared to the control group in NDI, and • NI (defined as 15%) of the P-15 group compared to the control group in Neurological Success, and • comparable or favorable AE outcomes in the P-15 group compared to the control group. NI margins in the PAS were set to the same values as for the primary analysis of the IDE study. The outcome of the P-15 subjects was determined to be non-inferior to the control subjects at 72 months post-op. secondary endpoints: neck and arm/shoulder pain using VAS SF36v2 quality of life modified Odom’s criteria for surgical success VAS Arm Pain: Mean arm pain was 7.34 in the P-15 group and 6.92 in the control group at baseline and dropped to 1.51 in the P-15 group and 2.45 in the control group by 72 months post-op. Difference in the pain score between the study groups reached statistical significance at 3, 6, and 72 months. VAS Neck Pain: At most time points the mean pain score was lower for the P-15 group than for the control group. Quality of Life (SF36v2 Physical and Mental Component Summaries): Elevations in both of these components were maintained throughout the study in both treatment groups. In addition, Bodily Pain, Mental Health, Vitality, General Health, Physical Functioning, Role limitation emotional, Role Limitation physical, and Social Functioning scale changes were consistently elevated from baseline and maintained throughout the PAS in both groups. Surgical Success (Modified Odom’s Criteria): There was comparable improvement in both groups at all provided visits. Any differences between groups were not statistically significant.
Study Strengths & Weaknesses	The study described the longer-term clinical, radiographic and safety performance of the i-FACTOR Peptide Enhanced Bone Graft for instrumented cervical spine fusions to treat single level degenerative disc disease compared to the same treatment using allograft bone rings filled with local autograft bone. The population consisted of continued follow-up of the original IDE study subjects. No new subjects were enrolled. Subjects, radiologists and neuro evaluators remained blinded. Subjects were informed of their treatment after the last evaluation. While the follow-up rates at the longer timepoints were lower than those that would be excepted for ongoing follow-up during the course of an IDE and for filing a PMA, they are reasonable rates for a post-approval study collecting data out to 6 years post-op.
Recommendations for Labeling Changes	There are no new safety or efficacy findings that alter the conclusions that led to PMA approval, or would require addition to labeling. The sponsor has been instructed to submit a modified package insert containing the updated timecourse distributions of AEs and clinical and radiographic outcome out to 72 months post-op.
General
Study Status	Completed
Application Number / Requirement Number	P140026 S016/ PAS001
Date Original Protocol Accepted	04/28/2022
Date Current Protocol Accepted	07/20/2023
Study Name	ROADSTER 3 PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Open label, single arm, multicenter study; To evaluate real world usage of the ENROUTE Transcarotid Stent System (ENROUTE TSS) when used in conjunction with the ENROUTE Transcarotid Neuroprotection System (ENROUTE NPS) in patients at standard risk for adverse events from carotid endarterectomy (CEA).
Study Population	Patients at standard risk for complications from CEA with atherosclerotic extracranial internal carotid artery (ICA) stenosis with or without involvement of the contiguous common artery (CCA) determined by duplex ultrasound, CT/CTA, MR/MRA or angiography. Patients must meet one of the following criteria regarding neurological symptom status and degree of stenosis: Symptomatic (greater than or equal to 70% stenosis of the common or internal carotid artery by ultrasound or greater than or equal to 50% stenosis of the common or internal carotid artery by angiogram), OR Asymptomatic (greater than or equal to 70% stenosis of the common or internal carotid artery by ultrasound or greater than or equal to 60% stenosis of the common or internal carotid artery by angiogram)
Sample Size	No. of subjects: A maximum of 400 patients treated per protocol. No. of sites: A minimum of 30 and up to a maximum of 60 sites. Sites location: US Assumptions for Sample Size Estimation: Primary Endpoint Assumed Incidence – 4% Priori threshold – 8% Power – 80% Nominal alpha – 2.5% Calculated sample size is 315 Key Secondary Endpoint Incidence of cranial nerve injury within 30 days of the index procedure Assumed incidence – 0.5% Priori threshold – 2.7% (reported from VQI standard risk patients, ) Nominal alpha -2.5% Power -80% Calculated Sample size is 300 The testing strategy is to reject 2.7% with 97.5% confidence To account for the larger of the 2 calculated sample sizes, a maximum of 400 patients will be enrolled.
Key Study Endpoints	Safety Endpoints Primary: Hierarchical composite of Major Adverse Events (MAEs) defined as any death, stroke, or myocardial infarction (MI) within 30 days of the index procedure and ipsilateral stroke within 31 days to 365 days of the index procedure. Key Secondary Endpoints: Incidence of cranial nerve injury within 30 days of the index procedure Other Key Secondary Endpoints: Stroke within 30 days of the index procedure Death within 30 days of the index procedure MI within 30 days of the index procedure Stroke/Death/MI within 30 days of the index procedure Ipsilateral stroke at 1 year Additional secondary endpoints: Persistent cranial nerve injury at 6 months and 1 year Rate of cardiac death within 30 days of the index procedure Rate of neurological death within 30 days of the index procedure Rate of hierarchical ipsilateral stroke, death, and MI within 30 days of the index procedure Cardiac death at 1 year of patients who experienced an MI within 30 days of the index procedure Access site complications (arterial/venous) Serious Hematoma/bleeding complications (arterial/venous access site) Rate of stent thrombosis or occlusion within 30 days of the index Procedure Rate of dissection within 30 days of the index procedure (during index procedure or a reintervention procedure)
Follow-up Visits and Length of Follow-up	1 year
Interim or Final Data Summary
Actual Number of Patients Enrolled	344 intent-to- treat patients were enrolled 319 per protocol patients were enrolled
Actual Number of Sites Enrolled	54
Patient Follow-up Rate	99.7% (318/319) of per protocol patients completed 30-day follow-up visit. 93.7% (299/319) of per protocol completed 1 year follow-up visit.
Final Safety Findings	The primary endpoint was defined as the hierarchical composite of major adverse events (MAEs) defined as any death, stroke, or myocardial infarction within 30 days of the index procedure and ipsilateral stroke within 31 days to 365 days following the index procedure. The composite 1-year MAE rate which comprised of strokes only, was 1.4%. The 1-sided 97.5% upper bound of the MAE rate of 2.78% was significantly less than the priori threshold of 8% (p<0.0001). Therefore, the primary endpoint was met. Key Secondary Endpoint Incidence of cranial nerve injury (CNI) within 30 days of the index procedure was a key secondary endpoint. The CEC adjudicated all suspected CNIs that occur within 30 days of index procedure. The rate for cranial nerve injury (CN)I within 30 days of the index procedure was 0.63% (2/319). The one-sided 97.5% Upper CI of 2.25% was significantly less than the priori threshold of 2.7%, p= 0.0079. Rate of Stroke/Death/MI within 30 days of index procedure was 0.6% (2/319), 95% CI: 0.1%, 2.2%. Rate of stroke within 30 days of index procedure was 0.6% (2/319), 95% CI: 0.1%, 2.2%. Rate of death within 30 days of index procedure was 0.0% (0/319), 95% CI: 0.0%, 1.1%. Rate of MI within 30 days of index procedure was 0.0% (0/319), 95% CI: 0.0%, 1.1%. Rate of ipsilateral stroke within 31 days to 365 days of index procedure was 0.7% (2/305), 95% CI:0.1%, 2.3%. Cranial nerve injury at 6 months was 0.0%, 0/309). Cranial nerve injury at 1 year was 0.0% (0/304). Rate of dissection (during index procedure or a reintervention procedure) was 1.6% (5/319). Rate of stent thrombosis or occlusion was 0.3% (1/319).
Final Effect Findings	Same as above
Study Strengths & Weaknesses	The study met the primary endpoint of composite MAE defined as any death, stroke, or MI within 30 days of the index procedure and ipsilateral stroke within 31 days to 365 days of the index procedure (1-sided 97.5% upper CI was 2.78% for MAE rate of 1.41% versus priori of 8%, p< 0.0001). The study also met the key secondary endpoint of incidence of cranial nerve injury within 30 days of the index procedure (1 -sided 97.5% upper CI was 2.25% for CNI rate of 0.63% vs priori of 2.25%, p= 0.0079). This was an open label, single arm- study.
Recommendations for Labeling Changes	Labeling update is recommended with the final PAS results.
General
Study Status	Completed
Application Number / Requirement Number	P140002 / PAS001
Date Original Protocol Accepted	05/22/2015
Date Current Protocol Accepted
Study Name	OSPREY Extended f/u study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the long-term safety and effectiveness of the Misago stent at 36 months in the US cohort of the OSPREY pivotal study. This study is a multi-center, single arm, prospective continued follow-up of the OSPREY pivotal US study.
Study Population	US subjects implanted with the Misago stent from OSPREY pivotal study
Sample Size	All 198 remaining patients (15 patients exited due to death and 3 lost to follow-up) of the 216 OSPREY pivotal study US patients enrolled from 31 investigational sites. A minimum of 173 subjects at 36 months are required to provide >80% power assuming an underlying freedom from event proportion of at least 66% and two-sided 0.05 alpha.
Key Study Endpoints	Primary Endpoint Freedom from clinically driven TLR assessed at 36 months post-procedure Co-Primary Endpoint Freedom from clinically driven TLR assessed at 24 months post-procedure. Secondary Endpoints ¿X Freedom from the composite endpoint of acute death (within 30 days), amputation of the target limb, or clinically driven TLR assessed at 24 and 36 months post-procedure. ¿X Ankle-Brachial Index (ABI) change from 30 days through 36 months post-procedure for durability of results ¿X Rutherford sustained (without increase of one or more in the score) at 36 months post-procedure from 30 days post-procedure for durability of results ¿X Quality of Life Measurements: Quality of Life Survey (SF-36) and the Walking Impairment Questionnaire (WIQ) long-term sustainability at 24 months post-procedure through evaluation of the change from baseline and from 30 days. ¿X Evaluation of all AEs through 24 and 36 months post-procedure ¿X Device failure defined as the occurrence of either of the following through 36 months: − Malfunctions (when used in accordance with the IFU, but does not perform according to the IFU, Or − Stent fracture as evidenced by plain X-ray evaluation ¿X Device related complications through 36 months defined as any of the following: − Target lesion revascularization (TLR) of the treated limb − Amputation of treated limb − All-cause Mortality − Distal embolization − Thrombosis of target vessel − Arterial dissection /perforation/rupture/injury − Hemorrhage − Hypotension − Arterial spasm − Arteriovenous fistula − Arterial embolism/thrombosis/occlusion − Stent Fracture − Leg Pain/Claudication
Follow-up Visits and Length of Follow-up	36 months post-implantation Frequency of Follow-up Assessments Annual visits at 24 and 36 months post-implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	216 original 197 PAS
Actual Number of Sites Enrolled	31 sites
Patient Follow-up Rate	24mo – 176/197 = 89% 36mo – 161/197 = 82%
Final Safety Findings	Freedom from clinically driven TLR at 24 and 36 months were 77.43% and 73.43%, respectively. The lower confidence limit at 24 months was 70.9%, which is greater than the pre-specified performance goal of 60%. The lower bound of the confidence limit at 36 months was 66.4%, which is greater than the pre-specified performance goal of 55%.
Final Effect Findings	The mean Rutherford Score improved from a baseline value of 3.6 to a value of 1.6 at 24 Month follow-up and a value of 1.4 at 36 Month follow-up. The mean ABI improved from a baseline value of 0.693 to a value of 0.897 at 24 Month follow-up and a value of 0.913 at 36 Month follow-up.
Study Strengths & Weaknesses	The main study strength was the wide margin by which the PGs were met. The most frequent study deviations were being out of window study visits (98), missed study lab/assessments (82), and aspirin discontinuation (64). None of the recorded deviations affect the safety and welfare of the subjects or the integrity of the study results.
Recommendations for Labeling Changes	No labeling changes recommended.
General
Study Status	Completed
Application Number / Requirement Number	P140026 / PAS001
Date Original Protocol Accepted	08/03/2015
Date Current Protocol Accepted	04/13/2017
Study Name	ROADSTER 2 Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: The purpose of this PAS is to further evaluate the safety and effectiveness of the ENROUTE Transcarotid Stent when used with the ENROUTE Transcarotid Neuroprotection System by physicians of varying experience with the transcarotid technique Design: This is an open-label, single arm, multi-center new enrollment PAS
Study Population	Patients with atherosclerotic extracranial internal carotid stenosis (ICA) with or without involvement of the contiguous common artery (CCA) determined by duplex ultrasound, CT/CTA, MR/MRA or angiography to be symptomatic (greater than or equal to 50% stenosis) or asymptomatic (greater than or equal to 80% stenosis). Patients will serve as their own comparison group.
Sample Size	A minimum of 600 newly enrolled patients from a minimum of 30 sites to a maximum of 100 sites in the US. A maximum of 30 patients per physician will be included in the first 600 patients. The sample size is based on the rate of procedural success within 30 days of the stent implant in comparison to an a priori threshold of 85% derived from the ROADSTER Study. An observed rate of procedural success greater than 89% in the ROADSTER 2 Registry will be significant with a minimum of 600 patients (at 89% success among 600 total cases, the lower binomial confidence limit would be 86.22%).
Key Study Endpoints	The primary endpoint is the rate of procedural success (defined as technical success in the absence of hierarchical stroke, death, or MI) through 30 days following stent implant. The secondary endpoints include the following (through 30 days post index procedure): - Acute device success defined as the ability to insert the device, establish flow reversal, and remove the device - Technical success, defined as acute success plus the ability to deliver interventional tools - Rate of cranial nerve injury - Rate of hierarchical stroke, death, or myocardial infarction (MI) - Rate of hierarchical stroke, death or MI by symptom status - Acute device, technical and procedural success by physician experience - Acute device, technical and procedural success by physician training level - Acute device, technical and procedural success by enrollment quartile.
Follow-up Visits and Length of Follow-up	Patients will be followed for 30 days (+7 days) post index procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	692
Actual Number of Sites Enrolled	41 US; 2 OUS
Patient Follow-up Rate	ITT: 98.0% (678/692); PP: 98.9% (625/632)
Final Safety Findings	30-day MAE rate (death, stroke, MI): ITT 3.2% (22/692); PP 1.7% (11/632) In the ITT cohort, there were ten (10) cranial nerve injuries. There were ten (10) adverse events beyond death, stroke, myocardial infarction and cranial nerve injury. Nine (9) of these events were arterial dissections (1.3%). Two (2) arterial dissections were converted to CEA (0.3%). The remaining event was stent thrombosis (0.1%). In the Per Protocol (PP) cohort, there were eight (8) cranial nerve injuries. There were eight (8) adverse events beyond death, stroke, myocardial infarction and cranial nerve injury. Seven (7) of these events were arterial dissections (1.1%). Two (2) arterial dissections were converted to CEA (0.3%). The remaining event was stent thrombosis (0.2%).
Final Effect Findings	Procedural success: ITT: 96.5% (668/692) ; PP: 97.9% (619/632) Procedural success is defined as technical success in the absence of hierarchical stroke, death or myocardial infarction at 30 days.
Study Strengths & Weaknesses	The strengths of the ROADSTER 2 PAS include the larger sample compared to the pivotal ROADSTER study. Acute device, technical and procedural success were presented to show operator/device interaction. Additionally, major adverse event (clinical outcomes) were analyzed in the same manner as in the pivotal ROADSTER study to demonstrate consistency of the results. All major adverse events, which are components of the primary endpoint, were independently adjudicated to ensure a lack of bias in event reporting. The ROADSTER 2 PAS was not randomized thereby lacking a contemporaneous comparator to other carotid revascularization modalities. Enrollment was based upon pre-defined inclusion/exclusion criteria which would otherwise exclude cohorts of patients in whom the safety and efficacy was not assessed. Non-consecutive enrollment could reflect patient selection bias. Low numbers of enrolling physicians in Levels 2 and 3 potentially limit the generalizability of the results.
Recommendations for Labeling Changes	updated labeling is currently under review
General
Study Status	Completed
Application Number / Requirement Number	P140013 / PAS001
Date Original Protocol Accepted	07/27/2015
Date Current Protocol Accepted
Study Name	Minerva Single-Arm Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Minerva Single-Arm Study is a single-arm, non-randomized, multicenter study to evaluate the safety and effectiveness of the Minerva Endometrial Ablation System. The Post Approval Study will collect extended effectiveness and safety data at 2-3 years post treatment.
Study Population	Pre-menopausal women with menorrhagia (excessive uterine bleeding) due to benign causes for whom childbearing is complete or who no longer wish to retain fertility.
Sample Size	Up to 110 women
Key Study Endpoints	Any treatments or hysterectomy for dysfunctional uterine bleeding Compliance with contraception Any pregnancies Menstrual status (questions assess bleeding, i.e., amenorrhea, spotting hypomenorrhea, eumenorrhea or menorrhagia) Any gynecological adverse events Completion of Quality of Life Questionnaire
Follow-up Visits and Length of Follow-up	Three years One year (data were provided premarket), two year, and three year
Interim or Final Data Summary
Actual Number of Patients Enrolled	110 subjects
Actual Number of Sites Enrolled	7 study sites
Patient Follow-up Rate	12 month follow-up: 104/110 subjects (94.5%) 24 month follow-up: 72/101 subjects (71.3%) 36 month follow-up: 93/101 subjects (92.1%)
Final Safety Findings	There were a total of 199 adverse events, including one serious adverse event (SAE) and 198 non-serious adverse events, reported at the 2-4 weeks, 3 month, 6 month, and 12 month follow-up. There was one report of pregnancy at the 12 month follow-up. There was one serious adverse event (SAE) and 11 non-serious gynecological adverse events reported at the 2- and 3-year follow-up. The one SAE was due to pelvic pain in one subject which was not determined to be device or procedure-related. There were no unanticipated device-related adverse events in the study through the 3-year follow-up
Final Effect Findings	Primary effectiveness endpoint: The overall success rate based on PBLAC results was 91.8% (101/110) at 12 months. Other effectiveness endpoints: At 12 months 80.8% of subjects responded that they observed a decrease in pre-menstrual symptoms, 54.8% observed a decrease in dysmenorrhea, 97.6% reported satisfied or very satisfied with the procedure, and 98.8% of subjects responded that they would recommend the procedure based on the Menstrual Impact Questionnaire (MIQ). At 24 months and 36 months the overall success rate (reported by blood loss assessment of eumenorrhea or less) was 92.1% and 93.1%, respectively. At 24 months and 36 months 97.2% and 98.9% of subjects reported being satisfied or very satisfied with the procedure, respectively.
Recommendations for Labeling Changes	Yes, labeling change recommended to update the device labeling with the final study results.
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S028/ PAS002
Date Original Protocol Accepted	11/20/2017
Date Current Protocol Accepted
Study Name	SAPIEN 3 Mitral Valve-in-Valve Comp Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Patients will be enrolled into the TVT registry for the 2 years following device approval (from June 5, 2017 to June 4, 2019). All patients enrolled in the registry will be followed by the registry for the first year and then linked to CMS claims data for follow-up through five years. The data collected through this surveillance plan will be submitted to the FDA bi-annually for the first 2 years after device approval and annually until the last enrolled patients reaches 5 years.
Study Population	Patients with symptomatic heart disease due to a failed bioprosthetic mitral valve (stenosed, insufficient or combined) who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e. predicted risk of surgical mortality greater than or equal to 8% at 30 days, based on the STS risk score and other clinical co-morbidities unmeasured by the STS risk calculator).
Sample Size	Enrollment will consist of all patients with SAPIEN 3 transcatheter heart valve in the STS/ACC TVT Registry for the 2 years following device approval (i.e. from June 5, 2017 to June 4, 2019). All mitral transcatheter SAPIEN 3 Valve in Surgical Valve patients who have the procedure date in the period of June 5, 2017 to June 4, 2019 will be included in the analysis.
Key Study Endpoints	TVT-Captured Safety Endpoints (at discharge, 30 days and 12 months): All-cause mortality Heart failure rehospitalization* Mitral valve reintervention Device or procedure-related adverse events Life threatening/major bleeding complications* Stroke TIA Myocardial Infarction New requirement of dialysis New onset atrial fibrillation Unplanned mitral valve surgery due to device/procedure failure or malfunction Requirement for valve replacement Unplanned cardiac surgery for any cause Requirement/insertion of an implantable cardiac defibrillator *endpoints not available at discharge TVT-Captured Effectiveness Endpoints (30 days and 12 months): 6-minute walking distance KCCQ Change in NYHA functional class Mitral valve hemodynamics CMS-Captured Safety Endpoints (year 2 to 5): All-cause mortality All Stroke Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
Follow-up Visits and Length of Follow-up	5 year post-implantation
Interim or Final Data Summary
Interim Results	TVT-R at 12 Months: All-cause mortality: 13.1% All stroke: 3.1% Transient ischemic attack (TIA): 0.6% Life-threatening/major bleeding: 4.5% Mitral valve reintervention: 1% Readmission – heart failure: 10.4% Myocardial infarction: 0.4% New Requirement for dialysis: 1.8% New onset atrial fibrillation: 2% Cardiac surgery or intervention – other unplanned: 3.6% Requirement for valve replacement: 0.5% Unplanned mitral valve surgery due to device/procedure failure or malfunction: 0.2% Implantable cardiac defibrillator: 0.4% NYHA (% in class I/II): 88.1% Six Minute Walk Test Distance (feet) (Change from Baseline): 248 KCCQ (Mean Change from Baseline): 40.2 Transvalvular mean gradient: 7.1 mmHg Greater than or equal to Moderate Mitral Regurgitation: 0.2% Greater than or equal to Moderate Mitral Paravalvular Regurgitation: 0.3% CMS Linked at 60 Months: All-cause mortality: 51.6% All-stroke: 17.0% Aortic Valve Reintervention: 3.6%
Actual Number of Patients Enrolled	TVT Registry: 1,178 (attempted); 1,148 (implanted)
Actual Number of Sites Enrolled	TVT Registry: 282 sites
Patient Follow-up Rate	TVT-R (patient status known at 1 year): 73.9% CMS Linked: 80.7% (794) of eligible patients matched with the CMS database. CMS data was available for 100% of the matched patients at 1 – 5 years.
General
Study Status	Completed
Application Number / Requirement Number	P160035 / PAS001
Date Original Protocol Accepted	05/21/2018
Date Current Protocol Accepted
Study Name	Berlin Heart Comprehensive Reg Based Surv
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the surveillance plan is to evaluate the occurrence of stroke (ischemic or hemorrhagic) while on EXCOR Pediatric support within the first 180 days post-implant and if differences exist based on anticoagulation strategy.
Study Population	Children who are transplant eligible in need of mechanical circulatory support and are supported with the EXCOR Pediatric will be included in this surveillance. No additional inclusion/exclusion criteria will apply. No comparative group will be included.
Sample Size	A minimum of 62 subjects implanted with EXCOR Pediatric will allow comparison to a pre-specified performance goal for stroke while on device of 30%.
Key Study Endpoints	The primary endpoint for this study will be the rate of stroke (ischemic or hemorrhagic) within the first 180 days post- implant. The primary endpoint will also be stratified by anticoagulation regimen. Secondary safety endpoint: Adverse Events will be summarized as the rate per patient-month. Secondary effectiveness endpoint: Device effectiveness will be summarized as the proportion of subjects experiencing a successful outcome. Successful outcome is defined as survival to recovery/successful weaning, or survival to transplant, or survival on EXCOR® Pediatric at 180 days post-implant.
Follow-up Visits and Length of Follow-up	Patients are to be followed for 180 days post implant or to outcome (whichever is earlier).
Interim or Final Data Summary
Interim Results	Interim Effectiveness Results reflect a cumulative incidence of “Success” (defined as survival to transplant, successful weaning, or survival on device at 180-days post-implant) in 32 of 44 subjects who have reached an endpoint (transplant, successful weaning, survival on device at 180-days post-implant, escalation of therapy, or death). Twelve subjects did not meet the success criteria for the study and either died (6) or were escalated from Berlin Heart therapy to a different therapy (6). Nine additional subjects were alive on-device at the data lock date for this report but had not yet reached the 180-day endpoint.
Actual Number of Patients Enrolled	Fifty-three (53) subjects have been enrolled into the Action Learning Network’s Pediatric Ventricular Assist Device Registry for this study of the Berlin Heart EXCOR device.
Actual Number of Sites Enrolled	Thirty-five sites have agreed to participate in the ACTION Learning Network Registry, 24 have the necessary paper work in place to start enrolling subjects and 16 of those sites are enrolling subjects.
Patient Follow-up Rate	The follow-up rate is near 100 percent with some subjects not having data entered for interim follow-up visits.
Study Strengths & Weaknesses	Strengths: This study collects detailed data from a registry that has the potential to provide an accurate representation of the safety and effectiveness of this device as it is used in “real world” practice. The follow-up rate is currently high and the registry is collecting data on the concomitant medication regimen being used. Weaknesses: Adverse event data is not yet adjudicated. There is some data missingness for variables of interest. Additionally, it is not clear yet if these results of this registry can be assumed to be representative of the larger Berlin Heart population in North America. The sponsor will be asked to provide a comparison of the sites entering data to all implanting centers.
General
Study Status	Completed
Application Number / Requirement Number	P120006 S031/ PAS001
Date Original Protocol Accepted	06/16/2020
Date Current Protocol Accepted
Study Name	Case Selection and Sizing Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post approval study is to compare Endologix Imaging Service’s assessment of the suitability for implantation and device sizing recommendations for the Alto Abdominal Stent Graft System (Alto Device) to the suitability assessment and device sizing recommendations for patients' physicians have selected as suitable to receive the Alto device. It is a prospective, consecutively enrolling, multi-center, single-arm clinical study.
Study Population	The study population is patients with an infrarenal abdominal aortic aneurysm who a treating physician has determined meet the anatomic criteria for implantation with the Alto device as specified in the approved labeling.
Sample Size	100 commercial subjects enrolled consecutively at each study site and who receive an implantation recommendation for the Alto device from the treating physician.
Key Study Endpoints	Physician’s assessments of patients they select to receive the Alto device will be compared to Endologix Imaging Service’s assessment of these patients on the following: • Key anatomic sizing measurements (e.g., aortic diameter, aneurysm neck length, aneurysm neck angulation) • General suitability for endovascular aneurysm repair (EVAR) • Compliance with the Alto anatomic Indications for Use and a recommendation for implantation with the Alto device • The Alto Aortic Body size appropriate for treatment. All product complaints occurring in subjects within 30 days of an Alto implantation procedure will be captured through the Endologix quality system and reported.
Follow-up Visits and Length of Follow-up	While follow-up visits will not be conducted for this study, any complaint data received for subjects in the study through 30 days after attempted implantation will be reported.
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	26
Patient Follow-up Rate	100%
Final Safety Findings	Physician user measurement data compared to Endologix Imaging Services shows substantial agreement in anatomical measurements for all vascular characteristics. The overall results show no more than a few millimeters variance in any direction across all anatomical measurements captured. Both the site and Endologix Imaging Services aligned 100% on all Aortic Body recommendations. The patient population receiving the first commercial implants of the Alto device is consistent with the patient population enrolled in the ELEVATE pivotal study and are found to have met the anatomic criteria for device implantation as specified in the approved labeling for the Alto Abdominal Stent Graft System.
Final Effect Findings	n/a
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	Endologix acknowledges FDA’s position that a labeling update is not needed at this time, but agrees to revise the labeling if we identify any data in the PAS study that would warrant a revision.
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S058/ PAS001
Date Original Protocol Accepted	08/16/2019
Date Current Protocol Accepted	12/23/2023
Study Name	Cont fu-Low Risk Pivotal Trial Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the pivotal cohort under the IDE. The objective of this study is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE pivotal cohort.
Sample Size	All living subjects.
Key Study Endpoints	All-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results As-Treated Population (all K-M rates): - All-cause mortality: 20.9% (TAVR) vs. 18.7% (SAVR) - Cardiovascular mortality: 11.1% vs. 11.0% - All stroke: 10.8% vs. 9.6% - Disabling stroke: 4.4% vs 4.6% - Reintervention: 6.5% vs. 3.6% - Valve thrombosis (clinical): 0.3% vs. 0.2% - Valve endocarditis: 1.4% vs. 3.2% - Myocardial infarction: 7.5% vs. 4.8% Effectiveness Results: Implanted Population (year 5 result; in-person visit not required at year 6): - Prosthetic valve dysfunction: 2.3% vs. 1.0% o greater than or equal to moderate total aortic regurgitation: 1.3% vs. 0.3% o Moderate or severe aortic valve stenosis: 0.8% vs. 0.6% - Mean gradient: 10.70 -/+ 6.56 vs. 12.81 -/+ 6.91 mmHg - EOA: 2.07 -/+ 0.62 vs. 1.89 -/+ 0.63 cm2 - Total aortic regurgitation (>=moderate): 1.3% vs. 0.3% As-Treated Population (year 5 result; in-person visit not required at year 6): - NYHA I/II: 97.7% vs. 97.2% (evaluable patients only) - KCCQ: 88.3 -/+ 15.8 vs. 88.5 -/+ 15.8
Actual Number of Patients Enrolled	1478 randomized (Intent-to-Treat Population): 737 (TAVR) vs. 741 (SAVR)
Actual Number of Sites Enrolled	87
Patient Follow-up Rate	At 6 years (As-Treated patients): 87.8% (TAVR) vs. 82.5% (SAVR)
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S107/ PAS002
Date Original Protocol Accepted	07/22/2020
Date Current Protocol Accepted
Study Name	CAP Cohort and Low Risk Bicuspid RWU Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objectives of the surveillance are to characterize the clinical outcomes of the CAP cohort annually through 10 years post implantation and to assess the real-world use of the commercial SAPIEN 3 and SAPIEN 3 Ultra Transcatheter Heart Valve System to ensure that the device is used in appropriate circumstances, respectively.
Study Population	The surveillance of the CAP cohort will consist of all living CAP patients who were enrolled at participating institutions, and the surveillance of the real-world use will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All living CAP subjects and all consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry; and the follow-up data from year 2 through year 10 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database. The surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-10 year post implantation.
Follow-up Visits and Length of Follow-up	10 years - All subjects are followed annually through 10 years post procedure
Interim or Final Data Summary
Interim Results	Bicuspid Low Risk TVTR CAP at 1 Year: All-cause death: 0.0% All stroke: 1.1% Transient ischemic attack (TIA): 0.0% Rehospitalization (Device or procedural related or heart failure): 7.1% Aortic valve re-intervention (site reported): 1.0% Life-threatening/major bleeding (site reported): 0.0% Major vascular complications (site reported): 3.1% New requirement for dialysis (site reported): 0.0% NYHA (% in class I/II): 98.9% KCCQ (Mean Change from Baseline): 30.4 Transvalvular mean gradient: 13.0 Greater than or equal to Moderate PVL: 3.0% Bicuspid Low Risk TVTR CAP (CMS-linked) at 3 Years: All-cause death: 3.7% Stroke: 1.2% Aortic valve reintervention: 3.7% TVTR Bicuspid Cohort at 1 Year: All-cause death: 3.0% All stroke: 2.1% Life-threatening bleeding: 1.2% Myocardial infarction: 0.3% New requirement for dialysis: 0.2% Transient ischemic attack (TIA): 0.7% Major Vascular Complications: 0.8% Aortic valve reintervention: 0.8% New permanent pacemaker implantation: 8.3% Prosthetic valve endocarditis: 0.3% Prosthetic valve thrombosis: 0.5% NYHA (% in class I/II): 97.1% KCCQ (Mean Change from Baseline): 27.2 Transvalvular mean gradient: 13.6 Greater than or equal to Moderate PVL: 2.9%
Actual Number of Patients Enrolled	Bicuspid Low Risk TVTR CAP: 98 subjects TVTR Bicuspid Cohort: 3,546
Actual Number of Sites Enrolled	Bicuspid Low Risk TVTR CAP: 34 sites TVTR Bicuspid Cohort: 531 sites
Patient Follow-up Rate	Bicuspid Low Risk TVTR CAP: 93.9% TVTR Bicuspid Cohort: 85.3%
General
Study Status	Completed
Application Number / Requirement Number	P200022 S003/ PAS001
Date Original Protocol Accepted	05/28/2021
Date Current Protocol Accepted
Study Name	Extended f/u of the 2-Level Simplify
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the 5 year long-term safety and effectiveness of the two-level Simplify Cervical Artificial Disc in subjects with cervical radiculopathy with or without neck pain or myelopathy due to abnormalities localized to the levels of the two contiguous disc spaces that are unresponsive to conservative management. Design: A continuation of the prospective, multi-center, historically controlled IDE study population to evaluate the long-term safety and effectiveness of the Simplify Cervical Artificial Disc.
Study Population	Investigational Device: Simplify Cervical Artificial Disc Historical Control: Anterior Cervical Discectomy and Fusion (ACDF)
Sample Size	170 Simplify Cervical Artificial Disc IDE subjects and 151 historical ACDF control subjects are eligible for the PAS study
Key Study Endpoints	Safety Endpoints: Collection and evaluation of all adverse events for severity and device and/or procedure-relatedness Evaluation of device failure (device breakage, migration, or mechanical failure) as defined in Radiographic Evaluation Protocol Subsequent surgical procedures (revision, removal, reoperation, or supplemental fixation) at the index levels Neurologic evaluation Dysphagia Handicap Index (DHI) Effectiveness Endpoints: Neck Disability Index (NDI) assessment Radiographic evaluation Pain assessments (neck and arm; neck, left arm and right arm) Treatment satisfaction SF-36 Health Survey Gait Assessment
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	157 of 170 eligible investigational subjects and 134 control subjects were enrolled in the PAS.
Actual Number of Sites Enrolled	18 investigational, 31 control
Patient Follow-up Rate	At month 60, the follow-up rate is 89% for the investigational group and 79% for the control group.
Final Safety Findings	In this PAS, the overall AE and SAE rates were comparable between treatment groups. The observed AE rate for the Simplify Disc group was 75.8% (119/157) compared with 94% (126/134) in the historical ACDF control group with an SAE rate of 25.5% (40/157) in the Simplify Disc group compared with 40.3% (54/134) in the historical ACDF control group. As previously reported under the IDE study, 4 secondary surgical interventions (SSIs) occurred in the Simplify Disc group and 14 SSIs occurred in the historical ACDF control group through Day 730. Between Day 730 and Day 1825, an additional 5 SSIs occurred in the Simplify Disc group and an additional 4 SSIs occurred in the historical ACDF control group.
Final Effect Findings	The composite clinical success for the Simplify Disc group was 85.0% compared to 73.3% for the historical ACDF control group. The study success criteria for non-inferiority as well as for superiority have been met.
Study Strengths & Weaknesses	This 5-year follow-up study had high follow-up rates for the investigational group but lower than the recommended 85% follow-up rate for the historical control group.
Recommendations for Labeling Changes	It is recommended that the labeling be updated with the results of the PAS study (i.e., data at 60-months).
General
Study Status	Completed
Application Number / Requirement Number	P200029 / PAS001
Date Original Protocol Accepted	05/14/2021
Date Current Protocol Accepted	12/02/2022
Study Name	The Patient Exposure Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To calculate the radiation-absorbed dose of Technetium-99m macroaggregated albumin (Tc-99m MAA).
Study Population	Patients who are being evaluated for TheraSphere administration.
Sample Size	5 PT, up to 3 sites
Key Study Endpoints	Mean absorbed dose (Gy) and activity (Bq) will be summarized for the whole body and for critical non-liver organs (including whole body effective dose).
Follow-up Visits and Length of Follow-up	3 times within 24 hours
Interim or Final Data Summary
Actual Number of Patients Enrolled	5
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	100%
Final Safety Findings	All analyses were performed on the intent to treat population (ITT), there were no major protocol deviations impacting the primary endpoints.
Final Effect Findings	BSC provided 99mTc-MAA mean absorbed dose for critical organs and mean whole-body effective dose in terms of unit activity, and total overall dose
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P130026 S070/ PAS001
Date Original Protocol Accepted	08/17/2022
Date Current Protocol Accepted
Study Name	SE Persistent AF (PsAF) PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The proposed study is a prospective, non-randomized, single arm, multi-center, observation PAS study
Study Population	200 Persistent Atrial Fibrillation subjects
Sample Size	200
Key Study Endpoints	The acute primary safety endpoint is the rate of device and/or procedure-related serious adverse events (SAE) with onset within 7-days of the index ablation procedure utilizing the study catheter. The secondary, long-term safety endpoint will be the rate of device and/or procedure-related SAEs from the index ablation procedure, descriptively evaluated at 12 months, 24 months, and 36 months. The primary effectiveness endpoint will be the proportion of subjects with freedom from AF recurrence post 90-day blanking period at 12 months. The secondary effectiveness endpoint will be the proportion of subjects with freedom from AF recurrence post 90-day blanking period at 24 months and 36 months
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Interim Results	No summary of interim results available as of the most recent report.
Actual Number of Patients Enrolled	181
Actual Number of Sites Enrolled	19
Patient Follow-up Rate	Insufficient time from subject enrollment to determine follow-up rate.
Study Strengths & Weaknesses	Insufficient information available to determine strengths and weaknesses.
General
Study Status	Ongoing
Application Number / Requirement Number	P210020 / PAS001
Date Original Protocol Accepted	01/19/2022
Date Current Protocol Accepted
Study Name	ROBUST-LT Post-Approval Study (PR1277)
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ROBUST-LT PAS is a continuation of the ROBUST clinical program (ROBUST I, II and III clinical studies). ROBUST-LT is designed to verify the continued safety and effectiveness for the Optilume Urethral Drug-Coated Balloon (DCB). It is intended to assess durability of outcomes after 1 year follow-up of the 194 patients currently enrolled in the ROBUST clinical program. Each patient’s follow-up will be continued out to 5 years post-treatment. The harmonized primary effectiveness endpoint is defined as a patient experiencing a =30% improvement in International Prostate Symptom Score (IPSS) from baseline without the need for additional intervention. Additional harmonized endpoints include freedom from repeat intervention, uroflowmetry, IPSS, adverse event summary, and International Index of Erectile Function (IIEF). The primary safety endpoint is mortality rate that will be calculated for each study and reported as the number of deaths per 100 patient years. All adverse event (AE) data will be collected. Progress reports will be submitted to the FDA annually after PMA approval.
Study Population	ROBUST I: Adult men 18 years of age or older with anterior urethral stricture = 2 cm in length and with = 1 prior dilation. ROBUST II: Adult men 18 years of age or older with anterior urethral strictures = 3 cm in length and with = 2 prior dilations. ROBUST III: Adult men 18 years of age or older with with anterior urethral strictures = 3 cm in length in subjects with = 2 prior dilations
Sample Size	No. of subjects: 194 subjects No assumptions for sample size estimation. Enrollment is complete. No. of sites: ROBUST I (4 sites), ROBUST II (5 sites), ROBUST III (22 sites). Sites location: US and the following countries: ROBUST I (Panama and Dominican Republic), ROBUST II (U.S.), ROBUST III (U.S. and Canada).
Key Study Endpoints	Safety Endpoints Primary: The mortality rate that will be calculated for each study and reported as the number of deaths per 100 patient years. Secondary: Frequency and severity of adverse events, erectile function (EF), orgasmic function (OF), and overall satisfaction IIEF subdomains. Effectiveness Endpoints Primary: Responder rate: A patient experiencing a =30% improvement in International Prostate Symptom Score (IPSS) from baseline without the need for additional intervention. Secondary: Additional harmonized endpoints include freedom from repeat intervention, uroflowmetry (Qmax and PVR), IPSS, adverse event summary, and International Index of Erectile Function (IIEF).
Follow-up Visits and Length of Follow-up	Each subject will be followed annually for 5 years with assessments as described in the Study Endpoints section, above.
Interim or Final Data Summary
Interim Results	Safety Results The rate of mortality in the total Optilume cohort is 0.4 which is consistent with the expected rate for males in this age rage (1.7 deaths per 100 patient years). There were no new deaths since the last report for the individual studies. Most treatment-related AEs occurred within 12 months of the Optilume DCB procedure. No treatment-related SAEs have been reported after 1 year. 3 SAEs were reported (see comment below). 11 total non-serious treatment-related events were reported after 1 year. 5 in ROBUST I, 2 in ROBUST II, 3 in ROBUST III (Randomized), 1 in ROBUST III (Crossover) and none in the PK group. These AEs included: Urinary tract infection (0.5%), Benign Prostatic Hyperplasia (0.5%), Hematuria (1.0%), Urethral stenosis (1.0%), Urethral stricture (0.5%), Urinary retention (1.5%), and Painful ejaculation (0.5%). Effectiveness Results The overall responder rate in the Optilume (Pooled) group was: (As observed) 84% at 30 day follow-up and was 84% at the 4-year follow up (70 subjects reported). (FCF) 48% at 4-year follow-up (59/123 subjects) (LOCF) 71% at 4-year follow-up (136/193 subjects). Freedom from Repeat Intervention: The Kaplan-Meier estimates of the proportion of subjects free from intervention through 4 years post-treatment was consistent between studies, with an overall estimate of 68% of subjects being free from reintervention through 4 years across the ROBUST clinical program. This compares to only 23.6% of subjects in the standard-of-care dilation Control arm in the ROBUST III study at 1-year post-treatment. IPSS Over Time (Optilume pooled group): 22.7 at baseline to 6.9 (As Observed), 10.8 (FCF), and 10.4 (LOCF) at the 4-year follow-up. Uroflowmetry - Peak Flow Rate (Qmax) (Optilume pooled group): 7.1 at baseline to 14.5 (As Observed), 11.8 (FCF), and 13.2 (LOCF) at the 4-year follow-up. Uroflowmetry - Post-Void Residual Volume (PVR) (Optilume pooled group): 133.8 at baseline to 103.6 (As Observed), 116.9 (FCF), and 102.6 (LOCF) at the 4-year follow-up.
Actual Number of Patients Enrolled	194
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	Subjects are still undergoing annual follow up per the previous approved protocol. ROBUST I completed 5 year follow up on September 2022. ROBUST II completed annual follow up on April 2024. ROBUST III is projected to complete annual follow up June 2025 (Randomized, PK) and February 2026 (Crossover).
General
Study Status	Ongoing
Application Number / Requirement Number	P100045 S056/ PAS001
Date Original Protocol Accepted	09/15/2022
Date Current Protocol Accepted	06/01/2026
Study Name	CMEMS RWE PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The CMEMS RWE PAS is aimed to collect evidence for continued safety and effectiveness of the CardioMEMS HF System for 3+ years after implant. It is a prospective, observational, single-arm, real-world evidence (RWE) study to be conducted in the US. Subjects will be identified in Abbott’s Merlin.net remote monitoring database. Merlin.net will be linked to Medicare fee-for-service (FFS) claims data at the individual subject level through probabilistic linking methods (based on subject date of birth, sex, and date of implant) to longitudinally track outcomes. The analysis will compare survival in a subset of subjects from the Primary Cohort and Full Cohort to a pre-specified performance goal of 71.7% survival at 2 years, established based on data from the literature.
Study Population	NYHA Class II and NYHA Class II and III subjects
Sample Size	The enrollment target is 1000 subjects for the Primary Endpoint Population while 2500 subjects in the Secondary Endpoint Population.
Key Study Endpoints	The primary endpoint for this study is survival from all-cause mortality in the Primary Endpoint Population at 2 years. The secondary endpoint for this study is survival from all-cause mortality in the Secondary Endpoint Population at 2 years.
Follow-up Visits and Length of Follow-up	The duration of enrollment for the Primary Cohort is expected to be approximately four years from enrollment of the first subject to the last subject, with an additional three years of follow-up. Study completion will occur once data sources for the complete 3-year follow-up of the last subject become available.
Interim or Final Data Summary
Actual Number of Patients Enrolled	19851
Actual Number of Sites Enrolled	1041
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S141/ PAS001
Date Original Protocol Accepted	09/23/2022
Date Current Protocol Accepted	09/23/2022
Study Name	S3UR Real World Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objective of the surveillance is to assess the real-world performance of the SAPIEN 3 Ultra RESILIA Transcatheter Heart Valve.
Study Population	The surveillance will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening /major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-10 year post-implantation.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: K-M Rates: Native Aortic Valve Stenosis Cohort (n=46,391): 30-days: All-cause death: 1.3%; All strokes: 1.7%; Aortic valve reintervention: 0.1% 1-year: All-cause death: 8.3%; All strokes: 3.2%; Aortic valve reintervention: 0.4% THV in Failing Aortic Surgical Valve Cohort (n=1,3024: 30-days: All-cause death: 3.0%; All strokes: 2.3%; Aortic valve reintervention: 0.4% 1-year: All-cause death: 8.8%; All strokes: 3.4%; Aortic valve reintervention: 0.8% THV in Failing Aortic Transcatheter Valve Cohort (n=451): 30-days: All-cause death: 3.6%; All strokes: 2.5%; Aortic valve reintervention: 0.2% 1-year: All-cause death: 16.8%; All strokes: 4.0%; Aortic valve reintervention: 0.7% THV in Failing Mitral Surgical Valve Cohort (n=674): 30-days: All-cause death: 3.5%; All strokes: 1.1%; Mitral valve reintervention: 0.3% 1-year: All-cause death: 12.4%; All strokes: 3.5%; Mitral valve reintervention: 1.3% THV in Failing Mitral Ring Cohort (n=137): 30-days: All-cause death: 2.9%; All strokes: 2.2%; Mitral valve reintervention: 8.1% 1-year: All-cause death: 15.0%; All strokes: 4.1%; Mitral valve reintervention: 11% Effectiveness Results: KCCQ Overall Summary Score (Change from baseline to 30-day/1-year visit): Native Aortic Valve Stenosis Cohort: 30-days: 26.1 + 0.14 (n=34,661); 1-year: 28.0 + 0.17 (n=23,902) THV in Failing Aortic Surgical Valve Cohort: 30-days: 38.5 + 0.96 (n=902); 1-year: 41.0 + 1.15 (n=620) THV in Failing Aortic Transcatheter Valve Cohort: 30-days: 38.5 + 1.75 (n=282); 1-year: 42.5 + 2.32 (n=164) THV in Failing Mitral Surgical Valve Cohort: 30-days: 37.3 + 1.49 (n=401); 1-year: 38.7 + 1.64 (n=244) THV in Failing Mitral Ring Cohort: 30-days: 21.2 + 3.14 (n=78); 1-year: 21.4 + 4.41 (n=41)
Actual Number of Patients Enrolled	Native Aortic Valve Stenosis Cohort: 46,391 procedures attempted; 46,310 patients implanted; THV in Failing Aortic Surgical Valve Cohort: 1,304 procedures attempted; 1,301 patients implanted; THV in Failing Aortic Transcatheter Valve Cohort: 451 procedures attempted; 451 patients implanted; THV in Failing Mitral Surgical Valve Cohort: 674 procedures attempted; 669 patients implanted; THV in Failing Mitral Ring Cohort: 137 procedures attempted; 136 patients implanted.
Actual Number of Sites Enrolled	Native Aortic Valve Stenosis Cohort: 677 sites; THV in Failing Aortic Surgical Valve Cohort: 313 sites; THV in Failing Aortic Transcatheter Valve Cohort: 206 sites; THV in Failing Mitral Surgical Valve Cohort: 209 sites; THV in Failing Mitral Ring Cohort: 81 sites.
Patient Follow-up Rate	Native Aortic Valve Stenosis Cohort: Patient status known: 30 days: 97.4% (45,196/46,391); 1-year: 84.1% (39,023/46,391) THV in Failing Aortic Surgical Valve Cohort: Patient status known: 30 days: 97.2% (1,268/1,304); 1-year: 85.3% (1,112/1,304) THV in Failing Aortic Transcatheter Valve Cohort: Patient status known: 30 days: 97.3% (439/451); 1-year: 84.7% (382/451) THV in Failing Mitral Surgical Valve Cohort: Patient status known: 30 days: 96.3% (649/674); 1-year: 82.2% (554/674) THV in Failing Mitral Ring Cohort: Patient status known: 30 days: 98.5% (135/137); 1-year: 89.1% (122/137)
General
Study Status	Ongoing
Application Number / Requirement Number	P130013 S043/ PAS001
Date Original Protocol Accepted	10/28/2022
Date Current Protocol Accepted	03/25/2026
Study Name	WATCHMAN FLX NESTed DAPT PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The WATCHMAN FLXTM DAPT Post Approval Analysis is designed to assess safety outcomes associated with the use of dual antiplatelet therapy (DAPT) as an alternative to an oral anticoagulant (OAC) and aspirin as the post-implant medication regimen for the WATCHMAN Left Atrial Appendage (LAA) Closure Technology in a routine clinical setting. Data will be captured from the Left Atrial Appendage Occlusion Registry (LAAO Registry) within the American College of Cardiology Foundation’s (ACCF) National Cardiovascular Data Registry (NCDR) conducted in the United States.
Study Population	All adults implanted with a WATCHMAN FLX device and prescribed DAPT at discharge
Sample Size	~5600 patients expected
Key Study Endpoints	The composite event rate is defined as all-cause death, stroke (ischemic and/or hemorrhagic), major bleeding, and systemic embolism. The composite event endpoint will be assessed in subjects who were successfully implanted between the date of hospital discharge and 45 days and between hospital discharge and 6 months post-procedure. Additional analyses will include evaluation of the proportion of the following individual events between the date of hospital discharge, 45 days, and 6 months post-procedure prior to and post DAPT labeling implementation: *All death *All stroke *Ischemic stroke *Hemorrhagic stroke *Device-related thrombus *Systemic thromboembolism *Major bleeding *Device margin residual leak *Device embolization
Follow-up Visits and Length of Follow-up	All cohorts will be followed between date of hospital discharge and 45-day post-procedure (October 2022 [date of NESTed DAPT labeling implementation] through September 2023) and between discharge, 45 days and 6 months (August 2021 and September 2022 [date prior to NESTed DAPT labeling implementation])
General
Study Status	Completed
Application Number / Requirement Number	P210015 / PAS001
Date Original Protocol Accepted	10/31/2022
Date Current Protocol Accepted	10/31/2022
Study Name	Avive AED Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective observational study comparing the Avive AED Rhythm Recognition Detector performance to objective performance criterion.
Study Population	N/A
Sample Size	200 cases
Key Study Endpoints	The primary study endpoint for this PAS is a >90% sensitivity on Course VF rhythms for the Avive AED, with a 90% One-sided Lower Confidence Limit that is >87%. The following will also be reported: -Performance on Rapid VT rhythms for the Avive AED -Performance on Normal Sinus rhythms for the Avive AED -Performance on Asystole rhythms for the Avive AED -Performance on other non-shockable rhythms for the Avive AED, including Atrial Fibrillation, Supraventricular Tachycardia, Sinus Bradycardia, Heart Block, Idioventricular rhythms, and Premature Ventricular Contractions -Performance on Fine VF for the Avive AED -Performance on Other VT for the Avive AED In addition to the ECG analysis performance, the PAS will also report the usability performance of the Avive AED represented by the time elapsed from AED activation to pads placed and if shockable, time to first shock delivered. These data will be extracted and reported from the same AED device log. This information provides the most objective metric of the device usability, incorporating the critical tasks that are required to provide patient treatment.
Follow-up Visits and Length of Follow-up	No follow-up required
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,909 ECG rhythm segments total. 222 ECG rhythm segments with Coarse VF.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	No follow-up needed in this study. Overall, the study demonstrates a 95.5% sensitivity on Coarse VF rhythms with a 90% one-sided lower confidence limit that is 93.7% across 222 collected cases.
Final Safety Findings	There were 11 instances out of 287 (3.8%) where the adjudicator consensus was either Coarse VF (10/11 instances), or Rapid VT (1/11 instances), and the AED assessed a non-shockable rhythm. None of these 11 instances had 3/3 agreement amongst the three cardiologist adjudicators. Most included a combination of shockable (Rapid VT or Coarse VF) and intermediate (Other VT or Fine VF) classifications. In 7/11 of the instances, the rhythm presented with a slow rate (<160 BPM), a low-amplitude, and semi-organized electrical activity where an Other VT, Fine VF or Pulseless Electrical Activity (PEA, which is not an option that the adjudicators can select) could have reasonably been an appropriate classification. In 10/11 of the instances, the rhythm had large deflections and/or errant QRS complexes mid-rhythm. By design, a rhythm presenting with significant indeterminate artifact can influence the AED rhythm recognition detector to not advise a shock due to safety considerations.
Final Effect Findings	The results were a 95.5% sensitivity on Coarse VF rhythms for the Avive AED, with a 90% one-sided lower confidence limit that is 93.7% across 222 collected cases.
Study Strengths & Weaknesses	The study collected data from real-world use of the Avive AED and demonstrated an acceptable performance for detection of Coarse VF and an acceptable time from power on to both pad placement and shock (if delivered). ECG segments seen by the Avive AED in the field are borderline rhythms, may be deteriorating from one arrythmia type to another, contain noise and artifact, and when viewed in an isolated 7-second segment can be interpreted differently even by board certified cardiologists.
Recommendations for Labeling Changes	None
General
Study Status	Terminated
Application Number / Requirement Number	P210039 / PAS001
Date Original Protocol Accepted	11/04/2022
Date Current Protocol Accepted
Study Name	The Chocolate Touch Continued Follow-up Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To show sufficient long term safety and effectiveness of the Chocolate Touch® for use in superficial femoral or popliteal arteries. The Chocolate Touch Study was designed as a global, multicenter, single blind, randomized (1:1 Chocolate Touch DCB to Lutonix DCB) trial. This study is continued follow-up of premarket cohorts.
Study Population	Adult patients with PAD
Sample Size	313 patients enrolled
Key Study Endpoints	The primary effectiveness endpoint is true DCB success of the target lesion, defined as a composite of primary patency (peak systolic velocity ratio <2.4 without the need for clinically-driven target lesion revascularization) in the absence of a clinically driven bail-out stent (core lab adjudicated). The primary safety endpoint is a composite of freedom from major adverse events (MAE), defined as a composite of target limb-related death, major amputation of the target limb, and re-intervention of the target limb. The endpoints to be assessed through 3 years post-procedure are rate of: (1) major adverse events (MAE), (2) VIVA safety endpoint, (3) true DCB success, (4) clinically-driven target lesion revascularization (CD-TLR), (5) all TLR, (6) primary patency, (7) major amputation, and (8) clinical improvement. Mortality is to be assessed through 5 years post-procedure
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S162/ PAS001
Date Original Protocol Accepted	05/23/2024
Date Current Protocol Accepted
Study Name	Intermediate Risk Indication Real-World Use Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The objective of the surveillance is to assess the real-world performance of the SAPIEN 3 platform for the mitral valve-in-valve intermediate-risk indication.
Study Population	Adults
Sample Size	All patients entered into the TVT Registry database with a failing surgical mitral valve (stenosed, insufficient, or combined) who are judged by a heart team to be at intermediate risk for open surgical therapy and treated with the SAPIEN 3, SAPIEN 3 Ultra, or SAPIEN 3 Ultra RESILIA THV Systems within the first 3 years after the date of PMA approval or a total of 1,000 treated patients, whichever is greater. Data collection will continue for underrepresented racial and ethnic groups until each group has enrolled the following minimum number of patients: 150 Hispanic, 150 Black/African American, 100 Asian, 50 American Indian/Alaskan Native, 25 Native Hawaiian/Pacific Islander.
Key Study Endpoints	Intra-Procedural: Device implanted successfully; 30 Days and 1 year: All-cause mortality, all stroke, life threatening/major bleeding, new requirement for dialysis, myocardial infarction, mitral valve reintervention, TIA, vascular complications, 6-minute walk distance, Quality of life (KCCQ), change in NYHA functional class from baseline, mitral valve hemodynamics; Annually years 2-10: all-cause mortality, all stroke, mitral valve reintervention.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: Device implanted successfully: 98.6% At 30-days: All-cause mortality: 1.5% All-stroke: 0.9% Transient ischemic attack (TIA): 0% Mitral valve reintervention: 0% New requirement for dialysis: 0% Myocardial infarction: 0.3% Life-threatening/major bleeding: 0.3% Vascular complications: 2.3% Effectiveness Results: At 30-days: Improvement from baseline in NYHA functional classification: 82.8% KCCQ Overall Summary Score change from baseline: 31.4 Mitral valve area: 1.86 cm2 Mean Mitral Gradient: 6.0 mmHg Moderate or greater Paravalvular Mitral Regurgitation: 0%
Actual Number of Patients Enrolled	A total of 358 patients were treated. All patients were included in the valve implanted (VI) population.
Actual Number of Sites Enrolled	193
Patient Follow-up Rate	Patient status known at thirty days is 91.9%.
General
Study Status	Delayed
Application Number / Requirement Number	P230040 / PAS001
Date Original Protocol Accepted	10/04/2024
Date Current Protocol Accepted	01/17/2025
Study Name	PROACTIVE-HF Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A randomized control trials will be conducted in NYHA Class III. This is a prospective, open label, randomized, controlled, multicenter clinical trial to evaluate the safety and effectiveness of the Cordella PA Sensor System in patients enrolled with NYHA Class III Heart Failure.
Study Population	Adults diagnosed with NYHA Class III Heart Failure at enrollment
Sample Size	NYHA Class III Phase I aims to explore the trend at 6 months between the treatment and control arms. With 600 patients and 6 months of follow-up, and assuming a 5% dropout rate per year, this phase will descriptively examine trends in cumulative count curve separation between the two arms without conducting formal hypothesis testing. No formal Type I error rate will be assigned. Assumptions for sample size estimation: 600 patients Number of sites: 120 Sites location: US and Europe
Key Study Endpoints	Safety Endpoints Primary: 1. Freedom from device/system related complication at 6 months 2. Freedom from pressure sensor failure at 6 months Secondary: 1. Freedom from device/system related complication at 12 and 24 months 2. Freedom from pressure sensor failure at 12 and 24 months 3. Pressure sensor failure rate throughout the study 4. Frequency of serious adverse events throughout the study 5. Frequency of implant procedure and procedure related adverse events and serious adverse events 6. Phase II only: Incidence of serious adverse events at 12 months Effectiveness Endpoints Primary Phase I: The primary efficacy endpoint is a composite of HF events (HF hospitalizations or urgent HF visits) or deaths from cardiovascular disease (CVD). Statistical analysis will be based on negative binomial regression, with the log follow-up time as an offset term, to descriptively assess event rates through 6 months. Results will be displayed using a cumulative event count curve. This analysis is intended for descriptive purposes, and no formal hypothesis testing, or control of Type I error will be performed
Follow-up Visits and Length of Follow-up	3, 6, 12, 18, 24, 36, 48, and 60 months after the study initiation
Interim or Final Data Summary
Actual Number of Patients Enrolled	13
Actual Number of Sites Enrolled	51
Patient Follow-up Rate	They expect to have the last PAS patient enrolled in 2026 and the Follow-up period will be 5 years for each study subject, which is expected in 2031
General
Study Status	Progress Adequate
Application Number / Requirement Number	P140031 / PAS002
Study Name	Comprehensive/Linked-Registry
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score ¡Ý8% or at a ¡Ý15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri- procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non- stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years 30 days, 12 months as per clinical practice
General
Study Status	Completed
Application Number / Requirement Number	P130024 S009/ PAS001
Study Name	ISR and LL Cohorts of the Global SFA Reg
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry
Study Population	DCB
Key Study Endpoints	the composite of freedom from all-cause peri-procedural (=30 day) death and freedom at 1 year and 2 years from: index limb amputation, index limb re-intervention, and index limb death and (2) freedom from TLR at 1 year and 2 years
Follow-up Visits and Length of Follow-up	2 years yearly
General
Study Status	Completed
Application Number / Requirement Number	P130024 S009/ PAS002
Study Name	SFA ISR IDE Continued f/u study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up
Study Population	DCB
Key Study Endpoints	the composite of freedom from all-cause peri-procedural (=30 day) death and freedom at 1 year and 2 years from index limb amputation (above or below the ankle), index limb re-intervention, and index-limb-related death and (2) primary patency at 1 year and 2 years
Follow-up Visits and Length of Follow-up	3 years yearly
Interim or Final Data Summary
Actual Number of Patients Enrolled	82 DCB Subjects (53) Control Subjects (29)
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	Missing data (lost + withdrew) was 9.4%% (5/53) in the DCB arm and 20.7% (6/29) in the PTA arm.
Final Safety Findings	At 12 months (365 days), the KM estimate of primary safety was 73.1% in the DCB group and 64.0% in the PTA group. At 36 months, the KM estimate of primary safety was 54.4% in the DCB group and 43.6% in the PTA group. At 36 months, the KM estimate of freedom from all cause death for the DCB arm was 88.1% for the DCB arm and 87.8% for the PTA arm.
Final Effect Findings	The primary patency at 12 months by KM estimate was 67.0% in the DCB arm and 49.5% in the PTA arm. At 24 months the primary patency was 28.9% in the DCB group and 31.0% in the PTA group by KM estimate.
Study Strengths & Weaknesses	The strengths of the study include looking at the ISR indication and the extended safety follow up. Study weaknesses include the small sample size unbalanced randomization.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P130024 S009/ PAS003
Study Name	Lutonix Long Lesion SFA Cont f/u study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up
Study Population	DCB
Key Study Endpoints	the composite of freedom from all-cause peri-procedural (=30 day) death and freedom at 1 year and2 years from the following: index limb amputation and (above or below the ankle) and index limb re-intervention and (2) primary patency at 1 year and 2 years
Follow-up Visits and Length of Follow-up	2 years yearly
Interim or Final Data Summary
Actual Number of Patients Enrolled	125 DCB Subjects (118) Control Subjects (7)
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	DCB Subjects 89.0% (105/118) Lost to follow up plus withdrew from study.
Final Safety Findings	The primary safety endpoint for the DCB group was 78.7%% (85/108) [69.8, 86.0] and was defined as the composite of freedom from all-cause peri-procedural (less than or equal to 30 day) death and freedom at 1 year from the following: index limb amputation (above or below the ankle) and index limb re-intervention.
Final Effect Findings	The primary effectiveness endpoint for the DCB group was DCB group: 58.3% (60/103) [48.1, 67.9] and represents primary patency at 12 months. Primary Patency is defined as Freedom from Clinically-Driven TLR and from Binary Restenosis.
Study Strengths & Weaknesses	The strengths of the study include looking at the long lesion length indication and the extended safety follow up. Study weaknesses include the small sample size and lack of control group.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P160003 / PAS001
Study Name	Extended Study of Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up PAS (PRO-Kinetic Energy Cobalt Chromium (CoCr) Coronary Stent System BIOHELIX-I Study) was a prospective, non-randomized, multi-center, Investigational Device Exemption (IDE) study designed to demonstrate the safety and effectiveness of BIOTRONIK’s PRO-Kinetic Energy Cobalt Chromium (CoCr) Coronary Stent System in subjects with atherosclerotic disease of native coronary arteries.
Study Population	All 329 subjects were in the device group
Sample Size	329 subjects total
Key Study Endpoints	Primary Endpoint: TVF rate at 9 months post-index procedure. Secondary Endpoints: Secondary endpoints were not tested with formal hypotheses and only reported with descriptive statistics, including estimated rates and the associated exact, two-sided 95% confidence intervals. TVF rate (primary endpoint at 9 months) Individual components of the TVF rate (cardiac death, MI, ischemia-driven TVR) Overall TVR rate Target Lesion Failure (TLF) rate, including individual components of the TLF rate (cardiac death, MI, ischemia-driven Target Lesion Revascularization (TLR)) Overall TLR rate Rate of all-cause mortality and all cause MI, including individual components Stent thrombosis rate Index procedure success Device success Lesion success Angina pectoris classification Rates for individual adverse event
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	329
Actual Number of Sites Enrolled	33
Patient Follow-up Rate	97.8%
Final Safety Findings	(Primary endpoint was TVF, a combined safety and effectiveness endpoint) TVF at 9 months: 9.06% for ITT population. TVF at 12 months: 10.76% TVF at 24 months: 13.26% TVF at 36 months: 17.61%
Study Strengths & Weaknesses	An independent Clinical Events Committee adjudicated all suspected cases of target vessel revascularization (TVR), myocardial infarction (MI), access site complications, bleeding events, vascular events as well as any deaths. The CEC determined if an event met the protocol definition of TVR or TLF (target lesion failure), and classified the relationship of an event to procedure or stent, as well as serious or non-serious in nature. An independent data safety monitoring board had oversight on safety aspects of the study and monitored the study for accumulating evidence regarding process of the study to meet its primary objective. Specific groups of patients and lesion types were excluded from the study, including those with complex lesions, left main or coronary bypass graft lesions. In addition, patients with acute MI were not included. These exclusions may limit generalizability of the results. Secondary endpoints should be interpreted with caution as the sample size was calculated to provide adequate statistical power for the primary endpoint.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P160014 / PAS001
Study Name	Cont f/u of PzF SHIELD IDE Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort
Study Population	Single arm study with COBRA device
Sample Size	296 (already enrolled)
Key Study Endpoints	The primary combined safety and effectiveness endpoint is the incidence of target vessel failure (TVF) within 270 days of treatment with the COBRA PzF™ Coronary Stent System. In-stent late lumen loss at 9 months post-implant is a powered secondary endpoint. These endpoints have already been met. Additional secondary endpoints include clinically driven target lesion revascularization and definite or probable stent thrombosis.
Follow-up Visits and Length of Follow-up	5 years Annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	296
Actual Number of Sites Enrolled	35
Patient Follow-up Rate	30, 180, 270, 360, 720, 1080,1 440, 1800 days
Final Safety Findings	At 5 year follow-up, there were a total of 11 deaths adjudicated as cardiac and 23 as non-cardiac, for an all-cause mortality rate of 12.0%. There were a total of 29 Mis by ARC definition within 5 years for an MI rate of 11.3%. The clinically driven TLR rate at 1800 days was 13.5%. There were 9 cases of possible stent thrombosis events through 5 years but no definite or porpable stent thrombosis was reported.
Final Effect Findings	The trial primary endpoint was met: The rate of TVF at 270 days was 11.4% (33/290 patients). The upper limit of the one -sided exact 95% CI was 14.81%, which met the performance goal of 19.62%. The trial powered secondary endpoint was met: The mean in-stent late loss per patient at 270 days was 0.84 (± 0.48)mm with an upper bound of the one-sided 95% CI of 0.93 mm. This was below the performance goal of 1.1 mm.
Study Strengths & Weaknesses	Single arm trial with a limited sample size for confirmatory analysis
Recommendations for Labeling Changes	The sponsor should update their labeling to include the final data from the study.
General
Study Status	Completed
Application Number / Requirement Number	P150002 / PAS001
Date Original Protocol Accepted	11/27/2018
Date Current Protocol Accepted
Study Name	Long Term INSPIRATION Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post approval study is to evaluate the long-term safety and effectiveness of the INCCRAFT AAA Stent Graft System. It is a prospective, multi-center, single-arm clinical study. It involves the long-term follow-up of the premarket cohort.
Study Population	The study population is patients with an infrarenal abdominal aortic aneurysm who met the study selection criteria.
Sample Size	A total of 190 patients were enrolled.
Key Study Endpoints	The primary endpoint is successful aneurysm treatment through 1 year post-procedure. Additional endpoints will be collected and reported at each follow-up point through 5 years post procedure (through 10 years for patients with stent fracture(s) identified within the first 5 years), including Major Adverse Events (MAE), aneurysm enlargement (>5mm), aneurysm-related mortality, all types of endoleaks, aneurysm sac rupture, device integrity (e.g. stent strut fracture), device migration (>10 mm), graft occlusion, stenosis or kink, conversion to open surgery and secondary interventions.
Follow-up Visits and Length of Follow-up	Patients will be followed for 5 years. Patients identified with stent fracture(s) within the first 5 years will be followed for an additional 5 years (total 10 years of follow-up).
Interim or Final Data Summary
Actual Number of Patients Enrolled	190 subjects. Stent fractures were observed in 20 of the 190 subjects enrolled in the study, with 9 of those subjects being reconsented for an additional 5 years of follow-up.
Actual Number of Sites Enrolled	A total of 32 sites (27 in the U.S. and 5 in Japan) enrolled subjects for the IDE trial. Of these, 7 sites across the U.S. and Japan enrolled subjects with fracture stent fracture for the long- term follow-up study.
Patient Follow-up Rate	Clinical Follow-Up | CT Imaging Follow-Up: 1 Month: 99.5% (189/190) | 98.9% (188/190) 6 Months: 96.8% (182/188) | 94.7% (178/188) 1 Year: 96.7% (177/183) | 95.6% (173/181) 2 Years: 94.1% (162/172) | 91.2% (155/170) 3 Years: 91.9% (148/161) | 89.3% (142/159) 4 Years: 87.1% (129/148) | 79.5% (116/146) 5 Years 93.1% (121/130) | 83.6% (107/128) 6 Years: 87.5% (7/8) | 87.5% (7/8) 7 Years: 87.5% (7/8) | 75% (6/8) 8 Years: 100% (6/6) | 83.3% (5/6) 9 Years: 100% (6/6) | 100% (6/6) 10 Years 100% (5/5) | 100% (5/5)
Final Safety Findings	Major Adverse Events and Procedure-Related Adverse Events: The overall rate of MAEs is 7.0% at 6 month, 10.9% at 1 year, 18.8% at 2 years, and 22.7% at 3 years, 29.8% at 4 years and 36.4% at 5 years. For the stent fracture subjects followed through 10 years, the overall rate of MAEs is 12.5% at 6 years, 28.6% at 7 years, 42.9% at 8 years, 42.9% at 9 years, and 57.1% at 10 years Aneurysm-Related Mortality There has been one (1) ARM in the study (1/190, 0.5%). The subject died of an acute myocardial infarction on post-operative day two. All-Cause Mortality Through 10 years, 47 deaths occurred in the study (47/190, 24.7%). Two (2) of these deaths occurred after 5 years (at 7 years and 10 years), Other than the one ARM reported above, all of these deaths were adjudicated as unrelated to the device or procedure per the CEC. Rupture There was one (1) incidence of aneurysm sac rupture after completing the 5.5 year follow-up visit (1/190, 0.5%). This subject also experienced a Type Ia endoleak. This required conversion to open repair. This subject underwent an emergency laparotomy and implantation of a bifurcated graft on the same day as the rupture to repair the aneurysm with no major complications.
Final Effect Findings	Stent Fractures Stent fractures were observed in 20 subjects (20/190, 10.5%) through 5-year follow-up. All fractures were observed in the transrenal stent component (bare stent without graft) and none were located on the fabric-covered stents. Seven (7) subjects were observed with more than one stent fracture, two (2) of whom had multiple fractures observed from the initial imaging and the remaining five (5) of whom had one fracture observed from the initial imaging and additional fractures observed at subsequent follow-up visits. Aneurysm Sac Expansion (>5 mm) Through 5 years, there were a total of 31 subjects (31/190, 18.4%) with aneurysm expansion noted. Through 9 year follow-up, 2 more subjects had sac enlargement (> 5 mm). At 10 years, there was 1 subject presenting aneurysm enlargement. Endoleaks Through 5 years, there were 18 Type Ia endoleaks in 15 subjects (15/190, 7.9%) and 3 Type Ib endoleaks in 3 subjects (3/190, 1.6%). There was one Type III endoleak observed at 3 years in 1 subject (1/190, 0.5%). Beyond 5 years, two new subjects reported with type Ia endoleaks: one subject reported type Ia endoleak on 6-year imaging as well as rupture, which required conversion to open repair; one new type Ia endoleak was reported on 8-year imaging, which was treated with chimney stent grafts. Stent Graft Migration (>10 mm) Through 10 years post-procedure, there were no subjects observed with bifurcate stent graft migration > 10 mm. However, there are two subjects that each have aortic bifurcate migration of 10 mm noted at the 3-year and 4-year follow up visit. The one subject with migration at the 4-year follow-up visit also experienced a stent fracture. This case was accompanied by aortic neck dilatation but did not require secondary intervention. There was bifurcate stent graft movement > 5 mm observed at 2-, 3-, 4- and 5-years post-procedure in the same subject. Through 5 years post-procedure, five (5) subjects (5/190, 2.6%) have been observed with proximal iliac limb migration by the Core Lab. Through 10 years post-procedure, limb migration was observed across multiple time points in two (2) subjects with stent fractures. These two incidences of limb migration/movement were cranial in direction and there were no limb separations. There were no secondary interventions performed. Stent Graft Patency Events (CEC-Adjudicated) Through 10 years, a total of 11 subjects were reported with 11 stent graft occlusions by the site (11/190, 5.8%); 17 subjects were reported with 19 stent graft stenosis by the site (17/190, 8.9%); only one kink was reported at 3 years (1/190, 0.5%). Conversions to Open Surgery There were three (3) conversions to open surgery reported in the study (3/190, 1.6%). One (1) was due to complete occlusion of the aortic bifurcate component. One (1) was due to bilateral iliac limb stenosis. One (1) of the 20 subjects with stent fracture had conversion to open surgery due to rupture and type Ia endoleak (as noted above), which was reported beyond 5 years. Secondary Interventions Through 5 years, a total of 35 subjects (35/190, 18.4%) underwent 51 secondary interventions to address endoleaks, vascular injury, procedure complications, device patency and device migration events. Two secondary interventions were necessary beyond 5 years post-procedure in two (2) subjects, one to treat rupture/type Ia endoleak and the other to repair a type Ia endoleak. Device Malfunctions Although there were 20 subjects observed with stent fracture, only five (5) of these subjects were determined by investigators as device malfunctions. Three (3) of these five (5) subjects reconsented to the long-term study. There were no other device malfunctions reported.
Study Strengths & Weaknesses	Strengths: This was a prospective, consecutively enrolling, single-arm, multi-center study that consisted of continued follow-up of all available subjects from the INSPIRATION pivotal study. Core Lab analyzed the imaging, and an independent clinical events committee adjudicated event relatedness to the procedure, technique, and/or device. Subjects who experienced stent fractures within the first 5 years of the study were eligible for an additional 5 years of follow-up (total of 10 years of follow-up). There was CEC adjudication involved in the study. Weaknesses: The study is a non-randomized study with inherent biases. There is limited patient follow-up through 10 years. Only 20 out of the 190 subjects initially enrolled in the study experienced stent fracture. Of those 20 subjects, only 9 subjects were followed after 5 years, with only 5 of those subjects reaching the 10-year time point and 4 subjects exiting the study. Two of the four that exited the study died, while the other two withdrew consent. Of the other 5 subjects, one subject experienced persistent aneurysm enlargement, and the other four subjects did not experience device related effects.
Recommendations for Labeling Changes	A labeling supplement was approved on September 23, 2020 with data out to 5 years. The data through 10 years will not be recommended for a labeling supplement. These results will be available in the latest Clinical Update.
General
Study Status	Terminated
Application Number / Requirement Number	P150002 / PAS002
Date Original Protocol Accepted	03/26/2019
Date Current Protocol Accepted
Study Name	INCRAFT US Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The INCRAFT U.S. Post Approval Study is a multi-center, open label, single arm, prospective post approval study. The objective of the study is to collect real-world safety and effectiveness outcomes of the INCRAFT® AAA Stent Graft System in an all-comers population eligible for the endovascular treatment of abdominal aortic aneurysms in routine clinical practice.
Study Population	All-comers population
Sample Size	A minimum of 250 patients will be enrolled.
Key Study Endpoints	The primary endpoint is successful aneurysm treatment through 2 years post-procedure. Technical success at the conclusion of the index procedure, defined as: Successful delivery, (i.e. ability to deliver the implant to the intended location without the need for unanticipated corrective intervention related to delivery); Successful and accurate deployment, defined as: deployment of the endovascular stent graft in the planned location; - patency of the endovascular stent graft, absence of device deformations, (e.g. kinks, stent eversion, mal-deployment, misaligned deployment) requiring unplanned placement of an additional device within the endovascular stent graft, and; Successful withdrawal (i.e. successful withdrawal of the delivery system, without the need for unanticipated corrective intervention related to withdrawal) ¿ Absence of post-operative aneurysm enlargement (growth > 5 mm) or stent graft migration (> 10 mm) compared to the one-month size measurement; - Absence of aneurysm rupture, endoleak Type I / III, or graft occlusion (including unilateral or bilateral limb occlusion); - Absence of post-operative conversion to open surgery - Absence of secondary intervention to address migration, patency-related events, Type I/III endoleaks, or fracture.
Follow-up Visits and Length of Follow-up	All patients will receive 2 years of follow-up. Patients identified with fracture(s) within the first 2 years will be followed annually for an additional 3 years for a total of 5 years of follow-up.
General
Study Status	Ongoing
Application Number / Requirement Number	P130013 S035/ PAS002
Date Original Protocol Accepted	05/21/2021
Date Current Protocol Accepted
Study Name	WATCHMAN FLX LAA Closure Device w/Delivery RW Use
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The WATCHMAN FLX Device Surveillance Post Approval Analysis is an observational, prospective, nonrandomized, multicenter registry surveillance analysis plan using real world data. The study is designed to assess long-term safety and effectiveness outcomes associated with the use and implantation of the WATCHMAN FLX Left Atrial Appendage (LAA) Closure Device with Delivery System in a routine clinical setting. This surveillance analysis will utilize data captured in the Left Atrial Appendage Occlusion Registry (LAAO Registry) within the American College of Cardiology Foundation’s (ACCF) National Cardiovascular Data Registry (NCDR).
Study Population	The study consists of all subjects enrolled in the LAAO Registry for the first two years.
Sample Size	Estimated enrollment is 30,000 subjects
Key Study Endpoints	The surveillance will be carried out to characterize clinical outcomes (including: implant success rate, procedural safety, effective closure of the orifice of the left atrial appendage, and stroke [including ischemic or hemorrhagic] through one- year post-implant] and longer term identified occurrence of all stroke (including ischemic or hemorrhagic) and to assess the real-world use of the commercial WATCHMAN FLX LAA Closure Device with Delivery System.
Follow-up Visits and Length of Follow-up	24 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	Enrollment is complete as of September 30, 2022. A total of 97,529 ITT subjects have been enrolled over the course of the full 24-month enrollment period.
Actual Number of Sites Enrolled	N/A – All sites entered into LAAO registry
Patient Follow-up Rate	Intent to treat follow-up rates: 45 day – 91.2% 6 month – 81.2% 12 month – 74.6% 24 month – 43.1%
Final Safety Findings	As of this progress report, 0.46% (451/97,529) / 0.41% (388/95,125) of the subjects have had 1 or more key safety events in the ITT/Implanted data sets, respectively.
Final Effect Findings	In the Implant data set to-date, the adjudicated rates of ischemic stroke or systemic embolism was 0.04% at discharge, 0.13% at 7 days, 0.25% at 45 days, 0.71% at 182 days, 1.34% at 365 days, and 2.46% at 730 days (Kaplan-Meier estimates). In the Intent to Treat data set-to-date ischemic stroke or systemic embolism was 0.05% at discharge, 0.13% at 7 days, 0.25% at 45 days, 0.71% at 182 days, 1.34% at 365 days, and 2.46% at 730 days (Kaplan-Meier estimates).
General
Study Status	Completed
Application Number / Requirement Number	P150003 S054/ PAS001
Date Original Protocol Accepted	03/19/2021
Date Current Protocol Accepted
Study Name	Synergy Megatron PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a post-market, standard of care, real-world observational study to assess the clinical outcomes of the SYNERGY XLV Coronary Stent System for the treatment of subjects with atherosclerotic lesion(s) less than or equal to 28 mm in length (by visual estimate) in native coronary arteries greater than or equal to 3.50 mm to less than or equal to 5.00 mm in diameter (by visual estimate).
Study Population	A patient is an acceptable candidate for treatment with a SYNERGY XLV stent if treated in accordance with the applicable guidelines on PCI, the SYNERGY IFU, and the Declaration of Helsinki. Sites should follow their local standard of care and approach consecutive patients for inclusion in the trial.
Sample Size	A minimum of 100 subjects will be enrolled at up to 20 US sites.
Key Study Endpoints	The primary endpoint is the rate of Target Lesion Failure (TLF) rate at 12-months. Secondary endpoints include rates of TLR, TLF, TVR, TVF, MI (Q-Wave and non-Qwave), Death (All, Cardiac, Non-Cardiac), Cardiac Death or MI, All Death or MI, All Death or MI or TVR, Stent Thrombosis (ARC Definitions) at 6-months, 12-months, 2-years, and 3-years. In addition, secondary endpoints will technical and clinical success rates.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	100% of patients have >= 365 days follow-up, 89.8% have >= 730 days follow-up. 8/100 of subjects were lost to follow-up, and 1 subject declined to take part in 2-year follow-up.
Final Safety Findings	There were a total of 12 deaths, with 6 being cardiac-related. 11 non-Q-wave MIs were reported that were related to the target vessel and 3 of these were peri-procedural. TLR occurred in 5 patients that were treated with PCI (3 patients) or CABG (2 patients). One patient experienced a definite ST on the day of the index procedure
Final Effect Findings	The rate of TLF at 24 months was 17.7% (17/96) in the ITT population. The 95% upper confidence bound (one-sided) is 18.3%. The rates of technical and clinical procedural success were 96.0%.
Study Strengths & Weaknesses	This was a single-arm post-approval study with a high technical and clinical procedural success rate (96.0%) supporting the safety and effectiveness of using the SYNERGY XLV (Megatron) coronary stent system to treat patients with atherosclerotic lesions <=28mm in length and between 3.5 and 5.0mm in diameter. The study enrolled patients with more health complications than typically present in similar studies (average patient age ~70 years, 82% had 3V CAD, 19.8% LM disease, and 21.4% presented with STEMI) which may have increased the number of non-procedure or device related deaths observed in the study.
Recommendations for Labeling Changes	The Megatron IFU should be updated to include this trial, including the study purpose, study design, primary and secondary endpoints, patient population & demographics, lesion criteria, follow-up rate & duration, adverse events, 12-month and 2-year results, final safety findings, and final effectiveness findings
General
Study Status	Delayed
Application Number / Requirement Number	P200028 / PAS001
Date Original Protocol Accepted	11/02/2021
Date Current Protocol Accepted	10/10/2025
Study Name	DIAMOND AF PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the DIAMOND AF Post Approval study is to describe clinical performance and safety data in a broad patient population treated with the DiamondTemp™ Family of Cardiac Ablation Catheters. This clinical study is a prospective, global, multi-center, non-randomized, single-arm observational trial.
Study Population	Patients greater than or equal to 18 years of age with a diagnosis of recurrent symptomatic AFib with planned de novo pulmonary vein isolation procedure using the DiamondTemp Ablation System.
Sample Size	The study is expected to be conducted at a minimum of 6 sites located in multiple geographies and will enroll up to 225 subjects to ensure 175 subjects are treated with ablation. At least 50% of the subjects will be enrolled and treated in the United States. The study protocol was subsequently modified to limit enrollment to 81 subjects.
Key Study Endpoints	Primary Efficacy Estimate the 36-month freedom from AF/AFL/AT recurrence following ablation procedure using the DiamondTemp™ Ablation System Primary Safety Estimate primary safety adverse event rate for ablation using the DiamondTemp™ Ablation System through 12 months
Follow-up Visits and Length of Follow-up	36 months post-ablation. The study protocol was subsequently modified to limit follow-up following a final adverse event assessment.
Interim or Final Data Summary
Actual Number of Patients Enrolled	24
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	Study visits will occur at 3, 6, 12, 24, and 36 months, including required 12-lead ECG review at each follow up visit and 24 Holter monitoring at each follow up except the 3 month visit
Final Safety Findings	No adverse events have been reported.
Final Effect Findings	N/A
General
Study Status	Completed
Application Number / Requirement Number	P130009 S034/ PAS001
Date Original Protocol Accepted	10/09/2015
Date Current Protocol Accepted	11/04/2019
Study Name	Continued f/u of the premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohorts. The objective of this study is to characterize the cumulative clinical outcomes of all subjects at discharge or 7 days, whichever comes first, 30 days, 1 year, and annually thereafter through 5 years post procedure.
Study Population	The study will consist of all living subjects who were enrolled in Nested Registry 3 under the IDE, including those enrolled under the continued access protocol.
Sample Size	All living subjects
Key Study Endpoints	The safety and effectiveness endpoints include all-cause mortality, all stroke, moderate or severe obstruction (defined as Doppler Velocity Index [DVI] < 0.25), or moderate or severe paravalvular leak (through 1 year only); all-cause mortality; all stroke or transient ischemic attack (TIA); all-cause mortality or major stroke; all stroke, major vascular complication, or aortic valve reintervention; New York Heart Association (NYHA) classification (additional data point at 6 months); change in 6-minute walk distance (6MWD) from baseline (through 1 year only); echocardiographic assessment of valve performance; clinical improvement per quality of life (QoL) instrument Kansas City Cardiomyopathy Questionnaire (KCCQ); and index hospitalization length of stay.
Follow-up Visits and Length of Follow-up	5 years All subjects are followed at discharge or 7 days, whichever comes first, 30 days, 1 year, and annually thereafter through 5 years post procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	372 patients were enrolled, of which 367 are included in the as treated population, and 365 are in the valve implant population.
Actual Number of Sites Enrolled	47
Patient Follow-up Rate	The follow-up rate through five years is approximately 87%.
Final Safety Findings	Site-Reported Safety Outcomes at 5 years: All-cause death: 49.9% All-stroke: 10.4% Bleeding: 29% Myocardial infarction: 11.8% New permanent pacemaker: 10.6% Atrial fibrillation: 23.8%
Final Effect Findings	Improvement in NYHA functional class was demonstrated in 85.6% of subjects at 5 years KCCQ (change from baseline at 5 years was 31.2 -/+ 2.40 for the overall summary score and 22.6 -/+ 2.35 for the clinical summary score Moderate or Severe Obstruction (Doppler Velocity Index < 0.25) at 5 years: 12.1% Mean Gradient at 5 years: 16.4 mmHg Peak Gradient at 5 years: 30.6 mmHg Structural valve deterioration at 5 years: 3.3% (8 events, 7 subjects with the event)
Study Strengths & Weaknesses	Good THV hemodynamic valve performance was demonstrated at each follow-up visit by an improvement from baseline in mean gradient and peak gradient. At 5 years, total and paravalvular aortic regurgitation was graded mild or less in 97.3% and 97.2% of patients, respectively. Structural valve deterioration rates increased from 0.3% at 1 year to 3.3% at 5 years.
Recommendations for Labeling Changes	No, SAPIEN XT has been discontinued.
General
Study Status	Progress Adequate
Application Number / Requirement Number	P130009 S034/ PAS002
Study Name	Comprehensive Linked Registry-Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry.
Study Population	Patients with symptomatic heart disease due to either severe native calcific aortic stenosis or failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., Society of Thoracic Surgeons operative risk score greater than or equal to 8% or at a greater than or equal to 15% risk of mortality at 30 days)
Sample Size	All implanted patients in the TVT-registry within 5 years of device approval
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy, acute events associated with index TAVR procedure), peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually through 5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years 30 days, 12 months as per clinical practice; then annually up to 5 years through linking to CMS claims database.
General
Study Status	Progress Adequate
Application Number / Requirement Number	P150004 / PAS001
Date Original Protocol Accepted	05/26/2016
Date Current Protocol Accepted	08/05/2021
Study Name	F/U Axium Neurostimulator System (FANS)
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The “FANS PAS” is a prospective, multicenter, single arm, observational post-approval study to be conducted at up to 45 centers in the United States in order to demonstrate continued safety and effectiveness of the “Axium Neurostimulator System” or the “Proclaim DRG Neurostimulator System”. The primary objective of the “FANS PAS” is to demonstrate that the proportion of serious adverse events (SAEs) at 12 months for subjects who receive a permanent implant is lower than a pre- specified performance goal. Secondary objectives of the “FANS PAS” are to evaluate change in overall pain intensity, change in physical function and change in quality of life over the study period.
Study Population	A maximum of 426 adult subjects with moderate to severe chronic, intractable pain of the lower limbs due to CRPS types I and II will undergo a trial of the neurostimulator system at up to 45 study sites in the United States. Inclusion Criteria: Male or female between the ages of 22 and 75 years. Moderate to severe chronic intractable pain of the lower limbs resulting from Complex Regional Pain Syndrome (CRPS) types I or II. Baseline VAS score of > 60 mm for overall pain at the time of the baseline assessment. Willing and able to comply with the study requirements. Able to provide written informed consent. Exclusion criteria: Subject has an active implantable medical device including but not limited to cardiac pacemakers and cardiac defibrillators. Subject is currently involved in medically-related litigation, including workers compensation. Subject has a life expectancy of less than one year. Subject is pregnant or of child bearing potential and not using adequate contraception as determined by the investigator. Subject has, or plans to have, a spinal cord stimulation system or infusion pump system implanted. Subject has, or plans to have, a peripheral nerve stimulation system (PNS) or peripheral nerve field stimulation system (PNfS) implanted. Subject is considered a poor surgical or study candidate, which may include, but is not limited to the following: any medical, social, or psychological problem that could complicate the implant procedure and/or recovery from the implant procedure or could complicate the required procedures and evaluations of the study in the judgment of the investigator.
Sample Size	The primary objective of this study is to demonstrate that the proportion of serious adverse events for subjects who receive a permanent Axium or Proclaim DRG IPG is lower than a pre-specified performance goal. The primary endpoint is the 12-month serious adverse event rate for subjects receiving an Axium or Proclaim DRG IPG permanent implant. The performance goal is based on the 12- month serious adverse event rate for Axium subjects in the ACCURATE IDE study, where the observed rate was 10.5%. A non-inferiority margin of 5% is assumed. A total of 8 out of 76 (10.5%) subjects experienced a serious adverse event in the ACCURATE IDE study. The sample size required to reject the null hypothesis for the primary endpoint at the 5% significance level with 80% power assuming a 12-month serious adverse event rate of 10.5% is 287 subjects receiving the permanent Axium or Proclaim DRG IPG. Assuming an attrition rate of 25% from trial to permanent Axium or Proclaim DRG IPG implant, and an attrition rate of 10% from permanent implant to 12-month follow-up, a total of 426 (=287/0.9/0.75) subjects will be implanted with a trial system. The target number of subjects for permanent Axium or Proclaim DRG IPG implants is 319, and the target number of subjects for the primary endpoint analysis is 287.
Key Study Endpoints	Primary Endpoint The primary endpoint is the 12-month SAE rate for subjects receiving the permanent DRG IPG. Secondary Endpoints Percent change from baseline to 12 months post-permanent implant for overall pain intensity measured using the Visual Analog Scale (VAS) Change from baseline to 12 months post-permanent implant for physical function measured using the PROMIS-29 Profile Change from baseline to 12 months post-permanent implant for quality of life measured using the PROMIS Global Health Scale Descriptive Endpoints Safety Proportion of subjects with device, procedure or stimulation related SAEs and non-SAEs among subjects who receive the permanent implant Proportion of subjects who have AEs related to the trial implant procedure among subjects who fail the trial neurostimulator phase Summary of procedure-related SAEs and non-SAEs by implanter experience Effectiveness Change from baseline to 1, 3, and 6 months post permanent implant for overall pain intensity measured using the Visual Analog Scale (VAS) Change from baseline to 1, 3, and 6 months post permanent implant for physical function measured using the PROMIS-29 Profile Change from baseline to 1, 3, and 6 months post-permanent implant for quality of life measured using the PROMIS Global Health Scale Change from baseline to 1, 3, 6 and 12 months post-permanent implant for neuropathic pain measured using the Neuropathic Pain Scale (NPS) Change from baseline to 1, 3, 6 and 12 months post-permanent implant for sleep disturbance, anxiety, depression, fatigue, ability to participate in social roles and activities, pain interference and pain intensity measured using the PROMIS-29 Profile Patient Global Impression of Change (PGIC) at 1, 3, 6 and 12 months post-permanent implant Additional Data All descriptive endpoints above will be examined at 18 and 24 months for all subjects with evaluable data for those study visits. Additional data, including but not limited to, percentage of subjects achieving at least a 30% and 50% pain reduction, demographics, paresthesia coverage and intensity, subject satisfaction, programming parameters, implant procedure information, and system information may be compiled.
Follow-up Visits and Length of Follow-up	up to 24 months
General
Study Status	Ongoing
Application Number / Requirement Number	P110042 S077/ PAS001
Date Original Protocol Accepted	09/29/2017
Date Current Protocol Accepted	12/08/2023
Study Name	EMBLEM S-ICD Electrode Model 3501 PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Primary analyses will use existing data sources from patients implanted with the EMBLEM S-ICD Electrode Model 3501 and represented in the following databases: NCDR: ICD Registry; LATITUDE NXT Patient Management System; CMS Claims Database; and National Death Index (linage to NCDR patients).Each database is associated with a unique; independently-powered co-primary endpoint. Comparisons will be made to the predecessor EMBLEM S-ICD Electrode Model 3401. An unpowered secondary analysis will be performed using patients from Truven Marketscan Database (private insurance claims).
Study Population	Patients will come from the US implant population with EMBLEM S-ICD Electrode Model 3501 whose data are captured in one of the databases utilized for this study.
Sample Size	The primary analysis cohorts will consist of consecutive patients implanted with EMBLEM S-ICD Electrode Model 3501 identified in the following databases: NCDR ICD Registry (N=2;100); LATITUDE NXT Patient Management System (N=2;000); CMS Claims Database (N=2;100); and National Death Index linkage to NCDR patients (N=2;100).The sample sizes given in the parentheses were calculated based on the provisional statistical assumptions given in Table 1-2 and will be updated based on PAS data for the EMBLEM S-ICD Electrode Model 3401. The sample sizes will be re-estimated and patients will be added if needed to ensure 90% power is maintained.T
Key Study Endpoints	Primary Endpoints: NCDR: The first primary endpoint evaluates the rate of Model 3501 implant and periprocedural complications. Remote Monitoring (LATITUDE NXT): The second primary endpoint evaluates the five-year rate of Model 3501 EMBLEM S-ICD Electrode integrity alerts. Administrative Claims (CMS): The third primary endpoint evaluates the five-year rate.
Follow-up Visits and Length of Follow-up	5 year follow-up
Interim or Final Data Summary
Interim Results	Safety Results: The LATITUDE data sample size has been met; therefore, primary endpoint analysis was performed. The performance target was set at 1.22%. The alert rate from 0 to 5 years for the 3501 electrode was 0.38% with a one-sided 95% upper confidence limit of 0.49% and passed the primary endpoint. Effectiveness Results: No significant findings at time of report.
Actual Number of Patients Enrolled	NCDR: 11,228 LATITUDE: 34,121 CMS: 5,179
Actual Number of Sites Enrolled	N/A. Data from all US sites that contribute data to any of the databases used in the analysis.
Patient Follow-up Rate	Data will be collected during the course of routine device follow-up and patient care. No additional follow-ups or procedures are required. Each primary analysis cohort will have a minimum of 5 years of follow-up.
General
Study Status	Completed
Application Number / Requirement Number	P170008 / PAS001
Date Original Protocol Accepted	11/28/2017
Date Current Protocol Accepted
Study Name	Cont f/u of BIONICS Clinical Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort
Study Population	Prospective, multicenter, single-blind, two-arm 1:1 randomization (EluNIR versus Resolute)
Sample Size	1919 subjects (already enrolled)
Key Study Endpoints	The primary safety and effectiveness endpoint is TLF at 12 months post-index procedure. The secondary angiographic endpoint is in-stent late lumen loss at 13-months post-index procedure. Additional clinical secondary endpoints include acute success (device, lesion, and procedure), cardiac death, target vessel MI, target lesion revascularization, MACE, target lesion failure, target vessel failure and stent thrombosis.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1919 Patients
Actual Number of Sites Enrolled	76 Clinical sites in the US, Canada, EU and Israel
Patient Follow-up Rate	Minimum of 95% follow-up rate
Final Safety Findings	12 months The 12-month primary effectiveness was met. Adverse event: ([EluNIR] 86.1% vs. [Resolute] 85%) Serious Adverse event: ([EluNIR] 55% vs. [Resolute] 54.2%)
Final Effect Findings	The main safety and effectives endpoint rates through 5 years in the BIONICS study are: Target lesion revascularization (TLR): ([EluNIR] 7.8% vs. [Resolute] 6.8 %), Target lesion failure (TLF): ([EluNIR] 12.5% vs. [Resolute] 11.4%), Target vessel revascularization (TVR): ([EluNIR] 12.7% vs [Resolute] 9.3%, Target vessel failure (TVF): ([EluNIR] 18.8% vs. [Resolute] 18.0%), myocardial infraction : ([EluNIR] 11% vs. [Resolute] 10.3%), Cardiac death : ([EluNIR] 3.5% vs. [Resolute] 2.4%), Definite + probable Stent thrombosis : ([EluNIR] 1.0% vs. [Resolute] 0.9%, MACE: ([EluNIR] 17.4% vs. [Resolute] 15.8%, p = 0.46)
Study Strengths & Weaknesses	This was a randomized controlled trial that met its primary endpoint. However, the trial was conducted primarily in a non-US population
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow –up visits etc.), final results and study strengths and limitations of the PAS.
General
Study Status	Terminated
Application Number / Requirement Number	P140032 / PAS001
Date Original Protocol Accepted	07/27/2018
Date Current Protocol Accepted
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The ISR PAS is a prospective, open-label, observational, multi-center study. 50 newly implanted US subjects will be followed for five years. Primary Objectives: To estimate the freedom from catheter-related complications through 5 years post-implant. To estimate the freedom from ISR pump-related complications through 5 years post implant. Ancillary Objective The ancillary objective is descriptive in nature and is intended to gain additional information about the performance of the ISR pump: Plot pump fluid delivery accuracy ratio over time and compare to the intended market-release labeling describing flow rate accuracy performance expected versus refill number.
Study Population	Patients intended to be implanted with an ISR are eligible for enrollment into the ISR PAS.
Sample Size	50
Key Study Endpoints	The endpoint of this objective is catheter-related complications. If an adverse event indicates that there is unknown relatedness to the catheter, and the event is classified as a complication, it will be counted as a catheter-related complication. Additionally, in the event of a pneumothorax being adjudicated by the CEC as procedure-related, and the event is classified as a complication, it will count toward the primary objective. A patency test for suspected occlusion or elective removal of the implanted system will not be considered a complication. The endpoint of this objective is pump complications. Pump-related complications will be defined as any adverse device event that results in death, involves any termination of significant device function, or requires an invasive intervention. A patency test for suspected occlusion, pump refill, elective change-out of the pump during a catheter replacement/revision, or elective removal of implanted system will not be considered a complication. Plot pump fluid delivery accuracy ratio over time and compare to the intended market-release labeling describing flow rate accuracy performance expected versus refill number.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P160022 / PAS001
Date Original Protocol Accepted	12/27/2017
Date Current Protocol Accepted	05/19/2021
Study Name	Reconfirmation Analysis Mode Algorithm PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective observational study with newly enrolled patients. Enrollment for this study is approximately 70 months. Subjects are enrolled once the Zoll X Series, R series, AED Pro, or Zoll AED 3 is connected to the patient via electrodes and ECG data capture begins. Data collection will contine to through the duration of the resuscitation event while the ECG capture is in place.
Study Population	Subjects are enrolled in this study when they are found in cardiac arrest and receive attempted resuscitation by participating EMS agencies and treatment with the ZOLL X-Series defibrillator. Subjects meeting the labeled indications for use will be recruited into the study with the following inclusion and exclusion criteria based on the current labeling for X-Series. Inclusion Criteria: Candidates for this study must meet all of the following criteria: 1. Age greater than or equal to 8 years and weight greater than or equal to 55 pounds (25 kg) 2. Out-of-hospital cardiac arrest (OOHCA) 3. Non-traumatic arrest Exclusion Criteria: Candidates will be excluded from the study if any of the following conditions are present: 1. Weight less than 55 pounds (25 kg) 2. Do-not-attempt-resuscitation (DNAR) orders.
Sample Size	Approximately 2500 subjects are planned to be enrolled in the study to provide adequate data for all rhythms in the final analysis. Currently, the rate limiting rhythm is anticipated to be Rapid VT as it quickly degrades to VF and is rare to capture in waveform data. Historically, only 2% of all rhythms assessed in previous datasets were categorized as rapid VT. To satisfy the minimum of 50 subjects for rapid VT, 2500 subjects will be enrolled. Based on Kerber’s sample size and performance goals listed in the Kerber et al. 1997 article referred above, the following minimum sample sizes for five different categories of rhythm will be required for this study. For Coarse VF, When the sample size is 200, a one-sided 90.0% confidence interval for a single proportion using the large sample normal approximation will extend 0.027 from the observed proportion for an expected proportion of 0.900. For Rapid VT When the sample size is 50, a one-sided 90.0% confidence interval for a single proportion using the large sample normal approximation will extend 0.078 from the observed proportion for an expected proportion of 0.750. For Non-Shockable Rhythm When the sample size is 100, a one-sided 90.0% confidence interval for a single proportion using the large sample normal approximation will extend 0.013 from the observed proportion for an expected proportion of 0.990. For Other Non-Shockable Rhythms (AF, SB, SVT, PVCs) When the sample size is 30, a one-sided 90.0% confidence interval for a single proportion using the large sample normal approximation will extend 0.051 from the observed proportion for an expected proportion of 0.950. For Asystole When the sample size is 100, a one-sided 90.0% confidence interval for a single proportion using the large sample normal approximation will extend 0.028 from the observed proportion for an expected proportion of 0.950.
Key Study Endpoints	The primary endpoint is the accuracy of the RAM algorithm (i.e., measured as sensitivity for shockable rhythms and specificity for non-shockable rhythms for the algorithm) compared to manual annotation for each rhythm type. Primary outcome measure: ECG data files will be manually annotated as shockable or non-shockable by two (2) non-physician experts in ECG cardiac rhythm analysis and one (1) physician expert in ECG analysis. This annotation will be based on the ECG waveform immediately following the end of the CPR compression interval only; that is, the annotation will be done only with the portion of the ECG waveform that is free from CPR artifact. The shock determination decision reached by the cardiac monitor will be compared with the manual annotations of the same ECG data by the three (3) experts.
Follow-up Visits and Length of Follow-up	No follow-up visits
Interim or Final Data Summary
Actual Number of Patients Enrolled	2574
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	The 2574 participants enrolled accounted for 14555 rhythm analyses where RapidShock was deployed. Of these 14555, 1445 segments were determined to have a noisy ECG signal due to compression interference or artifact occurring while the algorithm was attempting analysis and are excluded from the sensitivity and specificity analyses below. One hundred thirty-six of these noisy segments were ultimately determined by the algorithm to be shockable while 1309 were determined to be non-shockable.
Final Safety Findings	There were no Adverse Events reported during the study. A total of 16 Device Deficiencies were reported during the duration of the study. These deficiencies were managed through ZOLL’s complaints system and none of the deficiencies were determined to be novel device issues.
Final Effect Findings	The algorithm performance appears to meet the performance goals.
Study Strengths & Weaknesses	The study adequately met sample size requirements and performance goals for shockable rhythm analysis. The study would have been strengthened by inclusion and subgroup analysis of patient characteristics such as age, sex, ethnicity, BMI, etc.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P150005 S014/ PAS001
Date Original Protocol Accepted	11/01/2018
Date Current Protocol Accepted	03/25/2024
Study Name	INTERRUPT (Zero) AF PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The INTERRUPT AF study is a global, prospective, non-randomized, multicenter study, to assess acute and long-term outcomes for the Rhythmia Mapping System in conjunction with the Blazer and IntellaNav Open-Irrigated Ablation Catheters to treat Paroxysmal Atrial Fibrillation for de novo cases.
Study Population	The study will enroll patients with symptomatic drug-refractory paroxysmal atrial fibrillation undergoing AF ablation.
Sample Size	The sample size of 415 subjects’ enrollment at 25-50 centers worldwide will ensure the minimum of 329 treatment subjects in the study. The calculation of sample size is driven by hypothesis. The sample size required to assess the Primary Safety Endpoint hypothesis was 329. The assumptions for the sample size calculation were an expected primary safety endpoint event-free rate at one year of 90%, a performance goal of 85%, an alpha of 0.05, 80% power, and an expected attrition (per year) of 7.5%. The performance goal of 85% is based on the Primary Safety Endpoint results from the ZERO-AF clinical study data (G120082).
Key Study Endpoints	The primary safety endpoint will be evaluated by the primary safety event-free rate at 12 months post-procedure. Primary safety events will consist of a composite of acute primary safety events (events occurring within seven days post-procedure or hospital discharge, whichever is later), and chronic primary safety events (events occurring through 3 months or 12 months post-procedure). Acute primary safety events will be defined as the following: Death Myocardial infarction (MI) Vagal Nerve Injury/Gastroparesis Transient ischemic attack (TIA) Stroke/Cerebrovascular accident (CVA) Thromboembolism Pericarditis Cardiac tamponade/perforation Pneumothorax Vascular access complications Pulmonary edema/heart failure AV block Chronic primary safety events will be defined as the following: Atrial esophageal fistula (occurring through 3 months) Pericardial effusion (ocurring through 3 months) Pulmonary vein stenosis (symptomatic and requiring intervention) (occurring through 12 months) Primary effectiveness events will be defined as the following: Acute procedural failure More than one repeat procedure during the blanking period (90 days post index procedure) Documented atrial fibrillation, or new onset of atrial flutter or atrial tachycardia event (greater than or equal to 30 seconds in duration from an event monitor or Holter Monitor, or from a 10 second 12-lead EKG) between 91 days and 365 days post index procedure Any of the following interventions for atrial fibrillation, or new onset of atrial flutter or atrial tachycardia between 91 days and 365 days post index procedure: Repeat procedure Cardioversion Prescribed any anti-arrhythmic drugs* (AAD*) *AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken for control of AF/AT/AFL recurrence The objective of the secondary effectiveness endpoint is that the secondary effectiveness event-free rate at 12 months post-procedure in each cohort is greater than the specified performance goal 50% for De Novo Cohort. Secondary effectiveness events will be defined as the following: Acute procedural failure More than one repeat procedure during the blanking period (90 days post index procedure) Documented symptomatic atrial fibrillation, or new onset of atrial flutter or atrial tachycardia event (greater than or equal to 30 seconds in duration from an event monitor or Holter, or from a 10 second 12-lead EKG) between 91 days and 365 days post index procedure Any of the following interventions for atrial fibrillation, or new onset of atrial flutter or atrial tachycardia between 91 days and 365 days post index procedure: Repeat procedure Cardioversion Prescribed a higher dose of any AAD* documented at baseline Prescribed a new AAD* not documented at baseline *AADs for endpoint will consist of all Class I/III and Class II/IV medications taken for control of AF/AT/AFL recurrence Tertiary Endpoint: Chronic Effectiveness: Evaluation of chronic recurrence at 24 months and 36 months. Center Experience: Outcomes in centers performing five or more procedures using the Blazer OI catheter during the ZERO AF IDE study will be compared to all other centers in the study using descriptive statistics. Safety: Reportable Adverse Events rates at 12, 24 and 36 months. Reportable events include: All Serious Adverse Events All Study Procedure-Related Adverse Events All Study Device-Related Adverse Events All Study Device Deficiencies Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects previously not defined in the Directions For Use. Effectiveness: Acute Procedural Success Rate
Follow-up Visits and Length of Follow-up	The patients in De Novo cohort will be followed for 3 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	414
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	102 withdrawals. 84.1% with complete primary safety endpoint data at 12 months, 87.5% with complete primary effectiveness endpoint data at 12 months.
Final Safety Findings	A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown). No new concerns.
Final Effect Findings	There have been 23 device deficiencies overall, of which only 5 are new since the 48-month report. Acute procedural success is defined as pulmonary vein isolation achieved with a Boston Scientific OI ablation catheter as demonstrated by map-based entrance block with exit block and other maneuvers (such as adenosine testing) at the discretion of the physician. The acute procedural success rate was 97.13%. Eleven (11) subjects had acute procedural failures. Of these acute failures, 3 used a non-Boston Scientific catheter at index procedure to ablation the pulmonary veins, 7 did not have documented evidence of entrance/exit block for all clinically relevant PVs, and one did not ablate all clinically relevant PVs. The observed event-free rate at 12 months follow-up was 96.4% with a one-sided 95% confidence limit of 94.0%. The lower confidence limit is greater than the performance goal of 86%, resulting in a rejection of the null hypothesis and the primary safety endpoint is met. Ten (10) of the 276 subjects in the primary safety endpoint analysis experienced a safety event prior to the 12-month follow-up. A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown).
Study Strengths & Weaknesses	The sponsor requested early termination of the INTERRUPT (Zero) AF PAS, the INTERRUPT AF PAS, and the DirectSense RF Substudy due to challenges with enrollment, site fatigue, patient burden, and other factors. Based on the completion of study enrollment and additional data from literature, registries, and adverse event reporting, the FDA review team agreed to the early termination.
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P150005 S035/ PAS001
Date Original Protocol Accepted	11/01/2018
Date Current Protocol Accepted	03/25/2024
Study Name	INTERRUPT AF PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The INTERRUPT AF study is a global, prospective, non-randomized, multicenter study, to assess acute and long-term outcomes for the Rhythmia Mapping System in conjunction with the Blazer and IntellaNav Open-Irrigated Ablation Catheters to treat Paroxysmal Atrial Fibrillation for de novo cases.
Study Population	The study will enroll patients with symptomatic drug-refractory paroxysmal atrial fibrillation undergoing AF ablation.
Sample Size	The sample size of 415 subjects’ enrollment at 25-50 centers worldwide will ensure the minimum of 329 treatment subjects in the study. The calculation of sample size is driven by hypothesis. The sample size required to assess the Primary Safety Endpoint hypothesis was 329. The assumptions for the sample size calculation were an expected primary safety endpoint event-free rate at one year of 90%, a performance goal of 85%, an alpha of 0.05, 80% power, and an expected attrition (per year) of 7.5%. The performance goal of 85% is based on the Primary Safety Endpoint results from the ZERO-AF clinical study data (G120082).
Key Study Endpoints	The primary safety endpoint will be evaluated by the primary safety event-free rate at 12 months post-procedure. Primary safety events will consist of a composite of acute primary safety events (events occurring within seven days post-procedure or hospital discharge, whichever is later), and chronic primary safety events (events occurring through 3 months or 12 months post-procedure). Acute primary safety events will be defined as the following: • Death • Myocardial infarction (MI) Vagal Nerve Injury/Gastroparesis • Transient ischemic attack (TIA) • Stroke/Cerebrovascular accident (CVA) • Thromboembolism • Pericarditis • Cardiac tamponade/perforation • Pneumothorax • Vascular access complications • Pulmonary edema/heart failure • AV block Chronic primary safety events will be defined as the following: • Atrial esophageal fistula (occurring through 3 months) • Pericardial effusion (ocurring through 3 months) • Pulmonary vein stenosis (symptomatic and requiring intervention) (occurring through 12 months) Primary effectiveness events will be defined as the following: • Acute procedural failure • More than one repeat procedure during the blanking period (90 days post index procedure) • Documented atrial fibrillation, or new onset of atrial flutter or atrial tachycardia event (= 30 seconds in duration from an event monitor or Holter Monitor, or from a 10 second 12-lead EKG) between 91 days and 365 days post index procedure • Any of the following interventions for atrial fibrillation, or new onset of atrial flutter or atrial tachycardia between 91 days and 365 days post index procedure: • Repeat procedure • Cardioversion • Prescribed any anti-arrhythmic drugs* (AAD*) *AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken for control of AF/AT/AFL recurrence The objective of the secondary effectiveness endpoint is that the secondary effectiveness event-free rate at 12 months post-procedure in each cohort is greater than the specified performance goal 50% for De Novo Cohort. Secondary effectiveness events will be defined as the following: Acute procedural failure • More than one repeat procedure during the blanking period (90 days post index procedure) • Documented symptomatic atrial fibrillation, or new onset of atrial flutter or atrial tachycardia event (= 30 seconds in duration from an event monitor or Holter, or from a 10 second 12-lead EKG) between 91 days and 365 days post index procedure • Any of the following interventions for atrial fibrillation, or new onset of atrial flutter or atrial tachycardia between 91 days and 365 days post index procedure: • Repeat procedure • Cardioversion • Prescribed a higher dose of any AAD* documented at baseline • Prescribed a new AAD* not documented at baseline *AADs for endpoint will consist of all Class I/III and Class II/IV medications taken for control of AF/AT/AFL recurrence Tertiary Endpoint: • • Chronic Effectiveness: Evaluation of chronic recurrence at 24 months and 36 months. • • Center Experience: Outcomes in centers performing five or more procedures using the Blazer OI catheter during the ZERO AF IDE study will be compared to all other centers in the study using descriptive statistics. • Safety: Reportable Adverse Events rates at 12, 24 and 36 months. o All Serious Adverse Events o All Study Procedure-Related Adverse Events o All Study Device-Related Adverse Events o All Study Device Deficiencies o Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects o previously not defined in the Directions For Use. Reportable events include: • Effectiveness: Acute Procedural Success Rate
Follow-up Visits and Length of Follow-up	The patients in De Novo cohort will be followed for 3 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	414
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	102 withdrawals. 84.1% with complete primary safety endpoint data at 12 months, 87.5% with complete primary effectiveness endpoint data at 12 months.
Final Safety Findings	A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown). No new concerns.
Final Effect Findings	There have been 23 device deficiencies overall, of which only 5 are new since the 48-month report. Acute procedural success is defined as pulmonary vein isolation achieved with a Boston Scientific OI ablation catheter as demonstrated by map-based entrance block with exit block and other maneuvers (such as adenosine testing) at the discretion of the physician. The acute procedural success rate was 97.13%. Eleven (11) subjects had acute procedural failures. Of these acute failures, 3 used a non-Boston Scientific catheter at index procedure to ablation the pulmonary veins, 7 did not have documented evidence of entrance/exit block for all clinically relevant PVs, and one did not ablate all clinically relevant PVs. The observed event-free rate at 12 months follow-up was 96.4% with a one-sided 95% confidence limit of 94.0%. The lower confidence limit is greater than the performance goal of 86%, resulting in a rejection of the null hypothesis and the primary safety endpoint is met. Ten (10) of the 276 subjects in the primary safety endpoint analysis experienced a safety event prior to the 12-month follow-up. A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown).
Study Strengths & Weaknesses	The sponsor requested early termination of the INTERRUPT (Zero) AF PAS, the INTERRUPT AF PAS, and the DirectSense RF Substudy due to challenges with enrollment, site fatigue, patient burden, and other factors. Based on the completion of study enrollment and additional data from literature, registries, and adverse event reporting, the FDA review team agreed to the early termination.
Recommendations for Labeling Changes	N/A
General
Study Status	Terminated
Application Number / Requirement Number	P180010 / PAS001
Date Original Protocol Accepted	11/01/2018
Date Current Protocol Accepted
Study Name	SCAFFOLD Continued f/u study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multicenter, single-arm, prospective study comparing the GORE® Carotid Stent to a performance goal developed from carotid endarterectomy (CEA) outcomes
Study Population	Continued follow-up of IDE cohort
Sample Size	290 remaining IDE subjects, active at the end of the 1-year evaluation
Key Study Endpoints	1-year MAE rate compared to PG
Follow-up Visits and Length of Follow-up	3 years post-procedure
General
Study Status	Completed
Application Number / Requirement Number	P150005 S049/ PAS001
Date Original Protocol Accepted	05/29/2020
Date Current Protocol Accepted	03/25/2024
Study Name	DirectSense RF Sub-study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the DirectSense RF sub-study is to collect data to support the use and labeling for the new DIRECTSENSE™ RF feature used with IntellaNav MiFi Open Irrigated Ablation Catheters to treat Paroxysmal Atrial Fibrillation.
Study Population	The sub-study will enroll patients from the INTERRUPT AF PAS who are treated using the DirectSense RF feature during the cardiac ablation procedure.
Sample Size	156 subjects treated with DirectSense RF from INTERRUPT AF PAS will be included in the DirectSense RF sub-study.
Key Study Endpoints	Safety: The primary safety endpoint is defined as the safety event-free rate at 12 months post-procedure. Effectiveness: The primary effectiveness endpoint is defined as the event-free rate at 12 months post-procedure
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	414
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	102 withdrawals. 84.1% with complete primary safety endpoint data at 12 months, 87.5% with complete primary effectiveness endpoint data at 12 months.
Final Safety Findings	A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown). No new concerns.
Final Effect Findings	There have been 23 device deficiencies overall, of which only 5 are new since the 48-month report. Acute procedural success is defined as pulmonary vein isolation achieved with a Boston Scientific OI ablation catheter as demonstrated by map-based entrance block with exit block and other maneuvers (such as adenosine testing) at the discretion of the physician. The acute procedural success rate was 97.13%. Eleven (11) subjects had acute procedural failures. Of these acute failures, 3 used a non-Boston Scientific catheter at index procedure to ablation the pulmonary veins, 7 did not have documented evidence of entrance/exit block for all clinically relevant PVs, and one did not ablate all clinically relevant PVs. The observed event-free rate at 12 months follow-up was 96.4% with a one-sided 95% confidence limit of 94.0%. The lower confidence limit is greater than the performance goal of 86%, resulting in a rejection of the null hypothesis and the primary safety endpoint is met. Ten (10) of the 276 subjects in the primary safety endpoint analysis experienced a safety event prior to the 12-month follow-up. A total of 294 events have been reported overall, of which 54 are new since the 48-month report. There have been no unanticipated events. 20 complications were EP related. 5 deaths have been reported (1 arrhythmic, 3 noncardiac and 1 unknown).
Study Strengths & Weaknesses	The sponsor requested early termination of the INTERRUPT (Zero) AF PAS, the INTERRUPT AF PAS, and the DirectSense RF Substudy due to challenges with enrollment, site fatigue, patient burden, and other factors. Based on the completion of study enrollment and additional data from literature, registries, and adverse event reporting, the FDA review team agreed to the early termination.
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P150003 S055/ PAS001
Date Original Protocol Accepted	05/28/2020
Date Current Protocol Accepted
Study Name	SYNERGY PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To assess the FDA requirement for safety and effectiveness of the SYNERGY 48 mm Coronary Stent System for the treatment of subjects with atherosclerotic lesion(s) > 34 mm and less than or equal to 44 mm in length (by visual estimate) in native coronary arteries greater than or equal to 2.5 mm to less than or equal to 4.0 mm in diameter (by visual estimate).
Study Population	patients, including those with diabetes mellitus, with symptomatic heart disease, stable angina, unstable angina, non-ST elevation MI or documented silent ischemia due to atherosclerotic lesions in native coronary arteries from 2.50 - 4.00mm (nominal) in diameter, and > 34 mm and less than or equal to 44 mm lesion lengths
Sample Size	100
Key Study Endpoints	The primary endpoint is the 12-month Target Lesion Failure (TLF) rate, defined as any ischemia-driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave and non–Q-wave) related to the target vessel, or cardiac death.
Follow-up Visits and Length of Follow-up	1 year follow-up
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	10
Patient Follow-up Rate	1 year
Final Safety Findings	Two patients had a MI that was related to the target vessel None of the patients experienced a definite or probable ST through 12 months
Final Effect Findings	The trial primary endpoint was met: the rate of 12-month TLF was 4.1% in both the ITT and per-protocol population (one-sided 95% upper confidence bound of 9.1%), which was significantly less than the performance goal of 19.5% (P<0.0001) There was a total of 5 deaths at 12-months and 1 of these was cardiac-related The rates of technical and clinical procedural success were 100.0%
Study Strengths & Weaknesses	Single arm trial with a limited sample size for confirmatory analysis.
Recommendations for Labeling Changes	none
General
Study Status	Completed
Application Number / Requirement Number	P150012 / PAS001
Study Name	INGEVITY and SAMURAI
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Two studies (INGEVITY and SAMURAI) have been conducted by Boston Scientific to fulfill the pre-market requirement of the INGEVITY family of leads and ImageReady MRI Conditional Pacing System (IPGs). All study visits through 12 months have already been completed for the pre-market study report. Patients in both studies will be continually followed for 60 months to fulfill the post-market requirements. INGEVITY Study The INGEVITY Lead Clinical Study was a prospective, multi-center, global, nonrandomized clinical study conducted to establish the safety, performance and effectiveness of theINGEVITY non-MRI Active and Passive Fixation Pace/ Sense Leads. A total of 1599 leads implanted in 1036 patients that were used for premarket endpoint analyses will be continually followed to achieve the minimum number of leads evaluable at 60 months. All patients have been consented for five years. Study procedures or clinic visits will occur every six (6) months following implant through the final 60 month visit. SAMURAI Study The SAMURAI Clinical Study was a prospective, multi-center, global, open-label, two-group (MRI arm and Control arm) randomized clinical study conducted to establish the safety, performance and effectiveness of the ImageReady MRI Conditional Pacing System when used in the MRI environment under the labeled Conditions of Use. A total of 351 patients from both arms implanted with an ImageReady system that were used for premarket endpoint analyses will be continually followed to achieve the minimum number of IPS system evaluable at 60 months. All patients have been consented for five years.
Study Population	Subjects who were enrolled in INGEVITY study and SAMURAI study will be continually followed to achieve the proposed minimum number of leads/IPGs at 60 months. All patients have been consented for five years. There is no new enrollment proposed.
Sample Size	Between the INGEVITY and SAMURAI studies, Boston Scientific has implanted or attempted 2264 INGEVITY leads across 118 sites with over 50% of the leads from the US. Each of these 2264 leads will be followed for five years, minus attrition due to patient death and withdrawal and leads taken out of service. Based on an annual attrition rate of 6.3% (observed through early 2015), the 5 year attrition rate is expected to be 27.8%. This estimated 5 year attrition rate was then used to project that approximately 1634 INGEVITY leads will complete 5 years of follow-up. A minimum sample size of 245 leads is required to evaluate the INGEVITY Lead Post-Approval Safety Endpoint. This sample size was calculated via Monte Carlo simulations employing Kaplan-Meier methodology, using SAS version 9.3 with the following assumptions: Expected performance = 97.5% Performance goal = 92.5% Expected attrition/missing data = 27.8% (based on 6.3% annual attrition observed in the INGEVITY and SAMURAI studies) One-sided significance level = 5% Power = 95% A sample size of 171 MR Scans is required to evaluate the ImageReady MR Conditional Pacing System Safety Endpoint. This sample size was calculated using the normal approximation to the binomial and confirmed via Monte Carlo simulations employing Kaplan-Meier methodology, using SAS version 9.3 with the following assumptions: ? Performance goal = 95% ? Expected MR Scan-related CFR rate between MR Scan and 1 month post-scan =99% ? One-sided significance level = 5% ? Power = 95% To fulfill FDA post-approval requirements, there will be 75 patients with multiple MRI scans during the course of the five year follow-up.
Key Study Endpoints	Primary Outcome Measures: INGEVITY Lead Post-Approval Safety Endpoint: Lead-related Complication-Free Rate from 1 to 60 Months ImageReady MRI Conditional Pacing System Post-Approval Safety Endpoint: MR Scan-Related Complication-Free Rate between MR Scan and 1 Month following MR Scan Additional data includes, but is not limited to, adverse events, deaths, device deficiencies, protocol deviations, lead measurements and study visit compliance. Impacts of Multiple MRI Scans on MRI Scan-related Complications and Pacing Thresholds and Sensed Amplitudes.
Follow-up Visits and Length of Follow-up	60 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	The INGEVITY study enrolled 1060 subjects and the SAMURAI study enrolled 363 subjects
Actual Number of Sites Enrolled	77 sites for the INGEVITY Study and 41 sites for the SAMURAI Study
Patient Follow-up Rate	A total of 1417 leads achieved five years of follow-up, satisfying the requirement of following 1000 leads to five years. The sponsor states that the 60-month lead related complication free rate was 98.7% with a lower confidence limit of 98.3% for the INGEVITY Lead Safety Endpoint of Lead-Related Complication Free Rate from 1 to 60 months.
Final Safety Findings	The sponsor also states that there were 342 MR scans, and none have resulted in an MR related complication within 31 days post MR scan for the INGEVITY Lead Safety Endpoint of MR Scan-Related Complication-Free Rate.
Study Strengths & Weaknesses	Overall the results of this study show that there is no concern that the lead may fail its long-term performance endpoint and that there is no concern that the system may fail that endpoint.
Recommendations for Labeling Changes	FDA recommends that the sponsor update the labeling for these devices to reflect the long-term data from the Post Approval Study.
General
Study Status	Completed
Application Number / Requirement Number	P950039 S026/ PAS001
Study Name	ThinPrep 5000-Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of this study is to evaluate the performance of the TP-5000 processors in detection of ASC-H+ and HSIL+ disease in a clinical use setting compared to the detection of ASC-H+ and HSIL+ disease in the same clinical setting using the TP-2000 processors. This evaluation will be performed at multiple sites. A secondary objective is to compare the prospective and retrospective percent biopsy confirmed rate for all ASC-H+ and HSIL+ diagnosis. This evaluation will be performed at least one site.
Study Population	The study population is the entire routine screening population of the selected sites.
Sample Size	Sample size will be determined by the selection of clinical laboratories included in the study and duration of the study. There will be at least five (5) clinical laboratories participating in this study.
Key Study Endpoints	Data from all cytologic results for all patients screened during the study specific time period, which will be converted into prevalence rates for study reporting.
Follow-up Visits and Length of Follow-up	24 months Disease prevalence rates will be collected and reported on a quarterly basis.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Not applicable. This is a prevalence rate study and there are no study subjects.
Actual Number of Sites Enrolled	Five (5)
Patient Follow-up Rate	Not applicable. This is a prevalence rate study and there are no study subjects.
Final Safety Findings	The Post-Approval Study confirms the safety of the ThinPrep 5000 Processor for the same clinical use as the ThinPrep 2000 Processor.
Final Effect Findings	The Post-Approval Study confirms the effectiveness of the ThinPrep 5000 Processor for the same clinical use as the ThinPrep 2000 processor.
Study Strengths & Weaknesses	Study Strength: The study is a Multi-Center study of prospective data of cytological specimens prepared with the ThinPrep 5000 Processor and retrospective data of cytologic specimens prepared with the ThinPrep 2000 Processor. No clinical or laboratory workflow was impacted by the study. Study Weakness: The study duration (31 ½ months from site selection to final report) is the only weakness identified.
Recommendations for Labeling Changes	No labeling changes are recommended.
General
Study Status	Completed
Application Number / Requirement Number	P150017 / PAS001
Study Name	MOTION Extend Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Evaluate and confirm long-term the established safety and effectiveness of the Cartiva SCI implant.
Study Population	Subjects treated with Cartiva SCI in the PMA study.
Sample Size	All sites which enrolled subjects in the MOTION study will be invited to participate in the PAS, and all subjects at the participating sites and who meet the above inclusion/exclusion criteria will be invited to enroll in the PAS. This includes 135 Cartiva subjects (119 randomized and 16 roll-in) eligible for study participation. Assuming a 15% lost to follow-up rate, it’s estimated that 115 subjects will have 5-year device status determined. A one group ¿2 test with a 0.05 one-sided significance level will have 80% power to detect the difference between the Null hypothesis proportion, ¿0 + ¿, of 0.235 and the Alternative proportion, ¿A, of 0.142 when the sample size is 115.
Key Study Endpoints	The primary endpoint will evaluate the long-term safety of the Cartiva implant by demonstrating the following: 1. Durability of the implant over the longer term. This will be addressed using survival analysis starting at Month 24 to determine the rate of implant removals among devices that survived to Month 24. A complementary survival analysis starting at index surgery to end of study will also be performed. 2. There are no unanticipated safety concerns that arise after Month 24 up to 5 years. This will be addressed by a) determining the incidence of serious device-related adverse events per year and overall from Month 24 to Year 5; and b) summarizing device-related radiographic complications1 over time from Month 24 to Year 5. Note that this analysis will address both device and procedure related complications and serious device-related adverse events whether observed previously in the MOTION study or novel. Secondary 1) Evaluation of maintenance of range of motion 2) Wear characteristics or device degradation for any Cartiva implant removed 3) Pain and function over time (VAS, FAAM ADL and Sports) 4) Evaluation of radiographic findings (radiolucency, bony reactions, and heterotopic ossification) looking at presence or progression from 24 months to 5+ years as well as correlation with the 5+ years clinical outcomes (effectiveness and safety).
Follow-up Visits and Length of Follow-up	Each patient will be asked to return for clinical and radiographic evaluations at 5 years post-operative. If a subject, is already past their 5-year visit window, the subject’s 5+ year visit will be used for the 5-year time point. The follow-up window is 4 years and 8 months, or later from surgery. If a subject is unwilling to return to clinic but can provide the status of their implant that information will be included and used for the analysis of the primary endpoint which is survivorship of the implant. The subject will also be asked to complete the subject assessments (VAS and FAAM).
Interim or Final Data Summary
Actual Number of Patients Enrolled	112
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	At 60+ months, the follow-up rate for device survivorship was 88.8%, the follow-up rate for clinical assessment was 84.8%, and the follow-up rate for radiographic assessment was 77.6%.
Final Safety Findings	Primary Endpoint: Cumulative device removal rate from 2-5 years: 7.6% (9/119, 90% CI (0.0%, 11.28%)). This rate was non-inferior (margin 0.10) to the expected removal rate (13.5%) in the 2-5 year period estimated based on the 24 month data. No unanticipated safety concerns arose after Month 24 up to 5 years.
Final Effect Findings	Secondary Endpoint: Evaluation of maintenance of range of motion: At 5 years, mean active MTP dorsiflexion scores maintained an improvement compared to baseline and compared to the arthrodesis comparator group. Secondary Endpoint: Pain and function over time (VAS, FAAM ADL and Sports): Maintenance of improvement from baseline between 2-5 years.
Study Strengths & Weaknesses	This study met its performance goal and had adequate follow-up rates and sample size.
Recommendations for Labeling Changes	A labeling change is recommended to add a summary of the post-approval study results. The updated label will reflect the long-term (5 years) postmarket performance of the device.
General
Study Status	Completed
Application Number / Requirement Number	P150023 / PAS001
Study Name	ABSORB IV Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective Evaluate the safety of the use of Absorb in a real-world setting following commercial physician training Observe the effectiveness of commercial physician training on appropriate vessel sizing in the use of Absorb in a real-world setting Study Design Prospective, open-label, multi-center, single-arm, non-randomized trial designed to observe Absorb continued safety during commercial use in real world settings.
Study Population	Full Analysis Set (FAS): All subjects registered in the study. Absorb Only Population (AOP): Subjects who have had only Absorb study devices implanted. Pooled Absorb Population (PAP): Subjects from the ABSORB Post-Approval Clinical Study and ABSORB IV trial. The ABSORB PAS is projected to enroll approximately 75% ABSORB IV-like subjects (approximately N=1500), this will be pooled with approximately N=1500 Absorb subjects from the ABSORB IV trial.
Sample Size	Approximate 2000 subjects total
Key Study Endpoints	Primary Endpoint The powered primary endpoint of the ABSORB Post-Approval Study trial is the composite of cardiac death and myocardial infarction (CD/MI) at 1 year. MI is adjudicated per the Universal MI definition. Major Secondary Endpoint The major secondary endpoint is definite/probable scaffold thrombosis (per ARC definition) at 1 year. Other Endpoints: Commercial Training Assessment Endpoint (Angiographic Subgroup only) Percentage of very small vessels* Clinical Endpoints – evaluated in hospital and at each follow-up time point Component and Other Clinical Endpoints Death (Cardiac, Non-Cardiac) All Myocardial Infarction (All MI) Target Lesion Revascularization (TLR) Ischemia Driven TLR (ID-TLR) Target Vessel Revascularization (TVR) All coronary revascularization Scaffold thrombosis (per ARC definition) Composite Endpoints Death/All MI Cardiac Death/All MI Cardiac Death/All MI/TVR (Target Vessel Failure, TVF) Cardiac Death/TV MI/ID-TLR (TLF) Death/All MI/All revascularization
Interim or Final Data Summary
Actual Number of Patients Enrolled	2604
Actual Number of Sites Enrolled	147
Patient Follow-up Rate	85.9%
Final Safety Findings	The ABSORB IV trial met its primary endpoint of non-inferiority of Absorb BVS compared to XIENCE in target lesion failure (TLF) at 30 days, with rates of 5.0% in the Absorb BVS arm and 3.7% in the XIENCE arm (non-inferiority p-value = 0.0244) in the Intent-To-Treat population. A pre-specified secondary analysis showed that the primary endpoint was also met in the As-Treated population, where 30-day TLF rates were 4.6% and 3.7% for Absorb BVS and XIENCE, respectively, with a non-inferiority At 5-years post-procedure, the rates of hierarchical composite adjudicated endpoints DMR (All Death, All MI, All Revascularization), TVF (Target Vessel Failure), MACE (Major Adverse Cardiac Event), and TLF (Target Lesion Failure) were 26.1%, 22.0%, 19.6%, and 18.2% for the Absorb BVS arm, respectively, and 23.7%, 20.0%, 17.3% and 15.0% for the XIENCE arm, respectively. Of the above mentioned hierarchical composite endpoints, results showed that TLF was statistically significant in the Absorb BVS arm compared to the XIENCE arm through 5 years, while DMR, TVF, and MACE were not statistically significant between study arms through 5 years.
Final Effect Findings	Results of the landmark analyses for 0-3 years and 3-5 years, and 0-4 years and 4-5 years reinforce the difference in event rates for TLF, ST, TV-MI, and ID-TLR between Absorb BVS and XIENCE arms during the earlier stages of follow-up up to 3 years. Importantly, these event rates began to steadily decline after 3 years and eventually flattened out for the Absorb arm. Between 4 and 5 years, all event rates (TLF, ST, TV-MI and ID-TLR) were numerically lower for Absorb BVS, compared to the XIENCE arm. The trend of the results in the Absorb BVS arm after 3 years, such as a lower rate of events including TLF, and scaffold thrombosis compared to that in subjects with XIENCE is consistent with the expectation that no permanent implant is left in the artery around that time period after Absorb BVS treatment.
Study Strengths & Weaknesses	This was a randomized, controlled trial that met its primary endpoint. However, the trial demographics were not diverse with respect to race and sez, with a large percent of the subjects being White and/or male.
Recommendations for Labeling Changes	This device is no longer marketed by the company; therefore, a labeling change was not recommended.
General
Study Status	Terminated
Application Number / Requirement Number	P150023 / PAS002
Date Original Protocol Accepted	10/10/2017
Date Current Protocol Accepted
Study Name	ABSORB USA Post Approval Clinical Study
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P150024 / PAS001
Study Name	PATHWAY Clinical Trial PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohorts
Study Population	Subjects who are active participants in the PATHWAY pivotal trial under G120045
Sample Size	46 subjects are currently enrolled in the study
Key Study Endpoints	n/a
Follow-up Visits and Length of Follow-up	2 years post device explant Bi-monthly for six months and at one and two years
Interim or Final Data Summary
Actual Number of Patients Enrolled	31 patients
Actual Number of Sites Enrolled	7 sites
Patient Follow-up Rate	Year 3 - 73%, year 4 - 50%, year 5 - 33%
Final Safety Findings	11 adverse events in 11 patients were reported during the postapproval study (10 device related, and 1 procedure related. Four of these 11 adverse events were “Persistent fistula.” Only one serious adverse event classified as “A-Tube dislodgement” was reported. There were not eating disorders reported during the post approval study.
Final Effect Findings	The efficacy of the device while implanted was assessed by percent excess weight loss (%EWL) and total body loss (%TBL). Other efficacy study endpoints while the device was implanted included the change in obesity-related comorbidities (blood pressure, lipid levels, triglycerides, Hemoglobin A1c or HbA1c) and change in medications. %EWL: The results ranged from 44.7% on the third year of follow-up, 50.8% in the fourth year and 64.8% in the fifth or last year. %EWL Post-Explant: The results ranged from 24.0% at 2-months of follow-up, 27.1% at 4-months, 20.0% at 6-months, 9.8% at 1-year and 4.5% at 2 years post-explant. %TBL: The results ranged from 16.6% on the third year of follow-up, 18.7% in the fourth year and 24.3% in the fifth or last year. %TBL Post-explant: The results ranged from 8.9% at 2-months of follow-up, 9.8% at 4-months, 7.2% at 6- months, 3.5% at 1-year and 1.3% at 2 years post-explant. Co-morbidities: SBP: The average systolic blood pressure decreased from 124.4 (mmHg) on the third year of follow-up, 116.3 in the fourth year and 117.8 in the fifth or last year. DBP: The average diastolic blood pressure slightly decreased from 77.6 (mmHg) on the third year of follow-up, 77.0 in the fourth year and 73.7 in the fifth or last year. HbA1c: This laboratory measurement was only reported from one patient for years 3 and 4 of the follow-up, being 5.6 for the third year and 5.4 for the fourth year. Quality of Life (IWQOL): Seven patients completed the first-year and three completed the second-year post-explant follow-up milestones. When compiled, the standardized average quality of life scores at year 1 and 2 post-explant improved from baseline by about 19%. Eating Disorders (EDE): Seven patients completed the 1-year post-explant follow-up milestone to date, and three completed the 2-year post explant follow-up. Testing showed no signs of eating disorders.
Study Strengths & Weaknesses	Strength: long follow-up. Weaknesses: small sample size, low follow-up rate, and there is no comparator group.
Recommendations for Labeling Changes	Yes, the results of the post-approval study should be included.
General
Study Status	Terminated
Application Number / Requirement Number	P150024 / PAS002
Date Original Protocol Accepted	12/15/2016
Date Current Protocol Accepted	01/15/2019
Study Name	AspireAssist Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective new enrollment registry study of subjects implanted with the A-Tube, participating in AspireAssist therapy who provide consent to participate in the study.
Study Population	Inclusion Criteria: 1. Subjects eligible for AspireAssist: -Measured BMI of 35.0-55.0 kg/m2 at the time of screening -22 years of age at time of screening 2. Subjects willing to comply with follow-up evaluations for 5 years post-implant, 2 years post explant if therapy is ended within 5 years, and provide written informed consent Exclusion Criteria: 1. Subjects currently enrolled in the Aspire PATHWAY clinical study 2. Subjects currently participating in another weight loss therapy 3. Subjects contraindicated for AspireAssist: -Previous abdominal surgery that significantly increases the medical risks of gastronomy tube placement -Esophageal stricture, pseudo-obstruction, severe gastroparesis or gastric outlet obstruction, inflammatory bowel disease -History of refractory gastric ulcers -Ulcers, bleeding lesions, or tumors discovered during endoscopic examination -Uncontrolled hypertension (blood pressure>160/100) -History or evidence of serious pulmonary or cardiovascular disease, including acute coronary syndrome, heart failure requiringmedications, or NYHA class III or IV heart failure. -Coagulation disorders -Anemia -Pregnant or lactating -Diagnosed bulimia or diagnosed binge eating disorder (using DSM criteria) -Night Eating Syndrome -Chronic abdominal pain that would potentially complicate the management of the device -Physical or mental disability, or psychological illness that could interfere with compliance with the therapy -At high risk of having a medical complication from the endoscopic procedure or the AspireAssist weight loss program for any reason including poor general health or severe organ dysfunction such as cirrhosis or renal dysfunction
Sample Size	Consecutive patients receiving the device will be invited to participate in the PAS. A total of 323 subjects implanted with the A-Tube per device labeling will be enrolled, at 15 sites. Each site will enroll between 10 (minimum) and 50 (maximum) subjects. With an estimated attrition rate of 20%, 259 subjects should complete the 5 years of follow-up, and will provide 80% power to reject the null hypothesis, assuming the serious adverse event rate is the same as in previous studies (3%).
Key Study Endpoints	Primary Safety Endpoint: -5 year rate of Serious Adverse Events (SAEs), defined as any Adverse Event (AE) that is fatal, immediately life- threatening, requires inpatient hospital admission for more than 24 hours due to a device or therapy-related SAE, causes permanent or significant disability, or requires medical or surgical intervention to prevent permanent sequelae. All AEs will be adjudicated by a Safety Adjudication Committee (SAC). Secondary Effectiveness Endpoints: -Compliance with appropriate use of AspireAssist system: Weight loss, % Excess Weight Loss (EWL), and % Total Body Loss (TBL), and connector counts will be assessed. Excess weight will be determined from ideal body weights based on a BMI = 25kg/m2 -Percentage of patients achieving a 25% EWL -Percentage of patients who have a positive or negative change in medications related to comorbidities (hypertension, diabetes, and dyslipidemia) Secondary Safety Endpoints: -Percentage of patients with AEs related to eating disorders -Five-year rate of incidence, duration and severity of AEs related to stoma issues including infection (bacterial or fungal) and granulation tissue
Follow-up Visits and Length of Follow-up	Follow up of implanted subjects will be 5 years, and any explanted patients will be followed for an additional 2 years from the time of explant.
Interim or Final Data Summary
Actual Number of Patients Enrolled	17 (5%) enrolled patients out of 323 planned
Actual Number of Sites Enrolled	6 sites out of 15 planned
Patient Follow-up Rate	47% (8/17) for a 3.4 person-years of follow-up. No patient was followed for the required 5-year period (three patients were followed for 4.1 years, one 3.8, one 3.5, one 3.0, one 2.8, and one 1.8 years)
Study Strengths & Weaknesses	Weaknesses: The study was terminated early due to withdrawal of the PMA on April 15, 2022. Results cannot be interpreted in relation to the study plan due to low enrollment. Strengths: None
Recommendations for Labeling Changes	No labeling is necessary because the sponsor withdrew the PMA on 04/15/22, and as a result the PAS was terminated early on April 15, 2022, due to challenging enrollment
General
Study Status	Completed
Application Number / Requirement Number	P150012 S083/ PAS001
Date Original Protocol Accepted	12/16/2019
Date Current Protocol Accepted	06/19/2020
Study Name	INGEVITY+ Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is it to confirm the safety and effectiveness of the INGEVITY+ Active Fixation Pace/Sense Lead. The INGEVITY+ Clinical Study is a prospective, non-randomized, multi-center, post-market study.
Study Population	This is a one-armed study where every subject is assigned to treatment, where treatment means implanted, or attempted implant of INGEVITY+ leads in the right atrium and ventricle.
Sample Size	At least 105 subjects will be enrolled in the study to achieve 200 implanted or attempted leads. The study will include approximately 20 sites in North America.
Key Study Endpoints	Primary Safety Endpoint: Lead-related complication-free rate from implant through 3-months post-implant Primary Effectiveness Endpoint: Pacing capture threshold at 3-months post-implant Secondary Effectiveness Endpoint: Sensed amplitude and pacing impedance at 3-months post-implant
Follow-up Visits and Length of Follow-up	The study duration for each subject is expected to be approximately 3 months. Subjects will be exited from the study after their 3 month visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	109
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	One hundred and ninety-eight (198) leads among one hundred (100) subjects have completed either the 3-month visit or 91 days of follow-up. One hundred and one (101) subjects have completed the 3-month follow-up visit.
Final Safety Findings	The lead-related complication-free rate from lead implant to 3 months for all leads was 98.5%, with a lower confidence limit of 95.4%.
Final Effect Findings	As of the date of the report snapshot, 98.9% of leads (184 of 186) have reported a pacing capture threshold less than or equal to 2V with a 0.4ms pulse width.
Study Strengths & Weaknesses	The safety endpoint through 3 months of follow-up was met. All effectiveness endpoints at 3 months of follow-up were met. The data confirms the safety and effectiveness of the INGEVITY+ lead.
Recommendations for Labeling Changes	no
General
Study Status	Progress Adequate
Application Number / Requirement Number	P150028 / PAS001
Date Original Protocol Accepted	03/25/2016
Date Current Protocol Accepted
Study Name	Continued f/u of Premarket Cohorts
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will include patients in the COAST, COAST II, COAST CAP and COAST II CAP studies who were presented as part of the PMA application dataset and alive. The objective of this study is to evaluate the long-term safety and effectiveness of the CP stents and Covered CP Stents through five years post-implant.
Study Population	This study will include patients in the COAST, COAST II, COAST CAP and COAST II CAP studies who were presented as part of the PMA application dataset and alive. COAST: The study was a prospective, multi-center, single-arm clinical study comparing stent treatment of native or recurrent aortic coarctation to a performance goal (PG) derived from surgical treatment. Surgical PGs are derived from retrospective data collection at selected participating centers and from the literature. COAST CAP: The COAST Continued Access Protocol was a prospective, multi-center, single-arm clinical study allowing continued access to the CP Stent during regulatory review of the pre-market application for the CP Stent COAST II: The study was a prospective, multi-center, single-arm clinical study that evaluates the Covered CP Stent for treatment of coarctation of the aorta. For effectiveness, each patient serves as his or her own control. For safety, a performance goal was derived from surgical literature. COAST II CAP: The COAST II Continued Access Protocol was a prospective, multi-center, single-arm clinical study allowing continued access to the Covered CP Stent during regulatory review of the pre-market application for the Covered CP Stent.
Sample Size	COAST: 112 safety cohort patients, 105 effectiveness cohort patients The trial will be considered a success if the hypotheses relating to all four primary outcomes are confirmed. Primary Safety: 1) Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. 2) Occurrence of post-procedure paradoxical hypertension. Primary Effectiveness: 1) Reduction in arm-leg systolic blood pressure gradient from pre-dilation to the 12 month post-dilation follow-up. 2) Length of stay in the hospital, measured in days. The following table from the COAST Protocol V4 displays the power calculations and assumptions associated with each primary outcome. COAST CAP: Total of 16 possible patients in safety and effectiveness cohorts. COAST II: 82 patients enrolled for safety cohort and effectiveness cohort The trial will be considered a success if the hypotheses relating to all primary outcomes are confirmed. Primary Safety: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Primary Effectiveness: 1) Improvement of aortic wall injury and/or aortic arch obstruction by a median increase of at least one grade from pre-implantation baseline to 12-month follow-up using the Severity of Illness Scale (based on upper extremity (UE) systolic BP, UE to lower extremity (LE) systolic BP, and aortic wall injury). 2) Aortic wall injury and aortic arch obstruction at Grade 4 or above at the 12-month follow-up, based on the Severity of Illness Scale, with no clinical worsening. The following table from the COAST II Protocol V2 displays the power calculations and assumptions associated with each primary outcome. COAST II CAP: Total of 45 possible patients in the safety and effectiveness cohorts.
Key Study Endpoints	COAST: Primary Safety Endpoint #1: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Primary Safety Endpoint #2: Occurrence of post-procedure paradoxical hypertension. Primary Effectiveness Endpoint #1: Reduction in arm-leg systolic blood pressure gradient from pre-dilation to the 12-month post-dilation follow-up. Primary Effectiveness Endpoint #2: Length of stay in the hospital, measured in days COAST CAP: The primary safety endpoints were the occurrence of device or implant related serious adverse events and the occurrence of post-procedure paradoxical hypertension. The primary effectiveness endpoints were reduction in arm-leg systolic blood pressure gradient and length of stay in the hospital. COAST II: Primary Safety Endpoint: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Secondary Safety Endpoint: Proportion of patients experiencing any of the following adverse events related to the device or implant procedure post 1 year Underlying cardiac or non-cardiac disease, aortic wall injury, new aortic aneurysm formation within region of device, stent misplacement, malposition, stent fracture, aortic wall aneurysms, or restenosis requiring reintervention. Primary Effectiveness Endpoint #1: Improvement of aortic wall injury and/or aortic arch obstruction by a median increase of at least one grade from pre-implantation baseline to 12-month follow-up using the Severity of Illness Scale (based on upper extremity (UE) systolic BP, UE to lower extremity (LE) systolic BP, and aortic wall injury). Primary Effectiveness Endpoint #2: Aortic wall injury and aortic arch obstruction at Grade 4 or above at the 12-month follow-up, based on the Severity of Illness Scale, with no clinical worsening. COAST II CAP: The primary safety endpoint was the occurrence of device- or procedure- related serious adverse events. The primary effectiveness endpoint was improvement of aortic wall injury and/or aortic arch obstruction. In addition, the FDA requested reporting of the following outcomes annually: Blood pressure outcomes: i. Percent of patients with: 1. Systolic blood pressure (SBP) arm-leg differences under 20, 15 and 10 mmHg; 2. Average arm leg SBP difference; and 3. Proportion of patients with hypertension. b. Aortic Wall Injury (AWI) Outcomes: i. Clinical summaries for any patient with new or progressive AWI requiring follow-up imaging, intervention or surgery (imaging performed on a clinical basis ? descriptive summary only); and ii. Overall incidence of patients detected with new or progressive AWI (using baseline sample size as denominator). c. Stent Fracture Outcomes: i. Any new or progressive stent fracture; ii. Total incidence of stent fracture for bare metal and covered stents (using baseline sample size as denominator); iii. Descriptive summaries for each stent fracture, including need for re-intervention or surgery; and iv. Total incidence and types of late sequelae (e.g., none, recoarctation, pseudoaneurysm, aortic perforation, etc.).
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Progress Adequate
Application Number / Requirement Number	P150028 / PAS002
Date Original Protocol Accepted	03/25/2016
Date Current Protocol Accepted
Study Name	Cont f/u of premarket cohorts w/stent fra
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study should include all currently enrolled and alive patients in the COAST and COAST II studies with stent fractures and COAST CAP and COAST II CAP studies with stent fractures who had completed 2-year follow-up at the time of PMA submission. The objective of this study is to evaluate the long-term safety and effectiveness of the CP Stents and Covered CP Stents in patients with stent fractures through ten years post-implant.
Study Population	This study should include all currently enrolled and alive patients in the COAST and COAST II studies with stent fractures and COAST CAP and COAST II CAP studies with stent fractures who had completed 2-year follow-up at the time of PMA submission.
Sample Size	The following describes each study from which the patients will be selected, based on the presence of stent fractures, as described in the Study Population section above: COAST: 112 safety cohort patients, 105 effectiveness cohort patients The trial will be considered a success if the hypotheses relating to all four primary outcomes are confirmed. Primary Safety: 1) Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. 2) Occurrence of post-procedure paradoxical hypertension. Primary Effectiveness: 1) Reduction in arm-leg systolic blood pressure gradient from pre-dilation to the 12 month post-dilation follow-up. 2) Length of stay in the hospital, measured in days. The following table from the COAST Protocol V4 displays the power calculations and assumptions associated with each primary outcome. COAST CAP: Total of 16 possible patients in safety and effectiveness cohorts. Only 8 patients completed 2 year follow-up at the time of the PMA submission. Two stent fractures were observed in the COAST CAP, representing 16.7% of the subjects. There was loss of structural integrity in one patient. These two patients would likely be included in the PAS. COAST II: 82 patients enrolled for safety cohort and effectiveness cohort The trial will be considered a success if the hypotheses relating to all primary outcomes are confirmed. Primary Safety: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Primary Effectiveness: 1) Improvement of aortic wall injury and/or aortic arch obstruction by a median increase of at least one grade from pre-implantation baseline to 12-month follow-up using the Severity of Illness Scale (based on upper extremity (UE) systolic BP, UE to lower extremity (LE) systolic BP, and aortic wall injury). 2) Aortic wall injury and aortic arch obstruction at Grade 4 or above at the 12-month follow-up, based on the Severity of Illness Scale, with no clinical worsening. The following table from the COAST II Protocol V2 displays the power calculations and assumptions associated with each primary outcome. COAST II CAP: Total of 45 possible patients in the safety and effectiveness cohorts. Only 16 patients completed 2-year follow-up at the time of the PMA submission. One stent fracture was observed in the COAST II CAP, which did not result in loss of structural integrity. This patient would likely be included in the PAS.
Key Study Endpoints	COAST: Primary Safety Endpoint #1: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Primary Safety Endpoint #2: Occurrence of post-procedure paradoxical hypertension. Primary Effectiveness Endpoint #1: Reduction in arm-leg systolic blood pressure gradient from pre-dilation to the 12-month post-dilation follow-up. Primary Effectiveness Endpoint #2: Length of stay in the hospital, measured in days COAST CAP: The primary safety endpoints were the occurrence of device or implant related serious adverse events and the occurrence of post-procedure paradoxical hypertension. The primary effectiveness endpoints were reduction in arm-leg systolic blood pressure gradient and length of stay in the hospital. COAST II: Primary Safety Endpoint: Occurrence of any serious or somewhat serious adverse event attributed to the stent or implantation procedure within 30 days of the catheterization procedure. Secondary Safety Endpoint: Proportion of patients experiencing any of the following adverse events related to the device or implant procedure post 1 year Underlying cardiac or non-cardiac disease, aortic wall injury, new aortic aneurysm formation within region of device, stent misplacement, malposition, stent fracture, aortic wall aneurysms, or restenosis requiring reintervention. Primary Effectiveness Endpoint #1: Improvement of aortic wall injury and/or aortic arch obstruction by a median increase of at least one grade from pre-implantation baseline to 12-month follow-up using the Severity of Illness Scale (based on upper extremity (UE) systolic BP, UE to lower extremity (LE) systolic BP, and aortic wall injury). Primary Effectiveness Endpoint #2: Aortic wall injury and aortic arch obstruction at Grade 4 or above at the 12-month follow-up, based on the Severity of Illness Scale, with no clinical worsening. COAST II CAP: The primary safety endpoint was the occurrence of device- or procedure- related serious adverse events. The primary effectiveness endpoint was improvement of aortic wall injury and/or aortic arch obstruction. In addition, the FDA requested reporting of the following outcomes annually: Blood pressure outcomes: i. Percent of patients with: 1. Systolic blood pressure (SBP) arm-leg differences under 20, 15 and 10 mmHg; 2. Average arm leg SBP difference; and 3. Proportion of patients with hypertension. b. Aortic Wall Injury (AWI) Outcomes: i. Clinical summaries for any patient with new or progressive AWI requiring follow-up imaging, intervention or surgery (imaging performed on a clinical basis ? descriptive summary only); and ii. Overall incidence of patients detected with new or progressive AWI (using baseline sample size as denominator). c. Stent Fracture Outcomes: i. Any new or progressive stent fracture; ii. Total incidence of stent fracture for bare metal and covered stents (using baseline sample size as denominator); iii. Descriptive summaries for each stent fracture, including need for re-intervention or surgery; and iv. Total incidence and types of late sequelae (e.g., none, recoarctation, pseudoaneurysm, aortic perforation, etc.).
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Completed
Application Number / Requirement Number	P150030 / PAS002
Date Original Protocol Accepted	10/17/2016
Date Current Protocol Accepted	01/19/2024
Study Name	Short to Mid-Term f/u of New US Patients
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective: The primary objective is to confirm that the safety and effectiveness of the R3 Biolox delta Ceramic Acetabular System in the US population is consistent with the effectiveness and safety profile shown in the European study (PMA cohort). Study Design: Prospective, multicenter, observational study
Study Population	The study population is comprised of US patients who receive the device in the post-market environment. The comparator group is comprised of patients in the European premarket cohort. Subject must meet all of the following inclusion criteria in order to be enrolled in this study.
Sample Size	Number of Subjects: 183 Assumptions for sample size estimation: The sample size calculation included assumption of an overall success rate of 86.4% at 3 years post surgery for the Biolox delta ceramic-on-ceramic (DOD) treatment group. The delta was equivalent to 8%. For a power of 80% and a one-sided type 1 error of 5%, 146 subjects are needed. The total sample size after adjustment for 20% lost to follow-up is 183 subjects. The sample size was calculated assuming use of an Exact Binomial test.
Key Study Endpoints	Primary Endpoint: Overall success at 3 years postoperative, defined as: • No component revision • Modified Harris Hip Score (mHHS) of at least 80 points, and • No radiographic failure defined as no radiolucencies greater than 2 mm in 50% or more in any of the cup or stem zones, no femoral or acetabular subsidence greater than or equal to 5 mm from baseline, and no acetabular cup inclination changes greater than 4 degrees from baseline when accompanied by a “mild”, “moderate”, “marked”, or “disabled” mHHS pain score. Secondary Endpoints: Clinical assessments of pain and function using the modified Harris Hip Score, radiographic findings and implant survivorship.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	189 hips (Female: 110, Male: 79)
Actual Number of Sites Enrolled	10 sites (US)
Patient Follow-up Rate	The 3-year follow-up rate for subjects with all primary and secondary endpoints data is 65.8% (121/184) (all patients who completed the study within and beyond the follow-up window were considered).
Final Safety Findings	A total of 123 (65%) hips had adverse event data by 3 years of follow-up. There were 4 deaths (2.1%) unrelated to the device or procedure. There were 7 device-related adverse events (AEs) in 5.7% (7/123) of hips. There were no unanticipated adverse device effects. The most frequently reported device-related AEs were hip squeaking/clicking/popping/snapping or other noise. There were 24 procedure-related adverse events (AEs) in 19.5% (24/123) of hips, and one (1) hip revision (0.5%) due to recurrent dislocation related to procedure but not related to device. The most frequently reported procedure-related AEs were bursitis, and muscular/connective tissue.
Final Effect Findings	Survivorship: At 3-years post-surgery, Kaplan-Meier implant survivorship is estimated as 99.4% (95% confidence interval: 96.1%- 99.9%). Functional Outcomes: At 3-years of follow up, 91.9% (114/124) of patients were reported to have ‘Excellent’ or ‘Good’ modified Harris Hip Score (mHHS) (score >80) and 4.8% (6/124) were reported to have ‘Poor’ mHHS (score 60-69). Radiographic Outcomes: At 3-years post-surgery, • Absence of radiolucencies greater than 2 mm in 50% or more of the cup or stem zones (100% for a total of 119 hips) • Absence of migration or subsidence of the cup or stem greater than or equal to 5 mm (100% for a total of 119 hips) • Absence of cup inclination changes greater than 4 degrees from baseline when accompanied by a “Mild”, “Moderate”, “Marked” or “Disabled” mHHS pain score (98.1% for a total of 108 hips)
Study Strengths & Weaknesses	Strengths: The US study was able to demonstrate short- to mid-term device safety and effectiveness through 3 years post-surgery. Overall study success was determinable for 113 subjects. 88.5% (100/113) of these subjects met clinical success at 3 years with a 95% confidence interval from 81.1 to 93.7%. Weaknesses: High loss to follow-up or missing study success data (e.g., radiographic, mHHS, and AEs) for 40.2% (76/189) of subjects at 3 years. Caution is advised in generalization of these results to broader US patients or practice.
Recommendations for Labeling Changes	Yes, a labeling change is recommended to update the device labeling with the final study results
General
Study Status	Ongoing
Application Number / Requirement Number	P100010 S098/ PAS001
Date Original Protocol Accepted	02/11/2021
Date Current Protocol Accepted	09/25/2026
Study Name	STOP Persistent AF PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center prospective new enrollment study utilizing a sponsor-led registry to estimate the 36-month freedom from Atrial Fibrillation recurrence in patients treated with the Arctic Front Cryoablation system for Persistent Atrial Fibrillation.
Study Population	Patients at sites participating in Medtronic’s Cryoablation Registry, who are 18 years of age or older and are recommended for ablation with the Artic Front Cardiac Cryoablation Catheter System for treatment of persistent atrial fibrillation.
Sample Size	Up to 400 subjects will be enrolled in the study to obtain a minimum sample size of 355 patients treated. This sample size was determined to ensure sufficient statistical precision around the three-estimate of treatment effectiveness.
Key Study Endpoints	The Primary Effectiveness endpoint will be freedom from recurrence of Atrial Fibrillation, Atrial Flutter, or Atrial Tachycardia at 36-months post treatment. The Primary Safety Endpoint is the severe adverse event rate through 12-months post-procedure. Additional endpoints will: characterize the cryoablation procedure in terms of acute procedural success, time in the cath lab, duration of procedure, duration of fluoroscopy, etc. The change in Quality of Life from baseline through 36 months will be estimated using the EuroQoL five-dimension questionnaire. All adverse events occurring through 36-months will also be summarized.
Follow-up Visits and Length of Follow-up	Subjects will be followed for up to 36-months post-procedure.
Interim or Final Data Summary
Interim Results	Safety Results: Ten deaths have been recorded, none of which have an obvious association with the study procedure or device. There were no unanticipated adverse events in the study. Effectiveness Results: N/A - will be reported in final report.
Actual Number of Patients Enrolled	393
Actual Number of Sites Enrolled	17
Patient Follow-up Rate	95.1% at 12 months, 90.7% at 24 months, 98.9% at 36 months (including visits outside of window)
General
Study Status	Ongoing
Application Number / Requirement Number	P200015 / PAS001
Date Original Protocol Accepted	08/06/2020
Date Current Protocol Accepted
Study Name	SAPIEN 3 Pulmonic Long Term F/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects enrolled under IDE G150220, including the Continued Access Protocol subjects. The objective of this study is to characterize the clinical outcomes of these subjects annually through 5 years post-procedure.
Study Population	All living subjects enrolled under IDE G150220, including the Continued Access Protocol subjects.
Sample Size	All living subjects.
Key Study Endpoints	Mortality, transcatheter heart valve (THV) dysfunction, THV hemodynamic function, THV frame fracture, and device-related endocarditis.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: At 5 years: Freedom from Death with Vital Sweep: 98.6% Freedom from Valve Frame Facture: 100% Freedom from Device-related Endocarditis: 95.5% THV dysfunction: 12.2% (6/49): RVOT reintervention: 4.9% (3/61) Moderate or greater PR: 4.2% (2/48) Mean RVOT gradient >40 mmHg: 2.1% (1/48) Effectiveness Results: Mean RVOT gradient: Baseline: 27.4 mmHg; 5-year: 14.1 mmHg Peak RVOT gradient: Baseline: 47.5 mmHg; 5-year: 24.1 mmHg Paravalvular Regurgitation: 5-year: None – 95.8% (46/48); Trace – 2.1% (1/48); Mild – 2.1% (1/48) Total Pulmonary Regurgitation via TTE: Baseline: None: 5.9% (4/68); Trace: 1.5% (1/68); Mild: 10.3% (7/68); Moderate: 26.5% (18/68); Severe: 55.9% (38/68) Five-year: None: 72.9% (35/48); Trace: 6.3% (3/48); Mild: 16.7% (8/48); Moderate: 4.2% (2/48) Change in Total Pulmonary Regurgitation: Five-year: Improved: 89.6% (43/48); Stayed the same: 6.3% (3/48); Worsened: 2.1% (1/48)
Actual Number of Patients Enrolled	72 total subjects in main cohort and 14 in CAP were enrolled. 56 in main and 13 in CAP were implanted.
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	At 5 years, 54 subjects (known status) of 68 total subjects implanted (in the 5-year window) results in a 54/68 (79.4%) rate
General
Study Status	Ongoing
Application Number / Requirement Number	P200015 / PAS002
Date Original Protocol Accepted	04/16/2021
Date Current Protocol Accepted	02/24/2025
Study Name	SAPIEN 3 Pulmonic New Enrollment Study-COMPASSION
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm new enrollment study. The objective of the study is to monitor the device performance and clinical outcomes of the SAPIEN 3 THV System with Commander Delivery System in the real world for the approved indication.
Study Population	Pediatric and adult patients who have a clinical indication for intervention on a dysfunctional right ventricular outflow tract (RVOT) conduit or surgical bioprosthetic valve in the pulmonic position with greater than or equal to moderate regurgitation and/or a mean RVOT gradient of greater than or equal to 35 mmHg.
Sample Size	150
Key Study Endpoints	Device success, THV dysfunction, THV hemodynamic function, and New York Heart Association (NYHA) classification.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: Freedom from Death with Vital Sweep: 30-days: 100%; One-year: 100% Device Success: 90.8% (119/131): Single THV implanted in desired location: 99.3% (133/134) RV-PA peak-to-peak gradient < 35 mmHg: 93.2% (124/133) Less than moderate PR by discharge TTE: 98.5% (130/132) Free of explant at 24 hours post-implantation: 100% (134/134) At 1 year, THV Dysfunction Overall: 1.8% (2/111): RVOT reintervention: 0.7% (1/134) Moderate or greater PR: 0.9% (1/112) Mean RVOT gradient > 40 mm/Hg: 0.0% (0/111) Effectiveness Results: Mean RVOT gradient via TTE: Baseline: 27.8 mmHg; 30-day: 11.8 mmHg; 1-year: 11.4 mmHg Peak RVOT gradient via TTE: Baseline: 47.3 mmHg; 30-day: 20.9 mmHg; 1-year: 20.6 mmHg Change in Total Pulmonary Regurgitation: 30-day: Improved: 96.6% (113/117); Stayed the same; 3.4% (4/117) One-year: Improved: 95.3% (101/106); Stayed the same: 4.7% (5/106) Paravalvular Regurgitation: 30-day: None: 97.5% (116/119); Trace: 0.0% (0/119); Mild: 2.5% (3/119) One-year: None: 99.1% (111/112); Trace: 0.0% (0/112); Mild: 0.9% (1/112) Change in Tricuspid Regurgitation: 30-day: Improved: 28.6% (34/119); Stayed the same: 60.5% (72/119); Worsened: 10.9% (13/119) One-year: Improved: 31.5% (34/108), Stayed the same: 58.3% (63/108), Worsened: 10.2% (11/108)
Actual Number of Patients Enrolled	150 total subjects enrolled. 134 subjects successfully implanted.
Actual Number of Sites Enrolled	19
Patient Follow-up Rate	At 30 days, 132 subjects (known patient status) of 134 total subjects implanted results in a 98.5% (132/134) rate. At 1 year, 126 subjects (known patient status) of 134 total subjects implanted results in a 94.0% (136/134) rate.
General
Study Status	Delayed
Application Number / Requirement Number	P050050 S024/ PAS001
Date Original Protocol Accepted	03/13/2024
Date Current Protocol Accepted
Study Name	S.T.A.R. Ankle PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Study Objective: Demonstrate equal or better performance of the STAR TAR system with vitamin E (e+) mobile bearing relative to a historical control with respect to cumulative revision rate at 8 years post implantation. Study Design: Prospective, Multicenter, Single-Arm, Comparative Observational Study
Study Population	The study population includes adult subjects (aged 22 years and over) implanted with the STAR TAR System with the e+ mobile bearing for the treatment of painful arthritic ankle joints due to osteoarthritis, posttraumatic arthritis, or rheumatoid arthritis. The comparator is a historical control group consisting of a cumulative revision rate for all fixed bearing ankles from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) at eight (8) years post-implantation.
Sample Size	Number of Patients: 300 evaluable patients Assumptions: The sample size is determined using a precision – based method assuming a revision rate of 4.5% for the STAR TAR system with e+ mobile bearing at 7 years follow-up, a 95% confidence interval with an upper confidence limit of 6.8%, and a type 1 error of 5%. To account for a 20% attrition rate, at least 375 patients will be enrolled in this study. Number of Sites: 8 – 10 US Sites
Key Study Endpoints	Primary Endpoints: • Device cumulative revision rate of the STAR TAR system with e+ mobile bearing at eight (8) years post-implantation. • Within the primary endpoint, a quantitative assessment of the polyethylene fracture rate of the subject device to the historical control data will be performed Secondary Endpoints: • Device revision rate assessed at all timepoints post-implantation • Change from baseline for Total Buechel-Pappas Scale Score • Change from baseline for Pain Visual Analog Scale (VAS) (100mm scale) • Change from baseline for Quality of Life (SF-36) • Change from baseline for American Orthopedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Scale Score • Radiographic endpoints (anterior-posterior and lateral x-ray images of the treated ankle) o Quantitative and qualitative radiographic assessment of the total ankle arthroplasty including evaluation of both the femoral and tibial components, for the following outcomes: . radiolucency and osteolysis . subsidence . migration . rotation . integrity. . Assessment of polyethylene bearing for integrity (e.g., fracture, dislocation, subluxation, worn, intact). • Explant analysis of any explanted devices and all revisions • All adverse events including the nature, onset, duration, severity, and relationship to the device and/or procedure
Follow-up Visits and Length of Follow-up	8 years
General
Study Status	Completed
Application Number / Requirement Number	P150033 / PAS001
Date Original Protocol Accepted	03/08/2016
Date Current Protocol Accepted	06/17/2020
Study Name	Micra Rate Resp Conf Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Medtronic is sponsoring the Micra System Post-Approval Study (PAS) to further confirm safety and effectiveness of the system when used as intended, in real-world clinical practice, following commercial release. Data will be collected from following current premarket patients and new patients.
Study Population	Patients indicated for a VVIR pacemaker.
Sample Size	Accounting for attrition, an estimated enrollment of 1830 patients will be required to achieve the desired sample size for the primary objectives.
Key Study Endpoints	To estimate acute complication rate related to the Micra system and/or procedure: 1741 Micra system implant procedure ensure complication detection and produces a 2-sided 95% CI width of 1.0% when the event rate is 1% To estimate the 9-year Micra related complication free survival probability: 500 patients at 9-years produces a 2-sided CI width of 6.5% with a CI lower limit of 85.0%
Follow-up Visits and Length of Follow-up	The study aims to follow at least 500 patients out to 9 years. Annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	43 unique patients.
Actual Number of Sites Enrolled	Rate Response Study Sites: Six (6) in US. Pooled Data Sites: Micra IDE: One (1) site in US. Micra IDE: Five (5) sites OUS. Micra China Study: Five (5) sites OUS.
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	The Micra Rate Response sub-study confirmed the rate response operation
Study Strengths & Weaknesses	Enrollment challenges led to pooling of data sets and limited diversity amongst study subjects. Study subjects skewed male.
Recommendations for Labeling Changes	No recommended changes at this time.
General
Study Status	Ongoing
Application Number / Requirement Number	P150033 / PAS002
Date Original Protocol Accepted	03/08/2016
Date Current Protocol Accepted	04/22/2026
Study Name	Micra Transcatheter Pacing System PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Micra PAS is a global, prospective, observational, multicenter study.
Study Population	Patients intended to be implanted with a Micra system are eligible for enrollment into the Micra PAS. Micra IDE (G130245) Study and the Micra Continued Access Study (G130245) patients who remain active at the time of product approval are eligible for continued follow-up in the PAS.
Sample Size	The primary objective #1 requires a minimum of 1741 patients undergoing Micra system implant attempts. Primary objective #2 requires a minimum sample size of 200 at 9 years. It is anticipated that approximately 150 Micro End of Device Service events will be captured. To account for attrition due to consented patient withdrawing prior to an implant procedure, the projected enrollment number required for this study is 1830 patients. * In order to ensure the effective sample size at the end of the study this protocol states that the study attrition will be assessed annually. The annual attrition rate will be compared to the projected size indicated in Table 6 of the protocol (link below). If significant higher attrition (more than 5% increase) is observed, supplemental enrollments will be considered.
Key Study Endpoints	Primary Objective #1 (Acute - 30 days): To estimate acute complication rate related to the Micra system and/or implant procedure. Individual 30-day complication rates will be reported for but not limited to: cardiac perforation, pericardial effusion, dislodgement, embolization, serious groin complications and infections. - 1741 Micra system implant procedure ensure complication detection and produces a 2-sided 95% CI width of 1.0% when the event rate is 1% Primary Objective #2 (Chronic 9 years): To estimate the 9-year complication free survival rate of the Micra system. - 500 patients at 9-years produces a 2-sided CI width of 6.5% with a CI lower limit of 85.0% was conservatively assumed during the initial design stage of the study in the calendar year 2105 Secondary Objective (Micra TPS EDS): To characterize treatment and/or procedure related to Micra TPS End of Device Service. Any one of the following revision scenario contributes equally to the approximately 150 EDS events. Possible revisions scenarios include: - Explant of Micra System with new leadless pacemaker system - Explant of Micra System with new transvenous pacemaker system - Implant of new leadless pacemaker without explant of Micra System (e.g., set to OOO or programmed to a back-up pacing mode) - Implant of new transvenous pacemaker system without explant of Micra System (e.g., set to OOO or programmed to a back-up pacing mode)
Follow-up Visits and Length of Follow-up	The study will complete when a minimum of 200 patients have completed 9 years of follow-up. The total estimated PAS duration is 11 years.
General
Study Status	Other
Application Number / Requirement Number	P150034 / PAS001
Date Original Protocol Accepted	12/27/2016
Date Current Protocol Accepted	01/04/2022
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a new enrollment and continued follow-up of a single-arm, prospective, multicenter study to evaluate the long term safety of the Raindrop® Near Vision Inlay implanted in an emmetropic population (continued follow-up of premarket cohort). All subjects who meet the inclusion criteria will be followed over a 60-month period or 24 months post inlay removal.
Study Population	This is a continuation study of the IDE cohort and continued enrollment of about 75 subjects per month.
Sample Size	Not applicable for this study as this is a continuation study of the IDE cohort.
Key Study Endpoints	1. Preservation of best corrected visual acuity 2. Incidence of secondary surgical interventions
Follow-up Visits and Length of Follow-up	60-months Follow-ups at 1 day, 1 month, 6 months, 12 months, and 24 months. For subjects that have not had inlay removed then examinations will also occur at 48 months and 60 months.
Interim or Final Data Summary
Interim Results	Actual Number of Patients Enrolled: 150 subjects Actual Number of Sites Enrolled: 4 US sites Interim Results: This update reflects interim data as of July 24, 2018. Subject enrollment has been completed. The study cohort consisted of 150 subjects at various stages of patient follow-up. The first primary safety endpoint was preservation of best-corrected distance visual acuity (BCDVA). 5.3% [8/150] of subjects experienced a persistent BCDVA loss of 2 lines or more at the last available visit. Regarding the secondary primary safety endpoint of the rate of secondary surgical interventions (SSI) over 60 months postoperatively, 12.7% [19/150] of subjects underwent SSI. FDA publicly communicated on October 23, 2018, regarding two safety concerns identified from the most recent interim study report: the percentage of subjects with corneal haze, and the percentage of subjects requiring device removal. The rate of central corneal haze of any severity was 42% (63/150) at any time point. The rate of corneal haze at any location and of any severity was 75% (113/150). One patient first developed haze 6 months after removal of the device. Study follow-up is ongoing; however, of the subjects who completed 60 months of follow-up, twenty-two subjects developed their first episode of haze at the 60 month visit. The percentage of patients with two or more lines loss of BCDVA caused by corneal haze (2.0%, 3/150) was greater than what was observed at Month 36. In this study, 31 subjects (20.7%) were treated with steroids for corneal haze at any time. Of patients who still had the device implanted, 23.7% (29/122) were prescribed steroid eyedrops to treat corneal haze. Of these 29 patients who were treated with steroids, 8 patients were treated for 3 months or more, and an additional 10 patients were being actively treated at the time of the study report or left the study while on active treatment. Of the 150 patients enrolled in the post-approval study, 35 patients (23.3%) have had their device removed (for haze or other reasons) either during the post-approval study or after they exited the IDE study. In addition, some patients continued to have corneal haze after the device was removed.
General
Study Status	Other
Application Number / Requirement Number	P150034 / PAS002
Date Original Protocol Accepted	01/24/2018
Date Current Protocol Accepted	10/09/2019
Study Name	Raindrop Near Vision Inlay New Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Overview: This post-approval study (PAS) registry is a new enrollment single-arm, prospective, multicenter study to collect postoperative data for up to 5 years and evaluate the long term safety of the Raindrop® Near Vision Inlay in emmetropic patients. Study Design: The Study will be conducted in two phases. Phase One A questionnaire will be developed to elicit the reason(s) for device explantation, including the effects of visual symptoms. Subject who have previously had the Raindrop inlay removed or are considering having the inlay removed will be recruited for phase one. The questionnaire will be assessed qualitatively through hybrid concept elicitation and cognitive debriefing interviews. The qualitative assessment will evaluate: (1) The clarity of the items within the instrument; (2) How the respondents interpret the item(s); (3) Ease of completion of the patient-reported outcomes (PROs); (4) The comprehensiveness of the PROs; and (5) The appropriateness of the format, response scales, and recall period used in the PROs. Once the results of phase one are reviewed by FDA, patients will be enrolled in Phase two of the study. Phase Two The questionnaire developed in phase one of the study will be administered as a nested component of the post-approval study. The Phase two PAS will be a prospective, multicenter, single-arm clinical registry consisting of 528 eyes from 528 presbyopic patients with emmetropia (defined as having +1.00 D to -0.50 D manifest spherical equivalent) between the ages of 41 and 65 years, enrolled from up to 30 sites in the United States for unilateral implantation of the Raindrop inlay in the non-dominant eye to ensure that at least 422 patients (assuming an overall attrition rate of 20%) will be available for long-term follow-up at 60 months after implantation.
Study Population	A total of 528 eyes from 528 presbyopic patients 41 to 65 years of age, who have manifest refractive spherical equivalent of (MRSE) +1.00 diopters (D) to -0.50 D with less than or equal to 0.75 D of refractive cylinder, who do not require correction for clear distance vision, but who do require near correction of +1.50 D to +2.50 D of reading add. Patients must have provided informed consent for the Raindrop inlay implantation, who are capable of comprehending the nature of the study, and who are likely to comply with the visit schedule are to be entered into Phase 2 of the study.
Sample Size	528 eyes /patients are needed to determine the safety of the inlay (co- primary safety endpoints), to provide a statistical power of at least 80% at the one-sided significance level of 0.025, with an assumed attrition rate of 20% over the 60-Month follow-up period.
Key Study Endpoints	Primary Safety Endpoints: 1) Loss of two (2) lines or more of best corrected distance visual acuity (BCDVA) at 60 months after inlay implantation, or 24 months after removal, whichever is longer, is fewer than 5%. 2) Incidence rate of inlay removal secondary surgical interventions will be 10% or less. Both of the alternative hypotheses should be met in order to determine the safety of the inlay. Secondary Safety Endpoints: 1) The rate of secondary surgical interventions overall and by type (e.g. exchange); and 2) The rate of adverse events categorized as ocular, device and/or procedure related, unanticipated, or other.
Follow-up Visits and Length of Follow-up	60 months postoperatively or 24-months post-removal, whichever is longer after initial implantation.
General
Study Status	Delayed
Application Number / Requirement Number	P130008 S090/ PAS001
Date Original Protocol Accepted	08/04/2023
Date Current Protocol Accepted
Study Name	Inspire UAS High AHI/High BMI PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multi-center, two-arm study of subjects with an Apnea-Hypopnea Index (AHI) > 65 and <= 100 events/hr and/or Body Mass Index (BMI) >32 and <= 40 kg/m2, who are undergoing implant of the Inspire Upper Airway Stimulation (UAS) System for the treatment of obstructive sleep apnea (OSA). Subjects will be followed for 5 years post-implant
Study Population	Subjects will be recruited in accordance with the approved indication for use and will only include those subjects who are within the new AHI (65 < AHI <=100 events/hr) and BMI (32 < BMI<=40 kg/m2) ranges. Subjects will be considered enrolled at the time of informed consent. Implanted subjects must meet the study eligibility criteria and will be followed for 5 years post-implant. Those subjects that are enrolled but fail to meet the eligibility criteria will be considered screen failures. Study arms: AHI Cohort: Includes subjects with 65 < AHI<=100 events/hr BMI Cohort: Includes subjects with 32 < BMI<=40 kg/m2
Sample Size	Number of subjects: 70 implanted subjects - 35 implanted subjects in each arm Assumptions for sample size estimation: NA Number of sites: 5 Sites location: US
Key Study Endpoints	Safety Endpoints Primary: Evaluation of device and/or procedure related adverse events over time: relevant adverse events will be collected and reported through 5 years post-implant Secondary: NA Effectiveness Endpoints Primary: • Evaluation of improvement in Apnea Hypopnea Index (AHI) over time: baseline (pre-implant) AHI compared to AHI after implant (collected and reported at annual study visits) • Evaluation of improvement in Oxygen Desaturation Index (ODI) over time: baseline (pre-implant) ODI compared to ODI after implant (collected and reported at annual study visits) • Evaluation of improvement in T90 (defined as total sleep time spent with arterial oxygen saturation (SaO2) < 90%) over time: baseline (pre-implant) T90 compared to T90 after implant (collected and reported at annual study visits) • Evaluation of improvement of Epworth Sleepiness Scale (ESS) over time: baseline (pre-implant) ESS compared to ESS after implant (collected and reported at annual study visits) Subjects enrolled in the BMI cohort will have their BMI monitored yearly throughout the study Secondary: NA
Follow-up Visits and Length of Follow-up	• Baseline • Implant • Activation (1 Month Post-Implant) • 6 Months Post-implant • 1, 2, 3, 4, 5 Years Post-Implant
Interim or Final Data Summary
Interim Results	N/A
Actual Number of Patients Enrolled	14
Actual Number of Sites Enrolled	6 activated centers
Patient Follow-up Rate	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P960013 S122/ PAS001
Date Original Protocol Accepted	05/11/2023
Date Current Protocol Accepted
Study Name	UltiPace Lead RWE Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval study is to evaluate the long-term safety of the Abbott UltiPace lead. The study uses real world evidence data methods to link and evaluate multiple datasets.
Study Population	All eligible patients who receive an Abbott IPG and UltiPace RA lead or RV lead (model LPA1231) for the first 12 months following UltiPace approval. . Patient inclusion will be further be restricted to those with Medicare Parts A & B coverage and not Part C (HMO) coverage at the time of implant to ensure data capture in Medicare FFS claims.
Sample Size	Estimated at 7,500 RA leads and 7,500 RV leads. Minimum sample sizes of 645 RA leads and 645 RV leads are needed to provide 80% power to reject the null hypotheses.
Key Study Endpoints	Primary Endpoints • Freedom from UltiPace right atrial (RA) lead-related complications through 5 years of follow-up. • Freedom from UltiPace right ventricular (RV) lead-related complications through 5 years of follow-up. Secondary Endpoint • Rate of cardiac tamponade or cardiac perforation events
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: Freedom from RA lead-related complications (n=1,585 leads) was 98.8% (95% CI: 98.3%, 99.2%) at 27 months follow-up. Freedom from RV lead-related complications (n=935 leads) was 99.0% (95% CI: 98.3%, 99.4%) at 27 months follow-up There were 13 patients with cardiac tamponade and 0 patients with cardiac perforation events through the data cut-off date. The worst-case scenario rate of RA lead-related cardiac tamponade was 17 events in 11 leads (0.6811% of RA leads). The worst-case scenario rate of RV lead-related cardiac tamponade was <11 events in <11 leads (<1.1555% of RV leads) To comply with the CMS cell size suppression policy, a cell containing a value of 1 to 10 cannot be reported directly. Hence '< 11' is used to report a value of 1 to 10. Subjects continue to be followed within the study so that the follow-up period will be updated as the study progresses. The minimum sample size for enrollment has been met.
Actual Number of Patients Enrolled	1,719 subjects were enrolled as of this 36-month report
Actual Number of Sites Enrolled	202
Patient Follow-up Rate	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S010/ PAS001
Date Original Protocol Accepted	07/23/2018
Date Current Protocol Accepted	07/23/2018
Study Name	Continued f/u of premarket cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the PIIS3i cohort under the IDE (G090216). The objective of this PAS is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke, transient ischemic attack (TIA), myocardial infarction, new permanent pacemaker, new-onset atrial fibrillation, rehospitalization from symptoms of aortic stenosis and/or complications of the valve procedure, improvement per New York Heart Association (NYHA) Class, improvement per Kansas City Cardiomyopathy Questionnaire (KCCQ) and Euro Health Related Quality of Life (EQ-5D), valve performance and durability, and aortic valve re-intervention.
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S010/ PAS002
Study Name	Comprehensive/Linked-Registry Based Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor the device performance in the post-approval setting through the national TVT-registry
Study Population	Patients with symptomatic heart disease due to either severe native aortic stenosis who are deemed to be at intermediate or greater surgical risk, defined as having predicted risk of surgical mortality of = 3% at 30 days based on the STS risk score and other clinical co-morbidities not included in the STS risk score assessment.
Sample Size	All implanted patients, with intermediate or greater risk for open surgical therapy, in the TVT-registry within five years of the device approval.
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological complications (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-5 years post implantation.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P150037 / PAS001
Date Original Protocol Accepted	11/03/2016
Date Current Protocol Accepted	11/03/2016
Study Name	COMPASS Extension Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up PAS (COMPASS trial; protocol TMI-09-01-E) is a long-term safety, multicenter, observational study with no planned interventions. The aim of the study is to evaluate the long-term safety of CyPass® Micro-Stent glaucoma implant in subjects who have completed participation of the IDE clinical trial (TMI-09-01).
Study Population	Subjects who completed the protocol TMI-09-01, are able to understand the study requirements and willing to follow study instructions and are willing to return for required study follow-up visits.
Sample Size	480 eyes of 480 subjects. This is based on the number of subjects implanted with the CyPass Micro-Stent, completed 24 month follow-up in study Protocol TMI-09-01 and will meet the study eligibility criteria
Key Study Endpoints	• Primary safety outcome: o Rate of occurrence of sight-threatening adverse events (AEs) • Secondary outcomes- Safety: o Best Corrected Visual Acuity (BCVA) o Rate of occurrence of ocular AEs o Slit lamp, goniscopy and fundus findings o Visual field mean deviation (MD) o Central corneal thickness o Central corneal endothelial cell density (ECD) o Rate of occurrence of CyPass movement, defined as a change by at least 1 in the number of CyPass rings visible (e.g., from 0 rings to 1 rings or from 3 rings to 2 rings) that does not result in clinical sequelae (e.g., secondary surgical intervention to modify device position, corneal endothelial touch by device, corneal edema leading to loss of BCVA > 2 lines at the last postoperative visit in comparison with preoperative BCVA, progressive endothelial cell loss (ECL), erosion of device through sclera, or device obstruction requiring secondary surgical intervention), and that is not attributable to: - variations in gonioscopic viewing angle or illumination, - changes in angle anatomy due to concomitant findings such as resolution of hyphema, - changes in anterior chamber depth, or - development of focal peripheral anterior synechiae • Secondary outcomes- Effectiveness: o Mean change in intraocular pressure (IOP) o Proportion of subjects who are not using ocular hypotensive medication with = 20% reduction in IOP from baseline in the COMPASS Trial o Proportion of subjects who are not using ocular hypotensive medication with IOP = 6 mmHg and = 18 mmHg
Follow-up Visits and Length of Follow-up	5 years after the post-randomization from the COMPASS trial.
Interim or Final Data Summary
Actual Number of Patients Enrolled	282 US subjects
Actual Number of Sites Enrolled	23 US sites
Patient Follow-up Rate	Only 58.75% (282/480) of the eligible subjects were enrolled in the COMPASS-XT study. Of the 282 subjects enrolled, 253 completed the study.
Final Safety Findings	The key finding from the COMPASS-XT study were the differences in mean endothelial cell density (ECD) and the percent change in ECD from baseline between the CyPass and Control groups after Month 24. Mean central ECD showed a greater loss in the CyPass group compared to Control. The proportion of eyes with >30% loss in ECL between baseline and 60 months was greater in the CyPass group compared to the Control group. Sight-threatening adverse events (AEs) were reported including incidence of Best Corrected Visual Acuity (BCVA) loss (2/213; 0.96%) in the CyPass group and retinal detachment (1/67; 0.30%) in the Control group. The total number of ocular AEs was 88 in the CyPass group and 16 in the Control group and included: BCVA loss of 2 lines (10 letters) of more compared to BCVA reported in COMPASS study (24/215 (11.2%) in CyPass group and 4/67 (6.0%) in the Control group), Confirmed worsening of visual field MD of greater than or equal to 2.5dB compared to COMPASS 24 Month visual field (22/215 (10.25%) in the CyPass group and 6/67 (9.0%) in the Control group), Treatment of elevated IOP that is not satisfactorily managed using ocular hypotensive medication (10/215 (4.7%) in the CyPass group and 2/67 (3.0%) in the Control group), CyPass device obstruction by iris, vitreous, lens, fibrous overgrowth, fibrin or blood (10/215 (4.7%)), CyPass device malposition, dislodgement or movement (6/215 (2.8%)), CyPass trimming (4/215 (1.9%), Macular edema (3/215 (1.4%) in the CyPass group and 1.67 (1.5%) in the Control group), Other maculopathy (3/215 (1.4%) in the CyPass group and 1.67 (1.5%) in the Control group), Corneal edema (3/215 (1.4%) in the CyPass group and 1.67 (1.5%) in the Control group). Other AEs reported in the COMPASS-XT are not listed here and were reported under 1% rate in the CyPass group. Mean change in central corneal thickness from Month 24 were similar between the CyPass and Control groups. Mean changes in VFMD from Month 24 were similar between the 2 groups. Although no investigators reported device movement in the COMPASS-XT trial, changes in ring visibility not attributable to device trim were noted in 30 subjects.
Final Effect Findings	46% of the subjects in the CyPass group had a 20% or greater reduction from baseline IOP without ocular hypotensive medications compared to 32% for the Control group.
Study Strengths & Weaknesses	Strength: ¿ The continued IDE study identified long-term safety concerns that were not identified at 24 months. Weaknesses: ¿ Only 58.75% (282/480) of the eligible subjects were enrolled in the COMPASS-XT study. ¿ Goniscopy data was not consistently collected in the study. ¿ Due to the small sample size at Month 60, it is difficult to draw a conclusion regarding the ECL.
Recommendations for Labeling Changes	Labeling change is recommended to include the long-term safety information.
General
Study Status	Terminated
Application Number / Requirement Number	P150037 / PAS002
Date Original Protocol Accepted	03/15/2017
Date Current Protocol Accepted	08/18/2017
Study Name	CyPass Micro Stent New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To demonstrate that the rate of clinically relevant complications associated with CyPass Micro-Stent placement and stability using the CyPass 241-S applier, as determined at 36 months in the postmarket setting, is less than the pre- specified performance target, which is based on experience with the CyPass Model E applier in the COMPASS (TMI-09-01) Trial. This is a prospective, non-randomized, multicenter, single arm, post approval study of the CyPass System. This is a new enrollment study that is expected to last up to 37.5 months and include 10 study visits.
Study Population	Adults who must have Primary Open Angle Glaucoma (POAG) in the study eye and also be undergoing cataract surgery in that eye. No comparator group. Inclusion criteria: 1. Adults, 45 years of age or older at the time of surgery 2. Able to understand the requirements of the study and willing to follow study instructions, provide written informed consent, and agree to comply with all study requirements, including the required study follow-up visits 3. Diagnosis of primary open angle glaucoma (POAG) substantiated using funduscopic exam and at least one reliable visual field test with the Humphrey automated perimeter using the SITA Standard 24-2 testing algorithm. Mean deviation score must be greater than or equal to-12.0 dB and less than 0 dB. The visual field test may be historical (up to 6 months prior to screening – Visit 0). If needed, visual field testing may be repeated between screening (Visit 0) and surgery (Visit 00). NOTE: A reliable visual field test is defined as one in which fixation losses (FL) are less than or equal to 20% and the false positive (FP) response rate is less than or equal to 15% (Rao 2015). 4. Medicated intraocular pressure (IOP) of greater than or equal to 10 mmHg and less than or equal to 25 mmHg, or an unmedicated IOP of greater than or equal to 21 mmHg and less than or equal to 33 mmHg 5. Gonioscopy confirming normal angle anatomy 6. Shaffer grade of greater than or equal to III in all four quadrants 7. An operable age-related cataract with best corrected distance visual acuity (BCDVA) of 0.3 logMAR or worse (less than or equal to 85 letters read), eligible for phacoemulsification. If the BCDVA is better than 0.3 logMAR (greater than 85 letters read), testing with a Brightness Acuity Meter (BAT) on a medium setting must result in a BCDVA of 0.3 logMAR or worse (less than or equal to 85 letters read). 8. An intact and centered capsulorhexis or capsulotomy 9. An intact posterior capsular bag 10. A well-centered IOL implant placed in the capsular bag 11. A clear view of an open angle and visualization of the angle with direct gonioscopy post intracameral miotic instillation 12. No evidence of zonular dehiscence/rupture (uncomplicated cataract extraction)
Sample Size	640 subjects will be enrolled, 360 eyes of 360 subjects (limit one eye per subject) will complete the study and provide 36- month data for statistical analyses at approximately 20 sites (approximately 22 subjects implanted per site).
Key Study Endpoints	Primary Effectiveness Endpoints: None. Secondary Effectiveness Endpoints: All secondary effectiveness endpoints will be evaluated at 36 months postoperatively. Mean change in IOP Proportion of subjects with IOP reduction greater than or equal to 20% while using the same or fewer topical ocular hypotensive medications Proportion of subjects who are not using ocular hypotensive medication with IOP greater than or equal to 6mmHg and less than or equal to 18 mmHg Primary Safety Endpoints: The rate of clinically relevant complications associated with CyPass Micro-Stent placement and stability as determined at 36 months. Specific device-related complications include: Failure to implant CyPass, defined as inability to successfully deploy or insert the CyPass. Clinically significant CyPass malposition, defined as CyPass positioning after deployment such that: The device is not in the supraciliary space, or There is a clinical sequela resulting from device position including, but not limited to: Secondary surgical intervention to modify device position (eg, repositioning, proximal end trimming or explantation) Corneal endothelial touch by device Corneal edema leading to loss of BCDVA > 2 lines at the last postoperative visit, in comparison with preoperative BCDVA Progressive endothelial cell loss (ECL), defined as ongoing reduction in endothelial cell count of 30% or more relative to the screening endothelial cell density (ECD) value Erosion of device through sclera Device obstruction requiring secondary surgical intervention. Secondary Safety Endpoints: All secondary safety endpoints will be evaluated at 36 months postoperatively. Rate of occurrence of sight-threatening adverse events including Persistent (at time of study exit) BCDVA loss of 3 or more lines compared to best BCDVA achieved during the course of study Endophthalmitis Corneal decompensation Retinal detachment Severe choroidal hemorrhage or detachment o Aqueous misdirection The rate of ocular secondary surgical interventions (SSI) The rate of ocular SSIs associated with CyPass placement and stability Other Safety Endpoints: All other safety endpoints will be evaluated at 36 months postoperatively. Increase from baseline IOP of 10 mmHg or greater at any time at/after 30 days postoperative BCDVA loss of 2 or more lines compared to screening (Visit 0) BCDVA loss of 2 or more lines in comparison with best recorded BCDVA at any postoperative visit Device movement, defined as a change by at least 1 in the number of CyPass rings visible (e.g., from 1 ring to 2 rings or from 3 rings to 2 rings) that does not result in clinical sequelae (e.g., secondary surgical intervention to modify device position, corneal endothelial touch by device, corneal edema leading to loss of BCDVA > 2 lines at the last postoperative visit in comparison with preoperative BCDVA, progressive endothelial cell loss, erosion of device through sclera, or device obstruction requiring secondary surgical intervention), and that is not attributable to any one or more of the following: variations in gonioscopic viewing angle or illumination changes in angle anatomy due to concomitant findings such as resolution of hyphema changes in anterior chamber depth development of focal peripheral anterior synechiae
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Interim Results	As of August 31, 2021, 1 patient is reported with device malposition with device implantation in the choroidal space rather than the supraciliary space. There is one (1/43, 2.3%) sight-threatening adverse event of persistent BCDVA loss of 3 lines or more. There are three adverse events requiring secondary surgical intervention; two events were reported as elevated intraocular pressure treated with paracentesis. The third event was associated with device placement and stability. Two patients have reported device dislodgement or movement without sequelae. No eyes in the study had central ECD count below 1000 cells/mm2. At the 36-month evaluation the mean endothelial cell loss (ECL) was 21% with a median of 21%. The percentage of subjects at 36 months with >30% ECL is 24.2% (8/33). A reported 28% (12/43) of the patients in this PAS had greater than 1 ring visible at the time of surgery, 14% (6/43) of patients that had observed 0 or 1 ring at the time of surgery, later reported an increase in the number of visible rings at later post-operative reporting periods.
Actual Number of Patients Enrolled	79 enrolled; 43 patients received the implant. Enrollment was halted after the device was removed from the market in August 2018.
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	3-month visit: 100% (43/43) 6-month visit: 92.9% (39/42) 12-month visit: 97.6% (41/42) 24-month visit: 87.2% (34/39) 36-month visit: 89.5% (34/38)
Final Safety Findings	All secondary effectiveness endpoints will be evaluated at the conclusion of the study.
Study Strengths & Weaknesses	The study enrollment was stopped prematurely due to market withdrawal. Due to the small sample size, it is difficult to draw conclusions regarding the device effectiveness. The primary objective of this study was to evaluate device safety associated with placement and stability of the CyPass. The study was also limited by high variability in visualization and reporting of device dislodgement or movement.
General
Study Status	Delayed
Application Number / Requirement Number	P130008 S039/ PAS001
Date Original Protocol Accepted	06/12/2020
Date Current Protocol Accepted	12/16/2022
Study Name	Inspire Pediatric Post-Approval Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The objective of the registry is to collect safety and effectiveness data related to the new age indication, in a postmarket setting.
Study Population	Subjects will be recruited in accordance with the approved indication for use and will only include those subjects who are within the new age indication (18-21 years). Subjects will be considered enrolled at the time of informed consent. Implanted subjects must meet the registry eligibility criteria and will be followed for 5 years post implant. Those subjects that are enrolled but fail to meet the eligibility criteria will be considered screen failures.
Sample Size	This registry will collect safety and effectiveness data on 60 implanted subjects at minimum of 5 qualified centers in the United States.
Key Study Endpoints	An evaluation of safety will include the following: Evaluation of device and/or procedure related adverse events over time: relevant adverse events will be collected and reported through 5 years postimplant. An evaluation of effectiveness will include the following: Evaluation of improvement in Apnea Hypopnea Index (AHI) over time: baseline (pre-implant) AHI compared to AHI after implant (collected and reported at annual study visits) Evaluation of improvement in Oxygen Desaturation Index (ODI) over time: baseline (pre-implant) ODI compared to ODI after implant (collected and reported at annual study visits) Evaluation of improvement in T90 (defined as total sleep time spent with arterial oxygen saturation (SaO2) < 90%) over time: baseline (pre-implant) T90 compared to T90 after implant (collected and reported at annual study visits) Evaluation of improvement of Epworth Sleepiness Scale (ESS) over time: baseline (pre-implant) ESS compared to ESS after implant (collected and reported at annual study visits
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	12
Actual Number of Sites Enrolled	6
Patient Follow-up Rate	7 completed 6 months-12 months visit: 8 remain-active subjects.
Final Safety Findings	N/A
Final Effect Findings	N/A
General
Study Status	Completed
Application Number / Requirement Number	P150037 / PAS003
Date Original Protocol Accepted	04/09/2020
Date Current Protocol Accepted
Study Name	COMPASS XXT Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up PAS (COMPASS XXT; protocol GLD122-P004) is a long-term safety, multicenter, observational study with no planned interventions. The aim of the study is to evaluate the long-term safety of CyPass® Micro-Stent glaucoma implant in subjects who have completed participation of the IDE clinical trial (COMPASS trial; G080209; TMI-09-01).
Study Population	Subjects who completed the COMPASS trial, are able to understand the study requirements and willing to follow study instructions and are willing to return for required study follow-up visits.
Sample Size	374 eyes of 374 subjects. This is based on the number of subjects implanted with the CyPass Micro-Stent, completed 24-month follow-up in study Protocol TMI-09-01 and will meet the study eligibility criteria.
Key Study Endpoints	Safety outcome: Rate of occurrence of sight-threatening adverse events (AEs) Rate of occurrence of ocular AEs Central and peripheral (nasal) endothelial cell density (ECD) measurements Analyses of rate of loss and rate of low ECD (i.e., less than or equal to 1000 cells/mm2) Assessment of stabilization of endothelial cell loss (ECL) Corneal sequelae associated with ECL Association between peripheral and central ECD count and number of observed rings Secondary surgical interventions (SSIs) to modify the device position (e.g., repositioning, trimming, explanation) Effects of SSIs on central and peripheral ECD CyPass® Micro-Stent movement and/or malposition Corneal AEs (e.g., corneal decompensation, tube corneal touch, corneal edema, etc.) caused by CyPass® Micro-Stent Losses in Best Corrected Visual Acuity (BCVA) greater than or equal to 10 letters Change in visual field mean deviation (MD) Change in central corneal thickness Effectiveness outcomes: Mean intraocular pressure (IOP) Proportion of subjects with a 20% or better reduction in IOP from COMPASS washed out baseline and on zero medication Proportion of subjects with mean IOP less than or equal to 18 mmHg Number of ocular hypotensive medications
Follow-up Visits and Length of Follow-up	10 years after CyPass stent implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	54
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	Of the 374 subjects implanted in the COMPASS study, 210 (56.1%) were eligible for recruitment. Of these, 156/210 (74.3%) were unavailable (e.g., not qualified, deceased, declined enrollment, no reason provided) and 54/210 (25.7%) agreed to enroll. Forty-six of 210 subjects (21.9% of the total number of subjects available for recruitment) completed the study.
Final Safety Findings	The mean central ECD at baseline (N=373) was 2429.1 cells/mm^2. Mean central ECD was 1668.80 cells/mm^2 at 108 months (42/53) and 1574.73 cells/mm^2 at 120 months (38/53) postoperative. Mean peripheral ECD was 1739.44 cells/mm^2 for available participants at 108 months (42/53) and 1688.74 cells/mm^2 at 120 months (30/53) postoperative. The mean peripheral ECD was not available at baseline. The bullets below represent the changes in central ECD. There were no subjects available at 6 and 7 years. Due to small sample size (N=7), there is no meaningful information that can be drawn from the data at 8 years. At 3 months, 9.6% (5/52) of the participants had ECL >30%. At 2 years, 9.4% (5/52) had loss >30%, and one (1/53) had ECD < 1000 cells/mm^2. At 5 years, the proportion of participants with ECD < 1000 cells/mm^2 increased to 6.7% (3/45) and the proportion of those with ECL >30% increased to 26.7% (12/45). At 9 years, the proportion of participants with ECD <1000 cells/mm^2 increased to 26.2% (11/42) and the proportion of those with ECL >30% increased to 40.5% (n=17/42). At 10 years, the proportion of participants with ECD <1000 cells/mm^2 increased to 31.6% (12/38) and the proportion of those with ECL >30% increased to 52.6% (n=20/38). Sixteen ocular serious AEs (SAEs) were reported in 12 participants. Persistent best-corrected distance visual acuity (BCDVA) loss of 3 lines or more was reported in 21.7% (10/46) of the study participants. In two of these cases, the persistent BCDVA loss of 3 lines or more was assessed as related to the CyPass device (serious adverse device events [SADEs]). The other ocular SAEs were trabeculectomy (4.3% [2/46]), visual field defect (4.3% [2/46]), post-procedural complication (2.2% [1/46]), and trabeculoplasty (2.2% [1/46]). Ocular adverse events (AEs) occurring over 5% in the study were reduced visual acuity (45.7% [21/46]), visual field defect (43.5% [20/46]), corneal endothelial cell loss (13.0% [6/46]), post-procedural complication (device obstruction; 10.9% [5/46]), device placement issues (device malposition resulting in progressive ECL; 6.5% [3/46]). Non-optimal position of the device without associated clinical sequelae was reported in 50% (23/46) of participants. Worsening of visual field mean deviation (MD) >2.5 dB was reported in 39.1% (18/46) of participants at Month 120. Three participants underwent secondary surgical interventions (SSIs) to lower intraocular pressure (IOP) (trabeculectomy, glaucoma drainage device implantation after prior trabeculectomy during the COMPASS XT study, selective laser trabeculoplasty [SLT]). In the interim period between exit from the COMPASS XT study and participation in the COMPASS XXT study, one participant was reported with device malposition and two participants underwent device trimming due to corneal edema and corneal endothelial cell loss. These data highlight that the elevated rate of ECL continued even at 10 years after implantation without signs of stabilization.
Final Effect Findings	Effectiveness outcomes in this study are considered exploratory. Mean intraocular pressure (IOP) for the study participants was below the baseline mean (24.98 mm Hg, measured at the screening visit in the COMPASS study), ranging between 15.85 – 17.12 mm Hg at the postoperative visits in the study. At 120 months, participants had a mean IOP reduction of 8.90 mm Hg (35.04% decrease from baseline). At 120 months postoperative, 17.4% (8/46) of the participants who were not taking IOP-reducing medications achieved IOP reduction greater than or equal to 20% compared to their preoperative unmedicated IOP. At 120 months, mean IOP for 73.9% (34/46) of study participants was 18 mm Hg or lower
Study Strengths & Weaknesses	Enrollment was significantly underachieved due to low site participation and unavailability of the previously implanted cohort. Protocol deviations were reported for 96.3% of enrolled participants; 41% of these deviations were related to missing assessments or incorrectly performed assessments. Visualization of the device on gonioscopy was reported for only 35 participants. These issues impact the reliability of the information reported from the study, including whether gonioscopy alone is sufficient method to monitor for device position
Recommendations for Labeling Changes	The applicant voluntarily removed the CyPass Micro-Stent from the global market on August 29, 2018. Given that the device is not available for distribution, labeling changes are not recommended. However, on July 9, 2025, the applicant notified their customers of the results of this PAS and of their intent to not re-introduce the device into the market. Healthcare professionals should discuss with their patients the results of the COMPASS XXT 10-year PAS and available options that patients may want to pursue.
General
Study Status	Delayed
Application Number / Requirement Number	P150038 S006/ PAS001
Date Original Protocol Accepted	11/06/2020
Date Current Protocol Accepted	11/11/2022
Study Name	PAS Registry Study for ExAblate 4000 (PD012)
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multicenter, international single arm, observational post-approval registry study
Study Population	Single-arm study of male and female patients at least 30 years old who plan to be treated for TDPD using the Exablate Neuro System and who meet the specific enrollment criteria
Sample Size	50 patients are planned for this registry study. From the protocol: A total of 50 subjects will be enrolled. A t-test graph demonstrated that the power will be sufficient to determine any significant differences in long-term effectiveness at a=0.05. The graph showed that at 25 subjects, the number of subjects needed had plateaued. With an approximate average of an 8% dropout per year through Year 5, the remaining population is estimated to be approximately 30 subjects at year 5, which shows full power.
Key Study Endpoints	From the protocol: Safety Analysis Safety will be evaluated through descriptive analysis of the incidence and severity of adverse events. Adverse events will be recorded and categorized according to severity, expectedness, and relationship to Exablate Neuro system thalamotomy procedure and/or disease progression. Results will be tabulated and reported as follows: Post thalamotomy incidence and severity of adverse events (AEs). Comparison of post thalamotomy incidence and severity adverse event rates to the prior Exablate study for ET (PMA #P150038), and TDPD earlier study (P150038/S006). Comparison of post thalamotomy incidence and severity adverse events rates to prior Deep Brain Stimulation (DBS) rates Effectiveness Analysis Effectiveness will be evaluated through descriptive analysis of ON medication CRST scores for tremor/motor, posture/rest, and level of disability. Results will be presented as percent change from baseline to post thalamotomy study visits for all subjects where unilateral Exablate thalamotomy was attempted.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Table 5 below presents 31 adverse events in 13 of the 28 subjects. Fifteen subjects had no adverse events. Fourteen events are newly reported in this report. Of these 14, 5 were related to the thalamotomy procedure, and 9 were unrelated to the device or procedure. Additionally, of these 14 events, 4 were considered Mild, 4 were considered Moderate, and 6 were considered Severe. Of the 31 total adverse events, ten events were Mild in severity, ten events were Moderate, eleven events were Severe, and no events were Life Threatening. Twenty-one out of 31 adverse events were either transient (resolving within three days) or unrelated to the device or procedure. Nine events were Thalamotomy-related and one event was Procedure-related. Of all the reported events, no events were reported as Device-related. Effectiveness Results: Although the sample size is still small, the CRST generally improved from Baseline. The mean Tremor-Motor score improved from 14.6 to approximately 1-5 at during the follow-up period covering Month 3 through Year 3; the percent change of improvement was approximately 72-88% during this same period (Table 6 and Figure 1).The posture score is a sub-measure of the treated side Tremor Motor Score from the CRST Part A. Tremor as measured by posture showed improvement (Table 7 and Figure 2). The posture scores from Month 3 to Year 3 were approximately 0.4-0.9 with a Baseline of 2.6. The percent change from Baseline ranged from approximately 72% to 100% during this follow-up period. The Rest score is a sub-measure of the treated side Tremor Motor Score from the CRST Part A. Rest scores improved from a Baseline of 2.8 to a range of 0.0-0.8 at Months 3 through Year 3. Percent change from Baseline ranged from 74% to 100% during this follow-up period. The CRST Part C is an assessment of the impact of tremor on routine activities; speaking, eating, drinking, hygiene, dressing, writing, and working. The total Part C (average of each activity) measures the overall impact of tremor on daily activities. As can be seen in Table 9 and Figures 4a and 4b, although the Part is a broader measure of tremor impact, Part C Total score improved from 11.2 to a range of 2.6 – 6.3 at Month through Year 2 (percent change of 42-71%), but slightly increased from the respective Baseline scores of the 2 subjects who have reached the Year 3 timepoint (worsening of 4%). The improvement in tremor indicated by the CRST was also evident in the UPDRS Part III tremor scores. (Table 10 and Figure 5). The UPDRS Part III tremor scores were consistent with the CRST scores presented above. The Baseline mean score was 4.6 and follow up scores ranged from approximately 0.5 to 1.8 at Month 3 through Year 3 (percent change from Baseline of 63% to 90%).
Actual Number of Patients Enrolled	28
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	the expected subjects of Month 1, 3, 6, 12 are 28, 28, 22, and 19, respectively. The actual number of subjects completed the follow-up visits are 24 (86%), 22 (79%), 21 (95%), and 16 (84%).
General
Study Status	Delayed
Application Number / Requirement Number	P150038 S014/ PAS001
Date Original Protocol Accepted	06/30/2022
Date Current Protocol Accepted	07/29/2022
Study Name	ExAblate Neuro PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The objectives of this Registry are: Collect the safety and effectiveness data of performing pallidotomy for Parkinson’s Disease Motor Complications using the Exablate Neuro system through Year 5. This is a post-approval registry which is required by the approval under PMA P150038/S014 for the Exablate® Model 4000 (Exablate Neuro) Type 1.0 and Type 1.1 for unilateral pallidotomy in the treatment of advanced, idiopathic Parkinson’s disease with medication-refractory moderate to severe motor complications as an adjunct to Parkinson’s disease medication treatment. This protocol will enroll approximately 60 new subjects as Cohort 2. Cohort 1 includes the long-term follow-up from the G170237 IDE which will continue to Year 5
Study Population	The population enrolled in this registry will be comprised of male and female patients that plan to be treated using the Exablate Neuro system for advanced, idiopathic Parkinson’s disease with medication-refractory moderate to severe motor complications 1. Men and women, age 30 years and older 2. Subject undergoing a planned an Exablate procedure for their Parkinson’s Disease with Motor Complications per local institution standard of care. 3. Subject is willing to cooperate with the Registry requirements including compliance with the regimen and completion of all Registry visits 4. Subject has signed and received a copy of the approved informed consent form This is a single arm study, which is no comparison group.
Sample Size	The proposed registry will enroll 60 subjects and will be conducted at approximately 10 centers worldwide.
Key Study Endpoints	Safety will be evaluated through descriptive analysis of the incidence and severity of adverse events. Adverse events will be recorded and categorized according to severity, expectedness, and relationship to Exablate Neuro system pallidotomy procedure and/or disease progression. Results will be tabulated and reported as follows: • Post pallidotomy incidence and severity of adverse events (AEs). • Comparison of post pallidotomy incidence and severity of adverse event rates to the prior Exablate Registry for PD (PMA #P150038/S014). • Comparison of post pallidotomy incidence and severity of adverse events rates to Deep Brain Stimulation (DBS) rates as reported in the literature Primary Effectiveness will be evaluated through a Responder analysis. Responder is defined as the patient reaching a minimally clinically significant difference on: • UDysRS Objective Assessment ON Meds, without clinically significant worsening of MDS-UPDRS Part III OFF Meds aggregated extremity score for treated side • 2) MDS-UPDRS Part III OFF Meds Motor Exam on the treated side, without clinically significant worsening of UDysRS Objective Assessment ON meds Minimally clinically important difference for this Registry is defined as follows: • Control of dyskinesia will be captured using the UDysRS Objective assessment ON meds. A Responder will be identified as Improvement by more than 3 points (lower score than Baseline) and Worsening will be identified as more than 3 points higher (compared to Baseline). • Control of bradykinesia will be captured by Off meds state MDS-UPDRS Part III aggregated extremity questions for treated side. A Responder will be identified as at least 3 or more points Improvement (lower score than Baseline). Worsening is defined as at least 4 points or more higher (compared to Baseline) Additional Data. Additional data, including but not limited to, demographics, change from baseline to all Registry visits of each MDS-UPDRS (Parts I, II, III OFF, IV), UDysRS, CGIC, PGIC, patient satisfaction questionnaire may be compiled.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results S014 (PD006) 1. In the Exablate Main Group, one pallidotomy related adverse event was previously reported as ongoing at Month 12 (Table 4a); moderate dysarthria. However, the subject reporting dysarthria (115011) developed sepsis from a shoulder infection, died (see SAE narrative) and there was no follow-up resolution. There were no other ongoing procedure-related events as of Month 12 to follow. 2. Table 4b presents six adverse events in two subjects newly reported this period. All six events were mild or moderate in severity, none were reported as severe. All six events were reported as unrelated to the device or procedure by the investigators. The nausea and visual hallucinations resulted from a drug. 3. It should be noted that there have been no device/study related medical interventions under the PAS long term follow up. 4. In the Crossover there were three pallidotomy related events in two subjects ongoing at the Month 12 completion of the pivotal trial (Table 17a). The status of all ongoing adverse events were followed through to study exit/completion for each subject in the long-term study. S018 (PD015): N/A Effectiveness Results: S014 (PD006) 1. The OFF Medication UPDRS Part III is shown in Figures 1a and 1b, and Table 6 and the UDysRS Objective Impairment is shown in Figures 2a and 2b, and Table 7 (Section 5.4.2 below). The UPDRS Part III and the UDysRS formed the basis of the Responder/Non-responder analysis at the Month 3 visit in the PMA. The Baseline, and Month 12 represent data already presented in the FDA approved PMA. This is included here for background reference, and trending comparison to the pivotal PMA study. Baseline scores were used to calculate change and percent change from baseline. Data listings for the MDS-UPDRS Part III – Motor Examination treated side extremities and the UDysRS Objective Impairment are presented in Appendix 1 and Appendix 2, respectively 2. The algorithms used to calculate the PD006 results in this report are the same as those for the PD006 as presented in the PMA (P380015/S14). The Crossover efficacy results through Month 3 were calculated using multiple imputation for missing values. The results presented in the following tables and figures were reported in the PMA and thus used multiple imputation. Post-PMA results are calculated using the observed data with no imputation. Since the sample size at Year 5 is n=2 the following tables and figures present Years 2-4; for Year 5 only basic sample statistics are presented in the tables. 3.We continue to follow subjects in the long term PD006 PAS. Although visit completion is ongoing in the main and crossover groups, the results overall are as expected and comparable to Month 12. Parkinson’s is a progressive disease, and the condition of subjects can be expected to worsen over time. However, we expect only minor differences between analyses and completed visits presented in the annual and final reports. S018 (PD015): N/A
Actual Number of Patients Enrolled	S014 (PD006): 90 S018 (PD015): 6 Randomization in PD006 was 3:1, Exablate:Sham Control. For analysis there were initially 68 subjects in the PD006 Main Group and 22 subjects in the PD006 Crossover Group.
Actual Number of Sites Enrolled	S014 (PD006): 16 S018 (PD015): 5
Patient Follow-up Rate	S014 (PD006): Follow-up has been completed, and all subjects have exited the study. On page 13, the sponsor provided the follow-up date from Y2 to Y5 are 72%, 71 %, 70%, and 69%. S018 (PD015): Six subjects have been enrolled, 3 of which have reached at least one follow-up timepoint. Results will begin to be analyzed for efficacy once a minimum of ten subjects have reached at least the 3-month follow-up timepoint.
General
Study Status	Ongoing
Application Number / Requirement Number	P140003 S111/ PAS001
Date Original Protocol Accepted	12/03/2024
Date Current Protocol Accepted	12/03/2024
Study Name	Impella CPSA/5.5 Real-World Pediatric Use Surv
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continue monitoring the performance of the Impella CP with SmartAssist and Impella 5.5 with SmartAssist systems in pediatric patients through the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Registry.
Study Population	Consecutive pediatric patients treated with the two systems that are entered into the ACTION Registry.
Sample Size	A total of 60 patients, with a minimum of 20 patients treated with Impella 5.5 with SmartAssist.
Key Study Endpoints	Survival and adverse events.
Follow-up Visits and Length of Follow-up	Through device explant
Interim or Final Data Summary
Interim Results	Safety Results: A total of four device malfunctions occurred. One device malfunction was reported for the Impella CP with SmartAssist device and attributed to flow alarms. Three device malfunctions were reported for Impella 5.5 with SmartAssist devices and attributed to purge system block, difficulty with initial delivery and malfunction of an internal sensor used for aortic and ventricular placement signal monitoring, respectively Reported adverse events include bleeding/major bleeding (4 subjects), cardiac arrhythmias- SVT requiring defibrillation or cardioversion (4 subjects), major infection/infection (3 subjects), neurological dysfunction (2 subjects), hemolysis (2 subjects), respiratory failure requiring re-intubation (2 subjects), right heart failure (2 subjects), hypertension (1 subject), renal dysfunction requiring dialysis or hemofiltration (1 subject), vascular injury (1 subject), VT requiring medication (1 subject), fungemia (1 subject), and hematoma at Impella cut down site (1 subject). Effectiveness Results: A total of twenty-two (22) left/systemic ventricular Impella devices were placed in twenty (20) subjects across fourteen (14) sites in the ACTION registry with a mean subject age of 16.1 years and mean BSA was 1.8 m2. The mean duration of use for Impella CP with SmartAssist was 11.5 days, and Impella 5.5 with SmartAssist was 42.5 days. Out of the eighteen subjects with left/systemic ventricular Impella device implant information reported, three subjects received an Impella CP with SmartAssist device, and fifteen subjects received an Impella 5.5 with SmartAssist device. One subject had an Impella 5.5 SmartAssist device implanted as a single ventricular assist device (SVAD).
Actual Number of Patients Enrolled	20
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	Seventeen subjects met the criteria for end of study status. Fourteen subjects had the left/systemic ventricular Impella removed for transplant or recovery, two subjects had explant for transplant, and one device was removed due to malfunction. At the end of the study three subjects had devices not functioning normally. All the subjects who had their left/systemic ventricular Impella devices removed were alive at the time of the report. Three subjects are still being supported by the left/systemic Impella at the time of report.
General
Study Status	Ongoing
Application Number / Requirement Number	P240031 / PAS001
Date Original Protocol Accepted	08/15/2025
Date Current Protocol Accepted	08/15/2025
Study Name	PAS of the Neuspera SNM in Patients with UUI
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the PAS is to assess the long-term safety and effectiveness of the Neuspera SNM System (assessed annually through 72 months post-implant) following commercial approval of the Neuspera SNM System. This is a prospective, multi-center, single-arm, post-approval study using the Neuspera SNM System for treatment of urge urinary incontinence (UUI) in subjects who have failed or could not tolerate more conservative treatment.
Study Population	Study population will include all Phase I and Phase II subjects from the SANS-UUI pivotal clinical study who sign the PAS informed consent form.
Sample Size	Number of subjects: up to 116 subjects (at least 93 subjects) At least 80% of the SANS-UUI cohort must be followed out to 72 months post procedure. Number of sites: 21 sites( The PAS will be conducted at the SANS-UUI Phase I and II study sites.) Site location: U.S. and Europe
Key Study Endpoints	Safety Endpoints Primary: The primary safety endpoint is defined as the incidence of device- and procedure-related AEs. The analysis of the endpoint is the proportion of subjects experiencing a device- and/or procedure-related AE at yearly intervals through the 72-month post-implant. Secondary: - Comprehensive summary of all adverse events (AEs) for the duration of study participation, including all device- or procedure-related adverse events, including but not limited to, burns, erosions, implant migrations and fractures, explantations, and revisions - The percentage of subjects with device-related serious adverse events reported - Device fracture and migration rates* - Revision rates* - Explantation rates* *The device fractures and migration rates, revision rates, and explantation rates will be reported to FDA annually post commercial approval through the 72-month timepoint. The report will include a detailed report of fractures and migrations, including when it occurred, any cause of fracture/migration that was noted and how it was measured, and how the issue was resolved. Effectiveness Endpoints Primary: The primary effectiveness endpoint is defined as the percentage of all implanted subjects who experience an improvement in UUI episodes of at least 50% or more (therapy responders) at yearly intervals through 72-month post-implant. A therapy responder is defined as experiencing =50% reduction in the number of UUI episodes, relative to the number of UUI episodes at baseline. Secondary: - Change from baseline in quality of life as measured and assessed by the total ICIQ-OABqol score - Change from baseline in mean number of UUI episodes - The percentage of subjects who experience an improvement in ICIQ-OABqol of at least 10 points - Change in urgent voids per day calculated across all diary episodes with at least mild urgency - Change in average number of daily voids from baseline in subjects with at least 8 voids at baseline - Change in quality of life measured from baseline as measured and assessed by the ICIQ-OABqol subscale scores - Change in Male/Female Lower Urinary Tract Symptoms questionnaire - Patient Global Impression of Improvement (PGI-I) measured after implant during follow-up - Device parameters including but not limited to voltage, pulse width, frequency, and stimulating electrode Patient compliance with therapy at every 6-month visit, as measured by the number of stimulation hours per day for seven (7) days immediately prior to the telephone reminder call and by actual use data (including the stimulation daily use and duration of time) collected in the WT log and patient app.
Follow-up Visits and Length of Follow-up	Frequency of Follow-up Visits and Length of Follow-up SANS-UUI subjects will be enrolled in the PAS within 3 months of FDA marketing approval of the Neuspera SNM System. Subject follow-up visits will start with the next visit following their last completed SANS-UUI study visit; for example, if their last visit in the SANS-UUI study was at 18 months, their first PAS follow-up visit will be at 24 months post-implant.
General
Study Status	Completed
Application Number / Requirement Number	P150038 / PAS001
Date Original Protocol Accepted	09/29/2016
Date Current Protocol Accepted
Study Name	Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Long-term prospective, observational clinical trial to follow device related safety, and long term effectiveness and quality of life for subjects previously treated with the ExAblate Neuro under the IDE G120246.
Study Population	The study population includes those patient that have undergone the ExAblate Neuro thalamotomy treatment for the treatment of medication refractory Essential Tremor under G120246.
Sample Size	There are three main cohorts from the original pivotal study that will be included in this long term follow-up study: 1. The main IDE (G120246) study population that was randomized, N=56. 2. The cross-over population, N=21 3. The population that was part of the Continued Access study, N=59
Key Study Endpoints	Safety: Safety of ExAblate will be determined by an evaluation of the incidence and severity of device / treatment related complications from the treatment day visit through ALL study follow ups through Year 5. Adverse events (type, frequency, severity) are expected to be similar to those of previous studies using ExAblate TcMRgFUS for Thalamotomy Effectiveness: Primary effectiveness will be assessed using the Clinical Rating Scale for Tremor (CRST) as scored by the site neurologist. Secondary effectiveness will be assessed by using the Quality of Life inn Essential Tremor (QUEST) Questionnaire.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	The safety profile of the Exablate thalamotomy procedure continues to maintain a favorable and relatively benign safety profile as demonstrated by the following: • No related adverse events were reported in either the Exablate Pivotal Cohort or the Exablate Crossover Cohort after Month 3. • The safety profile in the Exablate Continued Access Cohort is very similar and shows a similar favorable and relatively benign safety profile. The Primary and Secondary Endpoints of the Pivotal Study were calculated in similar manner for each of the other cohorts and presented in both tabular format and graphically as shown in the tables and figures below. To easily compare the differences between cohorts, these data are compared graphically in a bar chart to demonstrate that the effect observed in the pivotal portion is similar across cohorts and durable over time
Actual Number of Patients Enrolled	61
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	34 subjects were screen failed for the reasons such as SDR3 disqualification (13 subjects), Personal Health issues/ claustrophobia/ anxiety/ kyphosis (7 subjects), Cognitive impairment (4 subjects), Misdiagnosed-had PD (2 subjects), and other reasons
Final Safety Findings	The main safety data were presented in the Attachment 004 (P150038/R024) which included Appendix 1 with the Listing of Adverse Events inclusive of those reported in previous PAS reports. In addition, Attachment 003 presented the Ongoing AE Survival Tables (not shown) stratified by follow-up year, body system, and other groupings. The AE profile of the ET002CA cohort was characterized by Insightec as favorable, with no unexpected AEs.
Final Effect Findings	The site assessor scoring across all time points was used for consistency through long-term follow-up visits. The Primary and Secondary Endpoints were calculated in a manner similar to the Pivotal Study and presented in tabular and graphic formats.
Study Strengths & Weaknesses	The main strength of this Continued Access PAS is the 5-year follow-up duration including more than 95% of the original population at the 12 Month visit. Twenty-six subjects completed the 5 Year visit despite COVID-19 pandemic. With respect to effectiveness, the duration of tremor/motor function, posture and activities of daily living were sustained through year 5. Regarding safety, no new adverse events were observed during long term follow-up that were related to the device, procedure or thalamotomy. Furthermore, some of the unresolved events at the end of 12 Month follow-up continued to resolve with time. All events were followed using the worst severity ever reported during the study. With respect to weaknesses of the study, the continued access study was performed using the original independent comparator. However, the study design was the same as the pivotal trial with respect to the test arm and the results were similar (Figure 10). Additionally, the study was performed as a unilateral procedure and was performed on the subject’s tremor dominant arm. While some patients might benefit from bilateral treatment, clinically meaningful improvements were observed in the unilateral side that permitted subjects to show improvement in their long-term activities of daily living
Recommendations for Labeling Changes	For this population of subjects diagnosed with idiopathic ET with medication-refractory tremor, the Exablate Neuro treatment is a safe and effective treatment for their Essential Tremor. The result from the pivotal study showed that the treatment is efficacious and safe; most of the adverse events were mild or moderate in severity. Similarly, the data from the Continued Access study with 5-year long-term follow-up results continues to support the reasonable assurance of device safety and effectiveness when used in accordance with the indications for use.
General
Study Status	Completed
Application Number / Requirement Number	P150039 / PAS001
Date Original Protocol Accepted	02/21/2017
Date Current Protocol Accepted
Study Name	TRYTON Side Branch Stent PIVOTAL RCT
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	TRYTON Pivotal Randomized Controlled Trial (RCT) - a prospective, multicenter, single blind controlled study. Subjects were randomized 1:1 to the TRYTON Side Branch Stent with main branch approved DES or side branch balloon angioplasty (POBA) and main branch approved DES for treatment of native coronary artery bifurcation disease.
Study Population	N = 769 704 Randomized (355 TRYTON, 349 POBA) 65 Roll-In (TRYTON)
Sample Size	664 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA 318 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA
Key Study Endpoints	Primary endpoint: Target vessel failure [TVF, a composite of cardiac death, target vessel MI, and target vessel revascularization (TVR) involving the main branch or side branch] at 9 months Powered secondary angiographic endpoint: Angiographic in-segment percent diameter stenosis (%DS) in the side branch at 9 months Other secondary endpoints included a range of safety and effectiveness parameters including acute success, the individual components of TVF (cardiac death, target vessel MI, and TVR), all-cause mortality, rate of stent thrombosis and MACE (and the individual elements of MACE) evaluated at 30 days, 6 and 9 months and annually up to 3 years.
Follow-up Visits and Length of Follow-up	3 years post-index procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 769 patients were enrolled in the TRYTON Pivotal randomized controlled trial (RCT), which included 704 randomized patients in Europe, Israel, and the United States and 65 US roll-in (non-randomized Tryton Side Branch Stent) patients. In the randomized cohort, 355 subjects were in the Tryton Side Branch Stent group, and 349 subjects were in the balloon angioplasty (POBA) group.
Actual Number of Sites Enrolled	66 sites
Patient Follow-up Rate	All patients were scheduled to return for clinical follow-up assessments at 30 days, 6 months, 9 months, 1 year, 2 years, and 3 years post-index procedure. Angiographic follow-up at 9 months was obtained in the first 374 randomized patients (N=195 TRYTON cohort, N=181 POBA cohort). Of those enrolled in the angiographic subgroup, an intravascular ultrasound (IVUS) subgroup included 59 TRYTON patients and 35 POBA patients.
Final Safety Findings	The TRYTON Pivotal RCT evaluated the safety and effectiveness of the TRYTON Side Branch Stent with an approved main branch drug-eluting stent (DES) compared to side branch POBA and an approved main branch DES in the treatment of de novo native coronary artery bifurcation lesions (Medina Classification 1.1.1; 0.1.1; 1.0.1). Other anatomic inclusion criteria included a side branch diameter stenosis of greater than or equal to 50%, a lesion length less than or equal to 5.0 mm, and reference vessel diameters (RVDs) greater than or equal to 2.5 mm to less than or equal to 3.5 mm in the side branch and greater than or equal to 2.5 mm to =4.0 mm in the main branch. Key trial results for the ITT population are as follows: In the ITT population, treatment with the TRYTON Side Branch Stent did not meet the non-inferiority primary clinical endpoint of 9-month target vessel failure (TVF; a composite of cardiac death, target vessel myocardial infarction (MI), and clinically-driven target vessel revascularization) with a TVF rate of 17.2% (60/348) for the TRYTON group compared to a TVF rate of 12.6% (43/341) for the POBA group, principally due to a higher rate of periprocedural MI in the TRYTON Stent group defined by CK-MB elevations (most of which were not associated with clinical sequelae). Implantation of the TRYTON Stent was associated with low rates of stent thrombosis, clinically significant MIs, cardiac deaths, and clinically-driven target vessel revascularization through 3-years post-procedure. Clinically-driven TVR was slightly higher in the TRYTON Stent group vs. the POBA group. At 9-months post-index procedure, the side branch in-segment percent diameter stenosis (%DS) was significantly lower in the TRYTON group compared to the POBA group. A post hoc analysis of the primary and secondary endpoints in subjects with side branch RVD greater than or equal to 2.25 mm by QCA (>2.5 mm by visual assessment, the “Intended Population”) demonstrated the following: Treatment with the TRYTON Side Branch Stent was comparable to POBA for TVF at 9-months with a rate of 10.5% (15/143) for the TRYTON group and 14.8% (21/142) for the POBA group. Clinically-driven TVR rates were comparable in the TRYTON group and the POBA group. At 9-months post-index procedure, the side branch in-segment %DS was significantly lower in the TRYTON group compared to the POBA group. Long-term safety endpoint results showed no safety signals in the Tryton Stent group through 3-years post-procedure.
Study Strengths & Weaknesses	Operators enrolled many patients with inappropriately small sized side branches. Only 41% of the ITT population (146 TRYTON subjects and 143 POBA subjects) met the study criterion for a side branch RVD =2.25 mm per quantitative coronary angiography (QCA) assessment, which is generally equivalent to a greater than or equal to 2.5 mm diameter by visual estimation. Enrollment of patients with small side branches was the key factor in the TRYTON Side Branch Stent not meeting the non-inferiority primary clinical endpoint of 9-month TVF compared with POBA. When the primary endpoint analysis was limited to subjects with side branch RVD greater than to equal to 2.25 mm by QCA (the Intended Population), the 9-month TVF rate was 10.5% (15/143) in the TRYTON group compared to 14.8% (21/142) in the POBA group. Since this was a post-hoc analysis of a selected subgroup, a formal conclusion of non-inferiority of the Tryton Stent vs. POBA cannot be made. In response to the results of the Tryton Stent Pivotal RCT, the EA Confirmatory Study was initiated to: (1) Confirm the ability of physicians to enroll patients with appropriately-sized side branch diameters to accommodate the TRYTON Stent; (2) Confirm the acute safety profile of the TRYTON Stent (consistent with the post hoc analysis of the pivotal RCT Intended Population) by demonstrating an acceptable periprocedural MI rate; and (3) Confirm the other clinical outcomes observed in the Pivotal RCT Intended Population.
Recommendations for Labeling Changes	The sponsor will be requested to add the complete 3-year follow-up data to the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P150039 / PAS002
Date Original Protocol Accepted	02/21/2017
Date Current Protocol Accepted
Study Name	TRYTON Side Branch Stent EA Confirmatory
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	TRYTON Extended Access (EA) Confirmatory Study - a non-randomized, single arm extension of the TRYTON Pivotal RCT. Subjects were implanted with the TRYTON Side Branch Stent with main branch approved DES for treatment of native coronary artery bifurcation disease.
Study Population	N = 133 TRYTON patients
Sample Size	127 subjects yields 90% power to reject the following null hypothesis in favor of the corresponding alternative hypothesis: • H0: pTRY greater than or equal to 0.179 (or 17.9%) • H1: pTRY less than 0.179 (or 17.9%) Where pTRY is the primary endpoint rate in the DES+TRYTON. Six additional subjects to be enrolled to account for an expected 4% loss to follow-up before the primary endpoint was measured, so the total enrolled sample size was planned to be 133. Enrolling 127 subjects affords 90% power to compare the primary endpoint rate from the EA Study to a performance goal of 17.9%, assuming a true endpoint rate of 8.9% for DES+TRYTON.
Key Study Endpoints	Primary endpoint: Periprocedural MI defined as PCI CK-MB elevation with value >3 times the upper range limit within the first 48 hours after PCI. Key secondary endpoints included all-cause mortality, Major Adverse Cardiac Events (MACE), and rates of stent thrombosis using the ARC definition.
Follow-up Visits and Length of Follow-up	1 year post-index procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	133 subjects
Actual Number of Sites Enrolled	28 sites
Patient Follow-up Rate	All patients were scheduled to return for clinical follow-up assessments at 30 days and 12 months post-index procedure.
Final Safety Findings	The EA Confirmatory Study provided additional procedural safety data on the TRYTON Side Branch Stent. There were three (3) primary goals of the study: (1) Confirm the ability of physicians to enroll patients with appropriately-sized side branch diameters to accommodate the TRYTON Stent; (2) Confirm the acute safety profile of the TRYTON Stent (consistent with the post hoc analysis of the pivotal RCT Intended Population of patients with a QCA assessed side branch RVD greater than or equal to 2.25 mm) by demonstrating an acceptable periprocedural MI rate; and (3) Confirm the other clinical outcomes observed in the Pivotal RCT Intended Population. The key study results are as follows: Treatment with TRYTON Side Branch Stent met its primary endpoint with an observed periprocedural MI (PPMI) rate of 10.5%, which supports the acute safety profile of the TRYTON Stent seen in the TRYTON Pivotal RCT post hoc analysis of the Intended Population. Physicians were able to select patients with appropriately sized side branches (RVD greater than or equal to 2.5 mm (greater than or equal to 2.25 mm by QCA, the Intended Population) in 99.2% (132/133) of subjects.
Final Effect Findings	In the EA Confirmatory Study, the TVR rate was 9.6% (12/125) at 1-year, which was numerically higher than the TVR rate of 9.3% (32/343) in the Tryton Stent ITT subjects in the Pivotal RCT at 1-year and 6.3% (9/142) in the Intended Population (side branch RVD greater than or equal to 2.25 mm) Pivotal RCT subjects at 1-year. However, conclusions based on these data are limited by small sample sizes.
Study Strengths & Weaknesses	Operators were successful in selecting 99.2% (132/133) of bifurcation lesions with appropriately sized side branches (greater than or equal to 2.25 mm in diameter by QCA).
Recommendations for Labeling Changes	The sponsor will be requested to add the complete 12-month follow-up data to the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P150039 / PAS003
Date Original Protocol Accepted	07/13/2017
Date Current Protocol Accepted	10/04/2020
Study Name	TRYTON Side Branch New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To assure the continued safety and effectiveness of the Tryton Side Branch Stent™ with main branch approved DES in the treatment of de novo native coronary artery bifurcation lesions with side branch diameter ranging from greater than or equal to 2.5 mm to less than or equal to 3.5 mm and main branch diameter ranging from greater than or equal to 2.5 mm to less than or equal to 4.0 mm. -A prospective, single arm, open label multicenter registry of newly enrolled patients.
Study Population	U.S. patients with symptomatic, ischemic heart disease due to a stenotic bifurcation lesion located in a de novo native coronary artery, with side branch diameter ranging from greater than or equal to 2.5 mm to less than or equal to 3.5 mm and main branch diameter ranging from greater than or equal to 2.5 mm to less than or equal to 4.0 mm. Patients must meet all inclusion and exclusion criteria per labeling. The comparator is performance goal (TVF rate of 18.9% at 1 year) derived from the Tryton IDE Tryton intended cohort, greater than or equal to 2.25 mm subset.
Sample Size	A maximum of 335 subjects will be enrolled at minimum of 60 sites and a maximum of 85 sites in the US. Sample size assumptions are as follows: Primary endpoint: Incidence rate of TVF (cardiac death, myocardial infarction, target vessel re- vascularization) within 1 year of index procedure. 1-sided test at 0.5 significance level Power of 85% Expected TVF rate: 13.4% Sampling variability adjustment: 5.5% Reference TVF rate: 18.9% (13.4% + 5.5%) Expected missing data/attrition: 10% A continuity-corrected normal approximation (z-test) to the binomial distribution was used in the determination of the sample size. A sub study of the first 150 patients treated by inexperienced operators will be enrolled and evaluated by the Angiographic Core Laboratory to assess side branch reference vessel diameter.
Key Study Endpoints	Primary Endpoint • TVF rate at 1 year post index procedure. TVF is a composite rate of cardiac death, target vessel myocardial infarction (Q Wave and Non-Q wave MI), and clinically driven TVR. Secondary Endpoints 1. Device success, defined as attainment of <30% residual stenosis within the side branch without device malfunction 2. Lesion success, defined as attainment of <30% residual stenosis using any percutaneous method 3. Procedure success, defined as lesion success without malfunction or in-hospital MACE, (cardiac death, Q wave or non-Q wave MI, or repeat revascularization of the target lesion during the hospital stay), and the following secondary endpoints which will be evaluated at 30 days, and annually to 3 years. 4. All-cause and cardiac mortality, 5. Myocardial infarction (MI), Q wave and non-Q wave 6. Clinically driven target lesion revascularization (CD- TLR) 7. Clinically driven target vessel revascularization (CD- TVR) 8. Stent thrombosis, using ARC definition of definite and probable
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	30
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	100% (30/30) at 1 year (primary endpoint); 37% (11/30) at 2 years when study terminated
Final Safety Findings	CEC-adjudicated event rates through 1 year are as follows: Stent thrombosis (ARC definite, probable)- 0.0% (0/30) MI (Peri-procedural after PCI) – 10.3% (3/29) MI (Spontaneous) – 3.3% (1/30) All-cause and cardiac death – 0.0% (0/30)
Final Effect Findings	CEC-adjudicated event rates through 1 year are as follows: Target vessel failure (primary endpoint) – 13.3% (4/30) Clinically driven target lesion revascularization – 0.0% (0/30) Clinically driven target vessel revascularization – 3.3% (1/30) Device success – 96.7% (29/30) Lesion success – 100% (30/30) Procedure success – 90.0% (27/30)
Study Strengths & Weaknesses	Due to difficulties with enrollment, only 30 of the planned 335 subjects were enrolled. Therefore, no statistical conclusions can be drawn from the results. The results reported are similar to those seen in the pivotal study and confirmatory study.
Recommendations for Labeling Changes	No. The TRYTON Side Branch Stent is no longer marketed.
General
Study Status	Completed
Application Number / Requirement Number	P150040 S003/ PAS001
Date Original Protocol Accepted	07/25/2019
Date Current Protocol Accepted	04/13/2023
Study Name	VisuMax SMILE New Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is designed to evaluate the patient experience of visual symptoms 6 months after bilateral treatment with the VisuMax SMILE procedure as measured by the Patient-Reported Outcomes with LASIK (PROWL) patient questionnaire. The study will be conducted in two phases. Phase 1 (validation phase) will evaluate the content of the PROWL questionnaire for use with patients previously treated with the SMILE procedure. Phase 2 is a prospective, multicenter, single arm, open-label, observational study of newly enrolled patients undergoing bilateral treatment with the approved SMILE procedure for the reduction or elimination of myopia with or without astigmatism. Each patient’s preoperative status is serving as the control for post-operative endpoints.
Study Population	The validation phase will enroll one group of five (5) to eight (8) patients P150040-S003 VisuMax Femtosecond Laser that have undergone bilateral SMILE for the reduction or elimination of myopia at least 6 months prior, and another group of five (5) to eight (8) patients that have undergone SMILE with astigmatism at least 6 months prior. The validation phase will be conducted at one (1) study site in the U.S.A. The phase 2 study will enroll and treat a maximum of 171 patients undergoing bilateral treatment with the approved SMILE procedure for the reduction or elimination of myopia with or without astigmatism from six (6) to ten (10) investigational sites in the U.S.A.
Sample Size	171 subjects from up to 10 investigational sites. Assuming a 10% of loss to follow-up rate, 171 patients are to be treated to ensure 154 evaluable patients at 6 months of follow up to estimate the primary study endpoints
Key Study Endpoints	All study endpoints refer to assessments based on responses to the corresponding scales of the PROWL questionnaire including: Visual symptoms for double images, glare, halo, and starburst (8 items each, total 32 items), Ocular Surface Disease Index (OSDI) scales for dry eye symptoms and environmental triggers (8 items), Satisfaction with current vision (1 item), Satisfaction with SMILE surgery (8 items). Specific study endpoints include: Primary Safety Outcomes: (PROWL) Development of clinically relevant visual symptoms: Proportion of patients that developed “very” or “extremely” bothersome visual symptoms from preoperative to 6 months postoperatively Proportion of patients that developed difficulty performing daily activities (2 highest categories) due to visual symptoms from preoperative to 6 months postoperatively Sbothersome visual symptoms from preoperative to 6 months postoperatively Proportion of patients that showed resolution of difficulty performing daily activities (2 highest categories) due to visual symptoms from preoperative to 6 months postoperatively Development and resolution of all visual symptoms: Proportion of patients that developed visual symptoms from preoperative to 6 months postoperatively Proportion of patients that showed resolution of visual symptoms from preoperative to 6 months postoperatively Dry eye: Proportion of patients that developed dry eye symptoms as compared to their preoperative status (OSDI score from normal at preoperative to abnormal at 6 months; categorized according to Miller et al. 2010) Proportion of patients that showed resolution of dry eye symptoms as compared to their preoperative status (OSDI score from abnormal at preoperative to normal at 6 months; categorized according to Miller et al. 2010) Satisfaction: Proportion of patients satisfied with their vision after the SMILE procedure (i.e. “completely satisfied”, “very satisfied”, or “somewhat satisfied” to the corresponding questionnaire item) Proportion of patients satisfied with the SMILE procedure (based on a score = 40 in the corresponding 8-item questionnaire domain) Distribution analyses to be performed: Visual symptoms: Distribution of visual symptoms pre- and 6 months postoperatively (with and without optical correction) Distribution of grades of bothersome visual symptoms pre- and 6 months postoperatively (with and without optical correction) Distribution of grades of difficulty with daily activities due to visual symptoms pre- and 6 months postoperatively (with and without optical correction)econdary study endpoints Resolution of clinically relevant visual symptoms: Proportion of patients that showed resolution of “very” or “extremely”
Follow-up Visits and Length of Follow-up	Eligible patients who are enrolled in the study will be followed for 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	186 subjects enrolled (15 withdrew prior to treatment) 171 subjects treated
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	Of treated subjects: 12/171 (7.0%) Discontinued or Lost to Follow-Up 159/171 (93.0%) Completed (final visit at 6-months)
Final Safety Findings	The primary study endpoints for safety were the changes in patient-reported outcomes of more severe visual symptoms, evaluating responses at the 6-month postoperative visit compared to those at baseline. - The percent of subjects that developed “very” or “extremely” bothersome visual symptoms was 11.3% (18/159) at 6-months. [34% (54/159) of patients had this level of visual symptoms at baseline that were resolved at 6-months] - The percent of subjects (assessed at 6-months post-op) that developed “very” or “extreme” difficulty performing daily activities due to visual symptoms was 1.3% (2/159). [14.4% (7/159) of patients had this level of difficulty performing activities at baseline that were resolved at 6-months] Adverse Events There were no serious adverse events reported in this study. No subjects were discontinued due to adverse events.
Final Effect Findings	The key study endpoints related to effectiveness were the patient-reported outcomes of “satisfaction” evaluating responses at the 6-month postoperative visit. The percent of subjects reporting that they were “completely,” “very,” or “somewhat” satisfied with vision after the SMILE procedure was 98.7% (157/159). - The percent of subjects reporting that they were “completely,” “very,” or “somewhat” satisfied with the SMILE procedure was 96.2% (153/159).
Study Strengths & Weaknesses	Study Strengths: The study collected patient-reported outcomes related to both safety and effectiveness of the SMILE (Small Incision Lenticule Extraction) procedure using a patient questionnaire demonstrated to have validity for subjects who received this specific type of refractive surgery that involves extraction of a corneal lenticule created through a femtosecond laser procedure. (The study included a preliminary phase to validate the questionnaire for this population.) Study Weaknesses: Because the study was focused mainly on how patient-reported outcomes changed from baseline to the final visit, the protocol called for only a single scheduled postoperative visit (at 6-months). This may have limited reporting of some adverse events, complications, or symptoms.
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P130021 S033/ PAS001
Date Original Protocol Accepted	07/10/2017
Date Current Protocol Accepted	12/23/2023
Study Name	Cont f/u Intermediate Risk Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the SURTAVI trial under the IDE (G120169). The objective of this PAS is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, acute kidney injury at stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	At 96 months: All-cause mortality (Without Vital Status): 57.3% (TAVR); 48.6% (SAVR) All-cause mortality (With Vital Status): 59.4% (TAVR); 52.3% (SAVR) All stroke: 17.1% (TAVR); 19.5% (SAVR) TIA: 10.3% (TAVR); 6.1% (SAVR) MI: 13.1% (TAVR); 6.9% (SAVR) Reintervention: 8.3% (TAVR); 4.5% (SAVR) New permanent pacemaker implantation: 45% (TAVR); 20.8% (SAVR) Prosthetic valve endocarditis: 3.7% (TAVR); 3.2% (SAVR) Prosthetic valve thrombosis: 1.2% (TAVR); 0.8% (SAVR) NYHA Mean Change from Baseline (84 months): -0.9 (TAVR); -1.1 (SAVR) Transvalvular mean gradient (site reported): 9.57 (TAVR); 11.75 (SAVR) Mean Effective orifice area (site reported): 1.88 (TAVR); 1.60 (SAVR) Greater than or equal to Moderate Total Aortic Regurgitation (site reported): 8.4% (TAVR); 3.7% (SAVR)
Actual Number of Patients Enrolled	1746 enrolled; 1660 attempted implanted (864 TAVR and 796 SAVR)
Actual Number of Sites Enrolled	87
Patient Follow-up Rate	At 96 months (patient status known): TAVR: 87% SAVR: 76%
General
Study Status	Ongoing
Application Number / Requirement Number	P150048 / PAS001
Date Original Protocol Accepted	07/29/2017
Date Current Protocol Accepted	09/21/2017
Study Name	PAS Aortic Continued Follow-up
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to collect continued follow-up of the premarket cohort and characterize the long-term safety and effectiveness of the Edwards Pericardial Aortic Bioprosthesis, Model 11000A.
Study Population	Study Population: Patients implanted with the Pericardial Aortic Bioprosthesis, Model 11000A. Indication: The Pericardial Aortic Bioprosthesis, Model 11000A, is indicated for the replacement of native or prosthetic aortic heart valves.
Sample Size	222 patients, 3 sites
Key Study Endpoints	The primary safety endpoint is the rate of implanted subjects that experience structural deterioration of Model 11000A. The secondary safety endpoints evaluates the following: thromboembolism, valve thrombosis, all bleeding/hemorrhage, major bleeding/hemorrhage, all/major paravalvular leak, non-structural valve deterioration, endocarditis, all-cause mortality, trial valve-related mortality, trial valve-related reoperation, explant, and hemolysis.
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P150048 / PAS002
Date Original Protocol Accepted	01/08/2018
Date Current Protocol Accepted	07/28/2023
Study Name	Model 11500A Prospective PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, observational, non-blinded cohort study with no active current control. The primary objective is to capture adverse event information andvalve measurement data from dysfunctional INSPIRIS RESILIA aortic valves before and after valve-in-valve (ViV) treatment. This is a new enrollment study.
Study Population	Adults age 18 or older at the time of the scheduled TAVR ViV treatment, determined to need routine ViV placement of an Edwards transcatheter aortic heart valve (TAVR) FDA-approved for ViV within a dysfunctional 19mm to 25mm Edwards INSPIRIS RESILIA aortic valve. Sizes 27mm and 29mm valves are not candidates for surveillance under this protocol.
Sample Size	50 subjects
Key Study Endpoints	Primary effectiveness endpoints (pre-ViV, early post-ViV and 3- month post-ViV): Quantitative measurements of the inner area of 19mm- 25mm INSPIRIS RESILIA aortic valves. Measurements will be taken prior to ViV placement (“pre-ViV”), after placement at discharge or Day 7 post ViV whichever comes first (“early post-ViV”) and 3-months following the ViV procedure (“3- months post-ViV”). Primary safety endpoints (up to 30 days): The composite endpoint for transcatheter aortic valve implantation evaluated up to 30 days. The composite endpoint consists of all-cause mortality, all stroke (disabling and non- disabling), life-threatening bleeding, acute kidney injury – stage 2 or 3 (including renal replacement therapy), coronary artery obstruction requiringintervention, majorvascularcomplication, and valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR). Secondary safety endpoints (through 3 months): Myocardial Infraction, conduction disturbance requiring pacemaker, transient ischemic attack, hemorrhagic stroke, device fracture, new requirement for dialysis, unplanned other cardiac surgery or intervention (excluding AVR or PCI), PCI, non- valve related readmission, minor vascular complication, major bleeding event, endocarditis, conduction disturbance requiring ICD, ischemic stroke, undetermined stroke, device thrombosis, aortic valve re-intervention, unplanned vascular surgery or intervention (for bleeding or access site complication), valve related readmission, major vascular complication, transapical related event, life threatening bleeding.
Follow-up Visits and Length of Follow-up	Three months after TAVR ViV treatment.
Interim or Final Data Summary
Interim Results	Number of study sites enrolled As of June 2020, there was no study site enrolled yet. Number of subjects enrolled As of June 2020, there was no subjects enrolled yet.
General
Study Status	Ongoing
Application Number / Requirement Number	P150035 S003/ PAS001
Date Original Protocol Accepted	06/29/2023
Date Current Protocol Accepted	11/22/2024
Study Name	Aveir DR Real-World Evidence Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post-approval study (PAS) is to evaluate the long-term safety of the dual-chamber Aveir Leadless Pacemaker device (aka DR LP) using real-world evidence (RWE) methods. The study utilizes a real-world evidence method merging multiple real-world datasets from Abbott and CMS to assess the Aveir DR LP safety in a large patient population.
Study Population	All de novo patients implanted with the Aveir DR LP who successfully link to Medicare FFS data will be included in the analysis, starting at market approval and continuing for approximately one year or longer, if necessary, to include a minimum of 1,805 subjects. Patients implanted with an Aveir atrial LP only (i.e., without a ventricular LP) will be analyzed in additional analysis and not in the primary and secondary analyses.
Sample Size	1805
Key Study Endpoints	Primary Endpoints: 1. Acute complications through 30 days post implant procedure 2. Freedom from chronic complications from 31 days through 5 years post implant procedure Secondary Endpoints: 1. Complication rate of the Aveir DR LP for key individual acute and chronic complications 2. Care of subjects at the end of device service Descriptive Endpoints and Analyses: 1. Rates of other procedure-related acute complications 2. Survival at 5 years 3. Device longevity 4. Device longevity by device (atrial, ventricular) 5. Acute complications by device (atrial, ventricular) 6. Chronic complications by device (atrial, ventricular) Additional analyses include: 1. Cohort demographics and comorbidities 2. Device-device interaction 3. Effect of implanter experience with DR leadless pacemakers 4. Acute and chronic complications in patients with an atrial LP only 5. Battery performance 6. i2i performance 7. Acute and chronic complications in all Aveir patients (de novo and non de novo)
Follow-up Visits and Length of Follow-up	The study completion is 5 years after the final implant.
Interim or Final Data Summary
Interim Results	Safety Results: The key acute complication rate through 30 days post implant was 6.6% (95% CI 5.7%-7.6%) as of the data cut-off date for 2,793 implants in the primary de novo analysis group. The primary de novo cohort includes subjects implanted with both AVEIR DR devices (atrial and ventricular LPs) that meet the de novo criteria defined as subjects who do not have evidence of a prior Cardiac Implantable Electronic Device (CIED). A CIED includes a leadless single-chamber pacemaker, transvenous single-chamber pacemaker, dual-chamber leadless pacemaker, dual-chamber transvenous pacemaker, implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy pacemaker (CRT-P) or defibrillator (CRTD). Effectiveness Results: Freedom from key chronic complications from 31 days to 5 years post implant was evaluated through 24-months based on data available through the data cut-off date for this 36-month report. The event-free survival rate was 99.4% at 24-months post implant for 2,793 implants in the primary de novo analysis group.
Actual Number of Patients Enrolled	5169
Actual Number of Sites Enrolled	589 enrolled
Patient Follow-up Rate	N/A
General
Study Status	Completed
Application Number / Requirement Number	P070008 S079/ PAS001
Date Original Protocol Accepted	05/04/2017
Date Current Protocol Accepted	09/24/2019
Study Name	QP ExCELS Sentus QP Ext CRT w/ Quad LV
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Confirm long-term safety of the Biotronik Sentus OTW QP left ventricular pacing leads. The evaluation of safety will be freedom from Sentus QP related complications at 5 years post-implant.
Study Population	CRT-eligible Heart Failure patients
Sample Size	Postmarket Sample Size Required: 979 Postmarket Sample Size Required including attrition = 1754
Key Study Endpoints	Primary Endpoint: The purpose is to evaluate the long-term Sentus related complication-free rate through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	2872
Actual Number of Sites Enrolled	N/A - RWE
Patient Follow-up Rate	N/A - RWE
Final Safety Findings	Primary safety objective of complication-free rate (CFR) greater than 92.5% at 5 years post-implant for Sentus LV leads was met. 84 complications noted in 2920 Sentus leads. Lower bound of the two-sided 95% confidence interval of CFR was 92.72%.
Final Effect Findings	N/A
Study Strengths & Weaknesses	This study’s use of real-world data captures a large representative assessment of device performance. While data granularity is limited, the study confirms there are no significant safety concerns with the device’s long term performance.
Recommendations for Labeling Changes	Labeling changes should include the study design, results, and strengths and weaknesses of the PAS.
General
Study Status	Hold
Application Number / Requirement Number	P160001 S020/ PAS001
Date Original Protocol Accepted	07/05/2019
Date Current Protocol Accepted
Study Name	Obalon NTS Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: New enrollment, single cohort group, prospective, observational, open-label, and multi-center study Objective: To collect continued safety and performance of the Obalon Navigation-Touch System (NTS) in the commercial setting and confirm safety results observed in the pre-market approval IDE study. Additionally, the study will evaluate the risk of esophageal inflation during balloon administration with the Obalon NTS.
Study Population	The study will have a single cohort group that includes subjects who commercially purchased the Obalon Balloon System intended to be administered with NTS and have consented to have their data collected to support this study. Not all subjects who are consented are considered enrolled in the study. Subjects may be enrolled in the study after they meet all the eligibility criteria based upon demographics and commercial Obalon therapy eligibility. To be eligible for enrollment subjects must meet the following criteria: Inclusion Criteria The study will have a single cohort group that includes subjects who commercially purchased the Obalon Balloon System intended to be administered with NTS and have consented to have their data collected to support this study. Not all subjects who are consented are considered enrolled in the study. Subjects may be enrolled in the study after they meet all the eligibility criteria based upon demographics and commercial Obalon therapy eligibility. To be eligible for enrollment subjects must meet the following criteria: Inclusion Criteria Subjects may be included if they satisfy the following: 1. Ages 22 years and older 2. Starting therapy or current BMI of 30.0-40.0 kg/m2 1. Commercially purchased the Obalon Balloon Device Exclusion Criteria Subjects will be excluded if they satisfy the following: 1. Known history of structural or functional disorders of the esophagus that may impede passage of the device through the gastrointestinal tract or increase risk of esophageal damage during an endoscopic removal procedure, including, Barrett’s esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, esophageal diverticula, esophageal perforation or any other disorder of the esophagus. 2. Known history of structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug refractory esophageal reflux symptoms. 3. Known history of structural or functional disorders of the stomach including, gastroparesis, gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (> 2 cm), cancer or any other disorder of the stomach. 4. Active implantable devices, such as a pacemaker or defibrillator, or with metal implants in the thoracic region. Sites are required to maintain all the study activity records for every subject who signed an IRB approved informed consent and document the reason for every subject who does not meet all the enrollment eligibility criteria in the enrollment log. Sites will maintain a list of all subjects consented. All subjects that are enrolled will be entered into the Electronic Data Capture System.
Sample Size	The study is to be performed at up to 40 sites in the United States. The study enrollment is a minimum of 3,951 balloon administrations with at least 1,317 balloon administrations for an individual balloon number (1st, 2nd, or 3rd) with Obalon NTS. Subject enrollment will include a minimum of one balloon administration and up to three total. The study will enroll a minimum of 1,400 and maximum of 1,600 subjects with least 1,000/1600 (at least 62.5%) subjects receiving all three balloons. Sites can perform up to 20% of the total study balloon administrations (approximately 792 evaluable balloon administrations or 264 for each individual balloon type).
Key Study Endpoints	Primary and Secondary Endpoints The study primary endpoint is to evaluate safety and performance of Obalon Balloon System administrations when using the Obalon Navigation/Touch System. Co-Primary Endpoints The endpoints will be evaluated based upon the percentage of Obalon Balloon administrations using the Obalon NTS with: • For 100% of balloon administrations, there will be zero unexpected esophageal inflations and the 97.5% one-sided upper exact confidence bound for the estimated esophageal inflation rate is less than 0.1%; • System Success, defined as appropriate inflation in the stomach with the use of the NTS only (without radiography) or correctly determining failed balloon transit (device in the esophagus) as confirmed by endoscopic removal. The endpoint is met if the one-sided 97.5% lower exact confidence bound is greater than 97%.
Follow-up Visits and Length of Follow-up	No follow-up is included in the study
General
Study Status	Ongoing
Application Number / Requirement Number	P170036 / PAS001
Date Original Protocol Accepted	08/02/2019
Date Current Protocol Accepted	10/08/2020
Study Name	M6-C Artificial Cervical Disc-Extended Follow-up
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the 10-year long-term safety and effectiveness of the M6-C™ Artificial Cervical Disc in subjects with symptomatic cervical radiculopathy with or without cord compression. Design: A continuation of the Prospective, multi-center, concurrently controlled IDE Study population to evaluate the long-term safety and effectiveness of the M6-C™ Artificial Cervical Disc.
Study Population	Treatment group: M6-C™ Artificial Cervical Disc Control group: Anterior Cervical Discectomy and Fusion (ACDF)
Sample Size	Expected 122 M6-C™ IDE subjects and 53 ACDF control subjects
Key Study Endpoints	Safety Endpoints: The evaluation of all adverse events including device related, device procedure related, and additional serious adverse events Explant and histological analysis Subsequent surgical interventions Neurological function Effectiveness Endpoints: Neck Disability Index (NDI) Neck and arm pain - Visual Analog Scale (VAS) Patient Satisfaction Quantitative and qualitative radiographic assessments. In addition to endpoints studied for the PMA, these assessments will be used to evaluate range of motion and adjacent segment degeneration.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results As of the time of this report, no statistically significant differences are observed between M6-C and the concurrently-enrolled ACDF groups in the rates of any adverse event, any serious adverse event, and device- or procedure- related adverse events. The most commonly reported adverse events in the study to date are Dysphasia/Dysphonia, Neck and/or Arm Pain, Neurologic complications. Effectiveness results: Effectiveness Results Significantly lower mean NDI scores are observed for the M6-C group at most post-operative time points, and a greater mean improvement in NDI is observed for M6-C subjects, compared to ACDF, at most post-operative assessment intervals. Similar benefits are observed for Neck and Shoulder/Arm Pain, as measured by the Visual Analogue Scale. Health and quality of life, as measured by the SF-12, reveal a greater benefit associated with M6-C as compared to ACDF in both Physical and Mental Health components.
Actual Number of Patients Enrolled	151
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	Follow-up Rate 95.4% for the investigation group and 93.6% for the control group at 72 months 90.8% for the investigational group and 70.2% for the control group at 96 months
General
Study Status	Completed
Application Number / Requirement Number	P160001 / PAS001
Date Original Protocol Accepted	07/19/2017
Date Current Protocol Accepted	10/18/2019
Study Name	Obalon Balloon System PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	*Please Note: P160001 and P160001/S003 are bundled* Design: New enrollment, prospective, single arm, observational, sequentially enrolling, open label multi-center study. Objective: The primary objective of the study is to assess the continued safety and performance of the Obalon Balloon System in the commercial setting.
Study Population	In addition to the patients’ ability to commercially purchase the device, patients shall meet all inclusion criteria and no exclusion criteria to be considered eligible for study enrollment. Inclusion Criteria 1. Minimum 22 years of age 2. BMI of 30.0-40.0 kg/m2 3. Previously attempted to lose weight unsuccessfully using a medically supervised or non-medically supervised diet 4. Study enrollment before or within 7 days of the initial balloon administration. Exclusion Criteria 1. Contraindicated for use of the Obalon Balloon System per Obalon Balloon System, Instructions for Use (LIT-7500-0011, page 3) 2. Use of medications or medical devices known to induce weight gain or weight loss within the preceding 6 months. 3. Known history of endocrine disorders affecting weight. 4. Participation in any clinical study which could affect weight loss within the past year. 5. Known history or present condition of structural or functional disorders of the esophagus that may impede passage of the device through the gastrointestinal tract, including, Barrett’s esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, diverticula, or any other disorder of the esophagus. 6. Life expectancy less than 1 year or severe renal, hepatic, pulmonary or other medical condition, in the opinion of the investigator.
Sample Size	The study will include 16 sites in the United States. A total of 200 subjects will be enrolled. Of the enrolled subjects, 180 are needed with data through 6 months. No single site is allowed to treat more than 15% of the maximum total or 30 patients.
Key Study Endpoints	Primary and Secondary Endpoints Safety Endpoints The study primary endpoint is a safety endpoint that evaluates the percentage of subjects who experience a Serious Adverse Event that is device or procedure related. Device or Procedure Related Serious Adverse Event Rate The percentage of subjects who experience a Serious Adverse Event that is device or procedure related will be evaluated. Effectiveness Endpoints This trial is designed to evaluate co-secondary effectiveness endpoints comprised of (1) the mean % TWL and (2) the proportion of subjects achieving at least 5% TWL. Co-Secondary Endpoint: Mean Percent Total Weight Loss The mean percent Total Weight Loss (%TWL) will be evaluated as the first portion of the co-primary endpoint. %TWL is calculated as the ratio of a subject’s weight loss to their starting weight as measured on the date of their first course, first administration procedure. Co-Secondary Endpoint: 5% TWL Responder Rate The responder rate will be evaluated as the second portion of the co-secondary endpoint. For the purpose of this co-secondary endpoint, a responder is defined as a subject that achieves at least 5% TWL based on their starting weight as measured on the date of receiving their first balloon.
Follow-up Visits and Length of Follow-up	52 weeks. Patient participation time includes up to 4 weeks for screening, 24 weeks of balloon therapy period and 24 weeks post-balloon removal. Patients will be followed after post-balloon removal regardless of weight loss results during balloon therapy period.
Interim or Final Data Summary
Actual Number of Patients Enrolled	201 subjects
Actual Number of Sites Enrolled	18 sites
Patient Follow-up Rate	201 (100% completed phase I of the study (end of balloon therapy). 180 (89.6%) completed phase II (1-Year Follow-up).
Final Safety Findings	All Adverse Events: 879 in 167 subjects. Serious Adverse Events: 0 device/procedure related; 1 Not Device/procedure related. Most of the adverse events (94.2%) are classified as mild. The most common reported adverse events are nausea (76.6%), retching (48.8%), vomiting (41.8%), and abdominal pain (16.9%). The other reported adverse events are observed in less than 10% of subjects.
Final Effect Findings	Weight loss data from 197 (98%) of the subjects that completed balloon therapy subjects is included in the results. Four (4) subjects were lost to follow-up. The mean weight loss results were 20.3 lbs. and 9.4% TBL. The mean weight loss results were higher compared to the pivotal SMART Study (14.4 lbs. and 6.6% TBL).
Study Strengths & Weaknesses	Strengths: Large enough sample size of sites (18) and patients (201) Weaknesses: No concomitant comparator group
Recommendations for Labeling Changes	Yes, the results of the post-approval study must be included in the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P160004 / PAS001
Study Name	Continued F/u Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a continued follow-up of the pre-market cohort (PCE 09-02). The PCE 09-02 study is a prospective, randomized, multi-center trial designed to study the long term safety and effectiveness of the GORE TIGRIS vascular stent when used in the treatment of atherosclerotic lesions of the superficial femoral and proximal popliteal arties.
Study Population	Subjects with the Tigris Stent and the Lifestent Comparator device
Sample Size	All 218 remaining subjects (56 subjects have completed or withdrawn from the study) of the 274 original study subjects enrolled in the PCE 09-02 study from 36 investigational sites.
Key Study Endpoints	Primary Effectiveness Endpoint: Primary Patency at 36 months after implant Secondary Endpoints: At 2 and 3 years post-implant Freedom from MAE (death, TVR, or index limb amputation) Freedom from TVR Freedom from TLR Rutherford Improvement: Improvement in Rutherford Classification by at least 1 class Ankle-Brachial Index (ABI) from pre-procedure Quality of Life: Change in overall Quality of Life (EQ-5D) and disease-specific Quality of Life (Peripheral Artery Questionnaire [PAQ]) from Baseline Primary patency at 24 months Assisted primary patency Secondary patency Freedom from fracture
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	274
Actual Number of Sites Enrolled	36
Patient Follow-up Rate	All follow-up visits for enrolled subjects through 36 months are complete with a total of 171 (87.7%) subjects who participated in the last 36 month visit on 30 Jun 2017. Two (2) additional subjects who were unable to physically attend the 36 month visit were able to call the site with completed questionnaires.
Final Safety Findings	Estimates of freedom from MAE (survival probability) for the GORE® TIGRIS® device (56.3%) are similar to the Bard® LifeStent® (59.7%) through the end of study at 36 months.
Final Effect Findings	The primary endpoint in this study is primary patency at 36 months after implantation, defined as uninterrupted patency without target lesion revascularization (TLR), including the proximal and distal margins, and no restenosis as documented by a peak systolic velocity ratio (PSVR) =2.5 by Color Doppler Ultrasound (CDUS). There is a similar primary patency rate at 36 months when comparing nominal values (46.0% Lifestent vs. 53.5% Tigris). The nominal difference between the groups with regard to TLR was smaller (63.8% Lifestent vs 65.7% Tigris) than the difference patency rates.
Study Strengths & Weaknesses	The follow-up compliance and study deviations were within reasonable expectations.
Recommendations for Labeling Changes	No additional information is available from these results that contradicts the information already contained in the publicly available SSED and labeling. Therefore, no labeling changes are recommended
General
Study Status	Ongoing
Application Number / Requirement Number	P160013 S002/ PAS002
Date Original Protocol Accepted	05/31/2019
Date Current Protocol Accepted	06/28/2023
Study Name	OCS-LUNG-PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm, prospective, multi-center post-approval U.S. registry study on double lung transplant recipients whose donor lungs were preserved on the OCS™ Lung System. This all-comers registry is designed to evaluate short- and long-term safety and effectiveness of the OCS™ Lung System for lung transplantation in a real-world setting.
Study Population	This is a single-arm study on double lung transplant recipients whose donor lungs were preserved on the OCS™ Lung System.
Sample Size	Enrollment of the SCDL Primary Analysis Population will continue until 266 eligible DLIDU Primary Analysis Population Recipients have been enrolled.
Key Study Endpoints	The primary effectiveness endpoint is 12-month patient and graft survival post double-lung transplant. Secondary effectiveness endpoints include: Standard Criteria Donor Lungs: Total ischemic time for OCS™-preserved lungs Incidence of Primary Graft Dysfunction (PGD) grade 3 within the initial 72 hours post-transplantation (T0, T24, T48, and T72 hours) Donor Lungs Initially Deemed Unacceptable for Procurement and Transplantation: Incidence of PGD grade 3 at T72 hours post-transplantation Donor lung utilization rate Incidence of PGD grade 3 within the initial 72 hours post transplantation Other Endpoints: For Both SCDLU and DLIDU: Number of lung graft-related serious adverse events (SAEs) through 30 days post-transplant or through initial transplant surgical admission if longer than 30 days, per subject, consisting of the following SAEs (at most one per type): Bronchial anastomotic complications Major pulmonary-related infection Survival incidence (simple proportion) at 30 days Survival incidence (simple proportion) at initial transplant surgery hospital discharge, if longer than 30 days Incidence of PGD3 at T72 hours Total ischemia and cross-clamp times for 1st and 2nd transplanted lungs Kaplan-Meier patient survival estimated at Month 1, 6, 12, 24, 36, 48 and 60 Kaplan-Meier BOS-free survival estimated at Month 12, 24, 36, 48 and 60 Kaplan-Meier Freedom from BOS and grading estimated at Month 12, 24, 36, 48 and 60 Kaplan-Meier graft survival (freedom from re-transplantation/graft failure) estimated at Month 12, 24, 36, 48 and 60
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	458
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	9 patients lost to follow-up
General
Study Status	Completed
Application Number / Requirement Number	P160036 / PAS001
Date Original Protocol Accepted	11/29/2019
Date Current Protocol Accepted
Study Name	Hintermann Series H3 TAR Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Other Data Source
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this single-center, single arm study is to determine the 10-year survivorship and effectiveness of total ankle arthroplasty using the H3 TAR System in comparison to historical literature controls for a legally marketed mobile bearing ankle.
Study Population	Primary Safety and Effectiveness Cohort from the PMA
Sample Size	All living subjects (n=298) from the Updated PSE cohort that were included in the PMA will continue to be followed until they reach the 10-year postoperative interval.
Key Study Endpoints	The primary effectiveness measurement for this study is a composite of the following parameters: AOFAS Score Survivorship (absence of removal/revisions to include polyethylene revision), Percentage of subjects with a serious device-related adverse event other than a revision or removal. The primary safety endpoint for this study is the evaluation of reoperations, revisions, or removals of the H3 device occurring within 10 years of surgery. Additional study endpoints are: Incidence, occurrence, and types of serious device-related adverse events. Nature, onset, duration, severity, relationship to the device, and relationship to the operative procedure and outcome of any adverse event.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	280 patients enrolled from the Primary Safety & Effectiveness cohort
Actual Number of Sites Enrolled	One (1) site
Patient Follow-up Rate	The follow-up rates were 81.3% (209/257) at 5 years and 78.5% (172/219) at 10 years for subjects with any data; and 30.4% (78/257) at 5 years and 44.3% (97/219) at 10 years for subjects with all data per protocol.
Final Safety Findings	The following results are based on the 10-year Kaplan-Meier analysis. The estimated 10-year removal/revision rate for any metal components was 14.9% (95% CI: 10.5%, 21.0%). The 5-year rate was 6.5% (95% CI: 4.0%, 10.4%). The estimated 10-year removal/revision rate for polyethylene only components was 19.8% (95% CI: 15.1%, 25.8%). The 5-year rate was 13.6% (95% CI: 9.9%, 18.5%). When including metal and polyethylene components, the estimated 10-year removal/revision rate was 31.8% (95% CI: 26.0%,38.4%). The 5-year rate was 19.2% (95% CI:14.9%, 24.5%). At 10-years post-implantation, 14.6% of subjects reported a serious, device-related adverse event other than a removal or revision.
Final Effect Findings	AOFAS Scores (mean +/- SD): Baseline: 39.3 +/- 12.3 points; 5 years: 79.9 +/- 16.3 points (improvement of 40.1 points); 10 years: 77.2 +/- 17.7 points (improvement of 36.6 +/- 20.63 points).
Study Strengths & Weaknesses	Strengths: The study was a continued follow-up of the premarket cohort with the intent to follow 280 subjects for 10 years post-implantation. The Kaplan-Meier analysis rates are based on a statistical calculation of the probability of device component removal or revision using the available time to additional surgery data of patients enrolled in the study. Weaknesses: All subjects were enrolled at a single center located outside the US with approximately 80% of implantations performed by the same surgeon, which may limit the generalizability of the study results to US patients and US clinical practice. The study had loss to follow-up or missing data for 69.6% (179/257) of subjects at 5 years and 55.7% (122/219) of subjects at 10 years. Due to safety concerns (i.e. higher than expected polyethylene (plastic) component fracture) with other available mobile bearing ankle devices, it was not feasible or appropriate in the final report to construct a Performance Goal (PG) as stated in the P160036 Condition of Approval (CoA) for this study. Therefore, the objective of using hypothesis testing to determine the 10-year survivorship and effectiveness of the H3 TAR System in comparison with historical literature controls for other available mobile bearing ankle devices could not be performed as required in the CoA. Hence, the change to the PAS study design (i.e., from hypothesis testing to descriptive analysis) was the most appropriate way to evaluate the final results.
Recommendations for Labeling Changes	A labeling change is recommended to update the device labeling with the final study results to help ensure that patients and providers are aware of the long-term risk of device failure.
General
Study Status	Completed
Application Number / Requirement Number	P160013 / PAS001
Study Name	INSPIRE Continuation PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Two-arm observational study – continued follow-up of subjects enrolled in the INSPIRE trial
Study Population	All U.S. patients enrolled in the INSPIRE trial in the UNOS database and all OUS patients in INSPIRE who consent to participation
Sample Size	A total of 349 patients were enrolled in the INSPIRE trial (mITT population). The sponsor has committed to aproaching all these patients to participate in the study and give Informed Consent. Additionally, the UNOS database will be queried to obtain endpoint data on all US INSPIRE patients in an anonymized fashion by arm.
Key Study Endpoints	BOS-free survival (freedom from BOS and mortality) through 5 years post-transplantation
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years post-transplant. Interim post-approval reports will be submitted at 6, 12, 18, 24, and 36 months after PMA approval.
Interim or Final Data Summary
Actual Number of Patients Enrolled	349 patients from the INSPIRE randomized trial
Actual Number of Sites Enrolled	17 sites
Patient Follow-up Rate	5-year follow-up rate: 99% (218/221)
Final Safety Findings	There were 118 deaths and 14 re-transplantation over 5 years post initial lung transplant
Final Effect Findings	5-year BOS-free survival (BOS grade 1, 2, 3, or ungradeable) was similar in the OCS and SOC treatment arms (PP population: 53% OCS vs. 49% SOC, p-value=0.50; mITT population: 52% OCS vs. 49% SOC, p-value=0.57). 5-year patient survival was similar in the OCS and SOC treatment arms (PP population: 68% OCS vs. 65% SOC, p-value=0.84; mITT population: 67% OCS vs. 64% SOC, p-value=0.98). 5-year freedom from BOS (grade 1, 2, 3, or ungradeable) was similar in the OCS and SOC treatment arms (PP population: 67% OCS vs. 65% SOC, p-value=0.49; mITT population: 68% OCS vs. 65% SOC, p-value=0.35).
Study Strengths & Weaknesses	Despite the acceptable number of patients and sites for a clinical study of this type and a high 5-year follow-up rate of 99%, it is concerning that the majority of participants were treated at a small number of sites. Of the 221 PAS patients, 124 patients (56%) were treated at 3 sites [Hanover (n=52); UCLA (n=47); and Leuven (n=25)]. This raises the concern that results of the overall trial may be driven by finding at these particular sites, thus limiting the generalizeability of the study findings to lung transplant patients at large. The PAS results need to be replicated in larger studies using real world evidence.
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P160013 / PAS002
Date Original Protocol Accepted	06/18/2018
Date Current Protocol Accepted	06/28/2023
Study Name	TOP PAS Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm, prospective, multi-center post-approval U.S. registry study on double lung transplant recipients whose donor lungs were preserved on the OCS™ Lung System. This all-comers registry is designed to evaluate short- and long-term safety and effectiveness of the OCS™ Lung System for lung transplantation in a real-world setting.
Study Population	This is a single-arm study on double lung transplant recipients whose donor lungs were preserved on the OCS™ Lung System.
Sample Size	Enrollment of the SCDL Primary Analysis Population will continue until 266 eligible DLIDU Primary Analysis Population Recipients have been enrolled.
Key Study Endpoints	Primary Safety Endpoint 12-month patient and graft survival post double-lung transplant Secondary Safety Endpoints Standard Criteria Donor Lungs: Total ischemic time for OCS™-preserved lungs Incidence of Primary Graft Dysfunction (PGD) grade 3 within the initial 72 hours post-transplantation (T0, T24, T48, and T72 hours) Donor Lungs Initially Deemed Unacceptable for Procurement and Transplantation: Incidence of PGD grade 3 at T72 hours post-transplantation Donor lung utilization rate Incidence of PGD grade 3 within the initial 72 hours post transplantation Other Endpoints: For Both SCDLU and DLIDU: Number of lung graft-related serious adverse events (SAEs) through 30 days post-transplant or through initial transplant surgical admission if longer than 30 days, per subject, consisting of the following SAEs (at most one per type): Bronchial anastomotic complications Major pulmonary-related infection Survival incidence (simple proportion) at 30 days Survival incidence (simple proportion) at initial transplant surgery hospital discharge, if longer than 30 days Incidence of PGD3 at T72 hours Total ischemia and cross-clamp times for 1st and 2nd transplanted lungs Kaplan-Meier patient survival estimated at Month 1, 6, 12, 24, 36, 48 and 60 Kaplan-Meier BOS-free survival estimated at Month 12, 24, 36, 48 and 60 Kaplan-Meier Freedom from BOS and grading estimated at Month 12, 24, 36, 48 and 60 Kaplan-Meier graft survival (freedom from re-transplantation/graft failure) estimated at Month 12, 24, 36, 48 and 60
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	458
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	9 patients lost to follow-up
General
Study Status	Ongoing
Application Number / Requirement Number	P150048 S012/ PAS001
Date Original Protocol Accepted	11/05/2018
Date Current Protocol Accepted	11/05/2018
Study Name	Mitral Model 11000M, Cont f/u Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to collect continued follow-up of the premarket cohort and characterize the long-term safety and effectiveness of the Edwards Pericardial Mitral Bioprothesis, Model 11000M
Study Population	Study Population: Patients implanted with the Pericardial term Bioprothesis, Model 11000M. Indication: The Pericardial Aortic Bioprosthesis, Model 11000M, is indicated for the replacement of native or prosthetic mitral heart valves.
Sample Size	25 patients, 3 sites
Key Study Endpoints	The primary safety endpoint is the rate of implanted subjects that experience structural deterioration of Model 11000M. The secondary safety endpoints evaluates the following: thromboembolism, valve thrombosis, all bleeding/hemorrhage, major bleeding/hemorrhage, all/major paravalvular leak, non-structural valve deterioration, endocarditis, all-cause mortality, trial valve-related mortality, trial valve-related reoperation, explant, and hemolysis
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Completed
Application Number / Requirement Number	P170034 / PAS001
Date Original Protocol Accepted	11/18/2015
Date Current Protocol Accepted
Study Name	Continuation of Premarket Cohort PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up PAS for the prospective, randomized, multicenter pivotal study (HORIZON Study, CP 11-001) conducted under IDE G110048 to collect additional long-term safety information. All available subjects in both the Hydrus Microstent and control groups who consented to continuation in the study will be followed 5 years postoperatively.
Sample Size	Of the 556 subjects treated in this study (369 Hydrus, 187 controls), 489 subjects (334 Hydrus, 157 controls) have completed 3-year evaluations. Based on the age of the study population and other factors, it is estimated that a minimum of 70% of subjects (233 Hydrus subjects and 110 control subjects) will complete 5-year postoperative evaluations in the continuation study.
Key Study Endpoints	Primary safety outcome (study eye): Rate of occurrence of sight-threatening adverse events Secondary safety outcomes (study eye): Best Corrected Visual Acuity (BCVA) Rate of occurrence of ocular adverse events Slit lamp, gonioscopy and fundus findings Visual field mean deviation (MD) Central corneal thickness Central corneal endothelial cell density (ECD) Rate of occurrence of device malposition1 Rate of occurrence of device obstruction Rate of occurrence of peripheral anterior synechiae (PAS) Secondary effectiveness outcome: Mean change in intraocular pressure (IOP) Proportion of patients who are not using ocular hypotensive medications with a 20% or greater reduction in IOP from baseline in the HORIZON Study 1 Device malposition is considered an AE if there are associated clinical sequelae, for example: secondary surgical intervention to modify device position (i.e., repositioning or explantation), corneal endothelial touch by device, central ECL =30%, device obstruction requiring secondary surgical intervention, or chronic inflammation or irritation.
Follow-up Visits and Length of Follow-up	postoperative visits at 3,4 and 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	556 subjects (331 US and 225 OUS)
Actual Number of Sites Enrolled	28 US and 17 OUS
Patient Follow-up Rate	Of the 556 participants in the intent-to-treat (ITT) cohort, 114 (61 Hydrus, 53 control) were missing at the 60-month visit due to death, withdrawal, or loss to follow-up. The frequency of missing participants has increased successively from 24 months to 60 months which is not unexpected since participants were originally consented for a 24-month follow-up for the pivotal trial. There are no remaining active participants. Overall 60-month accountability is 86.8% in the Hydrus and 77% in the control.
Final Safety Findings	The primary safety endpoint is the rate of sight-threatening adverse events (SAEs). At 60 months, the cumulative rate of SAEs is comparable between the two groups, 13/369 (3.5%) in Hydrus eyes vs. 8/187 (4.3%) in controls (difference = -0.8%, 95% CI -4.2% to 2.7%). There were no reports of BCVA loss =2 lines after 3 months in either group at 60 months; the cumulative rates were 1.9% (7/369) in the Hydrus group, 2.1% (4/369) control. Cystoid macular edema was reported in 2.4% (9/369) of the Hydrus group and 2.1% (4/187) of the control group. The most common adverse event in the Hydrus group was peripheral anterior synechiae (PAS) with or without concomitant partial or complete device obstruction (14.6%; 54/369); 37% (20/54) of the PAS cases were with concomitant device obstruction. The rate of device obstruction was 8.4% (31/369), complete 2.4% (9/369), partial 6.0% (22/369). The rate of device malposition was 1.4% (5/369).There were no serious sequelae from these PAS and obstructive events. There were no explantations. The rate of persistent anterior uveitis in the Hydrus group was 0.5% (2/369) and in the control group 2.1% (4/187). Worsening of visual field (change in MD =2.5 dB on two repeated tests) was reported in 8.4% Hydrus (31/369) and 9.6% control (18/187). Secondary surgical intervention (SSI) to lower inadequately controlled IOP was performed in 4.9% Hydrus (18/369) and 7.5% control (14/187). Corneal endothelial cell measurements were collected in three areas of the cornea (central, nasal, and temporal). Corneal edema was reported in 1.4% Hydrus (5/369) and 0.5% control (1/187). Mean central ECL at 60 months was -19% +/-16% Hydrus and -13%+/-13% control. Corneal endothelial cell loss (ECL) remains relatively stable in both groups after initial postoperative drops (in both groups). The frequencies of central ECL =30% and ECD<1000 cells/mm2 are higher in the Hydrus group (20.8% [62/298], 4.7% [14/298], respectively) versus control (10.6% [14/132], 0.8% [1/132], respectively). These patterns suggest that there is greater impact of the corneal endothelium from initial surgical trauma in the Hydrus group compared to the control group. The observed ECL did not manifest in clinically significant sequelae, with only one case of corneal decompensation requiring corneal transplantation (DMEK).
Final Effect Findings	Washed-out, diurnal IOPs were not performed at timepoints after Month 24, and hence the primary endpoint (proportion of eyes with unmedicated mean IOP reduction >20% from baseline) was not calculated at these later timepoints. After Month 24, there is a gradual decrease in the proportion of Hydrus participants who remain glaucoma medication-free, from 78.2% at Month 24 to 58.8% at Month 60. These numbers in the control group are lower (47.6% at Month 24 to 35.8% at Month 60). Among the Hydrus group participants who were medication-free, the mean IOP ranged from 16.5 to 16.7 mm Hg at Months 36, 48, and 60; among the control group participants who were medication-free, mean IOP ranged from 17.2 to 17.6 mm Hg at Months 36, 48, and 60. A secondary effectiveness outcome is the proportion of participants who are not using IOP-lowering medications and who achieve greater than or equal to 20% IOP reduction from baseline. At 5 years, this endpoint was achieved in 48.5% of the Hydrus group (149/307) versus 25.6% of the control group (34/133).
Study Strengths & Weaknesses	The overall safety profile of the device over 5 years of follow-up remains good. The most common adverse event is peripheral anterior synechiae (PAS) with or without concomitant partial or complete device obstruction (14.6; 54/369); 37% (20/54) of the PAS cases were with concomitant device obstruction. The rates of complete and partial device obstructions were 2.4% and 6.0%, respectively. There have been no serious sequelae from these PAS and obstructive events, including no explantations. The rate of persistent anterior uveitis in the Hydrus was low (0.5%). Corneal endothelial cell loss (ECL) remains relatively stable in both groups after initial postoperative drops (in both groups), but the distribution of loss is different between the two groups. The frequency of central, nasal, and temporal ECL greater than or equal to 30% and ECD<1000 cells/mm2 is slightly higher in the Hydrus group versus control. These patterns suggest that there is greater impact of the corneal endothelium from initial surgical trauma in the Hydrus group compared to the control group. The observed ECL largely did not manifest in clinically significant sequelae, with only one case of corneal decompensation requiring corneal transplantation.
Recommendations for Labeling Changes	In addition to including all of the PAS results, the CoA is fulfilled with an August 20, 2020 email request in P170034-R003 to update label in a future labeling supplement: The Hydrus Microstent is intended for implantation in conjunction with cataract surgery, which may impact corneal health. Therefore, caution is indicated in eyes with evidence of corneal compromise (e.g., Fuch’s dystrophy, corneal guttae or low endothelial cell density) or with risk factors for corneal compromise following cataract surgery (e.g., advanced age, dense nuclear sclerosis). In addition, glaucoma patients typically have larger endothelial cell losses from surgery than non-glaucoma patients. Therefore, surgeons should consider a patient’s specular microscopy endothelial cell density measurements to assess the risk of corneal decompensation after implantation of this device.
General
Study Status	Completed
Application Number / Requirement Number	P160017 S031/ PAS001
Date Original Protocol Accepted	06/21/2018
Date Current Protocol Accepted
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, randomized, parallel, adaptive controlled trial in adult and pediatric patients with Type 1 Diabetes using Hybrid Closed Loop System (HCL) and/or control (CSII, MDI, or SAP) in the home setting. Three cohorts, each consisting of a control arm (CSII, MDI, or SAP) and an HCL arm and further divided by A1C group (A1C > 8% or A1C < 8%), will participate in the 6-month study period followed by a 6-month continuation period where all subjects will use HCL. The purpose of this study is to demonstrate the safety and effectiveness of the HCL in the study population. The device is investigational in subjects ages 2-6 years and non-investigational in subjects 7 years and up.
Study Population	Adult and pediatric patients (2-80 years of age) with type 1 diabetes that meet the inclusion/exclusion criteria will be studied. The device is investigational in ages 2-6 years. The 2-6 year age group is also being studied under an approved IDE.
Sample Size	A minimum of 1120 subjects will be enrolled.
Key Study Endpoints	Primary Safety Endpoint The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both A1C Groups (baseline A1C > 8% and baseline A1C < 8%) during the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and DKA separately. The safety of the study will be evaluated and summarized per arm, including but not limited to the following: • Diabetic ketoacidosis (DKA) • Severe hypoglycemia • Severe hyperglycemia • Serious adverse events (SAEs) • Unanticipated adverse device effects (UADEs) Descriptive analyses will be performed to assess the primary safety endpoint. Event rates of severe hypoglycemia and DKA will be compared to: (1) the target event rate (defined by the medical literature and other studies) and (2) the control groups (CSII, MDI, SAP).
Follow-up Visits and Length of Follow-up	Follow-up visits are scheduled throughout the study period up to 6 months and throughout the continuation period up to 6 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	142 (eighteen 2-6 years old and one hundred twenty-four 7-13 years old)
Actual Number of Sites Enrolled	9 for the 2-6 years old cohort and 20 for the 7-13 years old cohort
Patient Follow-up Rate	A total of 142 subjects ages 2 - 13 years (eighteen 2-6 years old and one hundred twenty-four 7-13 years old) were enrolled across all three treatment cohorts of the study. The Sponsor had an overall minimum enrollment goal of 1,120 subjects for all age groups (participants 2 years and older). Results are summarized by treatment cohort below. Cohort 1 (Hybrid Closed Loop (HCL) vs Continuous Subcutaneous Insulin Infusion (CSII)): A total of 32 subjects (one 2-6 years old and thirty-one 7-13 years old) were enrolled in the study. A total of 28 subjects (one 2-6 years old and twenty-seven 7-13 years old) entered the Study Period. A total of 27 subjects (one 2-6 years old and twenty-six 7-13 years old) completed the Study Period. The follow-up rate was 96.4% (27/28). Cohort 2 (HCL vs Multiple Daily Injection (MDI)): A total of 39 subjects (eight 2-6 years old and thirty-one 7-13 years old) were enrolled in the study. A total of 39 subjects (eight 2-6 years old and thirty-one 7-13 years old) entered the Study period. A total of 37 subjects (seven 2-6 years old and thirty 7-13 years old) completed the Study period. The follow-up rate was 94.9% (37/39). Cohort 3 (HCL vs Sensor Augmented Pump (SAP)): A total of 71 subjects (nine 2-6 years old and sixty 7-13 years old) were enrolled in the study. A total of 61 subjects (nine 2-6 years old and fifty-two 7-13 years old) entered the Study period. A total of 50 subjects (seven 2-6 years old and forty-three 7-13 years old) completed the Study period. The follow-up rate was 82.0% (50/61).
Final Safety Findings	2-6 Years Old: Cohort 1: Of the 1 adverse events reported through the end of the Study Period, 100% (N=1) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), and bleeding at the sensor insertion site. There were no reports of DKA, no reports of severe hypoglycemia, and no reports of severe hyperglycemia. Cohort 2: Of the 31 adverse events reported through the end of the Study period, 23% (N=7) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin irritation), and bleeding at the sensor insertion site. There were no reports of DKA, no report of severe hypoglycemia, and 3 reports of severe hyperglycemia. Cohort 3: Of the 12 adverse events reported through the end of the Study period, 17% (N=2) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at the sensor site, skin infection at the infusion set site). There were no reports of DKA, no reports of severe hypoglycemia, and 2 reports of severe hyperglycemia. There were no reports of serious unanticipated adverse device effects or deaths. 7-13 Years Old: Cohort 1: Of the 76 adverse events reported through the end of the Study Period, 12% (N=9) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), and bleeding at the sensor insertion site. There were no reports of DKA, no reports of severe hypoglycemia, and 23 reports of severe hyperglycemia. Cohort 2: Of the 78 adverse events reported through the end of the Study period, 19% (N=15) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin irritation), and bleeding at the sensor insertion site. There were no reports of DKA, 1 report of severe hypoglycemia, and 5 reports of severe hyperglycemia. Cohort 3: Of the 152 adverse events reported through the end of the Study period, 30% (N=45) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at the sensor site, skin infection at the infusion set site). There were 3 reports of DKA, no reports of severe hypoglycemia, and 30 reports of severe hyperglycemia. There were no reports of serious unanticipated adverse device effects or deaths.
Final Effect Findings	The co-primary effectiveness endpoints for all three cohorts were stratified into two groups: Group 1 for subjects with a baseline A1C > 8%, and Group 2 for subjects with a baseline A1C = 8%. Ages 2-6: Cohort 1: Group 1 (baseline A1C >8%): change in A1C: There was no subject 2-6 years of age in Group 1 with baseline A1C > 8% enrolled in the CSII Cohort. Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: There was 1 subject 2-6 years of age in Group 2 with baseline A1C = 8% enrolled in the CSII Cohort. This subject did not have 3-month or 6-month time-in-hypoglycemic-range (%) measurements. Cohort 2: Group 1 (baseline A1C >8%): change in A1C: From baseline to end of study, the mean change in A1C was -0.8±1.0% (95% Confidence Interval (CI): -2.1, 0.5) for the HCL Arm (N=5). There were no subjects in the Control Arm. Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 2.6±0.5% (95% Confidence Interval (CI): -1.5, 6.7) for the HCL Arm (N=2). There were no subjects in the Control Arm. Cohort 3: Group 1(baseline A1C >8%): change in A1C: From baseline to end of study, the change in A1C was 0.6 for the HCL Arm (N=1) and 0.1 for the Control Arm (N=1). The difference (HCL vs SAP) was 0.5. Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 5.0±3.2% (95% Confidence Interval (CI): -0.2, 10.1) for the HCL Arm (N=4). There were no subjects in the Control Arm. Ages 7-13: Cohort 1: Group 1 (baseline A1C >8%): change in A1C: From baseline to end of study, the mean change in A1C was -1.1±0.5% (95% Confidence Interval (CI): -1.4, -0.7) for the HCL Arm (N=10) and -0.1±1.1% (95% CI: -1.0, 0.7) for the Control Arm (N=9). The estimated mean difference (HCL vs CSII) was -0.9±0.9% (95% CI: -1.7, -0.1). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 3.3±1.0% (95% Confidence Interval (CI): 1.8, 4.9) for the HCL Arm (N=4) and 2.8±2.2% (95% CI: -2.7, 8.4) for the Control Arm (N=3). The estimated mean difference (HCL vs CSII) was 0.5±1.6% (95% CI: -2.7,3.7). Cohort 2: Group 1 (baseline A1C >8%): change in A1C: From baseline to end of study, the mean change in A1C was -0.9±1.0% (95% Confidence Interval (CI): -2.0, 0.1) for the HCL Arm (N=6) and -0.4±0.7% (95% CI: -0.9, 0.2) for the Control Arm (N=8). The estimated mean difference (HCL vs MDI) was -0.5±0.8% (95% CI: -1.5,0.4). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 2.8±2.6% (95% Confidence Interval (CI): 1.0, 4.7) for the HCL Arm (N=10) and 13.2±12.1% (95% CI: -6.0, 32.5) for the Control Arm (N=4). The estimated mean difference (HCL vs MDI) was -10.4±6.4% (95% CI: -18.7, -2.1). Cohort 3: Group 1 (baseline A1C >8%): change in A1C: From baseline to end of study, the mean change in A1C was -0.4±0.9% (95% Confidence Interval (CI): -0.9, 0.1) for the HCL Arm (N=14) and 0.3±1.3% (95% CI: -0.8, 1.3) for the Control Arm (N=9). The estimated mean difference (HCL vs SAP) was -0.7±1.1% (95% CI: -1.6,0.2). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 3.1±1.6% (95% Confidence Interval (CI): 1.7, 4.5) for the HCL Arm (N=8) and 4.1±2.8% (95% CI: 2.3, 5.8) for the Control Arm (N=12). The estimated mean difference (HCL vs SAP) was -1.0±2.4% (95% CI: -3.3,1.3).
Study Strengths & Weaknesses	Strengths: This post-approval study included users aged 2-13 across 29 sites transitioning to the MiniMed 670G/770G Hybrid Closed Loop system from three different baseline therapy options (MDI, CSII and SAP). The incident rates of safety events (severe hypoglycemia and diabetic ketoacidosis) of users on the MiniMed 670G/770G were below the prespecified threshold for all cohorts. The post-approval study confirms that the MiniMed 670G/770G System is safe when used as intended. Weaknesses: The study did not reach its enrollment goals for pediatric users 2-6 and 7-13 years old despite multiple efforts from the sponsor to increase enrollment. However, available data from this post-approval study and additional data from the post-market surveillance program support safety of the MiniMed 670G/770G System when used as intended in these age groups.
Recommendations for Labeling Changes	Results of the post-approval study does not change the benefits and risks conclusions of the original PMA approval. Labeling changes are recommended to include PAS results.
General
Study Status	Completed
Application Number / Requirement Number	P160017 / PAS001
Date Original Protocol Accepted	12/22/2016
Date Current Protocol Accepted	04/19/2021
Study Name	MiniMed 670G Post Approval Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, randomized, parallel, adaptive controlled trial in adult and pediatric patients with Type 1 Diabetes using Hybrid Closed Loop System (HCL) and/or control (CSII, MDI, or SAP) in the home setting. Three cohorts, each consisting of a control arm (CSII, MDI, or SAP) and an HCL arm and further divided by A1C group (A1C > 8% or A1C < 8%), will participate in the 6-month study period followed by a 6-month continuation period where all subjects will use HCL. The purpose of this study is to demonstrate the safety and effectiveness of the HCL in the study population. This study includes the continued follow-up of premarket cohorts and new subject enrollment.
Study Population	Adult and pediatric patients (2-80 years of age) with type 1 diabetes that meet the inclusion/exclusion criteria will be studied. The device is investigational in ages 2-13 years. The 2-13 year age group will also be studied under an approved IDE.
Sample Size	A minimum of 1120 subjects will be enrolled
Key Study Endpoints	Primary Safety Endpoint The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both A1C Groups (baseline A1C > 8% and baseline A1C < 8%) during the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and DKA separately. The safety of the study will be evaluated and summarized per arm, including but not limited to the following: • Diabetic ketoacidosis (DKA) • Severe hypoglycemia • Severe hyperglycemia • Serious adverse events (SAEs) • Unanticipated adverse device effects (UADEs) Descriptive analyses will be performed to assess the primary safety endpoint. Event rates of severe hypoglycemia and DKA will be compared to: (1) the target event rate (defined by the medical literature and other studies) and (2) the control groups (CSII, MDI, SAP).
Follow-up Visits and Length of Follow-up	Follow-up visits are scheduled throughout the study period up to 6 months and throughout the continuation period up to 6 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	817
Actual Number of Sites Enrolled	34
Patient Follow-up Rate	A total of 817 subjects ages 14 years and older were enrolled across all three treatment cohorts of the study. The Sponsor had an overall enrollment goal of 1,120 subjects for all age groups (participants 2 years and older). Results are summarized by treatment cohort below. Cohort 1 (Hybrid Closed Loop (HCL) vs. Continuous Subcutaneous Insulin Infusion (CSII)): A total of 289 subjects were enrolled in the study. A total of 270 subjects entered the Study Period. A total of 251 subjects completed the Study Period. The follow-up rate was 93.0% (251/270). Cohort 2 (HCL vs Multiple Daily Injection (MDI)): A total of 237 subjects were enrolled in the study. A total of 209 subjects entered the Study period. A total of 189 subjects completed the Study period. The follow-up rate was 90.4% (189/209). Cohort 3 (HCL vs Sensor Augmented Pump (SAP)): A total of 291 subjects were enrolled in the study. A total of 263 subjects entered the Study period. A total of 242 subjects completed the Study period. The follow-up rate was 92.0% (242/263).
Final Safety Findings	Cohort 1: Of the 450 adverse events reported through the end of the Study Period, 11% (N=50) were classified as device related, including glycemic events (e.g., severe hyperglycemia, hypoglycemia), skin issues (e.g., abscess, dermatitis, skin infection at the infusion set site and skin irritation), and bleeding at the sensor insertion site. There was one report of DKA, 6 reports of severe hypoglycemia, and 50 reports of severe hyperglycemia. Cohort 2: Of the 316 adverse events reported through the end of the Study period, 16% (N=52) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin infection at the infusion set site and skin irritation), and bleeding at the sensor insertion site. There was one report of DKA, 6 reports of severe hypoglycemia, and 19 reports of severe hyperglycemia. Cohort 3: Of the 470 adverse events reported through the end of the Study period, 16% (N=76) were classified as device related, including glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at the sensor site, skin infection at the infusion set site). There were no reports of DKA, 11 reports of severe hypoglycemia, and 44 reports of severe hyperglycemia. There were no reports of serious unanticipated adverse device effects or deaths in any cohort.
Final Effect Findings	The co-primary effectiveness endpoints for all three cohorts were stratified into two groups: Group 1 for subjects with a baseline A1C > 8%, and Group 2 for subjects with a baseline A1C = 8%. Cohort 1: Group 1 (baseline A1C > 8%): change in A1C: From baseline to end of study, the mean change in A1C was - 1.7±1.3% (95% Confidence Interval (CI): -2.0, -1.3) for the HCL Arm (N=64) and -0.9±0.8% (95% CI: -1.1, -0.7) for the Control Arm (N=64). The estimated mean difference (HCL vs CSII) was -0.8±1.1% (95% CI: -1.2, -0.4). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 2.3±1.9% (95% Confidence Interval (CI): 1.8, 2.8) for the HCL Arm (N=62) and 7.6±5.3% (95% CI: 6.2, 8.9) for the Control Arm (N=60). The estimated mean difference (HCL vs CSII) was -5.2±4.0% (95% CI: -6.6, -3.8). Cohort 2: Group 1 (baseline A1C > 8%): change in A1C: From baseline to end of study, the mean change in A1C was - 1.5±1.0% (95% Confidence Interval (CI): -1.8, -1.2) for the HCL Arm (N=39) and -0.7±1.0% (95% CI: -1.0, -0.4) for the Control Arm (N=36). The estimated mean difference (HCL vs MDI) was -0.8±1.0% (95% CI: -1.3, -0.3). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 2.8±2.8% (95% Confidence Interval (95% CI): 2.0, 3.5) for the HCL Arm (N=53) and 7.1±5.3% (95% CI: 5.6, 8.6) for the Control Arm (N=51). The estimated mean difference (HCL vs MDI) was -4.3±4.2% (95% CI: -6.0,-2.7). Cohort 3: Group 1 (baseline A1C > 8%): change in A1C: From baseline to end of study, the mean change in A1C was - 0.7±0.7% (95% Confidence Interval (CI): -1.0, -0.5) for the HCL Arm (N=39) and -0.8±0.9% (95% CI: -1.1, -0.5) for the Control Arm (N=44). The estimated mean difference (HCL vs SAP) was 0.1±0.8% (95% CI: -0.3,0.4). Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range: From baseline to end of study, the mean change in time in hypoglycemic range was 2.3±2.3% (95% Confidence Interval (CI): 1.8, 2.8) for the HCL Arm (N=77) and 3.4±3.0% (95% CI: 2.7, 4.1) for the Control Arm (N=76). The estimated mean difference (HCL vs SAP) was -1.1±2.7% (95% CI: -2.0, -0.3).
Study Strengths & Weaknesses	Strengths: This post-approval study included users aged 14-80 across 34 sites transitioning to the MiniMed 670G/770G Hybrid Closed Loop system from three different baseline therapy options (MDI, CSII and SAP) which were representative of the standard of care for people with Type 1 Diabetes in the United States at the time of study initiation. The incident rates of safety events (severe hypoglycemia and diabetic ketoacidosis) of users on the MiniMed 670G/770G were below the prespecified threshold for all cohorts. The post-approval study confirms that the MiniMed 670G/770G System is safe when used as intended. Weaknesses: The post-approval study included mostly white device users. There is uncertainty remaining regarding the risk/benefit profile of the device when used in the broader intended use population. However, available data from this post-approval study and additional data from the post-market surveillance program support safety of the MiniMed 670G/770G System when used as intended in these age groups.
Recommendations for Labeling Changes	Results of the post-approval study does not change the benefits and risks conclusions of the original PMA approval. Labeling changes are recommended to include PAS results.
General
Study Status	Completed
Application Number / Requirement Number	P140033 / PAS001
Date Original Protocol Accepted	01/31/2017
Date Current Protocol Accepted	05/22/2020
Study Name	SJM Brady MRI PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Primary Objective: To determine the Tendril MRI RA and Tendril MRI RV lead-related complication-free rates at 5 years. Secondary Objective: To determine the rate of cardiac tamponade or cardiac perforation events through 5 years. The real-world approach to identify lead-related complications will use Abbott-maintained internal databases combined with CMS-maintained Medicare claims data. Every Abbott device has a unique combination of model and serial number that is preserved across Abbott databases and can be used to link data from these databases together.
Study Population	All patients who has an implant of an SJM system along with a Tendril MRI RA and/or RV lead, meet inclusion/exclusion criteria, and link to Medicare FFS claims will be included in the analysis of the endpoints.
Sample Size	Assuming the time to first complication follows an exponential distribution and the complication free survival at 5 years is 95%, a minimal sample size of 645 Tendril MRI RA and 645 Tendril MRI RV leads provides 80% power to reject the null hypotheses of 92.5% complication-free survival years at the 5% significance level. It is estimated that 23,230 Tendril MRI RA and 22,839 Tendril MRI RV lead implants will meet inclusion /exclusion criteria for this study, which greatly exceeds the minimal required sample size.
Key Study Endpoints	Primary Endpoint: Freedom from Tendril MRI RA and/or RV lead-related complications through 5-years of follow-up. Secondary Endpoint: The secondary outcome measure is the rate of cardiac tamponade or cardiac perforation events. The objective is to characterize the rate of these events. All cardiac tamponade and cardiac perforations will be evaluated for their relationship to the Tendril MRI RA or Tendril MRI RV leads, reported and summarized.
Follow-up Visits and Length of Follow-up	The study completion is 5 years after the final implant, June 30, 2018. The data retention period will be for 2 years after the submission of the final report.
Interim or Final Data Summary
Actual Number of Patients Enrolled	25,601
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	• Primary o Freedom from Tendril MRI lead-related complications through 5 years of follow up - RA leads: 98.2% (95% Lower Confidence Bound) vs Performance Goal of > 92.5% - RV leads: 98.3% (95% Lower Confidence Bound) vs Performance Goal of > 92.5% • Secondary o Characterization of rate (worst-case) of cardiac tamponade events - RA leads: 0.7378% - RV leads: 0.6692% o Characterization of rate (worst-case) of cardiac perforation events -RA leads: 0.1042% -RV leads: 0.0793%
Final Effect Findings	N/A
Study Strengths & Weaknesses	• Strengths o The RWE analysis included a much larger study population compared to a traditional prospective study design. o Fewer patients are lost to follow up in RWE studies since patients are not required to attend follow-up visits. o The study included a wide sample of operators and institutions. • Weaknesses o There is an approximate lag time of 5-8 months for availability of Medicare claims data for analysis. o RWE analysis is limited by the lack of specificity in various types of lead related complications that were determined based on diagnosis codes in Medicare claims data
Recommendations for Labeling Changes	Yes, recommend including a summary of the PAS including results in the IFU manual.
General
Study Status	Completed
Application Number / Requirement Number	P160021 / PAS001
Study Name	VBX FLEX Continued f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (VBX FLEX Continued Follow-Up Study) is to evaluate the long term safety and effectiveness of the GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis for treatment of iliac arterial occlusive disease. This study is a prospective, single-armed, multi-center follow-up of the BES 10-07 pivotal study (G120232).
Study Population	The study population included symptomatic (Rutherford Category 2-4) patients with angiographic confirmation of either de novo or restenotic unilateral or bilateral occlusive disease in the common and/or external iliac arteries, with a total treated lesion length of less than or equal to 110 mm and vessel diameters between approximately 5 mm and 13 mm. Patients were included who presented with up to two discrete lesions requiring treatment, either one lesion per side for patients presenting with bilateral disease, or two lesions on the same side. All subjects could be treated with up to three GORE® VIABAHN® VBX Balloon Expandable Endoprosthesis. Eligible patients in the study included those presenting with tortuous iliacs, severe lesion calcification, total occlusions, and those determined to need direct stenting (pre-dilatation optional) and/or kissing stent treatment at the aortic bifurcation.
Sample Size	All 133 remaining subjects (7 subjects have discontinued the study) of the 140 original study subjects enrolled from 26 sites in U.S. and 1 site in New Zealand.
Key Study Endpoints	Primary Endpoint: Freedom from target lesion revascularization at 36 months. Target lesion revascularization is defined as revascularization occurring within the treated segment(s) by means of a percutaneous vascular intervention, surgical bypass, thrombolysis, or other invasive means. Secondary Endpoints: Freedom from target vessel revascularization (TVR) at 12, 24 and 36 months. Freedom from target lesion revascularization (TLR) at 12 and 24 months. Primary patency at 12 months. Primary assisted patency at 12 months. Secondary patency at 12 months. Change in Rutherford category from pre-procedure at 12, 24 and 36 months. Change in resting Ankle-Brachial Index (ABI) or Toe Brachial Index (TBI) from pre-procedure at 12, 24 and 36 months. Change in functional status from pre-procedure based on EQ-5D at 12, 24 and 36 months. Change in functional status from pre-procedure based on Walking Impairment Questionnaire (WIQ) at 12, 24 and 36 months. Serious adverse events at 12, 24 and 36 months.
Follow-up Visits and Length of Follow-up	36 months Annual (12, 24, 36 months)
Interim or Final Data Summary
Actual Number of Patients Enrolled	140 Intent-to-treat population (134 per-protocol population)
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	133 (99.3%) at 30 days 107 (79.9%) at 36 months
Final Safety Findings	The safety endpoint of this study is a composite of Major Adverse Events (MAEs). Key elements and findings include the following: No device or procedure related deaths were reported within 30 days of the index procedure. No MIs were reported within 30 days of the index procedure. Three (3) cases of TLR were reported within 9 months of the index procedure. No amputation above the metatarsals were reported within 9 months of the index procedure.
Final Effect Findings	Key effectiveness endpoints and associated findings include the following: Kaplan-Meier estimate of freedom from TLR (survival probability) is 91.2% at 36 months. Kaplan-Meier estimate of freedom from clinically driven TLR (survival probability) is 98.1% at 36 months. Kaplan-Meier estimate of freedom from TVR (survival probability) is 91.4% at 36 months. Kaplan-Meier estimate of freedom from clinically driven TVR (survival probability) is 97.1% at 36 months. Kaplan-Meier estimate of primary assisted patency (survival probability) is 99.0% at 12 months. Change in Rutherford category from pre-procedure is 0.0% at 12 months, 1.0% at 24 months, and 0.0% at 36 months. Improvement or maintenance in functional status from pre-procedure based on EQ-5D is at 87.7% at 12-months, 87.1% at 24-months, and 86.5% at 36 months Median improvement in walking distance, walking speed, and stair climbing based on the Walking Impairment Questionnaire (WIQ) is shown in the table below at 12, 24 and 36 months Walking Impairment Questionnaire (WIQ) Timepoint, months Walking Distance Walking Speed Stair Climbing 12 9 5 3 24 11 5 3 36 9 5 4
Study Strengths & Weaknesses	The follow-up compliance and study deviations were within reasonable expectations.
Recommendations for Labeling Changes	Additional information is available from these results that supplements information already contained in the publicly available SSED and labeling. Therefore, labeling changes are recommended
General
Study Status	Completed
Application Number / Requirement Number	P010012 S436/ PAS001
Date Original Protocol Accepted	08/07/2017
Date Current Protocol Accepted	11/17/2017
Study Name	SMART-MSP PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Evaluate the effectiveness of Boston Scientific (BSC)’s LV MSP (Left Ventricular MultiSite Pacing) feature in the Resonate family of CRT-D devices1 and confirm safety in a post approval study when used in accordance with its approved labeling. Prospective, multi-center, single arm, post approval study to be conducted in the United States.
Study Population	Subjects who are non-responders to conventional Biventricular (BiV) CRT-D therapy
Sample Size	Primary Safety Endpoint: The overall study sample size of 586 subjects is driven by the primary effectiveness endpoint. The sample size of 61 subjects is required to evaluate the Primary Safety Endpoint. Since a power calculation cannot be directly calculated for a one group Kaplan-Meier analysis, an exact test was used. A power calculation using a sample size of 61 subjects as the non-responders with the LV MSP on was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions: Performance goal = 90% Expected LV MSP feature-related CFR rate between 6 and 12 Month Visit = 98% Significance level = 5% Power = 80% Primary Effectiveness Endpoint: The sample size of 110 subjects with paired CCS calculation from the 6 Month Visit through 12 Month Visit is required to evaluate the Primary Effectiveness Endpoint. For further details on overall sample size and attrition see Figure 12.3-1. The overall study sample size is driven by the primary effectiveness endpoint. This sample size was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions: Performance goal = 5% Expected performance = 15% One-sided significance level = 5% Power = 95%
Key Study Endpoints	The primary safety endpoint for SMART-MSP is LV MSP feature-related complication-free rate between the 6 Month Visit and the 12 Month Visit in non-responders with the LV MSP turned on for any duration and the primary effectiveness endpoint is Proportion of the LV MSP Group subjects with Improved Clinical Composite Score (CCS) from the 6 Month Visit through the 12 Month Visit.
Follow-up Visits and Length of Follow-up	The length of follow-up is maximum of 12 months. Subjects determined to be a responder at their 6 month visit will complete the study. Subjects in the non-responder group, including those subjects who have no LV MSP turned on, will complete the study at their 12 month visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	594 patients
Actual Number of Sites Enrolled	52 sites
Patient Follow-up Rate	The mean months +/- SD of all enrolled subjects was 7.0 +/- 3.1.
Final Safety Findings	The LV MSP feature related complication-free rate was 99.0% with a lower 95% confidence limit of 94.9%, which was higher than the performance goal of 90%.
Final Effect Findings	The proportion of Non-Responder subjects with an improved CCS from 6-12 months was 51.3% with a lower 95% confidence limit of 41.4%, which was higher than the performance goal of 5%.
Study Strengths & Weaknesses	The firm has fulfilled the conditions of approval by completing the study as planned. There are no safety concerns raised by this large study. Detailed review of the adverse events shows no specific adverse event types are increased over what we might see in this population. Overall, the MSP approach shows a substantial minority of subjects benefitted.
Recommendations for Labeling Changes	Yes, a labeling change is recommended. The study results are favorable, free of new safety signals and show a promising effectiveness signal. These results should be included in an update to the label.
General
Study Status	Delayed
Application Number / Requirement Number	P160030 / PAS001
Date Original Protocol Accepted	12/08/2017
Date Current Protocol Accepted	04/05/2024
Study Name	FreeStyle Libre Flash Glucose Monitoring PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	Safety Results: Compared to the previous 48-month report, there was no change in the number of primary endpoints adverse events for severe hypoglycemia and moderate hypoglycemia (6 months historical medical record data). Twenty-one (21) subjects had severe hypoglycemia (observed in 28 events) and eighteen (18) subjects had moderate hypoglycemia (observed in 28 events) based on 6 months of medical record data. In the intervention phase, one subject had severe hypoglycemia (observed in one event) and compared to the last 48-month report, there was one additional subject for a total of four (4) subjects that had moderate hypoglycemia (observed in 4 events), and none of these events were device related. Effectiveness Results:
Actual Number of Patients Enrolled	184
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	Out of the 184 subjects enrolled in the Intervention Phase, 7 withdrew consent, 2 were removed due to screening failure, 1 was discontinued from the study due to protocol deviation, 4 elected to discontinue participation in the study, and 1 was removed due to an adverse event. Forty (40) subjects were lost to follow-up. In all these cases, the subject either did not show up to a study visit and/or became unreachable. Multiple attempts, including phone calls, emails, and text messages, were made to locate each subject with no success.
General
Study Status	Completed
Application Number / Requirement Number	P160039 / PAS001
Date Original Protocol Accepted	12/21/2017
Date Current Protocol Accepted
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multicenter, single arm cohort study to evaluate long-term safety, long-term effectiveness, and survival rate in the continued follow-up of the premarket cohort for the remede System Pivotal Trial.
Study Population	Subjects who were previously implanted with the remede System and participated in the remede System Pivotal Trial
Sample Size	Up to 94 subjects are available for the extended follow-up
Key Study Endpoints	1. Evaluate the survival rate 2. Evaluate long-term three and five-year device-related SAEs 3. Evaluate long-term three and five-year therapy-related SAEs 4. Evaluate the AHI, CAI and obstructive apnea index (OAI) 5. Evaluate the change in quality of life from Baseline
Follow-up Visits and Length of Follow-up	Follow-up is planned for five years from the date of implant. Since all subjects have already completed 24 months of follow-up, total study duration is estimated to be three years. 30, 36, 42, 48, 54, 60 months follow-up assessments planned
Interim or Final Data Summary
Actual Number of Patients Enrolled	53
Actual Number of Sites Enrolled	18
Patient Follow-up Rate	30 month (0%), 36 month (0%), 42 month (17%), 48 month (45%), 54 month (73%), 60 month (98%) follow-up assessments
Final Safety Findings	There were no unanticipated adverse events or significant increase in events. There have been no deaths attributed to the device, procedure or delivered therapy, and the survival rates were comparable with other published data sets.
Final Effect Findings	The results continue to show a sustained improvement at similar levels as demonstrated in the pivotal trial for apnea-hypopnea index (AHI), central apnea index (CAI) as well as Epworth Sleepiness Scale (ESS).
Study Strengths & Weaknesses	Weaknesses: Poor enrollment (53 of 94 eligible subjects, 56%) and missed follow-up assessments due to slower than anticipated enrollment of subjects. Strengths: There was a high follow up rate at the 60 month visit (52 of 53 subjects enrolled, 98%), and this visit included assessment of all endpoints for safety and effectiveness, including an in-lab PSG study.
Recommendations for Labeling Changes	The safety and effectiveness data were similar to those previously reported in the pivotal trial and no new safety signal has been identified. Therefore, no labeling change is recommended.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P160036 / PAS002
Date Original Protocol Accepted	11/29/2019
Date Current Protocol Accepted	09/20/2024
Study Name	Hintermann Series H3 TAR Performance Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: The purpose of this multi-center post-approval study is to meet the conditions of the PMA approval for the H3 TAR, to evaluate the trends in performance among implant sizes, and to assess the outcomes of the primary surgeon of the premarket study that supported PMA approval, compared to other surgeons that are less familiar with the device. Design: Prospective multicenter single arm post approval study with data supplementation from the UK National Joint Registry (UK NJR).
Study Population	Patients who have discussed options for management of a painful arthritic ankle joint due to primary osteoarthritis, post-traumatic osteoarthritis, or arthritis secondary to inflammatory disease (e.g., rheumatoid arthritis, hemochromatosis, etc.), and who have decided to undergo total ankle replacement, are candidates for this study.
Sample Size	US Population: 94 subjects/ 10 Clinical Sites UK Population: 407 subjects / 45 Clinical Sites
Key Study Endpoints	Primary Endpoints for US population: • Survivorship (absence of revision to metal components only) • Survivorship (absence of revision to metal and polyethylene components) Additional Endpoints for US population: • American Orthopaedic Foot and Ankle Society (AOFAS) score at 2 years or more • Percentage of subjects with a serious device related adverse event, other than a revision or removal within 2 years • Incidence, occurrence, and types of serious device related adverse events • Nature, onset, duration, severity, relationship to the device, relationship to the operative procedure, and outcome of any adverse event • Visual Analog Scale (VAS) score • Subjects Satisfaction Surverys • SF-36 • Radiographs (loosening, osteolysis, implant migration, other findings) • Explant analysis UK population: • Survivorship (absence of revision to metal components only) • Survivorship (absence of revision to metal and polyethylene components)
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: US data: Twenty-six (26) operative site events representing 29.2% (26/89), and eight (8) systemic events representing 9% (8/89) were reported. There have been three (3) revisions and five (5) removals. No deaths have occurred since the study started. UK Registry data: There have been twenty-eight (28) reported revision surgeries in this cohort. Effectiveness Results: US data: AOFAS Alignment Score patients rated fair/good: at baseline 70.7% (58/82), 6-week 95.2% (60/63), 24-week 100% (45/45), 1-year 100% (12/12), and 2-year 100% (2/2).
Actual Number of Patients Enrolled	101 US subjects/ 407 UK subjects
Actual Number of Sites Enrolled	13 US subjects / 45 UK sites
Patient Follow-up Rate	US data: Follow-up rate (All data available per protocol) is 56.8% (50/88) at 6 weeks, 48.6% (36/74) at 24 weeks, 18.6% (8/43) at 1-year, and 50% (1/2) at 2-year. UK Registry data: The Kaplan-Meier estimate of survivorship at 5 years is 94.5% with a 95% confidence interval of (91.5%, 96.5%). At 10 years, the Kaplan-Meier estimate of survivorship is 91.3% with a 95% confidence interval of (87.4%, 94.0%).
General
Study Status	Ongoing
Application Number / Requirement Number	P180002 S005/ PAS001
Date Original Protocol Accepted	10/02/2019
Date Current Protocol Accepted	03/25/2023
Study Name	ZEVR-Zephyr Valve Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study: Multi-center, single-arm, prospective Registry to be conducted at up to 15 clinical sites. Approximately 150 patients with severe emphysema undergoing Zephyr Valve treatment will be enrolled and followed out to 3 years. Assessments will be performed at 45-days, 6-months, 12-months, 24-months and 36-months post-procedure. The Zephyr Valve Registry will be conducted at a minimum of 5, and a maximum of 10 clinical sites. Enrollment is anticipated to be completed over 24 months. A minimum of 20 subjects treated with at least one Zephyr 5.5-LP EBV will be enrolled.
Study Population	Adult patients with hyperinflation associated with severe emphysema in regions of the lung that have little to no collateral ventilation. Concurrent control comparison group.
Sample Size	150
Key Study Endpoints	Safety endpoints: Incidence rate of Pneumothorax at 45-days post-procedure. Incidence rate of device/procedure related Serious Adverse Events (SAE) including but not limited to COPD exacerbations, pneumonia, hemoptysis, valve expectoration, valve migration and respiratory failure. Effectiveness endpoints: Treated Lobar Volume Reduction (TLVR) assessed by HRCT at 45-days. Forced Expiratory Volume in 1 second (FEV1) at 6-months, 12-months, 24-months and 36-months. 6MWD at 6-months and 12-months. SGRQ at 6-months and 12-months. BODE Index at 6-months and 12-months. Percent of patients with a TLVR of =350mL10,11. Percent of patients with a TLVR of =563mL12. Responder rates reported as percent of patients meeting the Minimal Clinically Important Difference (MCID) for each variable at 6-months and 12-months. - MCID for FEV1: Increase of 10% (Liters) - MCID for 6MWD: Increase of +25 meters - MCID for SGRQ: Decrease of 4 points
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Interim Results	Safety Results Pneumothorax adverse event rate: 39.5% Effectiveness Results The mean reduction in TLV at 45 days was 1185.3 mL and at 12-months was 1185.0 mL representing a percent reduction of 64.37% and 65.47%, respectively.
Actual Number of Patients Enrolled	162
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	1-year post-procedure follow up: 68.5%
General
Study Status	Ongoing
Application Number / Requirement Number	P100020 S055/ PAS001
Date Original Protocol Accepted	05/14/2024
Date Current Protocol Accepted	03/27/2025
Study Name	SHIP-Sub-Protocol LMI-001-A-S02
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will include 1000 or more individuals (at least 500 individuals per self-collection device) with a cervix, 25 years or older, with referrals to colposcopy based on previous positive HPV test or abnormal cytology results and/or referrals to cervical excisional procedure. The study will provide additional data regarding clinical performance of the cobas HPV test and cobas HPV (hereafter referred to as the cobas HPV tests) with vaginal specimens in a U.S. population. The clinical sensitivity, clinical specificity, false positive rate, and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens will be evaluated. Additionally, the concordance of the cobas HPV tests’ results between the two specimen types will be evaluated.
Study Population	Individuals with a cervix, 25 years or older, who come to colposcopy with a referral based on previous positive HPV test or abnormal cytology results and who come to cervical excisional procedure with a referral. There is no comparison group.
Sample Size	At least 500 for the FLOQSwab #552C.80 self-collection device; at least 500 for the Evalyn brush collection device Study sites will be 10 or more.
Key Study Endpoints	The clinical sensitivity, clinical specificity and false positive rate, and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens. The concordance of the cobas HPV tests’ results between the two specimen types.
Follow-up Visits and Length of Follow-up	To be eligible to participate in this study, an individual must meet all the following criteria: • Willingness and ability to provide a documented informed consent. • Is 25 years or older. • Has an intact cervix. • Has had a colposcopy referral in which routine cervical cancer screening has included HPV testing (HPV primary screening, co-testing, or ASC-US cytology triage) or abnormal cytology performed within 12 weeks preceding the colposcopy visit. • Willing and able to undergo colposcopy, and if clinically indicated for Standard of Care (SOC) purposes, a biopsy, and/or endocervical curettage. This is a study with only a single clinic visit. There is no planned follow-up unless required by the SOC.
General
Study Status	Ongoing
Application Number / Requirement Number	P190028 S009/ PAS001
Date Original Protocol Accepted	05/14/2024
Date Current Protocol Accepted	03/27/2025
Study Name	SHIP Sub-Protocol LMI-001-A-S03
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will include 1000 or more individuals (at least 500 individuals per self-collection device) with a cervix, 25 years or older, with referrals to colposcopy based on previous positive HPV test or abnormal cytology results and/or referrals to cervical excisional procedure. The study will provide additional data regarding clinical performance of the cobas HPV test and cobas HPV (hereafter referred to as the cobas HPV tests) with vaginal specimens in a U.S. population. The clinical sensitivity, clinical specificity, false positive rate, and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens will be evaluated. Additionally, the concordance of the cobas HPV tests’ results between the two specimen types will be evaluated.
Study Population	Individuals with a cervix, 25 years or older, who come to colposcopy with a referral based on previous positive HPV test or abnormal cytology results and who come to cervical excisional procedure with a referral.
Sample Size	At least 500 for the FLOQSwab #552C.80 self-collection device; at least 500 for the Evalyn brush collection device Study sites will be 10 or more.
Key Study Endpoints	The clinical sensitivity, clinical specificity, false positive rate and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens. The concordance of the cobas HPV tests’ results between the two specimen types.
Follow-up Visits and Length of Follow-up	To be eligible to participate in this study, an individual must meet all the following criteria: • Willingness and ability to provide a documented informed consent. • Is 25 years or older. • Has an intact cervix. • Has had a colposcopy referral in which routine cervical cancer screening has included HPV testing (HPV primary screening, co-testing, or ASC-US cytology triage) or abnormal cytology performed within 12 weeks preceding the colposcopy visit. • Willing and able to undergo colposcopy, and if clinically indicated for Standard of Care (SOC) purposes, a biopsy, and/or endocervical curettage. This is a study with only a single clinic visit. There is no planned follow-up unless required by the SOC.
General
Study Status	Completed
Application Number / Requirement Number	P160037 / PAS001
Study Name	BD-USLHPV Post-Approval Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This post-approval study will support the primary screening indication for use of the BD Onclarity HPV Assay on cervical specimens collected in SurePath collection media. The study will consist of women aged 25 years or older who completed the colposcopy procedure in the baseline study but who did not receive treatment. In addition, a random selection of women aged 25 and older who were NILM/HPV negative in the baseline and did not undergo colposcopy/biopsy will also be included. This population encompasses women with abnormal cytology, women who are HPV positive, a subset of women who are HPV negative with normal cytology, and women with unsatisfactory cytology results. Subjects in the follow-up study will undergo annual cytology screening, with women who are ASC-US or worse invited to proceed to colposcopy. This study will provide additional longitudinal information regarding clinical performance of the Onclarity HPV Assay when used in the primary screening algorithm. Sensitivity, specificity, absolute risks, predictive values, and disease likelihood ratios will be calculated, and a benefit/risk analysis will be performed.
Study Population	Women 25 years of age or older who underwent colposcopy but did not receive treatment in the baseline study; a random selection of women 25 years of age or older who were NILM/HPV negative and did not undergo colposcopy/biopsy in the baseline study.
Sample Size	About 9,000 women
Key Study Endpoints	greater than or equal to CIN2 (Cervical Intraepithelial Neoplasia) and greater than or equal to CIN3 by colposcopic examination
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	6730 subjects are enrolled for this study.
Actual Number of Sites Enrolled	Not applicable for this study.
Patient Follow-up Rate	The complete follow-up rate is 64% (4313/6730).
Final Safety Findings	No procedure related serious adverse events reported. 12 adverse events were reported as probably related with procedure: 16.6% post biopsy bleeding (2/12), 8.3% pelvic cramping during colposcopy(1/12), 8.3% nausea during colposcopy(1/12), 8.3% hypotension (1/12), 8.3% abdominal cramping (1/12), 8.3% vaginal bleeding (1/12), 8.3% vaginal discharge (1/12), 8.3% abnormal uterine bleeding (1/12), 8.3% urinary tract infection (1), 8.3% vaginal burning (1/12), 8.3% vaginal spotting (1/12). Four adverse events were reported as possibly related with procedure: 25% vaginal spotting (1), 25% uterine bleeding (1), 25% vaginal bleeding (1), 25% abdominal cramps (1).
Final Effect Findings	The VBA cumulative risk of greater than or equal to CIN3 in women with an HPV HR negative result was 0.1% at baseline as well as Years 1 and Year 2, and 0.2% at Year 3. The VBA cumulative risk of greater than or equal to CIN3 in women with HPV 12 other HPV HR positive and NILM cytology was 1.9% at baseline, 2.3% at Year 1 and Year 2, and 2.5% at Year 3. The VBA cumulative risk of =CIN3 in women with HPV HR 16/18 positive was 12.2% at baseline, 13.9% at Year 1, 14.6% at Year 2, and 16.4% at Year 3. The VBA cumulative risk of greater than or equal to CIN3 in women with HPV 12 other HPV HR positive and greater than or equal to ASCUS cytology was 5.3% at baseline, 6.5% at Year 1, 7.8% at Year 2, and 8.8% at Year 3.
Study Strengths & Weaknesses	Strength: The study evaluated 3-year long term absolute risk and accumulated risk for =CIN3 in women with an HPV HR negative result and with HPV HR 16/18 positive result at baseline. The results are comparable with previously published results for similar HPV assays. Weakness: 1595 subjects, 23.7% of enrolled subjects, missed at least one follow-up, which may lead to delayed diagnoses and prevention. The follow-up rate at 3 year for subjects completed all three follow-ups is relatively low, 64%, which potentially may introduce bias to the study results.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoint, follow-up visits etc.), final results, study strengths and limitations of the PAS.
General
Study Status	Progress Adequate
Application Number / Requirement Number	P150028 S001/ PAS001
Date Original Protocol Accepted	10/24/2017
Date Current Protocol Accepted
Study Name	PARCS continued f/u survey
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The objective of this surveillance is to characterize longer-term safety and effectiveness of the CP Covered Stent when used for treatment of right ventricular outflow tract (RVOT) conduit disruptions that are identified during conduit pre-dilatation procedures performed in preparation for transcatheter pulmonary valve replacement (TPVR).
Study Population	Subject follow-up will be conducted via distribution of an annual survey to investigators who participated in the PARCS IDE and CAP. The investigational sites will be provided with the CASE ID numbers for all living subjects who were enrolled under the PARCS study or PARCS Continued Access Protocol (CAP) to assist with acquisition of follow up status. The survey distributed to the sites will request information on patients treated with a CP Covered Stent during transcatheter pulmonary valve implantation including: need for catheter or surgical reintervention for a new or enlarging RVOT aneurysm/pseudo-aneurysm, instances of progression of aneurysm or pseudo-aneurysm, instances of structural failure (fracture), or need for device explantation. Survey distribution will continue annually until all patients reach 10 years post-implant. The sponsor will acquire this information from PARCS investigators/hospitals and report results to FDA on an annual basis.
Sample Size	Those patients in the PARCS IDE and CAP
Key Study Endpoints	The survey distributed to the sites will request information on patients treated with a CP Covered Stent during transcatheter pulmonary valve implantation including: need for catheter or surgical reintervention for a new or enlarging RVOT aneurysm/pseudo-aneurysm, instances of progression of aneurysm or pseudo-aneurysm, instances of structural failure (fracture), or need for device explantation.
Follow-up Visits and Length of Follow-up	10 years
General
Study Status	Completed
Application Number / Requirement Number	P160043 S001/ PAS002
Date Original Protocol Accepted	11/16/2017
Date Current Protocol Accepted
Study Name	RESOLUTE ONYX PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	RESOLUTE ONYX Post-Approval Study
Study Population	Single arm study with Resolute Onyx Stent System
Sample Size	510 (up to 50 subjects may be enrolled prior to PMA approval)
Key Study Endpoints	The primary endpoint is incidence of Target Lesion Failure (TLF) at 12 months, defined as Cardiac Death, Target Vessel MI or Target Lesion Resvascularization.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	101 subjects
Actual Number of Sites Enrolled	17 -(14 US, 3 EU)
Patient Follow-up Rate	The rate of TLF in the XLV Cohort ITT population at 12 months was 10.9% (11/101), with two-sided 95% CI of [5.6%, 18.7%]. At 24-months, cardiac death rate was reported as 4.0% (4/101), TVMI (3rd UDMI) as 8.9% (9/101), clinically driven TLR 9.9% (10/101), clinically driven TVR 10.9% (11/101), TLF 17.8% (18/101) and TVF 18.8% (19/101). There was one ARC definite ST [1.0% (1/101)]. At 36-months, cardiac death rate was reported as 5.1% (5/99), TVMI (3rd UDMI) as 10.1% (10/99), clinically driven TLR 11.1% (11/99), clinically driven TVR 13.1% (13/99), TLF 19.2% (19/99) and TVF 21.2% (21/99). There was one ARC definite ST [1.0% (1/99)].
Final Safety Findings	The 12-month primary endpoint results of the RESOLUTE ONYX PAS XLV Cohort demonstrated the safety and effectiveness of Resolute Onyx for the treatment of lesions in coronary arteries amenable to treatment with a Resolute Onyx 4.5 mm – 5.0 mm stent. Results from the 24-month and 36-month data continue to support the safety and effectiveness of this device for stent sizes 4.5 mm and 5.0 mm in treating complex coronary lesions.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P160055 / PAS001
Date Original Protocol Accepted	03/04/2019
Date Current Protocol Accepted	02/16/2023
Study Name	LAL/LDD Postmarket RCT
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A two-phased study (Phase A and B) will be conducted that evaluate the following two safety questions: (1) What is the rate of endothelial cell density loss (ECL) for patients with the RxSight LAL/LDD? (2) What is the rate of retinal damage caused by UV treatment with the LDD that may not be detected by routine post-operative testing?
Study Population	• Must sign a written Informed Consent form and be willing to undergo cataract surgery for the implantation of an IOL with random assignment to either the RxSight LAL or the monofocal control IOL. • Between the ages of 40 and 80 inclusive on the day the cataract surgery is performed. • Preoperative corneal cylinder greater than or equal to 0.75 diopters (D) to less than or equal to 2.00 D or >2.00 D and < 2.5 D of corneal cylinder with a steep axis between 70 degrees and 110 degrees. • Study eye has best corrected distance visual acuity projected (by clinical estimate based upon past ocular history and retinal exam) to be 20/20 or better after cataract removal and IOL implantation. • Study eye has clear intraocular media other than cataract. • Willing and able to comply with the requirements for study specific procedures and visits. • Study eye has average dilated pupil diameter of greater than or equal to 7.0 mm. • Able to complete a written questionnaire in English. • Study eye requires an IOL power within the range available for the RxSight LAL.
Sample Size	Phase A – 24 English speaking patients in the EU at 1-3 sites Phase B – 500 subjects at 10 sites randomized 2:1 to receive either a RxSight LAL (333 eyes) or monofocal control (167 eyes). Only one eye per subject may be included in the study. Calculation is based on the two primary safety endpoints described below.
Key Study Endpoints	The primary effectiveness endpoints are: Mean absolute manifest refraction spherical equivalent (|MRSE|) at postop month 6 compared between the RxSight LAL and Control group Mean manifest cylinder at postop month 6 compared between the RxSight LAL and Control group The primary safety endpoints are: Mean rate of endothelial cell density loss at postop month 6 compared to preoperatively compared between the RxSight LAL and Control group Percent of RxSight LAL eyes with UV retinal damage at postop month 6
Follow-up Visits and Length of Follow-up	6 months minimum, except in cases where UV retinal damage is confirmed then 12 months minimum.
Interim or Final Data Summary
Actual Number of Patients Enrolled	592 enrolled and 500 eyes implanted with the LAL or control IOL.
Actual Number of Sites Enrolled	15 sites
Patient Follow-up Rate	All LAL eyes were seen at all required visits that they were eligible for through Lock-in #2. At Months 1-2, 1 eye (0.3%) was lost to follow-up leading to 99.7% (334/335) accountability. At Month 6, 3 eyes (0.9%) were lost to follow-up resulting in 99.1% (332/335) accountability for the LAL group. In the Control group, 1 eye (0.6%) missed the Day 1 visit. All Control eyes were seen at the Week 1 and Week 3 exams. At Months 1-2, one eye (0.6%) was lost to follow-up leading to 99.4% (164/165) accountability. At Month 6, accountability remained at 99.4% (164/165) accountability. Accountability throughout the study exceeded 99% at all times.
Final Safety Findings	Both co-primary safety endpoints were met. For the first co-primary safety endpoint, the median rate of endothelial cell loss (ECL) at Month 6 was 5.1% in the LAL group and 4.9% in the Control group compared to preoperative. The median observed difference was 0.2% (90% Hodges-Lehmann confidence interval: -1.00%, 1.66%). The median difference was compared against a 5% noninferiority margin for ECL using a right-tail Mann-Whitney-Wilcoxon test with a significance level of 0.05. This comparison showed that the LAL group was not inferior to the Control group (p-value <0.0001), indicating the first co-primary safety endpoint was met. For the second co-primary safety endpoint, no LAL eyes (0/331) were diagnosed with UV retinal damage at Month 6 or at any other time during the study.
Final Effect Findings	Both co-primary effectiveness endpoints were met. Analysis of the first co-primary effectiveness endpoint showed the mean |MRSE| at Month 6 was +0.210 ± 0.213 D in the LAL group compared to +0.345 ± 0.265 D in the Control group, representing a smaller residual refractive error for the LAL group compared with the Control group at Month 6. For the second co-primary effectiveness endpoint, the mean manifest refraction cylinder (MRCYL) at Month 6 was 0.262 ± 0.275 D in the LAL group compared to 0.820 ± 0.554 D in the Control group. The median MRCYL was 0.25 D in the LAL group compared to 0.75 D in the Control group. Additionally, at Month 6, 92.5% of LAL eyes had an MRCYL of 0.50 D or less compared to 37.2% for the Control group. MRCYL > 1.00 D was present in only 1.2% of LAL eyes compared to 28.1% of Control eyes.
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P100018 S015/ PAS001
Date Original Protocol Accepted	12/14/2018
Date Current Protocol Accepted
Study Name	PREMIER Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The “Prospective Study on Embolization of Intracranial Aneurysms with the Pipeline™ Device” (PREMIER) study is a prospective, multi-center non-randomized clinical study evaluating safety and effectiveness outcomes in patients with small or medium wide-necked intracranial aneurysms measuring less than or equal to 12 mm who are treated with the Pipeline™ device. The study includes continued follow-up of the premarket cohort for up to three (3) years post-procedure.
Study Population	The study enrolled patients with small or medium wide-necked intracranial aneurysms measuring =12 mm who were treated with the Pipeline™ device.
Sample Size	Out of 197 consented patients, 141 patients were implanted with the Pipeline device.
Key Study Endpoints	The primary safety endpoint is the rate of major or disabling strokes or neurological deaths. The primary effectiveness endpoint is the rate of patients who have complete (100%) Raymond-Roy Class I intracranial aneurysm occlusion without clinically significant parent artery stenosis or retreatment of the target aneurysm.
Follow-up Visits and Length of Follow-up	Three years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Consented 197 subjects to meet the 141 evaluable (ITT) subjects.
Actual Number of Sites Enrolled	23 sites with 22 US sites and 1 Canadian site
Patient Follow-up Rate	The follow-up rates for ITT population at 1-yr, 2-yr, and 3-yr follow-up visits are 98.6%, 95%, and 90.8%, respectively.
Final Safety Findings	Incidence of major stroke: Major strokes in the territory supplied by the treated artery or Neurological Death at long-term (2-year and 3-year follow-up) occurred in 2.8% (4/141) of subjects. The incidence rate of major stroke at long-term is comparable with the rate at 1-year follow-up (2.4%). Specifically, only 1 additional subject (Subject: 109-022) experienced a Major Stroke between 1- and 2-year follow-up; none of the subjects had neurological death in this period. No additional Major Stroke in the territory supplied by the treated artery or Neurological Death occurred between 2- and 3-year follow up. Delayed ICH: The rate of delayed ICH at long-term (1.4%) is comparable with the rate at 1-year follow-up (0.73%). Specifically, only one subject (Subject: 109-022) had a delayed ICH between 1- and 2-year follow-up. No additional delayed intracerebral hemorrhage occurred between the 2- and 3-year follow up. Device-Related Neurological Adverse Event Rate: Fifteen of the 141 subjects (10.6%, 15/141) experienced device-related neurological AE’s through 3-years post-procedure. The rate of device-related neurological AE is comparable to that at 1-year follow-up (7.8%). Specifically, 4 new subjects reported device-related neurological events between 1- and 2- year follow-up. No additional device-related neurological AE’s occurred between 2- and 3-year follow-up 10.6% (15/141) of subjects. Cerebrovascular Events: The incidence rates for intracranial hemorrhage (ICH) at 1-yr, 2-yr, and 3-yr follow-up are 0.7%, 0.7%, and 0% respectively. Similarly, the incidence rates for ischaemic stroke at 1-yr, 2-yr, and 3-yr follow-up are 0.7%, 0%, and 0% respectively. There is no increase in the annual incidence rates of hemorrhagic and ischaemic cerebrovascular events over time.
Final Effect Findings	Complete aneurysm occlusion rate without significant parent artery stenosis (= 50%) or retreatment of the target aneurysm at 1-year follow up is 78.98% (LCL: 72.05%) with 1-sided 97.5% exact binomial lower bound of 72.05%. Similarly the Complete aneurysm occlusion rates Using LOCF (last observation carry forward) approach at 2-year follow-up and 3-year follow-up are 78.8% (LCL: 70.8%) and 80.3% (LCL: 72.5%), respectively.
Study Strengths & Weaknesses	Strength: A prospective and long-term study with follow-up rate for ITT population above 90%. Weaknesses: Single arm study not controlling for confounding factors. Gender distribution is skewed. The majority of study subjects were female (87.9%) and male subjects were under presented, which leads to a limitation in the generalizability of the study results. Understanding of device performance in subjects vertebral aneurysms is limited due to small sample size (N=7).
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P160043 S012/ PAS001
Date Original Protocol Accepted	03/08/2019
Date Current Protocol Accepted
Study Name	RESOLUTE ONYX CTO Post-approval study
General Study Protocol Parameters
Study Design	Meta Analysis
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Meta-analysis of CTO patients enrolled in on-going studies. The objective of the RESOLUTE ONYX CTO Post-Approval Study (PAS) is to demonstrate the generalizability of the performance the Resolute family of drug-eluting stents for the treatment of chronic total occlusions (CTOs) in a real-world setting..
Study Population	The RESOLUTE ONYX CTO PAS will consist of pooled lesion- and patient-level meta-analyses of subjects with CTOs treated with the Resolute Onyx stent system that are enrolled in the Primary, XLV and Bifurcation Cohorts of the RESOLUTE ONYX Post-Approval Study and the ONYX ONE outside of the US randomized controlled trial. Subjects will be followed according to the procedures in each respective study.
Sample Size	Approximately 100 subjects between all three studies. No formal hypothesis will be conducted.
Key Study Endpoints	The primary safety and effectiveness endpoint will be freedom from MACE (death, myocardial infarction, and clinically-driven target lesion revascularization) at 30-days. Secondary endpoints will include acute success (device, lesion, and procedure), cardiac death, target vessel MI, TLR, TLF, TVF, and stent thrombosis.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	78
Actual Number of Sites Enrolled	28
Patient Follow-up Rate	92.3% (72/78)
Final Safety Findings	Target lesion revascularization (TLR) rate and contributing to an overall 33.3% (10/30) TLF, TVF, and MACE rate. Lesion success defined as attainment of <50% residual stenosis of the target lesion using any percutaneous method was 100% (47/47) and device success defined as attainment of <50% residual stenosis of the target lesion using only Resolute Onyx was reported at 97.9% (46/47). Procedure success defined as attainment of <50% residual stenosis of the target lesion and no in-hospital MACE was reported at 70.0% (21/30) where failures were solely driven by the nine (9) peri-procedural ARC MIs reported for this cohort.
Final Effect Findings	The study used a primary composite endpoint of Freedom from Major Adverse Cardiac Events (MACE) defined as any death, myocardial infarction (per ARC definition), or clinically-driven target lesion revascularization (TLR) at 30-days was established as the primary endpoint for these cohorts. In total the MACE rate was 79.5% (62/78). Primary Endpoint Onyx PAS CTO (N=30 subjects) Onyx ONE CTO (N=35 Subjects) Onyx ONE Clear CTO (N=13 Subjects) Freedom from MACE at 30 days 70.0% 88.6% 76.9% The freedom from MACE rate is a cumulative probability of event-free estimate based on the Kaplan-Meier Method. MACE (death, myocardial infarction (per ARC MI definition), and clinically-driven target lesion revascularization)
Study Strengths & Weaknesses	The strength of this study is that I captures a close approximation of a real world population. The data included a large number of investigators at multiple sites providing a wide range of patients. This data helps to reflect how the device will perform in the clinical community. However, this trial was a single arm investigation which is a limitation. While this is not noted as a major weakness of the trial, it should be noted as a limitation.
Recommendations for Labeling Changes	We have recommended that the sponsor submit a labeling amendment to include this information in their future DFU.
General
Study Status	Completed
Application Number / Requirement Number	P160024 / PAS001
Study Name	BOLSTER Continued f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (BOLSTER Continued Follow-Up Study) is to evaluate the long term safety and effectiveness of the LifeStream Balloon Expandable Vascular Covered Stent for treatment of iliac arterial occlusive disease. This study is a prospective, single-armed, multi-center follow-up of the BPV-12-001 pivotal study (G140138).
Study Population	The study population included symptomatic (Rutherford Category 2-4) patients with angiographic confirmation of either de novo or restenotic (non-stented) common and/or external iliac artery stenoses or occlusions, with reference vessel diameters between 4.5mm and 12.0mm in diameter and the target lesion = 100 mm in combined length (per side). Patients were included who presented with evidence of single, bilateral, or multiple de novo and/or restenotic (non-stented) lesion(s) in the native common and/or external iliac artery.
Sample Size	All 148 remaining subjects (7 subjects have discontinued the study) of the 155 original study subjects enrolled from 24 investigational sites.
Key Study Endpoints	Primary Endpoint: Freedom from target lesion revascularization at 36 months. Target lesion revascularization is defined as the first revascularization procedure (e.g., PTA, atherectomy, etc.) of the target lesion(s) following the index procedure as determined by an Independent Angiographic Core Lab (or CEC, as necessary). Secondary Endpoints: Freedom from target vessel revascularization (TVR) at 12, 24 and 36 months Freedom from target lesion revascularization (TLR) at 12 and 24 months Primary patency at 12, 24 and 36 months Primary assisted patency at 12, 24 and 36 months Secondary patency at 12, 24 and 36 months Sustained clinical success at 12, 24 and 36 months Quality of life at 12, 24 and 36 months Serious adverse events at 12, 24 and 36 months
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	155 subjects were treated with the study device and included in the Intent to treat population; 148 subjects were available at 9 months for the continued PAS.
Actual Number of Sites Enrolled	Twenty-four (24) sites were enrolled world-wide. Of these, 17 sites enrolled subjects
Patient Follow-up Rate	87.0% (107/123) at 36 months post index procedure
Final Safety Findings	Primary Endpoint The IDE study met the composite primary safety and effectiveness endpoint defined as device and/or procedure-related death or myocardial infarction (MI) through 30 days, or any target lesion revascularization (TLR), target limb(s) major amputation, or restenosis through 9-months post-index procedure. The proportion of subjects with the composite primary event rate was 11.6% (16/138), 93.5% confidence interval (CI) of 7.0%, 17.8% compared to the performance goal of 19.5%, p= 0.0095 (p-value is less than 0.0325). The primary endpoint for the continued follow-up study is freedom from target lesion revascularization (TLR) at 36 months. TLR is defined as the first revascularization procedure of the target lesion(s) following the index procedure, as determined by an Independent Angiographic Core Lab. The proportion of subjects with TLR through the 36-month visit was 17.6% (23/131) [95% CI: 11.5%, 25.2%). Secondary Endpoints Results The proportion of subjects with target vessel revascularization through 36-month visit was 17.6% (23/131) [95% CI: 11.5%, 25.2%]. The proportion of subjects with primary patency at 36-month visit was 68.6% (72/105) [95% CI: 58.8%, 77.3%]. The proportion of subjects with primary assisted patency through 36-month visit was 78.8% (78/ 99) [95% CI: 69.4%, 86.4%]. The proportion of subjects with secondary patency through the 36- month visit was 86.8% (79/91) [95% CI: 78.1%, 93.0%]. The proportion of subjects with sustained clinical success at the 36-month visit was 92.5% (98/106) [95% CI: 85.7%, 96.7%]. The proportion of subjects with any serious adverse events was 63.9% (99/155).
Study Strengths & Weaknesses	Strengths: The IDE study was a single-arm, prospective multicenter study conducted in the United States and OUS countries. The study met its composite primary safety and effectiveness primary endpoint. The PAS was a continued follow-up of the premarket subjects through 36 months, with a 36-month followup rate of 87%. Weaknesses: This was a single- arm observational study and therefore lacks the inherent advantages of a randomized control trial. There was no comparator for the continued follow-up study results. The results of the post-approval study were analyzed by descriptive analysis only.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow-up visits etc.), final results, strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P160043 / PAS002
Date Original Protocol Accepted	11/16/2017
Date Current Protocol Accepted
Study Name	RESOLUTE ONYX PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	RESOLUTE ONYX Post-Approval Study
Study Population	Single arm study with Resolute Onyx Stent System
Sample Size	510 (up to 50 subjects may be enrolled prior to PMA approval)
Key Study Endpoints	The primary endpoint is incidence of Target Lesion Failure (TLF) at 12 months, defined as Cardiac Death, Target Vessel MI or Target Lesion Resvascularization.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Interim Results	At 12 months (XLV cohort ITT Population): Target lesion Failure (TLF) was 10.9 (11/101) with 2- sided 95% CI of [5.6%, 18.7%] At 24 months (XLV cohort ITT Population): Major Adverse Cardiac Event was 21.8% (22/101), Cardiac death was 4.0% (4/101), clinically driven TVR 9.9% (10/101), clinically driven TLR was 8.9% (9/101), TLF 16.8% (17/101), target vessel failure 17.8% (18/101) and ARC definite Stent thrombosis 1.0% (1/101).
Actual Number of Patients Enrolled	101 subjects
Actual Number of Sites Enrolled	17 - (14 US, 3 EU)
Patient Follow-up Rate	The rate of TLF in the XLV Cohort ITT population at 12 months was 10.9% (11/101), with two-sided 95% CI of [5.6%, 18.7%]. At 24-months, cardiac death rate was reported as 4.0% (4/101), TVMI (3rd UDMI) as 8.9% (9/101), clinically driven TLR 9.9% (10/101), clinically driven TVR 10.9% (11/101), TLF 17.8% (18/101) and TVF 18.8% (19/101). There was one ARC definite ST [1.0% (1/101)]. At 36-months, cardiac death rate was reported as 5.1% (5/99), TVMI (3rd UDMI) as 10.1% (10/99), clinically driven TLR 11.1% (11/99), clinically driven TVR 13.1% (13/99), TLF 19.2% (19/99) and TVF 21.2% (21/99). There was one ARC definite ST [1.0% (1/99)].
Final Safety Findings	The 12-month primary endpoint results of the RESOLUTE ONYX PAS XLV Cohort demonstrated the safety and effectiveness of Resolute Onyx for the treatment of lesions in coronary arteries amenable to treatment with a Resolute Onyx 4.5 mm – 5.0 mm stent. Results from the 24-month and 36-month data continue to support the safety and effectiveness of this device for stent sizes 4.5 mm and 5.0 mm in treating complex coronary lesions.
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P150035 / PAS001
Date Original Protocol Accepted	03/31/2022
Date Current Protocol Accepted	06/11/2026
Study Name	The Aveir VR RWE Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post-approval study (PAS) is to evaluate the long-term safety of the single-chamber Aveir Leadless Pacemaker device (aka VR LP) using real-world evidence (RWE) methods. The study utilizes a real-world evidence method merging multiple real-world datasets from Abbott and CMS to assess the Aveir VR LP safety in a large patient population. The study also assesses acute and chronic complications through 6 months in patients implanted with the AVEIR VR leadless pacemaker via internal jugular vein access.
Study Population	Adult (22 years and older)
Sample Size	2100
Key Study Endpoints	Primary Endpoints are: - To assess freedom from key acute (30-day) complications post-implant procedure - To assess freedom from key long-term (31 days through 10-year) complications post-implant procedure Secondary Endpoints are: - Complication rate of the Aveir VR LP for key individual acute and chronic complications - Care of subjects at the end of device service Descriptive Endpoints are: - Rates of other procedure or device-related complications - Survival at 10 years - To assess device longevity - Summarize study cohort demographics and comorbidities - To assess device-device interaction - To analyze effect of implanter experience with Aveir VR LP on safety performance
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results Freedom from key acute complications through 30 days implant was 91.8% (95% CI: 90.8%-92.7%) for 3,427 devices. Freedom from key chronic complications from 31 days to 10 years post implant was evaluated through 36-months based on data available through the data cut-off rate for this 48-month progress report. The event-free survival rate was 99.2% at 36-months post implant for 3,210 devices. Subjects continue to be followed within the study so that the follow-up period will be updated as the study progresses. Subject enrollment is closed for this study. Enrolled subjects include patients with prior Cardiovascular Implantable Electronic Devices (CIED) as well as de novo patients (patients with no prior CIED implants).
Actual Number of Patients Enrolled	Actual number of patients enrolled is 3,418 (3,427 devices)
Actual Number of Sites Enrolled	Actual number of sites enrolled is 511
Patient Follow-up Rate	N/A
General
Study Status	Completed
Application Number / Requirement Number	P030016 S035/ PAS001
Date Original Protocol Accepted	05/04/2022
Date Current Protocol Accepted
Study Name	CP19-01 PAS F/u of PMA Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post-approval study is to evaluate the continued safety and effectiveness of the EVO/EVO+ Visian® Implantable Collamer® Lens (ICL) in the original PMA P030016/S035 cohort. The study design is a continued follow-up of premarket cohorts of the original PMA P030016/S035 study which enrolled and implanted 327 subjects (327 primary eyes and an additional 302 fellow eyes) at 14 clinical sites in the US. Post approval follow-up of the PMA cohort will continue through the Year 3 visit (Postoperative Visit 8, Day 1050 – 1170).
Study Population	The study population includes all subjects enrolled and who completed Postoperative Visit 5 under the original study protocol for Study CP19-01 (approved under IDE G190184).
Sample Size	In order to detect an AE with a true probability of occurrence among eyes of 1% with 95% probability, based on the binomial distribution, a sample of at least 300 eyes is required.
Key Study Endpoints	Co-Primary Endpoints Co-primary endpoints will be evaluated in all eyes (primary and fellow eyes) using descriptive statistics with comparisons to PMA data for the approved and currently marketed MICL and TMICL devices, where appropriate. The co-primary endpoints have no prespecified performance targets. Distribution of percent endothelial cell density (ECD) losses and the percent of eyes that have ECD <1500 and ECD <1000 through Postoperative Visit 8 (Day 1050 – 1170). Incidence of adverse events (AEs) through Postoperative Visit 8 (Day 1050 – 1170).
Follow-up Visits and Length of Follow-up	Subjects will be seen for 3 study visits in this PAS at the following timepoints after the original date of surgery: Year 1 (Days 330-420), Year 2 (Days 690-810) and Year 3 (Days 1050-1170).
Interim or Final Data Summary
Actual Number of Patients Enrolled	327 subjects (629 eyes)
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	All 327 subjects (629 eyes) had undergone surgery in the pre-approval phase. 619 eyes (98.6%) available for month 6 analysis (pre-approval end) 615 eyes (97.9%) available for year 1 analysis 585 eyes (93.6%) available for year 2 analysis 579 eyes (92.1%) available for year 3 analysis
Final Safety Findings	The mean (SD) percent endothelial cell density (ECD) loss three year following EVO/EVO+ Visian Implantable Collamer Lens (ICL) insertion was 6.7% (5.4) in all eyes. For comparison, the mean (SD) endothelial cell loss at 3 years reported in the ICL for Myopia (MICL) PMA Clinical Study for the consistent cohort of 154 eyes was 8.9%. The proportions of eyes with loss of greater than or equal to 10%, greater than or equal to 20% and greater than or equal to 30% ECD in the MICL PMA Clinical Study at 3 years were 33.3%, 9.1% and 1.5%, compared with 20.5%, 2.1% and 0.52% of eyes with loss of greater than or equal to 10%, greater than or equal to 20% and greater than or equal to 30% ECD in this study. No eyes in this study were reported to have ECD <1500 or <1000 cells/mm2 through Year 3. No unanticipated adverse events (AEs) or deaths caused by or associated with the use of the device were reported in subjects through Year 3.
Final Effect Findings	Accurate and stable refractive correction was achieved from -3 to almost -16 D spherical equivalent, with 90.7% of eyes within 0.50 D of target and 99.0% of eyes within 1.00 D of target at 3 years was achieved. At least 92% of eyes achieved uncorrected distance visual acuity (UDVA) of 20/25 or better at each time point from Month 6 to Year 3. The data show outstanding preservation of corrected distance visual acuity (CDVA), with 100% of eyes 20/32 or better at 3 years.
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	The Applicant did not request any labeling changes as part of the final PAS report.
General
Study Status	Completed
Application Number / Requirement Number	P160047 / PAS001
Study Name	AEGEA Pivotal Clinical Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The AEGEA Pivotal Clinical Trial (Protocol SE-3000) is a prospective, single-arm, non-randomized, multicenter, open label clinical trial to evaluate the safety and effectiveness of the AEGEA Vapor System™ for the treatment of excessive menstrual bleeding. Subjects were enrolled at fourteen investigational sites in the United States, Mexico, Canada, and The Netherland. The AEGEA Pivotal Clinical Trial was divided into two groups: Safety subjects (or Safety cohort) and Pivotal subjects (or Pivotal cohort). Sixty-six (66) Safety subjects and 155 Pivotal subjects were evaluated. The primary analysis population for safety and effectiveness for this study was the Intent-to-Treat (ITT) population for the Pivotal subjects. Safety results from the Safety subjects were considered as part of the evaluation of device safety. Data from the Pivotal cohort are the basis of effectiveness outcome analyses to support this PMA. Data from the Safety cohort is not included in the effectiveness analysis, but it is considered as a part of safety evaluation. Follow-up of Pivotal cohort occurred at 24 hours post-procedure, 2 weeks and 3, 6, and 12 months post-procedure prior to PMA submission. The applicant intends to continue follow-up in the post-market setting to collect long-term outcome in Pivotal cohort at two and three years.
Study Population	The demographics of the study population (Pivotal subjects) are typical for an endometrial ablation study performed in the United States. Seventy-six (76) patients were 30-39 years old, and seventy-nine (79) patients were 40-50 years old. The mean age of subjects at baseline was 39.8. An evaluation of these data confirmed the data could be pooled across sites and countries.
Sample Size	One hundred and thirty-seven (137) of 155 Pivotal subjects enrolled in the premarket study are available for postmarket follow-up.
Key Study Endpoints	Need for surgical or medical intervention to treat abnormal bleeding Subject self-report of pregnancy Contraception status (data to be collected at 3 years only) Menstrual status Gynecologic adverse events Quality of Life questionnaire Patient satisfaction
Follow-up Visits and Length of Follow-up	Three years
Interim or Final Data Summary
Actual Number of Patients Enrolled	155
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	12-month: 91.0% (141/155) 24-month: 98.5% (133/137) 36-month: 91.2% (125/137)
Final Safety Findings	There were 54 adverse events from 12 months to 36 months, including eight (8) serious adverse events (SAEs) and 46 non-serious adverse events. Of the eight (8) SAEs, one (hematometra) was related to the procedure. There were no unanticipated device-related adverse events in the study through the 3-year follow-up.
Final Effect Findings	Premarket effectiveness endpoints: The overall success rate based on PBLAC results was 78.7% (122/155) at 12 months. The amenorrhea (no menses) rate was 19.4% (30/155). Postmarket effectiveness endpoints: Need for surgical or medical intervention to treat abnormal bleeding: From 12 to 36 months, 6.8% subjects (9/133) had medical or surgical intervention to treat abnormal menstrual bleeding. Subject self-report of pregnancy: None Quality of Life: The Menorrhagia Impact Questionnaire (MIQ) score (mean +/- SD) was reduced from 14.7 +/- 2.9 (baseline) to 6.1 +/- 1.7 (n=133) at 24 months and 6.3 +/- 1.9 (n = 125) at 36 months. Patient Satisfaction: The percentages of patients reporting very satisfied or satisfied were 90% (118/132) at 24 months and 91% (114/125) at 36 months. The percentages of patients who would recommend the ablation procedure to a friend were 92% (122/132) at 24 months and 94% (118/125) at 36 months. Contraception Status: Method of Contraception 36 Month (N=127*) Surgical Tubal Ligation 64 (50%) Vasectomy 29 (23%) Barrier 21 (17%) Implantable (Essure) 6 (5%) Abstinence 3 (2%) None 2 (2%) Other (sterile subject; salpingectomy) 2 (2%)
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	The sponsor submitted P160047/S006 to request labeling changes based on the 24 and 36-month follow up from this pivotal study.
General
Study Status	Ongoing
Application Number / Requirement Number	P130017 S029/ PAS001
Date Original Protocol Accepted	09/20/2019
Date Current Protocol Accepted	08/26/2020
Study Name	A Post-Marketing Real World Study-Tidal
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Other Data Source
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective is to evaluate the performance of Cologuard for CRC screening in patients under the age of 50 by collecting real world data on subsequent CRC screening and CRC-related outcomes. This post-approval observational study is a largely automated multi-center study that will collect data from Integrated Delivery Networks (IDNs), hospital systems, and large primary care practices to generate a longitudinal record of patients’ journeys prior to and following an initial Cologuard screening. This approach relies on technology-based data collection to eliminate the need for ongoing manual data collection, abstraction, entry, and cleaning at the site level and ensures that all eligible patients are enrolled. The study will leverage digitized data from structured and unstructured fields (e.g., pathology reports) from multiple sources and systems [e.g., EMR, ambulatory procedure centers (for colonoscopies), laboratory data, pathology information]. It is anticipated that at least 50,000 eligible patients under the age of 50 at the time of routine screening with Cologuard will be included in the study. Both Cologuard-positive and Cologuard-negative patients will be followed for subsequent CRC assessments and CRC-related outcomes.
Study Population	All patients under the age of 50 undergoing CRC screening with a completed Cologuard test as part of routine clinical monitoring at each site, regardless of risk status, will be eligible for inclusion. Patients considered off-label, such as those meeting high-risk criteria and/or less than 45 years of age at the time of screening will be included and analyzed separately. Patients with orders for Cologuard but no recorded results will be excluded. Data from the EMR will be used to determine risk status after the patient is included in the study. Patients will be considered high risk based on the presence of any of the following: History of CRC, advanced adenoma, or other related cancer Inflammatory bowel disease (IBD) Chronic ulcerative colitis (CUC) Crohn’s disease Familial adenomatous polyposis (FAP) Relevant familial hereditary cancer syndromes Family history of CRC
Sample Size	At least 50,000 patients will be included, which is anticipated to yield 12 CRC cases. If by chance no CRC cases are identified in the first 50,000 enrollees, the study will continue to accrue patients until at least one CRC case is identified in the patient population. Based on preliminary studies, a positive Cologuard rate of approximately 7% (n=~3500) is expected.
Key Study Endpoints	The following outomes will be evaluated: Cologuard positivity rate Compliance to diagnostic colonoscopy within 12 months CRC detected on colonoscopy following a positive Cologuard result Advanced adenomas on colonoscopy following a positive Cologuard result Non-advanced findings or no findings on colonoscopy following a positive Cologuard result Observed specificity CRC-related diagnoses within 36 months of a negative Cologuard result Observed sensitivity
Follow-up Visits and Length of Follow-up	Total study duration is estimated at 72 months, depending on the rate of uptake of Cologuard in the target population. For patients with a positive Cologuard result, at least 12 months of follow-up after the patient index date (initial Cologuard screening date) will be evaluated for colonoscopy results. For patients with a negative Cologuard result, at least 36 months of follow-up after the index date will be evaluated to ensure capture of potential positive CRC cases.
General
Study Status	Ongoing
Application Number / Requirement Number	P160048 S006/ PAS001
Date Original Protocol Accepted	11/25/2019
Date Current Protocol Accepted	03/19/2026
Study Name	Eversense CGM Non-Adjunctive PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose is to demonstrate the long-term safety and effectiveness of the Eversense System when used non-adjunctively. The investigation will include both use of self-monitoring of blood glucose (SMBG) and either the Eversense CGM System, the Eversense E3 CGM System, or the Eversense 365 CGM System. The study will evaluate the effectiveness of SMBG for diabetes management decisions compared to Eversense System used non-adjunctive in study participants with either Type 1 or Type 2 diabetes. Subjects will serve as their own baseline using SMBG for the first 6 months followed by using the Eversense System non-adjunctively for the second six months, when enrolled with the Eversense or Eversense E3 CGM Systems. Subjects receiving the Eversense 365 CGM System at enrollment will be enrolled directly into the non-adjunctive phase of the study. All care decisions specific to diabetes to be based on blood glucose values in the first phase and the CGM system value in the second phase. Thus, this non-blinded, prospective, multi-center, single arm longitudinal cohort study (patient serves as their own control) will evaluate safety and effectiveness of the Eversense CGM System used non-adjunctively in the post-market setting.
Study Population	Subjects may be included in the PAS if they fit the following inclusion criteria: 1. Subject has diabetes 2. Subject is greater than or equal to 18 years of age 3. Subject has a smartphone that is internet enabled 4. Subject is able to comply with study protocol tasks and understand written and verbal instructions in the investigator’s opinion 5. Subjects is willing and able to provide written, signed and dated informed consent Subjects meeting any of the following exclusion criteria at the time of screening will be excluded from this study: 1. Subject is critically ill or hospitalized 2. Prior use of Eversense CGM systems 3. Subject has a known contraindication to dexamethasone or dexamethasone acetate 4. Subjects requiring intravenous mannitol or mannitol irrigation solutions 5. Subject is on dialysis at the time of enrollment 6. Female subjects who are pregnant, planning on becoming pregnant or nursing
Sample Size	Up to 665 subjects will be enrolled in the United States at up to 30 sites.
Key Study Endpoints	The primary safety endpoint is the rate of the composite of severe hypoglycemia and diabetic ketoacidosis. Other safety endpoints include: Rate of all device-related and insertion and removal procedure-related adverse events Rate of adverse events related to use of the user interface, patient training, or labeling materials. Change in HbA1c from baseline at 6 and 12 months Average hours of use per day Serious adverse events regardless of causality
Follow-up Visits and Length of Follow-up	Every 4 weeks (phone visits). Subjects who receive the Eversense 365 CGM System will participate for 12 months non-adjunctively.
Interim or Final Data Summary
Interim Results	Safety Results For Post-Approval Study (P160048): Three hundred thirty-four (334) adverse events (AE) have been reported as of the reporting period through April 10, 2023. Of these events, 93 are related to the study device and/or the insertion or removal procedure. For Eversense CGM Non-Adjunctive PAS (P160048/S006): One hundred fifty (150) adverse events (AEs) have been reported as of the reporting period through 01 May 2025. One hundred forty-five (145) of these events have complete adjudication by CEC members. Of the 145 total adverse events that have been adjudicated, 74 events were adjudicated as Serious Adverse Events (SAE), with none related to the device. Thirty-six (36) device malfunctions have been reported to date. Eleven (11) of the reported device malfunctions are documented as related to the Sensor. Of those 11, eight (8) are documented as early Sensor retirement (1.3%). The percent of early Sensor retirements is consistent with the PRECISE II study results, wherein 91% of Sensors remained functioning through 90 days, with the PROMISE study results, wherein 90% of Eversense E3 Sensors remained functioning through 180 days, and with the ENHANCE study results, wherein 90% of Eversense 365 Sensors remained functioning through 12 months. Effectiveness Results For Post-Approval Study (P160048): Effectiveness data will be presented once the primary endpoint of the study is reached at 12 months following the completion of all insertions. For Eversense CGM Non-Adjunctive PAS (P160048/S006): Effectiveness data will be based on data from all enrolled subjects who have data evaluable.
Actual Number of Patients Enrolled	For P160048: 273 For P160048/S006: 664
Actual Number of Sites Enrolled	For P160048 (Adjunctive Use): 6 For P160048/S006 (Non-Adjunctive Use): 25
Patient Follow-up Rate	For P160048: 97.4% (266/273) For P160048/S006: 53 out of 661 lost to follow-up; One hundred eighty (180) subjects have discontinued their participation in the study. One hundred twenty-seven (127) of the 180 withdrew and 53 of the 180 are documented as lost to follow-up. Prior to these subjects being designated as loss to follow-up, the sites attempted contact multiple times by phone and email which was then followed by a registered letter requesting the subject contact the site. Of the 127 subjects who withdrew, 87 were in Phase 1 and did not have a Sensor inserted and 40 of the subjects were in Phase 2. Forty-nine (49) of the 53 subjects who wee lost to follow-up were in Phase 1 and did not have a Sensor inserted and 4 of the subjects were in Phase 2 and have not had the Sensor removed as of the date of this report to the best of Sponsor's knowledge.
General
Study Status	Completed
Application Number / Requirement Number	P160048 / PAS001
Date Original Protocol Accepted	09/18/2018
Date Current Protocol Accepted	03/22/2023
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval study (PAS) is to provide long-term safety and effectiveness of the Eversense CGM System (PMA Application P160048) in the post-market setting. This is a prospective, multi-center study, whereby up to 400 subjects will be enrolled in the United States at up to 30 sites. The subjects will have one Sensor inserted by trained health care professionals approximately every 3 months. Sensors will be inserted in the upper arm of the subjects. This is a new enrollment study.
Study Population	Subjects may be included in the PAS if they fit the following inclusion criteria: 1. Subject has diabetes mellitus 2. Subject is greater than 18 years of age Subjects may not be included in the PAS if they fulfill the following exclusion criteria: 1. Subject will require a planned MRI during the period of Sensor insertion 2. Subject is critically ill or hospitalized 3. Subject has a known contraindication to dexamethasone or dexamethasone acetate 4. Subjects requiring intravenous mannitol or mannitol irrigation solutions 5. Female subjects who are pregnant, planning on becoming pregnant or nursing 6. Subjects on hybrid closed loop systems or closed loop systems 7. Subjects on other CGM systems
Sample Size	A total of 1400 Sensor cycles contributing to the analysis is planned. Based on data from the PRECISE (n=81 subjects), PRECISE II (n=90 subjects), PRECISION (n=35 subjects) and PMCF (n=1686 subjects) studies, a total of 31 events occurred that would meet the definition of the primary safety endpoint in this study. With a total of 1892 subjects, this equates to an observed rate of approximately 1.6% with an associated 95% confidence interval of 1.1% to 2.3%. As there is variability associated with this sample, as evidenced by the confidence interval, a conservative expected rate of events for this study is 2.3%. The planned sample size of 1400 total cycles) with this expected rate should provide greater than 95% power for the test of the performance goal of 4%. Meeting the performance goal of 4% for the planned sample size would require a worst-case observation of a rate of approximately 3% or less (i.e., 41 or fewer events among 1400 cycles). This result will be clinically acceptable and similar to results observed in past studies. A total of 273 enrolled subjects will achieve a total of at least 1400 Sensor cycles.
Key Study Endpoints	The primary safety endpoint is the incidence of the composite of infection, secondary procedures to remove the sensor, or procedure-related adverse events of at least moderate severity. Other safety endpoints include: Rate of all device-related and insertion and removal procedure-related adverse events (serious and non-serious events) through 27 months post-first sensor insertion Rate of device breakage through 27 months post-first sensor insertion Rate of device-related and insertion and removal procedure-related serious adverse events through 27 months post-first sensor insertion Subgroup analysis of safety endpoints based on: o Age (<65 years vs. >65 years, minimum 40 subjects) Diabetes type (I vs. II) Race (non-Caucasian vs. Caucasian)
Follow-up Visits and Length of Follow-up	Every 90 or 180 days (depending on whether a subject is using the 90-day or 180-day sensor) for sensor insertion/removal. Also 15 and 45 days postsensor insertion to enable documentation of any adverse events. Total duration of follow up is expected to be 24 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	For P160048: 273
Actual Number of Sites Enrolled	For P160048 (Adjunctive Use): 16
Patient Follow-up Rate	Two hundred seventy-three (273) subjects were inserted with an initial Sensor. Of the 273, 245 subjects had a second Sensor inserted, 219 subjects had a third Sensor inserted, 210 had a fourth Sensor inserted, 191 had a fifth Sensor inserted, 145 had a sixth Sensor inserted, 124 had a seventh Sensor inserted, 111 had an eighth Sensor inserted, seven (7) had a ninth Sensor inserted, and three (3) had a tenth Sensor inserted. Ten (10) subjects participated in additional Sensor cycle(s) because of an early Sensor retirement in a previous cycle. Therefore, to achieve a total length of participation of approximately two years per protocol, a 9th and 10th Sensor was inserted. One hundred (100) subjects discontinued their participation in the study early. Eighty-nine (89) of the 100 withdrew after removal of their last study Sensor, with the exception of three (3) subjects who withdrew prior to sensor removal and transitioned to commercial users. Eight (8) of the 100 are documented as lost to follow-up with the Sensor still in situ. Of the 92 subjects who withdrew, 27 subjects withdrew after completing the first sensor cycle, 22 after completing the second cycle, nine (9) after completing the third cycle, 11 after completing the fourth cycle, seven (7) after completing the fifth cycle, ten (10) after completing the sixth, and six (6) after completing the seventh cycle. In total, 173 subjects have completed all Sensor cycles and finished study participation.
Final Safety Findings	The primary safety endpoint of the incidence of the composite of infection, secondary procedures to remove the Sensor, or procedure-related adverse events of at least moderate severity is reported in Table 13. The composite rate was 42 events out of 1,528 sensor cycles (2.75%) with a 95% upper confidence limit of 3.54%, which met the primary endpoint performance goal (p=0.0054). There were five (5) cases of infection (0.33%), 24 secondary procedures to remove the sensor (1.57%), and 15 procedure-related AEs of at least moderate severity (0.98%). Three hundred sixty (360) adverse events (AEs) were reported during the study. All AEs have been adjudicated by CEC members. Appendix A contains the listing of all AEs adjudicated in the study. Of these events, 96 are related to the study device and/or the insertion or removal procedure, giving a rate of 6.28% per sensor insertion cycle (96 out of 1528 total sensor insertion cycles). The related adverse events (frequency, nature, and severity) are consistent with the safety profile from the clinical studies reported in the PMA application. Related adverse events for the PP population are provided and have a rate of 5.69% (72 out of 1265 sensor insertion cycles). Insertion and removal procedure-related AEs for HCPs with vs. without an MD degree are provided and did not result in a significant difference between HCP types (p=0.2908). Of the 360 total adverse events reported, 31 events were adjudicated as serious adverse events (SAE), two (2) of which were adjudicated as related to the device, one (1) that was adjudicated as possibly related to the device, and one (1) that was adjudicated as related to the insertion/procedure and possibly related to the device. The rate of related SAEs was 0.26% (four (4) out of 1528 total sensor insertion cycles). One hundred thirty-four (134) device malfunctions have been reported. Of those 58 are related to the Sensor and 37 are documented as Early Sensor Retirement (2.4%). The percentage of early Sensor retirements is consistent with the PRECISE II study results, wherein 91% of Sensors remained functioning through 90 days.
Final Effect Findings	The primary effectiveness endpoint of Time in Range (TIR), defined as glucose values between 70 mg/dL and 180 mg/dL, at 12 months compared to the first month post-first sensor insertion is reported in Table 24. The mean TIR was 62.7% for the first month of CGM System use and 62.4% for the 12th month of CGM system use. Sensitivity analyses for the primary effectiveness endpoint was performed using the PP analysis population and is provided. As with the entire population, the change is not statistically significant. The additional effectiveness endpoints of average hours of use per day and change in HbA1c levels at each 6-month interval from baseline are summarized. The Statistical Analysis Plan also specified six additional secondary endpoints, including: 1) patient satisfaction with CGM system use (CGM-SAT scale); 2) patient reported Diabetes Distress Scale (DDS); 3) success rate of insertion and removal procedures: overall and by HCP experience; 4) rate of serious adverse events based on HCP experience with the insertion/removal of Sensors; 5) HCP feedback questionnaire regarding insertion/removal; 6) residual dexamethasone level in explanted sensors. Overall, the sponsor states that the effectiveness endpoint of the study resulted in a time in range of 62.4% at 12 months compared to 62.9% at one month post-first Sensor insertion. This demonstrates a time in range that is consistent over multiple Sensor cycles and in line with prior studies on the Eversense CGM System, which reported Time in Range from 62.3-64.5%.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P160050 / PAS002
Date Original Protocol Accepted	05/07/2019
Date Current Protocol Accepted	05/19/2020
Study Name	Histological and Retrieval Analysis PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval evaluation is to investigate potential underlying mechanisms that may contribute to endplate lesion (EPL) initiation and/or growth through retrieval analysis and histological analysis of retrieved implants and/or peri-prosthetic tissue. This study is also intended to evaluate causes of device failure (fracture, migration, dissociation and wear particulate). Analysis of tissue and devices/material from retrieved (explanted) Barricaid® ACDs that were originally implanted following discectomy in real-world (i.e., commercial, not clinical study) experience.
Study Population	All patients implanted with a Barricaid® ACD in the United States.
Sample Size	This evaluation is not powered to demonstrate statistical conclusions, but rather to gather data for subsequent analysis and surveillance.
Key Study Endpoints	Histological analysis of tissue and explant material will be assessed per ASTM F561-13.
Follow-up Visits and Length of Follow-up	This evaluation shall remain in place for 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	n/a
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	No overt correlation between presence of osteolytic markers with the endplate lesions were found; however, substantive conclusions could not be made due to the limited sample size. Patient population also appeared to experience bony lesions at a lower frequency/distribution than in the RCT used for the PMA.
Final Effect Findings	No effectiveness endpoints in this study.
Study Strengths & Weaknesses	Strength: Provides firsthand clinical information regarding device failures through adjacent tissue and device analysis. Histologic data on retrievals are most translatable to help determine potential mechanism of the bony lesions. Weakness: Study is reliant on compliance of reporting and returning of explants and associated tissue, so limited data is available.
Recommendations for Labeling Changes	No definitive conclusions. Labeling change is recommended to document completion of PAS2 when PAS1 is complete and do a final labeling update together.
General
Study Status	Completed
Application Number / Requirement Number	P170030 / PAS001
Date Original Protocol Accepted	11/12/2019
Date Current Protocol Accepted	10/30/2020
Study Name	Bioflow-VII New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The BIOFLOW-VII study is a prospective, multi-center, single-arm study to confirm that the clinical performance of the Orsiro stent in a realworld setting is similar to the clinical performance observed for Orsiro in the BIOFLOW-V IDE pivotal trial. Subjects who undergo percutaneous coronary intervention (PCI) with a placed Orsiro stent within the prior 24 hours will be screened per the protocol inclusion and exclusion criteria to achieve the desired evaluable subject counts (N=500) for the primary endpoint. The study will enroll subjects at up to 50 sites in the US. The primary endpoint will evaluate the rate of target lesion failure (TLF) at 1 year post-index procedure. TLF is defined as a composite of cardiac death, target vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLR). Subjects may have received treatment of up to three target lesions in up to two separate target vessels (e.g., two target lesions in one vessel and one target lesion in a separate vessel). The target lesion(s) must have been de novo or restenotic (PTCA only) atherosclerotic lesion(s) of less than or equal to 36 mm in length in native coronary artery(ies), with a reference vessel diameter of 2.25–4.0 mm. All lesions treated during a single index procedure must meet target lesion criteria.
Study Population	Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Sample Size	A total of 556 subjects will be enrolled to achieve 500 evaluable subjects at 1 year. Subjects will be enrolled at up to 50 clinical sites. It is estimated that no more than 20% of the projected total subjects (approximately 111 subjects) will be enrolled at single site. Sample Size Assumption are as follows: Performance goal: 9.0% Target Orsiro TLF rate: 4.0% Statistical power: 80% Significance level: 1-sided 0.025 Evaluable sample size – 201 subjects (unadjusted). Per FDA recommendation- 500 (adjusted) Adjusted for 10% attrition - 556
Key Study Endpoints	Primary Endpoints The primary endpoint will evaluate the rate of TLF at 1 year post-index procedure. TLF is defined as a composite of cardiac death, target vessel myocardial infarction (MI) or clinically-driven target lesion revascularization (TLF). Secondary Endpoint: Secondary endpoints measured in-hospital and at 6 months, 12 months, 2 years, and 3 years after the index procedure include: TLR rate TLF rate (primary endpoint at 12 months) Target vessel revascularization (TVR) rate Target vessel failure (TVF) rate MI (Q-wave and non–Q-wave) rate Cardiac death rate Non-cardiac death rate All death rate Cardiac death or MI rate All death or MI rate All death/MI/TVR rate Stent thrombosis rates (by Academic Research Consortium [ARC] definitions)
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Death at 4-years was 6.06% (28/462) Any vessel MI was 5.44% (24/441) Any stent thrombosis was 1.3% (7/556) Effectiveness Results TLF at 1 year was 1.69% (9/531) TLF at 2 years was 4.45% (23/517) TLF at 3 years was 5.46% (26/476) TLF at 4 years was 8.43% (38/451)
Actual Number of Patients Enrolled	556
Actual Number of Sites Enrolled	31
Patient Follow-up Rate	465 subjects completed 4 years of follow-up with 17 visits missed. As of 4 years, 34 subjects have died, 12 withdrew consent, 4 exited for other reasons, and 44 subjects were otherwise lost to follow-up.
Final Safety Findings	Deaths at 5-year: 7.92% (37/467) Any-vessel MI at 5-year: 7.52% (33/439) Any stent thrombosis: 1.6% (9/556)
Final Effect Findings	TLF at 5-year: 10.79% (49/454)
Study Strengths & Weaknesses	This study confirmed the efficacy of the Orsiro stent in a real-world setting is similar to the clinical performance observed for Orsiro in the BIOFLOW-V IDE pivotal trial.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P110016 S080/ PAS001
Date Original Protocol Accepted	12/14/2022
Date Current Protocol Accepted
Study Name	LESS VT Continued F/u of IDE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study objective is to characterize the safety and effectiveness of the FlexAbility, SE Ablation Catheter for the treatment of monomorphic ventricular tachycardia in patients with non-ischemic structural heart disease through 12 months post-procedure. This study should be conducted per version H of the LESS VT protocol. The study will consist of all IDE patients who are currently enrolled and alive and will evaluate the protocol specified descriptive 12-month endpoints.
Study Population	The primary analysis population for the primary safety endpoint analysis will include subjects enrolled in the NICM cohort who have the catheter inserted in the EP lab for the VT ablation procedure (regardless of whether or not RF energy is delivered) and have crossed the 7-day post index ablation time point. Subjects who have an ablation procedure with an ablation catheter other than the FlexAbility SE catheter (regardless of whether or not RF energy is delivered) will have primary safety events that occur during or after the ablation with another catheter excluded from this analysis.
Sample Size	The sample sizes required for evaluation of the primary safety and effectiveness endpoints in the NICM cohort are 171 and 173 subjects, respectively. The primary effectiveness endpoint requires a larger sample size (N=173), and therefore determines the sample size for the subjects who have the catheter inserted in the EP lab in the NICM cohort. To account for 5% of subjects who may enroll but not have had the study catheter inserted in the EP lab, 182 NICM subjects may enroll in this trial. This follow up study will consist of all IDE patients who are currently enrolled and alive and will evaluate the protocol specified descriptive 12-month endpoints.
Key Study Endpoints	The primary safety endpoint is a composite of cardiovascular-related and procedure-related major complications through 7 days post index ablation procedure as adjudicated by CEC. The primary effectiveness endpoint is freedom from recurrent sustained MMVT at 6 months and a new or increased dose of Class I or III AAD at 6 months following the index ablation procedure, where sustained MMVT is defined as a continuous MMVT for >30 seconds, or MMVT requiring intervention for termination regardless of its duration. MMVT will be adjudicated by the ICD Event Review Committee. Descriptive endpoints 1. Changes in SF-12 Quality of Life physical and mental component score at 6 and 12 months follow-up post index procedure from baseline 2. Changes in HADS score at 6 and 12 months follow-up post index procedure from baseline 3. Freedom from appropriate ICD shocks at 6 months (183 days) post index procedure, adjudicated by the ICD Event Review Committee 4. Freedom from recurrent sustained MMVT and a new or increased dose of Class I or III AAD at 12 months 5. Spontaneous recurrence of any sustained VT during the follow-up periods of 6 months and 12 months 6. Freedom from VT in the absence of Class I and III AAD at 12 months 7. 12-month mortality 8. Number of VT recurrences during the follow-up periods of 6 months and 12 months (VT recurrence is defined as any episode of VT greater than 30s duration or that requires ICD intervention). 9. Proportion of procedures in which the acute procedural endpoint (as defined in Appendix D) was achieved 10. Procedure time 11. Fluoroscopic time 12. Rate of cardiovascular-related and procedure-related major complications through 30 days post index ablation procedure.
Follow-up Visits and Length of Follow-up	The total duration of the clinical investigation is expected to be approximately 3.5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	182
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	95.5% at 12 months
Final Safety Findings	20.5% of subjects experienced a serious adverse event that was adjudicated as related to the procedure or device.
Final Effect Findings	51.3% of subjects were free from MMVT or new or increased Class I/III AAD at 12 months
Study Strengths & Weaknesses	Continued follow-up of LESS-VT IDE NICM cohort from 6 to 12 months supported the approval order for the FlexAbility Ablation Catheter, Sensor Enabled for the treatment of monomorphic ventricular tachycardia (MMVT) in patients with structural, non-ischemic heart disease.
Recommendations for Labeling Changes	No labeling changes are recommended on the basis of this continued follow-up. Labeling changes will be considered at the completion of the prospective enrollment PAS.
General
Study Status	Completed
Application Number / Requirement Number	P160037 S017/ PAS001
Date Original Protocol Accepted	05/14/2024
Date Current Protocol Accepted	03/12/2025
Study Name	SHIP-Sub-Protocol LMI-001-A-S01
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will include 500 or more individuals with a cervix, 25 years or older, with referrals to colposcopy based on previous positive HPV test or abnormal cytology results and/or referrals to cervical excisional procedure. The study will provide additional data regarding clinical performance of the BD Onclarity HPV Assay with vaginal specimens in a U.S. population. The clinical sensitivity, clinical specificity and false positive rate and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens will be evaluated. Additionally, the concordance of the BD Onclarity HPV Assay results between the two specimen types will be evaluated.
Study Population	Individuals with a cervix, 25 years or older, who come to colposcopy with a referral based on previous positive HPV test or abnormal cytology results and who come to cervical excisional procedure with a referral. There is no comparison group.
Sample Size	500 or more Study sites will be 10 or more
Key Study Endpoints	The clinical sensitivity, clinical specificity and false positive rate and false negative rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens. The concordance of the BD Onclarity HPV Assay results between the two specimen types.
Follow-up Visits and Length of Follow-up	No follow-up, unless required for SOC clinical care purposes
Interim or Final Data Summary
Actual Number of Patients Enrolled	554
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	N/A
Final Safety Findings	No severe adverse events were reported.
Final Effect Findings	- The sensitivities of the assay for detecting greater than or equal to CIN2 with self-collected vaginal (SV) and clinician-collected cervical (CC) specimens are 83.7% and 90.7%, respectively, with a ratio of sensitivity (SV:CC) of 0.923. - The sensitivities of the assay for detecting greater than or equal to CIN3 with SV and CC are 89.2% and 96.9%, respectively, with a ratio of sensitivity (SV:CC) of 0.921. - The false positive rates of the assay with SV and CC are 68.1% and 59.9%, respectively, with a ratio of false positive rate (SV:CC) of 1.138. - The specificities of the assay with SV and CC are 31.9% and 40.1%, respectively, with a ratio of specificity (SV:CC) of 0.795. - For detection of HR HPV, the positive percent agreement and negative percent agreement of SV specimen as compared to CC specimen are 92.4% and 67.9%, respectively.
Study Strengths & Weaknesses	Study strength: The study provided additional data regarding clinical performance of the BD Onclarity HPV Assay with vaginal specimens in a U.S. population. Study weakness: The study subject enrollment was based on cervical sample test result.
Recommendations for Labeling Changes	Recommended labeling changes: addition of PAS results as well as appropriate labeling mitigations for the observed performance for self-collected vaginal specimens.
General
Study Status	Ongoing
Application Number / Requirement Number	P150026 S002/ PAS001
Date Original Protocol Accepted	05/02/2018
Date Current Protocol Accepted	07/01/2020
Study Name	CF HeartLight PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to evaluate the long-term safety and effectiveness of the device in a commercial population and to clarify the safety profile of the device among females. This will be accomplished through a new enrollment prospective single-armed study.
Study Population	Study subjects will be clinically eligible for treatment of paroxysmal atrial fibrillation with the HeartLight device.
Sample Size	250 subjects will be enrolled at up to 25 sites in the US, and a minimum 135 of those subjects will be female, will accommodate the hypothesis testing with 80% power and an alpha of 0.025 for each of the hypotheses.
Key Study Endpoints	The primary effectiveness endpoint will be freedom from symptomatic Atrial Fibrillation at one-year, and will be compared to a performance goal of 55% of subjects free from symptomatic AF at one year. The primary safety outcome for the entire cohort will be the percentage of subjects experiencing a Primary Adverse Event by one-year of follow-up, and will be compared to a performance goal of PAE rate of 14% at one year. The same safety outcome will be assessed for females with the same performance goal. Longer term (three year) safety and effectiveness will be assessed as secondary outcomes. The long-term effect of operator experience will also be assessed as a secondary outcome. If there are gender differences in safety outcomes, the factors contributing to these differences will be evaluated as secondary outcomes. All safety, effectiveness, and operator training results will also be stratified by version of the HeartLight Endoscopic Ablation System (i.e. with or without Excalibur Catheter) as an additional descriptive analysis.
Follow-up Visits and Length of Follow-up	Study subjects will be followed for three years. All subjects will undergo clinical follow-up pre-discharge, at 30 days, 90 days, 12 months, 24 months, and 36 months
Interim or Final Data Summary
Interim Results	Safety Results There have been no unanticipated adverse events. The number of participants with at least one AE is 46 (40.0%), with 14 having a serious event. There have been 2 deaths. Effectiveness Results Overall, acute success is 94.2%.
Actual Number of Patients Enrolled	124
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	Follow-up rate remains adequate.
General
Study Status	Completed
Application Number / Requirement Number	P160054 S008/ PAS002
Date Original Protocol Accepted	01/18/2019
Date Current Protocol Accepted
Study Name	Continued f/u of Continued Access Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To characterize the clinical outcomes through 2 years post implantation by continuing to follow the premarket continued access protocol (CAP) patients.
Study Population	Subjects (HeartMate 3 only) who were enrolled in the premarket CAP cohort.
Sample Size	All living subjects
Key Study Endpoints	The composite endpoint of survival to transplant or recovery, or on left ventricular assist device (LVAD) support free of debilitating stroke (Modified Rankin Score > 3) or reoperation to replace the pump; mortality; bleeding; major infection; hemolysis; device thrombosis; neurological dysfunction; and any other serious adverse events; as well as New York Heart Association (NYHA) classification and 6-minute walk distance (6MWD).
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1685
Actual Number of Sites Enrolled	68
Patient Follow-up Rate	98.3%
Final Safety Findings	The rates of adverse events at 2 years were largely similar between the CAP and Pivotal Cohorts.
Final Effect Findings	The survival rate, functional status and quality of life improvements in the CAP Cohort were also comparable to those observed in the Pivotal Cohort at 2 years.
Study Strengths & Weaknesses	The study’s main strength was its size in patient cohort, which was more than 3 times greater than the treatment arm of the pivotal cohort. The study’s main weakness was that it was a non-randomized study with inherent biases.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P150033 S166/ PAS001
Date Original Protocol Accepted	06/07/2023
Date Current Protocol Accepted
Study Name	Micra Jugular Access PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Micra Jugular Access Post Approval Study (PAS) is a prospective, observational, mutli-center study which is intended to characterize the safety and implant success of the Micra system when implant access is gained through the jugular vein.
Study Population	Patients meeting the following criteria may be enrolled: · Patient or legally authorized representative provides written authorization and/or consent per institution and geographical requirements. · Patient is intended to receive, or be treated with, an eligible Medtronic (1) Micra TPS product with a planned jugular access implant · Patient consented before implant · Patient who is, or will be accessible for follow-up · Participation is not excluded by local law · Patient is not enrolled in a concurrent drug and/or device study that may confound the PSR results
Sample Size	50 subjects
Key Study Endpoints	Main effectiveness objective 1: Characterize the rate of implant success of the Micra TPS through the jugular vein. A successful implant is defined as a Micra TPS implant via the jugular vein where a functioning device is placed within the right ventricle and the closure procedure is completed with the subject being alive at closure. Success rate of 98% (49/50) expected. Main effectiveness objective 2: Characterize the rate of access site major complications associated with the Micra TPS implant utilizing the jugular implant approach. An acute major complication will be defined as a major complication which occurs within 30-days (inclusive) of a subject’s first implant attempt. Acute major complication rate estimated to be <1%. Ancillary objectives: - Characterize implant technique (e.g. implant time, closure methods, implant location) - Summarize time to ambulation post implant - Summarize procedure related adverse events - Summarize system related adverse events - Characterize device electricals at implant and 30 days post-implant.
Follow-up Visits and Length of Follow-up	30 days
Interim or Final Data Summary
Actual Number of Patients Enrolled	53 patients enrolled
Actual Number of Sites Enrolled	13 clinical sites enrolled (7 US, 6 EU)
Patient Follow-up Rate	51 patients (98.1%) completed 30-days of follow-up. 1 patient (1.9%) was lost to follow-up.
Final Safety Findings	There were no major complications associated with the jugular access site. There were four system related adverse events: one major complication (not related to procedure), two minor complications, and one observation. There was one death due to a gastrointestinal bleed, which was classified by the independent Clinical Events Committee as unrelated to the procedure. There were no device deficiencies or new safety concerns identified during the study.
Final Effect Findings	53 patients (100%) had successful implants using jugular vein access. Among the 53 implant procedures, 52 (98.1%) used the right jugular vein and 1 (1.9%) used the left jugular vein to obtain venous access. Among the 53 implant procedures, 50 (94.3%) placed the device in the RV septum and 3 (5.7%) in the RV apex. Among the 53 implant procedures, 52 (98.1%) used three or less device deployments. Median procedure time was 20.5 minutes (IQR: 16 to 31 minutes) in the 48 patients (90.6%) with data available. Median fluoroscopy time was 5.4 minutes (IQR: 4 to 9 minutes) in the 51 patients (96.2%) with data available. Median time to ambulation following venous closure was 2.0 hours (IQR: 0 to 2 hours) in the 18 patients (34%) with data available.
Study Strengths & Weaknesses	Strengths: • The results appear to confirm that real-world implanting physicians can deliver the Micra TPS device successfully using a jugular venous approach without major bleeding issues. • There was a low complication rate, with 3 total adverse events related to jugular access procedure. Weaknesses: • There was missing patient characteristics data that was not reportable per local laws or regulations.
Recommendations for Labeling Changes	Recommend the Micra TPS device labeling is updated to include the study results.
General
Study Status	Ongoing
Application Number / Requirement Number	P170003 / PAS002
Date Original Protocol Accepted	02/26/2018
Date Current Protocol Accepted	12/16/2021
Study Name	New Enrollment PAS Registry
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To demonstrate safety and assess the clinical use and outcomes of the Lutonix DCB for treatment of dysfunctional AV fistulae located in the arm in a heterogeneous patient population in a real world clinical practice. A prospective, global multicenter, single arm, post-approval registry study of newly enrolled patients.
Study Population	Subjects presenting with clinical and hemodynamic abnormalities in arteriovenous fistulae located in the arm who meet all inclusion criteria and none of the exclusion criteria.
Sample Size	A total of 213 subjects will be enrolled at a minimum of 15 and a maximum of 30 U.S. and International sites. Approximately 50% of subjects enrolled and study sites will be from the U.S. Based on a TLPP rate of 71.4%, a non-inferiority margin of 10%, a 10% drop-out rate and one-sided exact binomial test p = 0.05, sample size of 213 provide 90% power for evaluating the primary effectiveness hypothesis comparing 61.4% PG. Based a primary safety endpoint rate of 95% (pivotal trial), a non-inferiority margin of 6%, and one-sided exact binomial test p = 0.05, sample size of 213 will provide 95% power evaluating the primary safety hypothesis comparing to 89% PG.
Key Study Endpoints	Primary Safety Endpoint: Freedom from any serious adverse event(s) involving the AV access circuit through 30 days Primary Effectiveness Endpoint: TLPP through 6 months defined as the interval following index procedure until clinically-driven reintervention of the target lesion or access thrombosis, through 6 months Secondary Safety Endpoints: 1. Freedom from any serious adverse event(s) involving the AV access circuit through 6, 12, 18 and 24 months 2. Rate of device and procedure related adverse events assessed at 6, 12, 18 and 24 months Secondary Effectiveness Endpoints: 1. TLPP evaluated at 12, 18 and 24 months 2. Number of reinterventions to maintain target lesion patency at 6, 12, 18 and 24 months 3. Time to loss of Target Lesion Primary Patency (i.e. time between index procedure to the first loss of patency) 4. Access Circuit Primary Patency (ACPP) evaluated at 6, 12, 18 and 24 months 5. Number of reinterventions to maintain access circuit patency at 6, 12, 18 and 24 months 6. Device, Procedural and Clinical Success 7. Abandonment of permanent access in the index extremity at 6, 12, 18 and 24 months 8. Secondary Patency of the Access Circuit at 6, 12, 18 and 24 months 9. Time to loss of target lesion secondary patency following DCB (i.e. time between first reintervention with a DCB to the next loss of patency)
Follow-up Visits and Length of Follow-up	24 months
Interim or Final Data Summary
Interim Results	Hypothesis testing on the primary safety and effectiveness endpoints will be provided as exploratory analyses in the final report. Interim Safety Results: Freedom from primary safety event at 30 days: 199/210 (94.8% | 95% CI: 90.8%, 97.4%) Interim Effectiveness Results: Target Lesion Primary Patency at 6 months: 139/190 (73.2% | 95% CI: 66.3%, 79.3%)
Actual Number of Patients Enrolled	213
Actual Number of Sites Enrolled	28 sites have enrolled subjects
Patient Follow-up Rate	Rate at data snap show date (January 5th, 2026): 190/200 (95.0%) completed 6- month follow-up visit (0 pending) 162/178 (91.0%) completed 12-month follow-up visit (9 pending) 123/142 (86.6%) completed 18-month follow-up visit (15 pending) 93/100 (93.0%) completed 24-month follow-up visit (6 pending) 51/213 subjects have discontinued the study before completion of the 24 month visit (1 withdrawal, 50 death)
General
Study Status	Completed
Application Number / Requirement Number	P160043 S001/ PAS001
Date Original Protocol Accepted	11/16/2017
Date Current Protocol Accepted
Study Name	Cont f/u of RESOLUTE ONYX 2.0 Clinical
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued Follow-up of premarket cohort (RESOLUTE ONYX 2.0 Clinical Study)
Study Population	Single arm study with Resolute Onyx Stent System
Sample Size	101 subjects (already enrolled)
Key Study Endpoints	Primary Endpoint is Target lesion failure (TLF) at 12 months, defined as Cardiac Death, Target Vessel Myocardial Infarction or Target Lesion Revascularization
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: 75 RESOLUTE ONYX 2.0 mm Clinical Study: 101
Actual Number of Sites Enrolled	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: 15 US sites RESOLUTE ONYX 2.0 mm Clinical Study : 21 US and 3 Japan
Patient Follow-up Rate	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: Subject follow-up compliance remained high through the 30 day, 6 month, 8 month, 12 month, 24 month, and 36 month follow-up visits. A total of 97.1% (67/69) completed their 36-month visit within the protocol defined follow-up window. RESOLUTE ONYX 2.0 mm Clinical Study: A total of 97.0% (98/101) of subjects completed their 30-day visit within the protocol defined follow-up window, 99.0% (100/101) of subjects completed their 6-month visit within the protocol defined follow-up window, 99.0% (100/101) completed their 12-month visit within the protocol defined follow-up window, 96.9% (95/98) completed their 24-month visit within the protocol defined follow-up window, and 100.0% (98/98) completed their 36-month visit within the protocol defined follow-up window.
Final Safety Findings	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: The TLF rate at 36 months is 14.7% (11/75), TVF is 18.7% (14/75), TVMI is 8.0% (6/75), MACE is 21.3% (16/75), and stent thrombosis is 1.3% (1/75). There were 6 deaths; 2 Cardiac and 4 Non-Cardiac Deaths at 36 months. Since the 24-month assessment, at 36 months, there were 3 more cases of TLF, TVF, TVMI, and Death, 5 more cases of MACE, and no cases of stent thrombosis. RESOLUTE ONYX 2.0 mm Clinical Study: The Resolute Onyx 2.0 mm event rates at 36 months post procedure are as follows: 13.9% (14/101) for TLF, 14.9% (15/101) for TVF, 4.0% (4/101) for TVMI, 14.9% (15/101) for MACE, and 0.0% (0/101) ARC definite/probable stent thrombosis. Rate of mortality is 3.0% (3/101), including cardiac mortality of 2.0% (2/101), and non cardiac mortality of 1.0% (1/101). There is no change in deaths, cardiac or non-cardiac from 24 months to 36 months. NOTE: The safety and effectiveness key endpoints are similar
Final Effect Findings	RESOLUTE ONYX (2.25 mm TO 4.0 mm) Clinical Study: o The TLF rate at 36 months is 14.7% (11/75), TVF is 18.7% (14/75), TVMI is 8.0% (6/75), MACE is 21.3% (16/75), and stent thrombosis is 1.3% (1/75). o There were 6 deaths; 2 Cardiac and 4 Non-Cardiac Deaths at 36 months. o Since the 24-month assessment, at 36 months, there were 3 more cases of TLF, TVF, TVMI, and Death, 5 more cases of MACE, and no cases of stent thrombosis. o ARC/SCAI defined major adverse events up to 1080 days. All MIs were adjudicated using two definitions; the Medtronic extended historical definition and the SCAI definition. Death and stent thrombosis were adjudicated using ARC definitions only. There were four (5.3%) non-cardiovascular deaths and two (2.7%) cardiac deaths, three (4.0%) SCAI defined MIs, and one (1.3%) ARC defined acute definite stent thrombosis. o There were no UADEs reported through 36 months. RESOLUTE ONYX 2.0 mm Clinical Study: • The primary endpoint of TLF at 12 months was only 5.0%, meeting the pre-specified performance criterion (upper 1-sided 95% CI of 10.1%, compared with the performance goal of 19%, p < 0.001). • The 12-month rate of key secondary clinical endpoints included 2.0% TLR, 3.0% TVMI, 5.0% TVF and 5.0% MACE rate. • The ITT analysis on principal safety and effectiveness at discharge, as well as at 30 days, 180 days, 360 days, 720 days and 1080 days are summarized in Table 25. • Follow-up data demonstrates that the 36-month rate of TLF was 13.9% (14/101), of TVF - 14.9% (15/101), of TVMI - 4.0% (4/101), and of MACE - 14.9% (15/101). • There were no cases of stent thrombosis 0.0% (0/101) at 36 months, and there was a total of 3 deaths, including 2 Cardiac Deaths and 1 Non-Cardiac Death. • Between 24 and 36 months, there was one additional event of TLF, TVF, and MACE, while the rates of TVMI, stent thrombosis, and death did not change.
General
Study Status	Completed
Application Number / Requirement Number	P170011 S035/ PAS001
Date Original Protocol Accepted	08/18/2022
Date Current Protocol Accepted	04/27/2023
Study Name	Impella RW Surveillance of Pts using Sodium Bicarb
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	Concurrent & Historical Control
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A multicenter, observational, records review study of routine clinical care. Subjects are from post-market cohorts and new enrollment.
Study Population	Device: The study will include up to 60 sites from the US. The population enrolled in this study are all subjects who received an Impella in which a bicarbonate-based purge solution was used. Comparator: The study will include up to 60 sites from the US. The population enrolled in this study are all subjects who received an Impella in which a heparin-based purge solution was used.
Sample Size	A sample size of 300 subjects is proposed for the study based on the following assumptions: Event rate 6% Target margin of error of +/-3% (the width of 95% confidence interval of 6%) While the sample size with the above assumptions is 275, the additional subjects ensure the target 3% margin of error for a potentially higher event rate in the all-comers population enrolled in the study. For Impella RP, the sample size will be the number of subjects available at the time the left-sided device population completes enrollment, up to 30 subjects. As the use of Impella RP is an order of magnitude less than the left-sided devices, a target margin of error is not feasible for this population.
Key Study Endpoints	1. Left-sided devices (Impella 2.5, Impella CP, Impella LD, Impella 5.0 and Impella 5.5): Hierarchical composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus [Time Point: Discharge] 2. Impella RP: Hierarchical composite of pulmonary thromboemboli and deep vein thrombosis (DVT) [Time Point: Discharge] 1. Bleeding, BARC greater than or equal to 3 [Time Point: Discharge] 2. For left-sided devices: Thrombotic events excluding LV thrombus, stroke and TIA [Time Point: Discharge] 3. For Impella RP: Thrombotic events excluding pulmonary thromboemboli and DVT [Time Point: Discharge]
Follow-up Visits and Length of Follow-up	Data will be collected, via records review, from the time of the index hospitalization where the subject received the Impella device through discharge
Interim or Final Data Summary
Actual Number of Patients Enrolled	312
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	100%
Final Safety Findings	The primary endpoint for left-sided Impella devices (Impella 2.5 System, Impella CP System, Impella LD System, Impella 5.0 System and Impella 5.5 System) was a composite of stroke, transient ischemic attack (TIA), left ventricular (LV) thrombus evaluated at discharge. Event data included all events during index hospitalization, including prior to, during and after Impella support. The composite event rate of 7.7% during the entirety of the index hospitalization fell within the expected event rate of the Impella device usage for the studied patient population. Additional descriptive endpoints included 1) BARC greater than or equal to 3 bleeding events through hospital discharge; 2) For left-sided devices, thrombotic events excluding LV thrombus, stroke, and TIA through hospital discharge; and 3) For right-sided devices, thrombotic events excluding pulmonary thromboemboli and deep vein thrombosis (DVT) through hospital discharge. The key contributor to the composite endpoint was stroke, with 22 of the 23 composite endpoint events being stroke events (22/300; 7.33%). The remaining event was one event of left ventricular thrombus. The observed rate of stroke (7.33%) fell within with the expected stroke rate derived from literature reports. When patients were grouped by Impella-only patients and Impella patients with other MCS (Impella + MCS), the endpoint rates were considerably lower in the Impella-only group. Specifically, the composite endpoint rate of stroke/TIA/LV thrombus was 3.1% in the Impella-only group versus 13.5% in the Impella + MCS group. Fourteen (14) out of 23 primary endpoints were reported to be unlikely or not related to the device, only two primary endpoints were found to be probably related to the device, four possibly related to the device, and relatedness of two other primary endpoints was classified as unknown. Similar to the finding seen with the primary endpoints, there is an appreciable difference in descriptive endpoint rates between Impella only and Impella + MCS sub-groups, with lower BARC greater than or equal to 3 bleeding event rates (15.4% versus 29.4%) and thrombotic event rates (3.1% versus 4.8%) seen in Impella only sub-group, with majority of the endpoints reported to be unlikely or not related to the device. The primary endpoint for right-sided Impella devices was a composite of pulmonary thromboemboli and DVT evaluated at discharge. No patients met the primary endpoint in the right-sided cohort. No right-sided cohort patient experienced the descriptive endpoint of thrombotic events, while BARC greater than or equal to 3 bleeding was seen in 15.0% of the patients. None of the BARC greater than or equal to 3 bleeding in the right-sided cohort was reported to be definitely or probably related to the device.
Final Effect Findings	The primary and descriptive endpoints of the study are described above in the “Final safety findings” section above.
Study Strengths & Weaknesses	The study’s main strength was its representation of the real-world experience, representing physician preference for the use of sodium bicarbonate in the purge fluid during Impella support for a variety of challenging clinical scenarios, indications, and procedural characteristics. The study provided rigorous data on this real-world cohort. The study’s main weaknesses were its lack of data to identify timing of the purge administration with respect to the timing of the endpoints, and lack of data to directly compare outcomes between bicarbonate and other purge fluids.
Recommendations for Labeling Changes	The clinical information in the Instructions for Use should be updated to include the results of the post-approval study.
General
Study Status	Ongoing
Application Number / Requirement Number	P170019 S014/ PAS001
Date Original Protocol Accepted	05/26/2023
Date Current Protocol Accepted	05/26/2023
Study Name	ROZYLTREK PAS
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This clinical post-approval study (PAS) is being conducted to confirm the clinical effectiveness of the F1CDx assay in detecting NTRK1/2/3 fusion positive patients with solid tumors for treatment with entrectinib. This study is intended to fulfil the clinical PAS issued in the approval order for P170019/S014. This PAS will supplement the premarket clinical bridging study with additional patients from the STARTRK-2 trial (non-NDA population) who have a later enrollment date as well as patients enrolled in the TAPISTRY trial (NCT04589845). The first objective of this clinical bridging study is to evaluate the concordance of F1CDx and LDT results in the identification of NTRK1/2/3 fusions. Samples from various tumor types will be included. The second objective of this study is to evaluate the overall response rate (ORR) and duration of response (DOR) for entrectinib treatment among clinical study subjects who solid tumor specimens are NTRK1/2/3 fusion positive, per the CDx biomarker definition, by retrospective testing with F1CDx, per the CDx biomarker definition.
Study Population	The study consists of approximately 101 NTRK1/2/3 fusion positive patients from the STARTRK-2 trial enrolled after April 2018 and by Q2 2022, and approximately 15 patients from Cohort B of the TAPISTRY trial enrolled by Q2 2022. Of these, an estimated 67 samples will have sufficient residual DNA (or total nuclei acid (TNA)) and patient consent for F1CDx testing. Approximately 250 NTRK1/2/3 fusion negative specimens of various disease ontologies from the FMI archive will be included in the agreement analysis.
Sample Size	Approximately 116 NTRK1/2/3 fusion positive patients and approximately 250 NTRK1/2/3 fusion negative specimens (for concordance analysis only)
Key Study Endpoints	Primary Effectiveness Endpoint: Concordance of F1CDx and LDT results in the identification of NTRK1/2/3 fusions Secondary Effectiveness Endpoints: ORR and DOR of entrectinib
Follow-up Visits and Length of Follow-up	1 year for the ORR
General
Study Status	Completed
Application Number / Requirement Number	P170011 / PAS001
Date Original Protocol Accepted	09/20/2017
Date Current Protocol Accepted	07/12/2021
Study Name	Impella RP-RWE Eval and Reporting
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective is to monitor post market safety and efficacy trends of the Impella system used to treat patients >= 18 years old with right heart failure. Observational, prospective/retrospective, multicenter, single arm, registry surveillance of newly treated subjects. Patients will be treated according to standard of care and per institution guidelines.
Study Population	All patients age greater than or equal to 18 years old, who received Impella RP catheters for the treatment of RV dysfunction post LVAD implantation, post myocardial infarction and post open heart surgery, after PMA post market approval and were enrolled in the cVAD registry.
Sample Size	A minimum of sixty (60) newly treated patients enrolled at participating US cVAD Registry sites (44 US sites). The sample size is similar to the total sample size of 60 subjects evaluated in the PMA. The study subjects will be divided in the following groups: Checklist group - A minimum enrollment of 30 subjects who would have met inclusion/exclusion criteria for the premarket clinical studies, which includes at least 10 subjects that will be similar to premarket Cohort A and at least 10 subjects similar to premarket Cohort B Real world use group - A minimum enrollment of 30 “all-comers” subjects who would not have met inclusion/exclusion criteria for the premarket studies. Enrollment of “all-comers” subjects must continue until the full enrollment of the checklist group is completed.
Key Study Endpoints	Primary Endpoint The primary endpoint is survival rate at 30 days, post device explant or hospital discharge (whichever is longer), or to induction of anesthesia to a longer-term therapy, which includes a heart transplant or an implant of a surgical RVAD. The primary endpoint will be reported for all patients, for each cohort treated: a) Patients that develop RVF post LVAD implantation, and b) Patients that develop RVF post myocardial infarction or postcardiotomy; and for each subgroup: checklist group and real world use group. Secondary endpoints During Support through device Explant the following secondary endpoints will be assessed: Central venous pressure, Cardiac index, LVAD flow and device malfunction At 30 days or discharge the secondary endpoints to be assessed are death, bleeding hemolysis and pulmonary embolism Additional data to be collected at 30 days, 90 days and 1 year include patient status, major cardiac and cerebrovascular adverse events (MACCE) and cardiac related readmission
Follow-up Visits and Length of Follow-up	1 year; 30 days, 90 days and 1 year post Impella RP explant.
Interim or Final Data Summary
Actual Number of Patients Enrolled	Total enrollment: 110 Enrollment by subgroups: Checklist Group Total: 37 Checklist Group Cohort A: 7 Checklist Group Cohort B: 30 Real-world Use Group Total: 73 Real-world Use Group Cohort A: 16 Real-world Use Group Cohort B: 57
Actual Number of Sites Enrolled	29
Patient Follow-up Rate	93.6%
Final Safety Findings	Death prior to 30 days post device explant or discharge: 32.4% in the Checklist Group and 80.08% in the Real-World Use Group Bleeding: 10.8% in the Checklist Group and 11.0% in the Real-World Use Group Hemolysis: 27.0% in the Checklist Group and 15.1% in the Real-World Use Group Pulmonary embolism: 0.0% in both groups Device malfunction: 8.1% in the Checklist Group and 2.7% in the Real-World Use Group
Final Effect Findings	Survival rate at 30 days post-device explant or hospital discharge (whichever is longer), or to induction of anesthesia to a longer-term therapy: Checklist Group: 69.7% (23 of 33 evaluable patients) Checklist Group Cohort A: 85.7% (6 of 7 evaluable patients) Checklist Group Cohort B: 65.4% (17 of 26 evaluable patients) Real-World Use Group Total: 18.6% (13 of 70 evaluable patients) Real-World Use Group Cohort A: 31.3% (5 of 16 evaluable patients) Real-World Use Group Cohort B: 14.8% (8 of 54 evaluable patients)
Study Strengths & Weaknesses	The study’s main strengths were its representation of the real-world experience and its size in patient cohort, which was nearly twice the size of the cohort in the premarket clinical studies. The study’s main weaknesses were the missing data associated with unconfirmed status for the primary endpoint evaluation in 4 patients in the Checklist Group and in 3 patients in the Real-World Use Group as well as the missing of the minimum enrollment target of 10 patients (7 enrolled) for Cohort A (patients who develop right heart failure within 48 hours post-implantation of an FDA approved implantable surgical left ventricular assist device) in the Checklist Group largely due to slow enrollment associated with changes in clinical practice patterns.
Recommendations for Labeling Changes	Yes - labeling changes were recommended and have been completed by the manufacturer. On December 5, 2022, the FDA approved updated labeling for the Impella RP device to include the final PAS results, and an update to the indications for use statement to better reflect the characteristics of the patients who may benefit the most from treatment with the device.
General
Study Status	Completed
Application Number / Requirement Number	P170011 / PAS002
Date Original Protocol Accepted	09/20/2017
Date Current Protocol Accepted	02/16/2018
Study Name	Impella RP Pediatric-RWE Eval and Report
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor post-market approval safety and outcomes trends of the Impella RP device in pediatric patients with RV failure deemed to require hemodynamic support. A single-arm multicenter registry study of patients from the premarket (i.e. the HDE Impella RP Pediatric Study) and newly treated patients after PMA approval. All data will be collected retrospectively after implant.
Study Population	Pediatric patients aged 15-17 years old (BSA greater than or equal to 1.5m2) with right heart failure supported with the Impella RP System. Patients who meet all eligibility criteria. There is no comparison group.
Sample Size	Fifteen (15) consecutive pediatric patients or all pediatric patients supported with the Impella RP over a 5-year time-period (whichever comes first) will be enrolled at a minimum of 5 participating clinical centers.
Key Study Endpoints	The primary endpoint is survival rate at 30 days post device explant or hospital discharge (whichever is longer), or to induction of anesthesia to a longer term therapy, which includes a heart transplant or an implant of a surgical RVAD. Secondary safety endpoints are the rates of the following major adverse events measured at hospital discharge or to induction of anesthesia to a longer-term therapy (including a heart transplant or an implant of a surgical RVAD): death (any cause death and cardiac), major bleeding, hemolysis, pulmonary embolism. Additional adverse events to be collected are device malfunction and device failure. Secondary effectiveness endpoints are improvement in the following hemodynamic parameters after Impella RP support through explant: cardiac index, central venous pressure, LVAD flow Technical success will be assessed at exit from operating room Survival only will be assessed at 30 days and 180 days.
Follow-up Visits and Length of Follow-up	180 days
Interim or Final Data Summary
Actual Number of Patients Enrolled	One (1) patient with a protocol deviation in age cutoff treated at a non-participating site
Actual Number of Sites Enrolled	One (1) non-participating site
Patient Follow-up Rate	The one patient was captured in the firm’s commercial database, which contains limited data entered by the firm’s field clinical personnel and only covers the time period from Impella device insertion through Impella device removal. The patient was known to have survived to induction of anesthesia to a longer-term therapy.
Final Safety Findings	No adverse events (death, major bleeding, hemolysis, and pulmonary embolism) were reported for the patient, to induction of anesthesia to a longer-term therapy.
Final Effect Findings	The patient survived to induction of anesthesia to a longer term therapy (surgical RVAD). The patient’s central venous pressure (CVP) decreased from 28 mmHg to 19 mmHg on Impella RP support.
Study Strengths & Weaknesses	The study was limited by the low enrollment (N=1) and limited dataset available.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P150003 S039/ PAS001
Date Original Protocol Accepted	03/29/2019
Date Current Protocol Accepted
Study Name	EVOLVE 4.5/5.0 Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the EVOLVE 4.5/5.0 Study is to confirm the safety and effectiveness of SYNERGY 4.50 mm and 5.00 mm Everolimus-Eluting Platinum Chromium Coronary Stent System (SYNERGY Stent System) for the treatment of patients with atherosclerotic lesions(s) less than or equal to 28 mm in length (by visual estimate) in native coronary arteries > 4.00 mm to less than or equal to 5.00 mm in diameter (by visual estimate).
Study Population	US patients who are acceptable candidates for treatment with a 4.50 or 5.00 mm SYNERGY stent if treated in accordance with the applicable guidelines on PCI, the SYNERGY DFU, and the Declaration of Helsinki. Sites should approach consecutive patients for inclusion in the trial
Sample Size	A minimum of 100 subjects will be enrolled at up to 20 US sites.
Key Study Endpoints	The primary endpoint is the rate of Target Lesion Failure (TLF) rate at 12-months. Secondary endpoints include rates of TLR, TLF, TVR, TVF, MI (Q-Wave and non-Q-wave), Death (All, Cardiac, Non-Cardiac), Cardiac Death or MI, All Death or MI, All Death or MI or TVR, Stent Thrombosis (ARC Definitions) at 6-months, 12-months, 2-years, and 3-years. In addition, secondary endpoints will technical and clinical success rates.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	All subjects have completed follow-up.
Final Safety Findings	This study has completed enrollment (n=100) and 3-years (36 months) of follow-up. Principal safety and efficacy outcomes are presented in Table 6.8-5. Within the 1 3-year timeframe: There were 4 additional cardiac deaths. A total of 4 patients experienced MI that was target vessel related. The incidence of TLR occurred in 2 patients.
Final Effect Findings	Principal safety and efficacy outcomes through 3 years of follow-up in the ITT population are shown in Table 6.8-5. The incidence of TLR occurred in 3 patients. There was a total of 10 deaths, with 7 being cardiac-related. Nine subjects experienced target-vessel related MI. None of the subjects experienced a definite or probable ST.
Study Strengths & Weaknesses	The study has a limited sample size with a fairly heterogenous patient population, however, the results continue to support the performance of the study device in the US patient population.
Recommendations for Labeling Changes	A labeling revision is recommended
General
Study Status	Other
Application Number / Requirement Number	P180024 / PAS001
Date Original Protocol Accepted	04/16/2019
Date Current Protocol Accepted
Study Name	ENDObesity PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multicenter, open-label study conducted in the United States. A total of 260 patients will be enrolled at up to 15 sites. Patients who meet the inclusion/exclusion criteria and sign the informed consent to participate the study will be enrolled. Patients will be followed for 12 months or until the device removal, whichever occurs earlier. Patients who lost at least 5% TBL will be followed for an additional 6 months after TPS removal for evaluation of weight loss maintenance.
Study Population	Male and female patients, greater than or equal to 22 years of age, with a BMI of 35.0 to 40.0 kg/m2, inclusive, or a BMI of 30.0 to 34.9 kg/m2 with at least one obesity-related comorbidity. Key inclusion criteria include: 1. Age 22 years and older 2. BMI 30-40 kg/m2, inclusive, or a BMI of 30.0 to 34.9 kg/m2 with at least one obesity-related comorbidity 3. History of failure of medically or commercially supervised weight loss program 4. Female patients of childbearing potential willing to avoid pregnancy during the course of treatment 5. Willing and able to comply with study procedures and study visits 6. Willing and able to comply with lifestyle modification program for two years Key exclusion criteria include: 1. Contraindicated for use of the TPS device per Instructions for Use 2. Known hormonal or genetic cause for obesity 3. History of gastropareses 4. History of pancreatitis 5. History of portal hypertension, cirrhosis, and/or esophageal varices varices 6. A history of cardiac arrhythmia, ischemic heart disease, myocardial infarction or chronic heart failure 7. History of cerebrovascular disease, transient ischemic attack, or stroke 8. A history of malignancy except non-melanoma skin cancer 9. Continuous therapy with known ulcerogenic medication (e.g., aspirin greater than 81 mg/day, NSAIDs) 10. On anticoagulation or antiplatelet therapy (e.g., Coumadin, Warfarin, Heparin, Pradaxa, Xarelto, Plavix) 11. Unable to take proton pump inhibitor (a daily 40+ mg of Omeprazole or equivalent), or where addition of PPI may cause adverse drug interaction with patient’s medication or interruption of treatment 12. History or severe psychiatric illness 13. Current smoker or user of nicotine product or smoking cessation within one year 14. Current abuse of drug or alcohol or past treatment for substance abuse 15. Diagnosis of bulimia nervosa or binge eating disorder 16. Any anatomical or endoscopic abnormalities/ characteristics that would preclude safe use of the TPS
Sample Size	260 patients will be enrolled at up to 15 sites
Key Study Endpoints	Primary Endpoint: Proportion of patients with device- or procedure-related serious adverse events Secondary Endpoints: Mean percent total body weight loss (%TBL) Proportion of patients who achieve at least 5% and 10% TBL Percent excess weight loss (%EWL) Change of BMI from baseline Proportion of patients who achieve at least one obesity class reduction Proportion of patients with device residence time less than 12 months Change in comorbid conditions: The components of metabolic syndrome: blood pressure, glucose, HDL-C, triglycerides and waist circumference Other obesity related metabolic indicators: insulin, and insulin resistance (as estimated by HOMA), total cholesterol, and LDL-C. Weight loss maintenance at 3 and 6 months post TPS removal Other Safety Endpoints: Incidence of device-related adverse events Incidence of procedure-related adverse events Incidence of upper GI ulcers
Follow-up Visits and Length of Follow-up	Treatment phase: 12 months or until the device removal, whichever occurs earlier Weight loss maintenance phase: Additional 6 months for patients who lost at least 5%TBL prior to TPS Removal
General
Study Status	Ongoing
Application Number / Requirement Number	P160054 S031/ PAS001
Date Original Protocol Accepted	12/17/2020
Date Current Protocol Accepted
Study Name	Heartmate 3 Real-World Pediatric Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry-based surveillance. The objective of the surveillance is to continue to monitor the performance of the HeartMate 3 LVAS in pediatric patients.
Study Population	Pediatric patients with advanced refractory left ventricular heart failure and with an appropriate body surface area who require short- or long-term mechanical circulatory support (e.g., as bridge to transplant or myocardial recovery, or destination therapy).
Sample Size	All consecutive pediatric patients treated with the HeartMate 3 LVAS within the first 2 years after the PMA approval that are entered into the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Registry.
Key Study Endpoints	Patient outcomes (e.g., transplanted, expired, and explanted for recovery) and adverse events at 3, 6, 12, and 24 months.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	95
Actual Number of Sites Enrolled	59 centers in the ACTION Registry
Patient Follow-up Rate	3-month follow-up: 46 subjects received heart transplant (48.4%); 4 expired (4.2%); 3 subjects terminated participation due to other causes (3.2%); and a total of 42 subjects remained on HM3 support (44.2%) 6-month follow-up: an additional 20 subjects received a transplant (for a total of 66 subjects who received a heart transplant at 6 months (69.5%)); 1 additional subject expired (for a total of 5 subjects who expired at 6 months (5.3%)); 1 additional subject transferred to nonparticipating ACTION site (for a total of 4 subjects who terminated participation due to other causes at 6 months (4.2%)); and a total of 20 subjects remained on HM3 support (21.1%) 12-month follow-up: an additional 10 subjects received a transplant (for a total of 76 subjects who received a transplant at 12 months (80%)); 1 additional subject expired (for a total of 6 subjects who expired at 12 months (6.3%)); 2 subjects were weaned for recovery (for a total of 6 subjects terminated participation due to other causes at 12 months (6.3%)); 7 subjects remained on HM3 support (7.4%) At data cutoff date: 78 subjects received a heart transplant (82.1%); 3 remained ongoing (3.2%); 7 expired (7.4%); 7 categorized as “other” (7.4%) included 3 subjects transferred to a new site (3.2%), 2 subjects withdrew support (2.1%), 2 subjects were weaned from HM3 LVAD (2.1%). At the time of the data cut-off, all subjects either had an outcome or were withdrawn before reaching 24 months follow-up or were ongoing with less than 24 months follow-up.
Final Safety Findings	3-months*: Bleeding 11 subjects (11.6%); major infection 24 subjects (25.3%); respiratory failure 4 subjects (4.2%); right heart failure 12 subjects (12.6%), stroke 4 subjects (4.2%) 6-months*: Bleeding 11 subjects (11.6%); major infection 29 subjects (30.5%); respiratory failure 4 subjects (4.2%); right heart failure 12 subjects (12.6%), stroke 4 subjects (4.2%) 12-months*: Bleeding 11 subjects (11.6%); major infection 30 subjects (31.6%); respiratory failure 4 subjects (4.2%); right heart failure 12 subjects (12.6%), stroke 5 subjects (5.3%) *Please note events are cumulative at each time point
Final Effect Findings	Survival rates at 3, 6, and 12 months were 94.6%, 91.6%, and 85.5%
General
Study Status	Completed
Application Number / Requirement Number	P130013 S035/ PAS001
Date Original Protocol Accepted	07/21/2020
Date Current Protocol Accepted
Study Name	PINNACLE FLX Cont f/u of IDE Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow up of the premarket cohort in the prospective, single arm PINNACLE FLX trial. The study objective is to characterize the safety and effectiveness of the WATCHMAN FLX LAA Closure Device with Delivery System through 24 months post-procedure.
Study Population	The study consists of all IDE patients who are currently enrolled and alive and are eligible for the secondary effectiveness endpoint evaluation. The secondary effectiveness endpoint is defined in the protocol as the occurrence of ischemic stroke or systemic embolism at 24 months from the time of implant.
Sample Size	Initial enrollment in the PINNACLE FLX study was 458 subjects (400 in the main cohort and 58 in the roll-in cohort). Of these 458 subjects, 425 subjects are potentially available for 24 month follow up.
Key Study Endpoints	The occurrence of ischemic stroke or systemic embolism at 24 months from the time of implant.
Follow-up Visits and Length of Follow-up	24 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	Initial enrollment in the PINNACLE FLX study was 458 subjects (400 in the main cohort and 58 in the roll-in cohort). Of these 458 subjects, 425 subjects were potentially available for 24 month follow up.
Actual Number of Sites Enrolled	29
Patient Follow-up Rate	84.3% (386/458) of subjects completed the 2 year visit.
Final Safety Findings	N/A
Final Effect Findings	The 24-month ischemic stroke or systemic embolism rate was 3.4%. This is below the prespecified performance goal of 8.7% (upper one-sided 95% confidence limit was 5.3%; P<0.001).
Study Strengths & Weaknesses	A strength of the study is that it provided results on the longer term (2 years) safety and efficacy of the device. A weakness of the PINNACLE FLX study is that this study is a single arm (non-randomized) study.
Recommendations for Labeling Changes	A labeling change is recommended to add the 24 month safety and efficacy results from the pre-market cohort into the label.
General
Study Status	Completed
Application Number / Requirement Number	P170019 S029/ PAS001
Date Original Protocol Accepted	04/13/2022
Date Current Protocol Accepted
Study Name	MK-3475 MSI-H FMI F1CDx Post Approval Analysis
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to confirm in a post marketing setting the clinical effectiveness of the F1CDx as a companion diagnostic in identifying MSI-H solid tumor patients for treatment with pembrolizumab. While the clinical validity of the F1CDx for this intended use has been established in the sPMA (P170019/S029) by demonstrating a clinically meaningful response to pembrolizumab in MSI-H solid tumor patients identified by the F1CDx (ORR: 43.0%, 95% CI: [33.5, 52.9]), the intent of the proposed study is to show that the response rate to treatment with pembrolizumab seen in the additional F1CDx-positive participants included in this analysis are qualitatively similar to the previously established (P170019/S029) response rate. The primary objective of this study is to estimate the objective response rate (ORR) for pembrolizumab treatment among clinical study subjects whose archived solid tumor specimens are MSI-H as determined by retrospective testing with the F1CDx (CDx). Primary analysis will be based on subjects with complete CDx status, and sensitivity analysis will include subjects with and without CDx results. The missing CDx results will be imputed in the sensitivity analysis. The imputation model obtained using the sPMA primary efficacy population (KN164 + KN158 cohort K post amendment 7) will be applied. The key estimate of interest is the objective response rate (ORR): the proportion of subjects with best overall response being PR or CR among patients whose tumors are MSI-H by the CDx. Duration of response (DOR) will be reported as an additional endpoint.
Study Population	This study consists of 41 additional participants from KN158 Cohort K that were not included in PMA Supplement P170019/S029. Cohort K in KN-158 is an ongoing multicenter, global, open-label, single-arm cohort of pembrolizumab in participants with any advanced MSI-H/dMMR solid tumor (except CRC) that was incurable and for which prior standard first-line treatment had failed. MSI/MMR status was determined locally for enrollment eligibility determination. As this is a single-arm trial, there is no control arm and participants were not randomized. KN158 Cohort K enrolled a total of 355 participants with MSI-H/dMMR tumors; enrollment is complete. The 41 participants included in the proposed study have been enrolled and treated with pembrolizumab. Data from these participants was not included in the sPMA (P170019/S029) because they either did not have 26 weeks of follow-up (31 patients) by the data cut-off date of October 5, 2022 or samples (from 10 participants) were inadvertently not sent to FMI for MSI testing, despite being eligible for the efficacy population of the sPMA dataset. These 10 samples were subsequently sent to FMI for MSI testing. Thus, the total number of participants with F1CDx MSI testing results that will be included in the proposed study is 41 (16 patients with endometrial cancer, 14 with gastric cancer, 1 with anal cancer, 2 with breast cancer, 2 with cervical cancer, 4 with glioma, 1 with ovarian cancer and one with small intestine cancer). Among the 41 participants whose samples were tested by the CDx, 21 had F1CDx-positive status (10 with endometrial cancer, and 11 with gastric cancer), 10 had F1CDx-negative status (1 with cervical cancer, 5 with endometrial cancer, 3 with glioma and 1 with small intestine) and 10 had non-evaluable CDx status due to failing CDx QC metrics. It is anticipated that the primary population for efficacy analysis will be the 21 CDx positive patients, supplemented by a missing data sensitivity analysis imputing CDx status in the 10 non-evaluable patients via application of the same imputation model built for the sPMA.
Sample Size	A total of 41 patients (21 F1CDx-positive, 10 F1CDx-negative and 10 F1CDx-nonevaluable)
Key Study Endpoints	Primary Endpoints: Investigator-assessed Objective Response Rate (ORR) The primary efficacy endpoint is Objective Response Rate (ORR) by RECIST v1.1 as assessed by the investigator. Sensitivity Analysis A sensitivity analysis based on multiple imputation of CDx status to incorporate clinical outcome data for the 10 nonevaluable participants will also be performed. Secondary endpoints: ORR will also be assessed in subjects with observed CDx-negative and CDx-non-evaluable status. DOR may be descriptively analyzed given that responder sample size is not large enough per each CDx status (CDx-positive, CDx-negative, and CDx-non-evaluable).
Follow-up Visits and Length of Follow-up	26 weeks
Interim or Final Data Summary
Actual Number of Patients Enrolled	Forty-one (41)
Actual Number of Sites Enrolled	20 sites across 9 countries
Patient Follow-up Rate	At least 26 weeks of follow up
Final Safety Findings	N/A
Recommendations for Labeling Changes	“An additional post approval study was conducted to evaluate the clinical effectiveness of F1CDx by retrospectively testing 41 patient samples from patients with non-CRC solid tumors with MSI-H/dMMR status as determined by CTAs enrolled and treated in Keynote 158 cohort K with KEYTRUDA. Of these 41 patient samples, 31 patients had F1CDx results that passed QC criteria, i.e., yielded evaluable/valid results with F1CDx. Of the 31 patients with F1CDx evaluable results, 21 were confirmed by F1CDx as MSI-H. The remaining 10 patients did not have MSI-H status confirmed by F1CDx; 8 patients had MSS status and 2 had MSI-cannot be determined status due to MSI scores being >0.0041 but <0.0124. The ORR in the 21 patients with confirmed MSI-H by F1CDx was 42.9%; 95% CI: 21.8, 66.0. The ORR in the 10 patients that did not have MSI-H status confirmed by F1CDx was 30%; 95% CI: 6.7, 65.2. The ORR in the F1CDx non-evaluable population was 10%; 95%CI (0.3, 44.5). The results of the post approval study further confirmed the clinical effectiveness for F1CDx to identify patients with solid tumors with MSI-H status that may benefit from KEYTRUDA therapy.”
General
Study Status	Completed
Application Number / Requirement Number	P170019 S043/ PAS001
Date Original Protocol Accepted	12/01/2023
Date Current Protocol Accepted
Study Name	RET Fusion Clinical Efficacy PAS for Selpercatinib
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose and objective of the PAS will be to confirm the clinical effectiveness of F1CDx as a CDx device for identification of patients with solid tumors with RET fusions, who may benefit from treatment with selpercatinib, by evaluating the objective response rate (ORR) for tissue agnostic patients from the LIBRETTO-001 clinical trial. The RET fusion-positive (i.e., clinical trial assay positive (CTA+)) samples from LIBRETTO-001 clinical trail will be used (i.e., patients enrolled under tissue agnostic). The clinical registrational samples from the LIBRETTO-001 clinical trial have already been evaluated by the CTA for enrollment purposes. The qualifying RET fusions are summarized in QSR-BPM-062: RET biomarker definition to support the selpercatinib CDx claim in the US, European Union (EU), and Japan using F1CDx. Approximately 29 TA patients enrolled in LIBRETTO-001 with available FFPE for F1CDx testing will be evaluated in this study (Table 6.1 below). TA patients were enrolled in LIBRETTO-001 as RET fusion positive by a local test result (i.e. CTA+) and retrospectively tested by F1CDx. Among the up to approximately 29 CTA+ TA patient samples, approximately 15 were previously tested under the clinical bridging study for the US (QSRVAL- RPT-410-02, evaluated under P170019/S043), approximately six were previously tested under the clinical bridging study for Japan (QSR-VALRPT- 425-02), and an estimated eight will be available from patients who were enrolled into LIBRETTO-001 until a later enrollment cutoff date (Q1 2024) and will be tested by F1CDx for the purposes of the PAS. Approximately eight unique FFPE tissue samples will be prospectively obtained from TA patients enrolled in the LIBRETTO-001 trial and processed in this study. Final numbers will be provided in the study report. The ORR will be calculated using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), consistent with the LIBRETTO-001 clinical study protocol. The ORR will be defined as the observed proportion of patients whose best overall response is confirmed complete response (CR) or partial response (PR), as determined by an independent review committee (IRC) and by the treating Investigator, and will be accompanied by a two-sided 95% confidence interval (CI) when applicable. The ORR will be calculated using a clinical cutoff date (for clinical outcomes) planned for Q2 2025 for all approximately 29 CTA-positive TA patients with a valid F1CDx test result (F1CDx evaluable). The ORR will be reported for the following groups: CTA + TA patients that are RET fusion positive as determined by CTA. F1CDx + CTA + TA patients that are RET fusion positive by both CTA and by F1CDx. F1CDx - CTA + TA patients that are RET fusion positive by CTA but RET fusion negative by F1CDx.
Study Population	RET fusion positive tissue agnostic patients Samples meeting the pre-defined criteria specified below will be included. Inclusion Criteria . FFPE tissue samples (blocks or slides) . DNA derived from FFPE samples . Samples obtained in accordance with QA-028, POL-01008, and IRB-approved protocols . Samples obtained in accordance with IRB#:120160955, Use of Leftover Nucleic Acid Samples that are Not Individually Identifiable for Analytical Validation Studies (FMI) . Sample that meet minimum criteria for F1CDx testing operational requirements. . Samples from the LIBRETTO-001 clinical trial with proper informed consent Exclusion Criteria . Samples failing to meet any of the inclusion criteria. LIBRETTO-001 clinical trial samples that lack clear identification or labeling Samples not obtained in accordance with QA-028 and POL-01008 or not receiving IRB approval. Samples not obtained in accordance with IRB#: 120160955, Use of Leftover Nucleic Acid Samples that are Not Individually Identifiable for Analytical Validation Studies (FMI)
Sample Size	A total of up to approximately 29 TA patients enrolled in LIBRETTO-001, with available FFPE for F1CDx testing, will be evaluated in this study. TA patients were enrolled in LIBRETTO-001 as RET fusion positive by a local test result (i.e., CTA positive) and retrospectively tested by F1CDx. Among the up to approximately 29 CTA-positive TA patient samples, ~15 will be from the clinical bridging study for the US, ~6 will be from the clinical bridging study for Japan, and an estimated ~8 will be available from patients who were enrolled into LIBRETTO- 001 until a later enrollment cutoff date (Q1 2024) and tested by F1CDx for the purposes of this post approval study.
Key Study Endpoints	To evaluate the clinical effectiveness of selpercatinib for TA patients with RET fusions from LIBRETTO-001, the ORR will be calculated using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), which is consistent with that in the LIBRETTO-001 clinical study protocol. The ORR will be defined as the observed proportion of patients whose best overall response is confirmed complete response (CR) or partial response (PR) as determined by independent review committee (IRC) and by the treating Investigator and will be accompanied by a two-sided 95% confidence interval (CI) when applicable. The ORR will be calculated using a clinical cutoff date (for clinical outcomes) planned for Q2 2025 for all approximately 29 CTA-positive TA patients with a valid F1CDx test result (F1CDx evaluable). The ORR will be reported for the following groups: CTA + TA patients that are RET fusion positive as determined by CTA. F1CDx + CTA + TA patients that are RET fusion positive by both CTA and by F1CDx. F1CDx - CTA + TA patients that are RET fusion positive by CTA but RET fusion negative by F1CDx.
Follow-up Visits and Length of Follow-up	For safety follow up: 28 days (+7 days) after final dose of study drug. For long-term follow up: approximately every 3 month (-/+ 1 month) after that last dose of study drug. Long term follow up will occur until the patient has withdrawn consent for further participation, is lost to follow up, has died, or the Sponsor makes a decision to close the study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 34 valid F1CDx test results were obtained from 39 tissue-agnostic (TA) CTA-positive patients from the LIBRETTO-001 clinical trial, including 15 subjects from the US clinical bridging study, 6 subjects from the Japan clinical bridging study, and 18 newly enrolled post-approval study subjects, utilizing formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens. Five samples from the post-approval cohort failed DNA extraction QC, yielding 34 evaluable samples (87.2% evaluability rate).
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	An additional post-approval study was conducted to evaluate the clinical effectiveness of F1CDx for RET fusion detection by testing 39 tissue-agnostic CTA-positive patients from the LIBRETTO-001 clinical trial, obtaining 34 valid F1CDx results (87.2% evaluability rate), including 15 subjects from the US F1CDx clinical bridging study previously reported in sPMA P170019/S043, 6 subjects from the Japan F1CDx clinical bridging study, and 18 newly enrolled subjects from the post-approval study for selpercatinib, utilizing formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens from the LIBRETTO-001 clinical trial. The ORR in the F1CDx RET fusion positive and clinical trial assay (CTA) positive population (F1CDx+|CTA+) was 61.54% (16/26) [95% CI: 42.53%, 77.57%], which is similar to the ORR observed in the original sPMA dataset of 61.54% (8/13) [95% CI: 35.1%, 88.0%], and comparable to the ORR of the F1CDx-evaluable CTA-positive population (n=34) of 58.82% [95% CI: 42.22%, 73.63%]. The results of the post-approval study further confirmed the clinical effectiveness of F1CDx to identify patients with solid tumors with RET fusions that may benefit from RETEVMO (selpercatinib) therapy.
Study Strengths & Weaknesses	The concordance analysis in the PAS results shows a positive percent agreement (PPA) for RET fusions of 76.5% (26/34), lower than the 86.7% (13/15) observed in the sPMA P170019/S043, with a discordance rate of 23.5% (8/34). Critically, 50% (4/8) of F1CDx-negative but CTA-positive patients responded to selpercatinib, including 100% response rates in neuroendocrine (1/1) and salivary (1/1) tumors. The discordances appear driven by technological differences between DNA-based F1CDx and RNA-based CTAs (~75% of discordant responders enrolled with RNA-based assays in sPMA analysis), F1CDx biomarker definition criteria (in-strand orientation, 3' RET positioning, breakpoint before kinase domain), contamination algorithm filtering, and technical factors (low tumor purity). Therefore, F1CDx as a DNA-based assay misses a significant number of patients (approximately 12% of evaluable patients, 4/34) who have RET fusions and may benefit from RETEVMO therapy, particularly in neuroendocrine and salivary gland tumors. A limitation to address this issue is already included in device labeling.
Recommendations for Labeling Changes	A summary of the PAS study results should be added to the technical information document. The final text will be finalized during the review of the labeling PMA supplement that FMI should submit 30 days after the completion of the review of P170019/R073.
General
Study Status	Ongoing
Application Number / Requirement Number	P220023 / PAS001
Date Original Protocol Accepted	11/07/2023
Date Current Protocol Accepted
Study Name	RADIANCE Cont f/u studies-SOLO, TRIO, RADIANCE II
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	randomized clinical trial
Study Population	Continued Follow-up: Device vs Sham
Sample Size	Continued Follow-up: 506 total; 179 remain active
Key Study Endpoints	Continued Follow-up: • Office, ambulatory and, home blood pressure • Renal imaging • Adverse events
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P170024 / PAS001
Date Original Protocol Accepted	07/13/2018
Date Current Protocol Accepted
Study Name	SCENT Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the trial is to determine the long-term safety and effectiveness of the Surpass Flow Diverter in the endovascular treatment of large or giant wide-necked intracranial aneurysms in the internal carotid artery up to the terminus.
Study Population	Subjects with a large or giant intracranial aneurysm in the internal carotid artery up to the terminus
Sample Size	213 Subjects Enrolled
Key Study Endpoints	The primary efficacy endpoint as determined by the angiographic core lab, is the percent of subjects with 100% occlusion (Raymond Class 1) without clinically significant stenosis (defined as = 50% stenosis) of the parent artery based on core lab evaluation of the 12 month follow up angiogram and without any subsequent treatment at the target aneurysm at the 12 month follow-up visit. Safety success is achieved with a primary safety event rate significantly less than 20%
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	236 subjects were enrolled in the SCENT Post-Approval Study; 213 subjects (90.3%) received treatment and 23 subjects (9.7%) were Enrolled but not Treated (ENT). Of the 213 subjects who completed the study procedure, 180 comprise the modified Intent to Treat (mITT) cohort and 33 comprise the Roll-in cohort.
Actual Number of Sites Enrolled	26 sites, including 25 US sites and 1 international site
Patient Follow-up Rate	The follow-up rates for mITT cohort at 1-yr, 2-yr, 3-yr, 4-yr, and 5-yr follow-up visits are 96.5%, 97.6%, 89.9%, 97.9% and 96.7% respectively. The follow-up rates for Roll-in cohort at 1-yr, 2-yr, 3-yr, 4-yr, and 5-yr follow-up visits are 100%, 100%, 89.3%, 100% and 100% respectively.
Final Safety Findings	Summary of primary safety and efficacy endpoints at 12 months follow-up The primary safety endpoint is the rate of neurological death or major ipsilateral stroke through 12-months. The primary safety rate in the SCENT Post-Approval Study mITT population was 11.1% [95% CI of (6.92% - 16.64%)], with the upper limit being less than the performance goal of 20%, rejecting the null hypothesis at p = 0.001. The primary efficacy endpoint is 100% target intracranial aneurysm occlusion (Raymond Class 1) without clinically significant stenosis (defined as = 50% stenosis of the parent artery) of the parent artery based on core lab evaluation at 12-months follow up angiogram and without any subsequent treatment at the target intracranial aneurysm at the 12-months follow up visit. The primary effectiveness rate in the SCENT Post-Approval Study mITT population was 62.8% [95% CI of (55.3% - 69.9%)], rejecting the null hypothesis at p = 0.001. Summary of long-term safety and efficacy endpoints for 12-60 months follow-up Description of the mITT cohort: Neurological Death: N=5, no change from the 12-months follow-up during the long-term follow-up; note, subject 28-007 died of a neurological death at 1849 days post-procedure, which is outside of the 5-year follow-up cut-off date which was defined as 1825 days. Clinical Events Committee (CEC) Adjudicated new or worsening major ipsilateral stroke: 11.1% (20/180) at 12-months and 21, 22, 23, and 23 subjects at 24, 36, 48, and 60 months respectively. Aneurysm Rupture: four subjects (2.2%; 4/180) at 12-month; no change from the 12-months follow-up during the long-term follow-up. Incidence of retreatment: 0.6% (1/180) at 12-months, 1.1% (2/180) at 24 months, and 2.8% (5/180) at 36 months. No additional retreatment occurred through 60 months. Unchanged or improved functional outcome scores (as measured by modified Rankin Scale (mRS) score compared to baseline): 82.8% (111/134) at 36 months and 80.7% (96/119) at 60 months. Worsening in mRS: 10.0% (18/180) at 12-months timepoint; at 36-months, the rate of change compared to baseline was 10.4% (14/134); at 60-months, the rate of change was 9.2% (11/119). Description of the Roll-in cohort: Neurological Death: N=3, per CEC adjudication, 1 neurological death was reported at 12 months, 1 neurological death occurred at 36 months, and 1 additional neurological death occurred at 60 months. No change in the number of neurological death since the last report. CEC Adjudicated new or worsening major ipsilateral stroke: 4, 4, 4, 5, and 5 at 12, 24, 36, 48 and 60 months, respectively. Aneurysm Rupture: No subject (0/0) in the Roll-In cohort experienced aneurysm rupture at any long-term follow-up time point. Incidence of retreatment: 0, 0, 1, 1, 1 at 12, 24, 36, 48 and 60 months, respectively. Unchanged or improved functional outcome scores (as measured by mRS compared to baseline): 88.0% (22/25) at 36 months and 85.7% (18/21) at 60 months, compared to the 78.8% (26/33) measured at 12-months. Worsening in mRS: at 12-months timepoint was 15.2% (5/33); at 36 months, the rate of worsening was (8%; 2/25); at 60 months, the rate of change was 9.5% (2/21).
Study Strengths & Weaknesses	Strength: A prospective and long-term study with follow-up rate for mITT and Roll-in cohorts at about 90%. Weaknesses: Single-arm study not controlling for confounding factors. Gender distribution is skewed. The majority of study subjects were female (91.1%) and male subjects were under represented, which leads to a limitation in the generalizability of the study results.
Recommendations for Labeling Changes	yes
General
Study Status	Study Pending
Application Number / Requirement Number	P140002 S032/ PAS001
Date Original Protocol Accepted	07/16/2026
Date Current Protocol Accepted	07/16/2026
Study Name	OSPREY Iliac Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study objective is to confirm the safety and efficacy of the Misago® RX Self-expanding Peripheral Stent for use in the common and/or external iliac artery.
Study Population	The target population is comprised of subjects with de novo, restenotic and/or occlusive atherosclerotic lesion(s) of the common and/or external iliac artery up to 120 mm in length with reference vessel diameters between 4.0 and 9.0 mm.
Sample Size	75 Subjects Enrolled, 64 remain in follow up.
Key Study Endpoints	Co-primary Endpoint: Freedom from the composite Major Adverse Event, defined as peri-procedural related death, amputation of the target limb, and clinically driven Target Lesion Revascularization (CD-TLR) assessed at 9 months post-procedure. Clinically driven TLR is defined as re-intervention of the target lesion in which subject has greater than or equal to 50% stenosis with worsening symptoms, or greater than or equal to 70% stenosis without symptoms. The date of the TLR is the date of the re-intervention. The primary objective will be to summarize the primary endpoint. The percentage of subjects not experiencing the MAEs (%) and the 95% Agresti-Coull confidence interval will be reported.
Follow-up Visits and Length of Follow-up	24 months
General
Study Status	Ongoing
Application Number / Requirement Number	P250055 / PAS001
Date Original Protocol Accepted	06/26/2026
Date Current Protocol Accepted	06/26/2026
Study Name	Continued Follow-up of IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Evaluate the safety and effectiveness of the AMDS Hybrid Prosthesis for the open surgical treatment of acute DeBakey Type I dissection with pre-operative malperfusion. This is continued follow up of the premarket cohort.
Study Population	Subjects diagnosed with acute DeBakey Type I dissection, with evidence of clinical and/or radiographic malperfusion as assessed by cardiac surgeons.
Sample Size	115 subjects: 93 subjects were enrolled in the pivotal study and 22 subjects were enrolled in the continued access study.
Key Study Endpoints	Clinical endpoints include major adverse events (all-cause mortality, new disabling stroke, new onset renal failure requiring dialysis, myocardial infarction) and distal anastomotic new entry (DANE) tears
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250055 / PAS002
Study Name	AMDS Post-Approval Study (RETHINK)
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250029 / PAS001
Study Name	SimpleScreen CRC Post-Approval Study
General Study Protocol Parameters
General
Study Status	Ongoing
Application Number / Requirement Number	P120007 S034/ PAS001
Date Original Protocol Accepted	02/03/2026
Date Current Protocol Accepted	02/03/2026
Study Name	CERVIVA Primary Screening Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	Other Data Source
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To collect clinical data evaluating the clinical performance of the Aptima HPV Assay and the Aptima HPV 16 18/45 Genotype Assay compared to an HPV test that is FDA-approved for primary screening in women aged 25-29 years from CERVIVA Primary Screening Study, confirming the safety and effectiveness of the device in this specific age group.
Study Population	All women aged 25 to 29 years presenting for cervical cancer screening.
Sample Size	1800 participants
Key Study Endpoints	The ratio (Aptima HPV Assay and Aptima HPV 16 18/45 Genotype Assay: FDA-approved HPV test) of clinical sensitivity and false positive rates for detection of CIN2+ and CIN3+.
Follow-up Visits and Length of Follow-up	None
General
Study Status	Protocol Pending
Application Number / Requirement Number	P030031 S141/ PAS001
Study Name	SmartPulse Post-Approval Study
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P170030 / PAS002
Date Original Protocol Accepted	02/22/2019
Date Current Protocol Accepted
Study Name	Bioflow-V Cont f/u PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The BIOTRONIK BIOFLOW-V clinical trial was a prospective, multicenter, randomized, controlled trial combining data on the randomized subjects with data from two prior studies by employing a Bayesian approach. The objective of this study was to assess the safety and efficacy of the Orsiro Sirolimus Eluting Coronary Stent System in the treatment of subjects with up to three native de novo or restenotic (after standard PTCA only) coronary artery lesions compared with the Xience coronary stent system. The primary endpoint was TLF rate at 12 months post index procedure. TLF was defined as all cardiac death, target vessel Q-wave or non–Q-wave MI, or clinically driven TLR. Subjects with CAD who qualified for PCI with stenting were screened per the protocol inclusion and exclusion criteria to achieve a total of up to 1,400 randomized subjects. Eligible subjects were randomized in a 2:1 ratio, stratified by study center, and underwent percutaneous coronary revascularization with either the Orsiro Sirolimus Eluting Stent System (treatment group) or the Xience Everolimus Eluting Stent System (control group). Subjects may have received treatment of up to three target lesions, one or two target lesions per target vessel, for a maximum of two target vessels. The target lesion(s) were required to be de novo or restenotic lesion(s) of =36 mm in length in native coronary artery(ies), with a reference vessel diameter of 2.25–4.0 mm. Treatment of restenotic lesions was allowed provided that the target lesion was previously treated with PTCA only. All treatment with study stents was to be performed during a single index procedure. Note: Concurrent treatment of non-target lesions during the index procedure was not allowed.
Study Population	Eligible patients were identified based on inclusion/exclusion criteria.
Sample Size	1334 patients and 92 sites
Key Study Endpoints	Primary Endpoints The primary endpoint was target lesion failure (TLF) rate at 12 months post–index procedure. Target lesion failure was defined as all cardiac death, target vessel Q-wave or non–Q-wave myocardial infarction (MI), or clinically driven target lesion revascularization. Secondary Endpoints 1. Device success, defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only. Note: Post-dilatation was allowed to achieve device success. 2. Lesion success, defined as attainment of < 30% residual stenosis of target lesion using any percutaneous method. 3. Procedure success, defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only without occurrence of in-hospital major adverse cardiac events (MACE). The following secondary clinical endpoints were evaluated prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up: 4. Death. 5. MI. 6. Cardiac death or MI. 7. MACE and individual MACE components (MACE: composite of all-cause death, Q-wave or non–Q-wave MI, and any clinically-driven target lesion revascularization [TLR]). 8. TLF and individual TLF components (TLF: composite of cardiac death, target vessel Q-wave or non–Q-wave MI, and any clinically-driven TLR). 9. Target vessel failure (TVF) and individual TVF components (TVF: composite of cardiac death, target vessel Q-wave or non–Q-wave MI, and any clinically-driven target vessel revascularization [TVR]). 10. Stent thrombosis (all, definite, definite/probable, probable, possible) according to Academic Research Consortium (ARC) criteria for acute, subacute, late, very late and cumulative stent thrombosis.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,334 subjects
Actual Number of Sites Enrolled	92 sites, both US and OUS (13 countries)
Patient Follow-up Rate	Minimum of 95% follow-up rate
Final Safety Findings	The Orsiro group maintained significantly lower rates of target vessel MI: 4.69% compared to 8.25% (P=0.016) in the Xience group (primary driver of lower TLF in Orsiro patients vs Xience patients). A total of 29.41% (260/884) Orsiro subjects and 31.78% (143/450) Xience subjects experienced at least one device/procedure related AE. A total of 8.94% (79/884) Orsiro subjects and 12.44% (56/450) Xience subjects experienced at least one device/procedure related SAE None of the device/procedure related AEs or SAEs was significantly more prevalent in the Orsiro group compared to the Xience group as evidenced by posterior probability rates < 97.5%. There have been no U(S)ADEs reported in the BIOFLOW-V clinical trial through 5 years post-procedure.
Final Effect Findings	In analysis of non-inferiority of Orsiro versus Xience with regards to the primary endpoint of 12-month TLF were 6.32% and 8.90%, respectively. Through 3 years post-procedure, the rates of clinically driven TLR and clinically driven TVR emerged to be significantly lower in the Orsiro group compared to the Xience group: 3.32% vs. 6.14% (P=0.024) for clinically-driven TLR and 5.53% vs 9.80% (P=0.008) for clinically-driven TVR. The numerical differences in clinically-drive TLR and clinically driven TVR were no longer statistically significant at 4 and 5 years. Driven by the significantly lower target vessel MI rate and lower clinically driven TVR rate, the rate of the composite of TVF was also significantly lower in the Orsiro group at 2, 3 and 4 years with a statistical trend at 5 years post procedure.
Study Strengths & Weaknesses	This was a randomized, controlled trial that met its primary endpoint. However, the trial demographics were not diverse with respect to race and sex, with a large percent of the subjects being White or male.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled site/subjects, key endpoints, follow-up visits, etc.), results and study strengths and limitations of the PAS.
General
Study Status	Delayed
Application Number / Requirement Number	P170034 / PAS002
Date Original Protocol Accepted	10/08/2019
Date Current Protocol Accepted	01/23/2020
Study Name	Modified Hydrus New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objectives are to evaluate device-related safety endpoints (e.g., malposition, obstruction, development of chronic inflammatory adhesions [peripheral anterior synechiae], repositioning, and other downstream clinical sequelae) to support the safety and effectiveness of the device. The new enrollment study is a prospective, non-randomized, multicenter, single arm, post approval study of the Hydrus Microstent. This is a new enrollment study, in which the subject enrollment phase to qualify and treat 330 eyes of 330 subjects at 15 to 20 sites is expected to last up to 24 months including enrollment and 8 study visits. Based on an estimated screen failure rate of 35%, up to 545 subjects who agree to participate in the study and are able to complete clinical follow-up will be enrolled and screened.
Study Population	This is a prospective, non-randomized, multicenter, single arm, post approval study of the Hydrus Microstent. This is a new enrollment study, in which the subject enrollment phase to qualify and treat 330 eyes of 330 subjects at 15-20 sites is expected to last up to 24 months including enrollment and 8 study visits. Based on an estimated screen failure rate of 35%, up to 545 subjects who agree to participate in the study and are able to complete clinical follow-up will be enrolled and screened. Study population: Adult patients with mild to moderate primary open angle glaucoma (POAG) undergoing cataract surgery. There is no comparator group. Inclusion criteria: Male and female patients, at least 45 years of age. An operable age-related cataract with BCVA of 20/40 or worse, eligible for phacoemulsification; if BCVA is better than 20/40, testing with a BAT meter on a medium setting must result in BCVA 20/40 or worse. Diagnosis of primary open angle glaucoma (POAG) treated with 1 to 4 hypotensive medications. Optic nerve appearance characteristic of glaucoma. Medicated IOP less than or equal to 31 mmHg. Visual field examination using Humphrey 24-2 SITA standard, meeting minimum criteria for glaucoma defined as: Visual field loss on Humphrey visual field testing, with mean deviation worse than 0 but no worse than -12dB; fewer than 50% of points depressed below the 5% level, and fewer than 25% of points depressed below the 1% level on pattern deviation plot; no points within central 5° with sensitivity of less than or equal to 0dB; and only one hemifield containing a point with sensitivity <15dB within 5° of fixation. Shaffer grade greater than or equal to III in all four quadrants. Cup:disc (c:d) ratio less than or equal to 0.8. Absence of peripheral anterior synechiae (PAS), rubeosis or other angle abnormalities that could impair placement of the implant. An intact and centered capsulorrhexis. An intact posterior capsular bag. A well-centered IOL placed in the capsular bag. A clear view of an open angle and visualization of the angle with direct gonioscopy following instillation of a miotic agent. No evidence of zonular dehiscence/rupture. No intraoperative floppy iris syndrome.
Sample Size	To estimate the rate of occurrence of clinically significant device malposition, 300 eyes/subjects are needed based on the premarket rate of 1.6% with a precision of 1.4%. The study will enroll up to 545 adult patients with mild to moderate primary open angle glaucoma (POAG) undergoing cataract surgery from 15 to 20 sites across different US geographies. Assuming no more than 35% screen failures and 10% drop-out rate at 24 months, approximately 330 subjects are to be treated to ensure 300 subjects evaluable at 24 months of follow up.
Key Study Endpoints	The study will evaluate: Device malposition and its associated clinical sequelae, intra-operative and post-op ocular adverse events. Specific outcomes include: Primary safety outcome: Rate of occurrence of clinically significant device malposition associated w/clinical sequelae, for ex: Secondary surgical intervention to modify device position or to remove the device (explantation) Corneal endothelial touch by device Iris touch by the device associated w/intraocular inflammation, pigment dispersion or other sequelae Central ECL greater than or equal to 30% Compromised corneal function, e.g., corneal edema, opacification, etc. Best-corrected visual acuity loss of 2 lines (10 letters) or more on the ETDRS chart Device obstruction requiring secondary surgical intervention Persistent anterior chamber inflammation with peripheral anterior synechiae Persistent anterior chamber inflammation without peripheral anterior synechiae Chronic pain Position of the implant will be assessed visually by gonioscopic examination, intraoperatively and on postop f/u. In cases of malposition where the implant location cannot be adequately evaluated by gonioscopy, ultrasound biomicroscopy (UBM) and/or anterior segment OCT should be used to further characterize the nature and extent of the malposition. Secondary safety outcomes: Rate of occurrence of intraoperative ocular adverse events including: Hyphema obscuring the surgeon’s view Choroidal hemorrhage or effusion (detachment with at least a partially hemorrhagic component that obstructs or causes pain, including both peripheral and “kissing” choroidal detachments lasting longer than 1 month) Choroidal detachment Significant iris injury or trauma Corneal abrasion Corneal edema Zonular dialysis Cyclodialysis, cyclodialysis cleft Iridodialysis Vitreous loss not associated with the cataract procedure Inadvertent perforation of the sclera Descemet’s membrane detachment Rate of occurrence of sight threatening, post-op adverse events including: Endophthalmitis Corneal decompensation Severe retinal detachment Severe choroidal hemorrhage Severe choroidal detachment Aqueous misdirection Rate of occurrence of other postop ocular adverse events (i.e. not associated with malposition or in categories above) including: Anterior uveitis/iritis, non-persistent (anterior chamber cell and flare requiring change in steroid treatment) Anterior uveitis / iritis, persistent (greater than or equal to Grade 1+ anterior chamber cells and/or flare lasting for more than 3 months postop or recurring less than 3 months after discontinuation of treatment (requiring change in steroid regimen) Best-corrected visual acuity loss of 2 lines (10 letters) or more on the ETDRS chart measured at or after 3 months postop Chronic pain greater than or equal to 3 months postop Device migration (dislodgement or movement) Device obstruction, partial or complete Peripheral anterior synechiae (PAS) Ocular secondary surgical interventions (SSI) for IOP or glaucoma management Best-corrected visual acuity loss of 2 lines (10 letters) or more on the ETDRS chart measured at or after 3 months postop Hypotony (defined as IOP < 6 mmHg) at or after 1 month postoperative Hyphema (>2mm at >1 day) Corneal opacification Corneal edema persisting > 1 month (mild to moderate) or severe corneal edema greater than or equal to 1 day Other retinal complications (i.e. flap tears) Elevated mean IOP greater than or equal to 10 mmHg than the qualifying screening mean IOP > 1 month postop Iris prolapse/wound incarceration Significant foreign body sensation at or after 3 months postop Surgical re-intervention (other than interventions for IOP or glaucoma management) Worsening of visual field (mean deviation worsening by 2.5 dB or more, confirmed by 2 repeat measurements)
Follow-up Visits and Length of Follow-up	Examination Schedule (8 visits total): Visit 1 – Preoperative Visit 2 – Operative Visit 3 – Day 1 Visit 4 – Week 1 Visit 5 – Month 1 Visit 6 – Month 3 Visit 7 – Month 6 Visit 8 – Month 12 Visit 9 – Month 18 Visit 10 – Month 24
Interim or Final Data Summary
Interim Results	No SAEs or sight threatening AEs reported to date. The reported AEs are anticipated. Too early for meaningful interpretation of safety results as the study is at interim status. The anticipated risks remain the same based on current interim data.
Actual Number of Patients Enrolled	358 subjects enrolled; 252 eyes have received the implant
Actual Number of Sites Enrolled	22 enrolled (IRB approved), 20 initiated
Patient Follow-up Rate	106 (29.6%) of the 358 enrolled subjects have been seen at up to 24 months, with 110 (30.7% includes screen failures) discontinued and 5 (1.4%) lost to follow-up
Study Strengths & Weaknesses	Strength: Study is being conducted according to protocol in alignment with the FDA Weakness: Enrollment slower than anticipated, additional implanting investigators recruited, increased sponsors/site interactions
General
Study Status	Ongoing
Application Number / Requirement Number	P160050 / PAS001
Date Original Protocol Accepted	05/07/2019
Date Current Protocol Accepted	05/12/2020
Study Name	Extended F/U-Barricaid ACD Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval clinical study is to examine the long-term survivorship of the Barricaid® ACD when used in conjunction with limited discectomy. This study is also intended to monitor the natural history of endplate lesions due to interactions with the device, potential interactions with the development of osteoporosis, lesion growth and lesion stability. The study is also intended to investigate potential underlying mechanisms that may contribute to any additional growth through retrieval analysis and histological analysis of periprosthetic tissue. Extended Follow-up From a 2-Year RCT
Study Population	Extended follow-up of RCT Subjects – investigational (Barricaid + Discectomy) vs control (Discectomy Alone)
Sample Size	This study is not powered to demonstrate statistical conclusions, but rather the sample size is based on the subjects from the original 2-year study who agree to participate in longer-term follow-up.
Key Study Endpoints	Secondary Surgical Intervention (SSI), SAEs, AEs, Device Failures, Radiographic Observations, Symptomatic Reherniations, All Reherniations VAS, ODI will all be collected. S005 - For Germany, Austria, Switzerland: CT for control subjects only when they experience a potentially related AE.
Follow-up Visits and Length of Follow-up	10 years, with potentially additional 3 year increments.
General
Study Status	Completed
Application Number / Requirement Number	P170038 / PAS001
Date Original Protocol Accepted	05/22/2020
Date Current Protocol Accepted	07/15/2024
Study Name	CentriMag FTW PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS is a prospective, single-arm clinical investigation designed to evaluate the continued safety and effectiveness of the CentriMag Circulatory Support System for patients who fail-to-wean from CPB. The study is intended to assess whether post-approval use of the CentriMag PAS enrolling real-world subjects produces results that are comparable to those reported in the CentriMag Pivotal Clinical Study. The study will only involve new enrollees with new data collection.
Study Population	Subjects greater than 18 years of age who have been implanted with a CentriMag Circulatory Support System due to failure-to-wean from cardiopulmonary bypass. Subjects or their legal representative must also have signed the Informed Consent Form.
Sample Size	The PAS will enroll up to thirty-two (32) subjects. This is equal to the number of subjects enrolled in the CentriMag pivotal trial. Assuming a primary endpoint success rate of 67%, enrolling 32 subjects will give a power of 0.994 to reject the null hypothesis at an alpha of 0.025.
Key Study Endpoints	The primary endpoint includes: a) In patients who recover and do not go onto transplantation or a long-term device: The proportion of subjects surviving to 30 days post CentriMag support or to hospital discharge (whichever is longer). b) In patients who do not recover and are bridged to a transplant or a long-term system: The proportion of subjects surviving to induction of anesthesia for surgery for transplant or a long-term device. Secondary Endpoints: Frequency and incidence of adverse events will be collected through 30 days post CentriMag support or hospital discharge (whichever is longer). Frequency and incidence of adverse events will be collected through induction of anesthesia for surgery for subjects who are bridged to therapy requiring another surgical procedure. Hemodynamic parameters will be collected at: Baseline, 4 hours post CentriMag implant, Daily during CentriMag support, Prior to explant, induction of anesthesia for heart transplant, or long-term VAD
Follow-up Visits and Length of Follow-up	Hospital discharge or 30 days post CentriMag support (whichever is longer)
Interim or Final Data Summary
Actual Number of Patients Enrolled	32
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	84.4%
Final Safety Findings	The relatively more frequent site-reported serious adverse events at 30 days or discharge, whichever is longer, included: bleeding (59.4%), infection (59.4%), cardiac arrhythmias (59.4%), neurologic dysfunction (25.0%), respiratory failure (25.0%), right heart failure (25.0%), and renal dysfunction (18.8%).
Final Effect Findings	The PAS’ primary endpoint of survival to 30 days, hospital discharge, or bridged to transplant or artificial heart was 87%. This met the pre-specified performance goal of 27% and demonstrated non-inferiority to the 63% historical performance goal using a 20% margin.
Study Strengths & Weaknesses	The study strengths were its high follow-up rate and meeting the performance goal by a large margin. The study’s main weakness was that almost all implants were for right-heart support.
Recommendations for Labeling Changes	The clinical information in the Instructions for Use should be updated to include the results of the post-approval study.
General
Study Status	Delayed
Application Number / Requirement Number	P170013 / PAS001
Date Original Protocol Accepted	11/17/2020
Date Current Protocol Accepted	08/21/2024
Study Name	PAS-Post-Market Surveillance Study/LongTerm Safety
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A multi-center, real-world evidence (RWE), single arm, retrospective and prospective study
Study Population	The study population conforms to currently approved Indications for Use: Subjects with wide-necked (neck greater than or equal to 4 mm or dome to neck ratio < 2) intracranial, saccular aneurysms arising from a parent vessel with a diameter greater than or equal to 2.0 mm and less than or equal to 4.5 mm who underwent treatment with LVIS device since approval in the local geography of researched sizes. Real-world data (RWD) will be collected from Medical Health Records of LVIS Device treatments for all patients who meet eligibility criteria and who were treated with the LVIS device sizes per protocol. At least 10 and no more than 35 subjects from each site that meet criteria will be included in the study to obtain data from at least 250 subjects. To mitigate bias, the records of consecutive patients will be screened to assess eligibility.
Sample Size	To mitigate selection bias, all LVIS sites under HDE (HDE # H130005) and the LVIS IDE pivotal study that treated greater than or equal to 10 and no more than 35 patients with LVIS Device models: 212517-LVIS, 212525-LVIS, 213015-LVIS, 213025-LVIS, 213041-LVIS, 214035-LVIS, 214049-LVIS; 212912-LVIS, 212917-LVIS, 212922-LVIS, 212928-LVIS, and 212931-LVIS, will be asked to participate in this study. Sites that treated patients with these LVIS device models since PMA approval may also be approached for participation.
Key Study Endpoints	All safety and effectiveness clinical outcomes will be prospectively reviewed in detail with an independent Clinical Events Committee, comprised of 3 members. The committee shall determine the event category using the following a priori clinical outcomes: 1. Complete or stable Raymond-Roy II intracranial aneurysm occlusion 2. Intracranial hemorrhage including SAH and IPH 3. All ischemic and hemorrhagic strokes 4. Neurological deaths 5. Transient Ischemic Attacks (TIAs) 6. Parent artery patency 7. In-stent stenosis 8. Target aneurysm retreatment 9. Cerebral vasospasm
Follow-up Visits and Length of Follow-up	Up to 5 years post-implant
General
Study Status	Delayed
Application Number / Requirement Number	P170039 / PAS002
Date Original Protocol Accepted	10/03/2019
Date Current Protocol Accepted
Study Name	Pediatric New Enrollment
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-masked, multicenter study to determine the long-term (60 months) safety and effectiveness of the CustomFlex™ Artificial Iris for the treatment of full or partial iris defects in pediatric subjects. The study will include follow-up data for up to 5 years from previously enrolled pediatric subjects who participated in the 12-month AI-001 IDE study and are participating in the AI-001 extended follow-up PAS (P170039/S001). In addition, this study will include additional newly enrolled pediatric subjects.
Study Population	The study includes the implanted subjects. There is no control arm. The postoperative outcomes are compared to their preoperative baseline.
Sample Size	The Pediatric New Enrollment Cohort will include enrollment of up to 125 additional pediatric eyes (depending on how many pediatric eyes are enrolled in the ODE led PAS), meeting all of the inclusion and exclusion criteria below, to provide a total of 125 treated pediatric eyes when the Pediatric New Enrollment Cohort is combined with the Pediatric Rollover Cohort. Treating a total of up to 125 pediatric eyes will ensure that ~100 pediatric eyes will be available for assessment at 5 years postoperatively.
Key Study Endpoints	The primary study outcome is to evaluate device related adverse events (AEs) postoperatively at Month 60. The secondary study outcome is to evaluate the cumulative rate of intraocular lens (IOL)-related AEs at Month 60. Other outcomes: Secondary surgical interventions, implant position, device or surgery related complications, and device malfunctions or defects. Outcomes that will be evaluated include, but are not limited to: Cumulative AEs Endothelial cell density (ECD) changes Device malfunction or defects Device related complications
Follow-up Visits and Length of Follow-up	60 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	0
Actual Number of Sites Enrolled	4
General
Study Status	Completed
Application Number / Requirement Number	P170042 S002/ PAS001
Date Original Protocol Accepted	03/01/2019
Date Current Protocol Accepted
Study Name	AVeNEW Cont f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the AVeNew study is to evaluate the long-term safety and effectiveness of the Covera Vascular Covered Stent. It is a prospective, multi-center, randomized, concurrently controlled clinical study and involves continued follow-up of the premarket cohort to 3 years. In addition to continued follow up of the premarket cohort, an additional cohort of 100 subjects treated with the Covera device will also be studied through 3 years of follow up.
Study Population	The study population is patients dialyzing with an AV fistula that have a stenoses in the venous outflow.
Sample Size	A total of 280 subjects are enrolled in the study. An additional 100 subjects will be enrolled in the post approval study.
Key Study Endpoints	Clinical outcomes at 30 days will include evaluation of safety, and at 90 days, 6, 12, 18, 24 and 36 months will include target lesion primary patency, access circuit primary patency, secondary patency, total number of target lesion reinterventions, access circuit reinterventions, index of patency function, index of patency function – target lesion, and rate of device and procedure related adverse events.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	280
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	199/280 completed 24 month follow-up. 85/280 completed 36 month follow-up (study extension)
Final Safety Findings	The primary safety endpoint was a measure of safety through 30 days post-index procedure. The primary safety endpoint was evaluated against standard PTA alone. Freedom from protocol-defined primary safety events through 30 days post-index procedure was 95.0% in the COVERA™ group and 96.4% in the PTA group. This confirms noninferiority of the COVERA™device with respect to primary safety with a p-value of 0.0022.
Final Effect Findings	The primary effectiveness endpoint was an effective measure based on Target Lesion Primary Patency (TLPP) at 6 months post-index procedure. To demonstrate clinically acceptable effectiveness, the primary effectiveness endpoint was evaluated against the rate of TLPP at 6 months for standard PTA alone. TLPP at 6 months post-index procedure using Kaplan-Meier analyses at Day 180 was 78.7% in the COVERA group and 47.9% in the PTA group. The primary effectiveness endpoint for superiority to PTA alone was met with a p-value of <0.001.
Study Strengths & Weaknesses	Strengths: The COVERA device is safe and its risk profile is comparable to PTA. The COVERA device has a strong early benefit in significantly improving TLPP up to 36 months. Weaknesses: At 36 months, the benefit of improved TLPP starts to diminish – at 36 months TLPP in the COVERA arm was 26.2% versus 13.2% in subjects with PTA. This benefit is not observed with regards to Access Circuit Primary Patency (ACPP) – ACPP in the COVERA arm was 2.4% versus 7.9% in the PTA treated subjects. The average number of reinterventions was equal in both treatment and control arms at 36 months (i.e. 5.5 procedures per subject). With regards to maintaining patency and avoiding reinterventions, the COVERA made a negligible long-term difference compared to plain PTA. The secondary patency rate at 36 months was actually marginally better for PTA at 97% versus 90% for PTA.
Recommendations for Labeling Changes	A labeling update is needed to make physician users aware that the benefit in TLPP seen at six months does not persist at 36 months, and for ACPP and minimizing need for reinterventions, the COVERA did not appear to improve late outcomes compared to plain PTA.
General
Study Status	Ongoing
Application Number / Requirement Number	P170042 S002/ PAS002
Date Original Protocol Accepted	10/31/2019
Date Current Protocol Accepted
Study Name	AVeNEW PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to collect post-market, real-world safety and effectiveness data of the COVERA Vascular Covered Stent for the treatment of stenotic lesions in the upper extremity venous outflow of the AV access circuit. This is a prospective, multi-center, non-randomized clinical study designed to assess the long-term safety and effectiveness of the COVERAVascular Covered Stent for the treatment of stenotic lesions in the upper extremity venous outflow of the AV access circuit of hemodialysis subjects dialyzing with an AV fistula.
Study Population	All-comers population
Sample Size	100 subjects
Key Study Endpoints	Safety through 30 days. TLPP through 30 days, 90 days, 6 months, 12 months, 18 months, 24 months and 36 months. ACPP through 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Rate of device and procedure related AEs involving the AV access circuit through 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Total Number of AV Access Circuit Reinterventions through 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Total Number of Target Lesion Reinterventions through 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Index of Patency Function (IPF) evaluated at 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Index of Patency Function – Target Lesion (IPF-T) evaluated at 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Secondary Patency evaluated through 30 days, 90 days, 6 months, 12 months, 18 months, and 24 months and 36 months. Acute Technical Success. Acute Procedure Success (Anatomic and Clinical Success).
Follow-up Visits and Length of Follow-up	All patients will receive 3 years of follow-up.
General
Study Status	Completed
Application Number / Requirement Number	P170042 / PAS001
Study Name	AVeVA Continued F/U Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the AVeVA study is to evaluate the long-term safety and effectiveness of the Covera Vascular Covered Stent. It is a prospective, multi-center, non-randomized, single-arm clinical study and involves continued follow-up of the premarket cohort.
Study Population	The study population is patients dialyzing with an AV graft that have a stenoses at the venous anastomosis.
Sample Size	A total of 110 subjects are enrolled in the study.
Key Study Endpoints	Clinical outcomes at 12, 18, and 24 months will include target lesion primary patency, access circuit primary patency, secondary patient, total number of target lesion reinterventions and access circuit reinterventions, index of patency function, index of patency function – target lesion, and rate of device and procedure related adverse events.
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	110 Subjects
Actual Number of Sites Enrolled	20 sites
Patient Follow-up Rate	68.2% (75/110) at 24 months; 24.5% (27/110) of subject discontinuation prior to 24-month follow-up was due to death.
Final Safety Findings	Primary Safety The primary safety endpoint for the pivotal trial was freedom from any adverse event(s) that required additional reintervention, in-patient hospitalization/prolongation or death through 30 days post index procedure. The primary safety endpoint for superiority to the performance goal (PG) of 88% Study was met. The proportion of subjects free from primary safety events was 96.4% (106/110) vs. 88% PG [90% CI: 91.9, 98.7] (p-value = 0.0021).
Final Effect Findings	The primary effectiveness endpoint for the pivotal study was Target Lesion Primary Patency (TLPP) through 6 months post-index procedure. The primary effectiveness endpoint for superiority to the performance goal (PG) of 40 % was met. The TLPP at 6 months was 70.3% (71/101), vs. 40% PG (p-value <0.0001). Secondary Endpoints TLPP at 12, 18 and 24 months was 50.5% (46/91), 38.4% (33/86) and 30.1% (25/83), respectively. Access Circuit Primary Patency (ACPP) at 12, 18 and 24 months was 14.4% (14/97), 7.4% (7/94) and 4.3% (4/94), respectively. The total number of AV access circuit reinterventions to maintain access circuit patency circuit was 222, 284 and 333 for 12, 18 and 24 months, respectively. At 24 months that equated to an average of 3.58 reinterventions per subject. The total number of target lesion reinterventions to maintain patency was 81, 100 and 116 for 12, 18 and 24 months, respectively. At 24 months that equated to an average of 1.55 reinterventions per subject. The Index of patency function (IPF) evaluated at 12, 18 and 24 months provided an average of 144 days, 163 days and 178 days respectively between interventions to maintain access circuit patency. The Index of patency function for target lesion patency (IPF-T) evaluated at 12, 18 and 24 months provided an average of 253 days, 326 days and 380 days, respectively between interventions to maintain target lesion patency. Secondary patency was 85.4 % (76/89), 80% (64/80) and 73.6% (53/72) at 12, 18 and 24 months, respectively. Proportion of subjects free from device- and/or procedure-related events at 12, 18 and 24 months was 88.5% (85/96), 87.5% (77/88) and 86.3% (69/80), respectively.
Study Strengths & Weaknesses	Strength: The pivotal study met both superior tests for primary safety and primary effectiveness compared to the respective performance goals (event free primary safety at 30 days, 96.4% vs. 88% PG, p=0.0021; Primary effectiveness, TLPP at 6 months 70.3% vs. 40% PG, p<0.0001). Follow-up was achieved in 68.2% of subjects at 24 months. Approximately 25% (27/110) of subject discontinuation prior to 24 months was due to death. Study was conducted at US sites only.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P170043 / PAS001
Date Original Protocol Accepted	04/16/2019
Date Current Protocol Accepted	04/30/2020
Study Name	Extended f/u Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (PAS) is to evaluate the long -term rate of clinically relevant complications associated with iStent inject® placement and stability in subjects who have completed participation of the IDE clinical trial (GC-008). This is a long-term safety, multicenter, observational study with no planned interventions.
Study Population	Randomized subjects in the GC-008 study who are able to understand the study requirements, willing to follow study instructions and are willing to return for required study follow-up visits.
Sample Size	Up to 475 eyes of 475 subjects. This is based on the number of randomized subjects who consented to 36-month follow-up in study Protocol the GC-008 and study followed for 24 months. Subjects will need to meet the study inclusion criteria.
Key Study Endpoints	Safety Endpoint: The rate of clinically relevant complications associated with iStent inject placement and stability as determined at 60 months. Specific device-related complications include clinical sequelae resulting from device position including, but not limited to: Secondary surgical intervention (SSI) to modify device position (e.g., repositioning or explantation) Corneal endothelial touch by device Corneal edema leading to best-spectacle corrected visual acuity loss (BSCVA loss) > 2 lines at the Month 60 visit, in comparison with preoperative BSCVA Other Safety Outcomes: Rate of occurrence of sight-threatening adverse events including: Persistent (at time of study exit) BSCVA loss = 3 lines compared to best recorded BSCVA at any postoperative visit Endophthalmitis Corneal decompensation Retinal detachment Severe choroidal hemorrhage or detachment or aqueous misdirection Rate of ocular secondary surgical interventions (SSI) Rate of other adverse events including: Increase from baseline IOP of greater than or equal to 10 mmHg at any time greater than or equal to 30 days postoperative BSCVA loss greater than or equal to 2 lines at Month 60 compared to screening BSCVA loss greater than or equal to 2 lines at Month 60 compared to best recorded BSCVA at any postoperative visit Device movement, defined as a stent not visible in the original location, that does not result in clinically relevant complications as described above (e.g., SSI to modify device position, corneal endothelial touch by device, or corneal edema leading to BSCVA loss > 2 lines at the Month 60 visit compared to preoperative BSCVA), and that is not attributable to any one or more of the following: - variations in gonioscopy, optical coherence tomography (OCT) or ultrasonic biomicroscopy (UBM) (or other standard imaging methods) viewing angle or illumination - changes in angle anatomy due to concomitant findings such as resolution of hyphema - changes in anterior chamber depth - development of focal peripheral anterior synechiae (PAS)
Follow-up Visits and Length of Follow-up	60 months post-randomization in the IDE trial
Interim or Final Data Summary
Actual Number of Patients Enrolled	227
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	Of the 475 potential subjects, 47.8% (227/475) (178 iStent, 49 control participants) were enrolled in this extended follow-up study. 100% of the participants completed the fifth year follow-up.
Final Safety Findings	The cumulative rate of postoperative adverse events (AEs) was 56.5% (218/386) in the iStent group (452 AEs in 218 participant) and 59.7% (71/119) in the control group (173 AEs in 71 participants). The cumulative rates of sight-threatening AEs (e.g., endophthalmitis, corneal decompensation, retinal detachment, several choroidal hemorrhage, or aqueous misdirection) was 24.4% (94/386) in the iStent group and 34.5% (41/119) in the control group. The cumulative rate of secondary surgical interventions (SSIs) was 12.2% (47/386) in the iStent group (56 SSIs in 47 participants) and 16% (19/119) in the control group (24 SSIs in 19 participants). The most frequently-reported SSI in both groups was selective laser trabeculoplasty (SLT; 22 SLTs in 20 participants in iStent group, 15 SLTs in 14 participants in control group). IOP-lowering SSIs (including canaloplasty, laser trabeculoplasty, trabeculectomy, and XEN stent implantation) were performed in 8.5% (33/386) of the iStent group and 15.1% (18/119) of the control group. 30 secondary surgical interventions (SSIs) that occurred after Month 36 were reported for 23 participants (12.9%) in the iStent inject group, and 16 SSIs were reported for 14 subjects (28.6%) in the control group. Laser for iStent obstruction was performed in four iStent participants. There were no iStent explantations. At Month 60, one iStent (0.6%, 1/178) and two control (4.1%, 2/49) participants had BSCVA loss =2 lines compared to at screening. These AEs were not device-related. The cumulative rate of non-visible (“deep”) iStents on gonioscopy (at the last three visits of GC-008) was 1.0% (4/386). Non-visualization of iStents on gonioscopy was reported for one iStent participant at Month 60, who did not follow up for recommended ultrasound biomicroscopy imaging. The cumulative rate of peripheral anterior synechiae reported on gonioscopy was 13.8%. One iStent participant had suspected iStent obstruction at Month 59 and underwent a subsequent laser procedure as an SSI. Corneal edema persisting for =30 days was reported in one iStent participant (0.3%, 1/386) and none in the control group. The mean percent change in endothelial cell density (ECD) from baseline to Month 60 was -14.3% (SD 13.4) for the iStent inject group and -14.8% (SD 10.3%) for the control group. The percentage of eyes with an endothelial cell loss (ECL) >30% at the Month 60 visit was 9.4% (16/170) in the iStent inject group and 6.3% (3/48) in the control group. The difference in the rate of ECL > 30% was estimated as 3.16%, 95% CI (-5.0%, 11.3%) and was not statistically or clinically significant. Forty-six minor protocol deviations (PDs) were reported due to out-of-window Month-60 visits (N=24), protocol-specified assessments not performed (N=26), and intraocular pressure assessment not performed per protocol (N=4).
Final Effect Findings	No effectiveness findings were reported
Study Strengths & Weaknesses	Strengths: The information from this continuation post-approval study (PAS) that provides additional long-term extended follow-up data for the iStent inject. Weaknesses: There was a 100% missing data rate at the Month 48 visit and most visits were out-of-window by at least 6 months or longer. Fewer than half of the original pivotal cohort enrolled in this continuation PAS. This PAS was not statistically powered for any safety endpoints.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P170043 / PAS002
Date Original Protocol Accepted	04/16/2019
Date Current Protocol Accepted	03/03/2021
Study Name	New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (PAS) is to evaluate the rate of clinically relevant complications associated with iStent inject placement and stability, as determined at 36 months in the postmarket setting compared to the pre-specified performance target of 2%. This is a prospective, non-randomized, multicenter, single-arm, post approval study of the iStent inject with follow-up through 3 years postoperative.
Study Population	358 eyes at a minimum of 15 and up to 30 investigational sites in the U.S. It is expected that the enrollment phase will last up to 37.5 months.
Sample Size	A sample size of 250 eyes can provide a statistical power of 80% at a true p of 0.05. Considering a drop-out rate of 30% at 36 months for this post-approval study, the study should treat at least 358 eyes of 358 subjects.
Key Study Endpoints	The rate of clinically relevant complications associated with iStent inject placement and stability as determined at 36 months. Specific device-related complications include clinical sequelae resulting from device position including, but not limited to: Secondary surgical intervention (SSI) to modify device position (e.g., repositioning or explantation) Corneal endothelial touch by device Corneal edema leading to BSCVA loss > 2 lines at the Month 36 visit, in comparison with preoperative BSCVA Other Safety Outcomes: Rate of occurrence of sight-threatening adverse events including: Persistent (at time of study exit) BSCVA loss greater than or equal to 3 lines compared to best recorded BSCVA at any postoperative visit Endophthalmitis Corneal decompensation Retinal detachment Severe choroidal hemorrhage or detachment or aqueous misdirection Rate of ocular secondary surgical interventions (SSI) Rate of other adverse events including: Increase from baseline IOP of greater than or equal to 10 mmHg at any time greater than or equal to 30 days postoperative BSCVA loss greater than or equal to 2 lines at Month 36 compared to preoperative BSCVA loss greater than or equal to 2 lines at Month 36 compared to best recorded BSCVA at any postoperative visit Device movement, defined as a stent not visible in the original location, that does not result in clinically relevant complications as described above (e.g., SSI to modify device position, corneal endothelial touch by device, or corneal edema leading to BSCVA loss > 2 lines at the Month 36 visit compared to preoperative BSCVA), and that is not attributable to any one or more of the following: variations in gonioscopy, OCT or UBM (or other standard imaging methods) viewing angle or illumination changes in angle anatomy due to concomitant findings such as resolution of hyphema changes in anterior chamber depth development of focal peripheral anterior synechiae (PAS)
Follow-up Visits and Length of Follow-up	36 months (3 years)
Interim or Final Data Summary
Interim Results	Of the 387 subjects enrolled, 19 subjects were a screen failure, and 367 subjects underwent implantation with the study device at the time of data cutoff. Enrollment accrual is complete, and the last subject was treated on June 23, 2022. A total of 172 postoperative study eye AEs were reported in 107/367 (29.2%) subjects. The most common AE was dry eye (18 events reported in 18 subjects; 4.9%). There were no reports of intraoperative ocular AEs or UADEs. 97.4% (342/351) at Month 12, 97.6% (326/334) at Month 24, 98.2% (270/275) at Month 36 had Best Spectacle Corrected Visual Acuity (BCVA) of 20/40 or better, and 86.0% (302/351) at Month 12, 86.5% (289/334) at Month 24, 85.8% (236/275) at Month 36 were 20/25 or better. 65/367 (17.7%) subjects had BSCVA worse than 20/40 preoperatively. 11 subjects had visual acuity worse than 20/40 at their last available visit prior to data cutoff, which includes 7 subjects with preoperative BSCVA worse than 20/40. Additionally, mild corneal edema was observed in 5 eyes at Month 1. There were no reports of moderate or severe corneal edema after the Day 1 visit. Observations involving 2+, 3+, and 4+ anterior chamber (AC) cells were limited to postoperative Day 1 and Week 1. 1+ AC cells were reported in 2 eyes at Month 1, 1 eye at Month 3, and 1 eye at Month 6; these 4 subjects had reports of inflammation. Postoperative goniosynechiae were reported in 8/367 subjects (6 by the same PI). 4/367 subjects had transient postoperative angle abnormalities. Visual Field Mean Deviation (MD) measurements showed a worsening of = 2.5 dB was reported in 6.9% of eyes (24/350) at Month 12 visit, in 9.7% of eyes (32/329) at Month 24, and in 14.1% of eyes (38/270) at Month 36. Lastly, a total of 238 protocol deviations were reported for 148/367 subjects. The total rate of protocol deviations was 0.064%.
Actual Number of Patients Enrolled	367
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	Accountability at 36 months was 91.6% (318/347). Sixty-four (64) participants were implanted with Model G2-M-IS. Accountability at 36 months for the Model G2-M-IS was 91.8% (n/N). For Model G2-W, 303 participants were treated and accountability at 36 months was 91.6% (n/N).
Final Safety Findings	The safety endpoint was the rate of clinically relevant complications associated with the iStent inject/iStent inject W placement and stability as determined at 36 months. Specific device-related complications included clinical sequelae resulting from device position including, but not limited to SSIs to modify device position (e.g., repositioning or explantation), corneal endothelial touch by the device, corneal edema leading to best spectacle corrected visual acuity (BSCVA) loss > 2 lines at the Month 36 visit, incomparison with preoperative BSCVA. None were reported; therefore, the rate of clinically relevant complications was (n =0%) at Month 36. A total of 61 sight-threatening adverse events (SAEs) was reported in 39 participants (10.6%; 39/367). Rates were similar for both models. SAEs were reported in 10.9% (33/303) of participants that received Model G2-W, and 9.4% (6/64) of participants that received Model G2-M-IS. Reported SAEs included age-related macular degeneration (AMD) or worsening of AMD at a rate of 1.9% (7/367), and best spectacle corrected visual acuity (BSCVA) loss of 3 lines or more at study exit and worse than 20/40 (LogMAR 0.3) at a rate of 1.1% (4/367). There was a total of 28 Secondary Surgical Interventions (SSIs) reported for 14 participants at a rate of 3.8% (14/367). Glaucoma-related SSIs of selective laser trabeculoplasty (SLT) was 1.9% (7/367). For Model G2-W, SLT as SSI was reported in 2.3% (7/303) of participants; no SLT as SSI was reported for Model G2-M-IS participants. Non glaucoma-related SSIs were performed for (recurrent) retinal detachment, retinal flap tear, vitreous hemorrhage, macular hole and worsening vitreous floaters in 2.2% (8/367) participants. A total of 168 postoperative ocular adverse events (AEs) were reported for 112 participants (30.5%, 112/367). There were 10 events for 7 participants (1.9%, 7/367) of increased intraocular pressure (IOP) = 10 mmHg at any time = 30 days postoperative. There was one event that was ongoing at study exit. A total of 11 events of BSCVA loss were reported for 10 participants at a rate of 2.7% (10/367) including: 1.1% (4/367) BSCVA loss 3 lines or more at study exit vs. baseline or best recorded BSCVA at any postoperative visit and worse than 20/40; 0.5% (2/367) BSCVA loss (transient) 2 lines or more at or after 3 months postoperative; 0.8% (3/367) for BSCVA loss 2 lines or more and less than 3 lines at study exit vs. best recorded BSCVA at any postoperative visit; and 0.3% (1/367) for BSCVA loss 3 lines or more at study exit vs. baseline or best recorded BSCVA at any postoperative visit and 20/40 or better. There was one (1) case (0.3%, 1/168) of stent obsruction by iris at week one. There were two (2) participants (0.5%, 2/367) reported with Clinically Significant Cystoid Macular Edema. There was one (0.3%, 1/367) case of suspected endophthalmitis reported. For changes in visual acuity from baseline, 1.5% (4/303) of Model G2-W participants and 1.8% (1/64) of Model G2-M-IS participant lost > 2 lines at the 36-month visit. Of the 367 participants enrolled, 364 participants were implanted with 2 stents, 2 participants were implanted with 3 stents and 1 participant was implanted with 1 stent. All implanted stents were visible from Month 1 through all later study visits. A total of 315 protocol deviations were reported for 175 participants. The total rate of protocol deviations (PDs) was 0.084% (315 of 375,546 potential deviations). The most common PDs were missed protocol required assessments (n=110) which included 74 PDs involving specular microscopy. There were 95 PDs of out of window visits and 57 PDs of assessment not performed per protocol.
Study Strengths & Weaknesses	Strengths: The information from this new enrollment post-approval study (PAS) provides long term safety data for Model G2-W. Weakness: There was a total of 49 participants (13%; 49/367) reported discontinued (n=20) or lost to follow-up (n=29).
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P180001 / PAS001
Date Original Protocol Accepted	12/31/2018
Date Current Protocol Accepted
Study Name	Continued f/u of pivotal study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to obtain long-term follow-up and additional information regarding the treatment of all types of dissections and reasons for repair.
Study Population	Patients with acute or chronic dissections.
Sample Size	Follow-up data on the surviving patients of the 73 enrolled in the IDE pivotal study will be reported in the Continued Follow-up of the Zenith Dissection Endovascular System Pivotal Study. 120 new patients with acute Type B dissections, who are treated using both the Zenith TX2 Dissection Endovascular Graft with Pro-Form and the Zenith Dissection Endovascular Stent, and 60 new patients with chronic Type B dissections, who are treated using the Zenith Dissection Endovasular System, will be included in the Zenith Dissection Endovascular System Post Approval Study.
Key Study Endpoints	The following endpoints will be reported through 5-years for the Continued Follow-up of the Zenith Dissection Endovascular System Pivotal Study: false lumen characteristics (i.e., diameter change, patency, and source of persistent flow), dissection-related deaths, aortic ruptures, aortic enlargements, extension of the dissection, major adverse events (i.e., paraparesis, paraplegia, new ischemia), losses of device integrity, and additional dissection-related interventions, including the reasons for the interventions.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Seventy-three (73) subject including 67 from the US and 6 from Japan
Actual Number of Sites Enrolled	Twenty-two (22) sites including 21 sites in the US at 1 site in Japan
Patient Follow-up Rate	Clinical follow-up was 86.1% (31/36) at 5 years; CT Scan was completed in 86.1% (31/36) of subjects at 5 years.
Final Safety Findings	The 30-day freedom from major adverse events (MAE) rate was 71.6% for the pivotal study compared to performance goal (PG) of 51.2% (p < 0.001). The 30-day survival rate was 95.5% compared to the PG of 79.4% (p < 0.001). Therefore, the pivotal study met both primary safety and effectiveness endpoints for the Zenith Dissection Endovascular System. Secondary Endpoints Serious Adverse Events (SAEs) at 5-year timepoint for all patients were: all-cause mortality 7.3% (3/41), Dissection related mortality 0% (0/41), Aortic Rupture 2.4% (1/41) and Conversion 0% (0/41). Major Adverse Events (MAEs): defined as myocardial infarction, Renal failure, Bowel ischemia, Stroke, paraplegia, paraparesis, prolong ventilatory support. A total of 26 patients experienced MAEs The rate at 5-year timepoint for each of the MAEs was 0% (0/41). Secondary intervention: Overall, 22 patients received secondary interventions through 5 years which includes ancillary component placement, balloon angioplasty, coil embolization, thrombectomy, percutaneous stent placement, conversion to open repair and surgical bypass procedure. True and False lumen diameters at location of maximum aortic diameter: (a) Within the stent-graft - mean true lumen diameter increased (> 5 mm) whereas the mean false lumen diameter decreased (> 5 mm) from post-procedure through 5-year in all patients and in the subgroups with and without a Dissection Stent. (b) Within the Dissection Stent region- mean true lumen diameter increased (> 5 mm) whereas the average false lumen diameter remained stable (less than or equal to 5 mm change) from post-procedure through 5-year follow-up. (c) Distal to treated Segment - mean true lumen diameter appeared stable from post-procedure through 5-year follow-up (= 5 mm change), whereas the average false lumen diameter appeared to increase (> 5 mm) through 5-year follow-up for all patients and the subgroups Change in transaortic diameter (true lumen + false lumen diameter) in the stent graft region compared to first post procedure exam: The percentage of all patients that experienced an increase in transaortic growth within the stent graft region at 2, 3, 4 and 5 years was 23.8% (10/42), 22.5% (9/40), 27.8% (10/36) and 17.2% (5/29) respectively. The percentage of patients that experienced a decrease in transaortic growth within the stent graft region at 2, 3, 4 and 5 years was 19.0% (8/42), 17.5% (7/40), 19.4% (7/36) and 20.7% (6/29) respectively. The percentage of patients with no change in transaortic growth within the stent graft at 2, 3, 4 and 5 years was 57.1% (24/42), 60.0% (24/40), 52.8% (19/36) and 62.1% (18/29), respectively.
Final Effect Findings	(continued) Entry Flow in the Thoracic Aorta The percentage of all patients with Type I (proximal) entry flow into thoracic false lumen at 2, 3, 4 and 5 years was 12.2% (5/41), 5.1% (2/39), 2.9% (1/35) and 0% (0/28), respectively. The percentage of all patients with Type I (distal) entry flow into thoracic false lumen from 2 through 5 years was zero (0%) at each time point. There were no reports (0%) of Type II, III or IV entry flow. The percentage of all patients with entry flow into thoracic false lumen via collateral at 2, 3, 4 and 5 years was 36.6% (15/41), 35.9% (14/39), 20.0% (7/35) and 17.9% (5/28) respectively. The percentage of all patients with entry flow into thoracic false lumen via secondary tear at 2, 3, 4 and 5 years was 14.6% (6/41), 25.6% (10/39), 20.0% (7/35) and 17.9% (5/28), respectively. Entry Flow in the Abdominal Aorta There were no reports (0%) of Type I, II, III or IV entry flow into the abdominal false lumen from 2 through 5 years in all patients. The percentage of all patients with entry flow into abdominal false lumen via collateral at 2, 3, 4 and 5 years was 64.9% (24/37), 70.3% (26/37), 68.6% (24/35) and 65.5% (19/29) respectively. The percentage of all patients with entry flow into abdominal false lumen via secondary tear at 2, 3, 4 and 5 years was 56.8% (21/37), 70.3% (26/37), 68.6% (24/35) and 58.6% (17/29), respectively. False lumen Status At 2, 3, 4 and 5 years the false lumen was completely thrombosed within the stent graft for 62.5% (25/40), 63.2% (24/38), 76.5% (26/34) and 75.0% (21/28) respectively for all patients. At 2, 3, 4 and 5 years, the false lumen was partially thrombosed within the dissection stent for 73.3% (22/30), 70.0% (21/30), 84.6% (22/26) and 61.9% (13/21), respectively for all patients who received dissection stent. At 2, 3, 4 and 5 years there were no apparent false lumen proximal to the treated region for 100% (41/41), 97.4% (38/39), 97.1% (33/34) and 100% (28/28), respectively of all patients. At 2, 3, 4 and 5 years, false lumen distal to the treated segment was partially thrombosed for 52.8% (19/36), 55.3% (21/38), 48.5% (16/33) and 50.0% (13/26) of all patients. Progression of Dissection: A total of seven (7) patients were reported to have had retrograde/proximal extension of dissection and two patients (2) had antegrade/distal extension of dissection. Device Integrity There were no reports of device integrity issues (0%) for all patients from 2 through 5 years. Device Migration Device migration was reported in 7.7% (3/39), 7.5% (3/40), 0% (0/35) and 0% (0/29) of all patients at 2, 3, 4 and 5 years respectively. Device Component Separation occurred in 2.4% (1/42), 4.8% (2/42), 2.9% (1/35) and 6.9% (2/29) of all patients at 2, 3, 4 and 5 years, respectively.
Study Strengths & Weaknesses	Study Strength: Majority of the study patients (91.7%, 67/73) were enrolled at sites in the United States. The primary safety endpoint for the Zenith Dissection Endovascular System was met in the pivotal study with 30-day MAE rate of 71.6% compared to PG of 51.2% (p <0.001) in support of safety of this device. Primary effectiveness of 30-day survival was also met with survival rate of 95.5% compared to PG of 79.4% (p< 0.0001). Clinical follow-up and CT scan evaluation were achieved for 86% all patients at 5 years for each assessment. Weakness: the long-term results are descriptive analyses only.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the Continued Follow-up Study. The labeling change should include a new section on the label showing a summary of the study results (final endpoint results, follow-up rate etc.), strengths and limitations of long-term Study.
General
Study Status	Ongoing
Application Number / Requirement Number	P180001 / PAS002
Date Original Protocol Accepted	12/31/2018
Date Current Protocol Accepted	05/19/2025
Study Name	SVS VQI Postmarket Surveillance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	New enrollment under the SVS VQI Dissection Project, which will be referred to as the Zenith Dissection Endovascular System Post Approval Study. The objective of this study is to obtain long-term follow-up and additional information regarding the treatment of all types of dissections and reasons for repair.
Study Population	Patients with acute or chronic dissections.
Sample Size	120 new patients with acute Type B dissections, who are treated using both the Zenith TX2 Dissection Endovascular Graft with Pro-Form and the Zenith Dissection Endovascular Stent, and 60 new patients with chronic Type B dissections, who are treated using the Zenith Dissection Endovasular System, will be included in the Zenith Dissection Endovascular System Post Approval Study.
Key Study Endpoints	The endpoints for the Zenith Dissection Endovascular System Post Approval Study are the following: Primary safety: Freedom from dissection-related mortality (all devices combined endpoint) Primary effectiveness: device technical success and device procedural success at 30 days (device-specific endpoints) Secondary endpoints: elements of device technical (during the procedure) and procedural success (30-day) for each project device; additional endovascular and surgical dissection-related interventions (30days, 1 year, yearly through 5-years); dissection treatment success and the individual elements of the composite endpoint dissection treatment success (30 days, 1 year, yearly through 5-years)
Follow-up Visits and Length of Follow-up	30-days, 1-year and yearly through 5 years
General
Study Status	Completed
Application Number / Requirement Number	P180002 / PAS001
Date Original Protocol Accepted	09/25/2018
Date Current Protocol Accepted	01/28/2019
Study Name	LIBERATE Extension Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, prospective, single-arm cohort study to evaluate long-term safety and long-term effectiveness in the continued follow-up of the premarket cohort for the LIBERATE Pivotal Trial.
Study Population	Subjects who were previously implanted with the Zephyr Endobronchial Valve System and participated in the LIBERATE Pivotal Trial i.e. initial cohort and crossover subjects.
Sample Size	Approximately 142 subjects are available for extended follow-up
Key Study Endpoints	Effectiveness Endpoint: FEV1 Safety Endpoint: Evaluation of adverse events, summarized by seriousness, severity, and relatedness.
Follow-up Visits and Length of Follow-up	Follow-up is planned for five years from the date of implant procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	190
Actual Number of Sites Enrolled	22
Patient Follow-up Rate	The present report is based on the final study data export, performed on April 27, 2023. A total of 93 subjects in the Zephyr EBV group and 33 subjects in the Crossover group had completed their 2-year follow-up; 79 subjects in the Zephyr EBV group and 25 subjects in the Crossover group had completed their 3-year follow-up; 56 subjects in the Zephyr EBV group and 16 subjects in the Crossover group had completed their 4-year follow-up; 52 subjects in the Zephyr EBV group and 15 subjects in the Crossover group had completed their 5-year follow-up.
Final Safety Findings	In the Zephyr EBV group, the most frequently occurring respiratory AEs continue to be COPD exacerbations across Years 2, 3, 4 and 5, followed by pneumonia in 5.5% to 11.5% of subjects, and respiratory failure in 1.8% to 11.5% of subjects across Years 2, 3, 4, and 5. The nature and frequency of respiratory adverse events during posttreatment Year 4 and 5 do not suggest any unique pattern for study subjects and are anticipated in this population. There have been no unanticipated adverse events to date.
Final Effect Findings	The improvement in lung function as assessed by FEV1 that was observed at 4-year post-procedure after treatment with the Zephyr EBV is similar at 5-years. The change from Baseline to 4-years postprocedure in FEV1 is an increase of 17.67% with 36.4% of the subjects achieving an improvement of equal to or greater than 15%. Improvement in FEV1 is similar in subjects at 5-year post-procedure with an increase of 13.45% from baseline with 30% of subjects achieving an improvement of equal to or greater than 15%.
Study Strengths & Weaknesses	Strengths: Multicenter and international study allowed accrual of diverse patient population. Weaknesses: The absolute change in FEV1 in the EBV cohort did not meet the MCID for FEV1 change in years 2,3, and 5 after treatment. The primary study endpoint of FEV1 % change was not met in years 2, 3, and 5 after treatment. And the crossover subjects did not meet the MCID for Absolute Change in FEV1 or the Primary Endpoint of FEV1 Percent Change in any of the years after treatment.
Recommendations for Labeling Changes	Include the following items: study design and protocol; table of “Post-Bronchodilator FEV1: Changes from Baseline to Follow-up for EBV Group (Completed Cases)” from the PAS final report; a statement that the absolute change in FEV1 in the EBV cohort did not meet the MCID for FEV1 change in years 2,3, and 5 after treatment; A statement that the Primary Study Endpoint of FEV1 percent change was not met in years 2, 3, and 5; and a statement that the crossover subjects did not meet the MCID for Absolute Change in FEV1 or the Primary Endpoint of FEV1 Percent Change in any of the years after treatment
General
Study Status	Ongoing
Application Number / Requirement Number	P180002 / PAS002
Date Original Protocol Accepted	05/03/2019
Date Current Protocol Accepted	03/25/2023
Study Name	ZEVR-Zephyr Valve Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study: Multi-center, single-arm, prospective Registry to be conducted at up to 15 clinical sites. Approximately 150 patients with severe emphysema undergoing Zephyr Valve treatment will be enrolled and followed out to 3 years. Assessments will be performed at 45-days, 6-months, 12-months, 24-months and 36-months post-procedure. The Zephyr Valve Registry will be conducted at a minimum of 5, and a maximum of 10 clinical sites. Enrollment is anticipated to be completed over 24 months. A minimum of 20 subjects treated with at least one Zephyr 5.5-LP EBV will be enrolled.
Study Population	Adult patients with hyperinflation associated with severe emphysema in regions of the lung that have little to no collateral ventilation. Concurrent control comparison group.
Sample Size	150
Key Study Endpoints	Safety endpoints: Incidence rate of Pneumothorax at 45-days post-procedure. Incidence rate of device/procedure related Serious Adverse Events (SAE) including but not limited to COPD exacerbations, pneumonia, hemoptysis, valve expectoration, valve migration and respiratory failure. Effectiveness endpoints: Treated Lobar Volume Reduction (TLVR) assessed by HRCT at 45-days. Forced Expiratory Volume in 1 second (FEV1) at 6-months, 12-months, 24-months and 36-months. 6MWD at 6-months and 12-months. SGRQ at 6-months and 12-months. BODE Index at 6-months and 12-months. Percent of patients with a TLVR of =350mL10,11. Percent of patients with a TLVR of =563mL12. Responder rates reported as percent of patients meeting the Minimal Clinically Important Difference (MCID) for each variable at 6-months and 12-months. - MCID for FEV1: Increase of 10% (Liters) - MCID for 6MWD: Increase of +25 meters - MCID for SGRQ: Decrease of 4 points
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Interim Results	Safety Results: Pneumothorax adverse event rate: 39.5% Effectiveness Results: The mean reduction in TLV at 45 days was 1185.3 mL and at 12-months was 1185.0 mL representing a percent reduction of 64.37% and 65.47%, respectively.
Actual Number of Patients Enrolled	162
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	1-year post-procedure follow up: 68.5%
General
Study Status	Completed
Application Number / Requirement Number	P180003 / PAS001
Date Original Protocol Accepted	10/04/2018
Date Current Protocol Accepted
Study Name	MIMICS-2 Continued f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (MIMICS-2 Continued Follow-Up Study) is to evaluate the long term safety and effectiveness of the Biomimics 3D Vascular Stent System for the treatment of superficial femoral and/or proximal popliteal occlusive disease. This study is a prospective, multi-center follow-up of the MIMICS-2 pivotal study (G140182).
Study Population	The study population included symptomatic (Rutherford Category 2-4) patients with angiographic confirmation of either de novo superficial femoropopliteal artery stenoses or occlusions, with reference vessel diameters between 4.0mm and 6.0mm in diameter and the target lesion(s) measure =40 mm to =140 mm in overall length.
Sample Size	All 249 remaining subjects (22 subjects have discontinued the study) of the 271 original study subjects enrolled from 43 investigational sites.
Key Study Endpoints	Primary Endpoint: Freedom from clinically driven target lesion revascularization (CDTLR) at 36 months. CDTLR is defined as the first revascularization procedure (e.g., PTA, atherectomy, etc.) of the target lesion(s) following the index procedure as determined by an Independent Angiographic Core Lab (or CEC, as necessary). Secondary Endpoints: Overall rate and incidence of type of serious adverse events from Day 0 through completion of Study follow-up at Month 36. Primary stent patency rate: determined at Month 24 per protocol definition of primary stent patency. Clinical outcome: comparison of Rutherford Clinical Category measured at Baseline and Month 24. Worsening of Rutherford Clinical Category is defined as an increase by one or more categories compared to Baseline or unexpected major amputation of the target limb. Comparison of Six-Minute Walk Test measured at Baseline and Month 24 (sub-group of investigational sites). Comparison of the ankle brachial index (ABI) measurement at Baseline and Month 24. Comparison of the Walking Impairment Questionnaire at Baseline and Month 24. Stent integrity measured as freedom from stent fracture, defined as clear interruption of a stent strut observed in a minimum of two projections, determined by core lab examination of X-rays taken with the leg in extension at 24 and 36 Months.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	271
Actual Number of Sites Enrolled	43
Patient Follow-up Rate	Of 271 enrolled subjects, 256 completed the 12-month follow-up visit, 225 completed the 24-month follow-up, and 208 completed the 36-month follow-up.
Final Safety Findings	Primary safety (CEC-adjudicated freedom from MAE through 30 days) was 99.6% [97.7% 100%]. The primary safety endpoint was met. In addition, through 36 months, the overall MAE rate was 29.1%, meaning the 36-month freedom from MAE was 70.9%.
Final Effect Findings	Primary effectiveness (primary stent patency at 12 months) was 73.1% [67.3% 78.2%]. The primary effectiveness endpoint was met. In addition, through 24 months, primary stent patency was confirmed in 62.9% of subjects. Patency was not assessed at the 36-month follow-up unless clinical signs or symptoms suggesting worsening claudication were present.
Study Strengths & Weaknesses	Strengths: The IDE study was a prospective, single-arm multicenter trial in the US and OUS countries. The IDE study met its primary safety and effectiveness endpoints. The PAS also met its primary endpoint of having a 36-month rate of freedom from CDTLR greater than the performance goal of 55%. Weaknesses: This was a single-arm observational study and therefore lacks the inherent advantages of a randomized control trial. There was no comparator for the continued follow-up study results.
Recommendations for Labeling Changes	To update the summary of clinical data within the Instructions for Use to reflect the complete clinical dataset.
General
Study Status	Completed
Application Number / Requirement Number	P180011 / PAS001
Date Original Protocol Accepted	09/18/2018
Date Current Protocol Accepted
Study Name	IMPERIAL Continued f/u study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort; RCT
Study Population	Test: Eluvia DES Control: Zilver PTX DES
Sample Size	485
Key Study Endpoints	Premarket: The primary safety hypothesis to be tested is that the 12-month MAE-free rate in subjects treated with ELUVIA is non-inferior to subjects treated with Zilver PTX by a margin of -10% (negative value) at one-sided significance level of 5%. The primary effectiveness hypothesis to be tested is that the 12-month primary patency in subjects treated with ELUVIA is non-inferior to subjects treated with Zilver PTX by a margin of -10% (negative value) at one-sided significance level of 5%. PAS: Above endpoints at 24 months (descriptively).
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 524 subjects were enrolled in the trial including 465 subjects in the RCT (Eluvia subjects, N=309 and Zilver PTX subjects N=156 subjects), 50 subjects in the Long Lesion substudy (LL) and 13 subjects in the Pharmacokinetic (PK) substudy. Four (4) subjects enrolled in the PK and LL substudies.
Actual Number of Sites Enrolled	Seventy -three (73) sites worldwide including the United States, Canada, Europe Japan and New Zealand
Patient Follow-up Rate	Overall compliance at 60 months: 75.7%, 296/391 for the RCT (74.3% for Eluvia and 78.5% for Zilver), 65.8%, 25/38 for the LL substudy and 88.9% (8/9) for PK substudy.
Final Safety Findings	Major Adverse Event (MAE) free rate at 60 months for RCT Eluvia subjects was 67.2% (156/232) versus 64.9% (74/114) for RCT Zilver PTX (control subjects), 95% confidence interval (CI) for the difference, 2.3% [-8.3%, 13.0%], p= 0.6662. MAE free rate for LL sub-study was 54.3% (19/35) with 95%CI: 36.6%, 71.2%. Target limb major amputation rate for RCT Eluvia subjects was 3.4% (8/232) versus 2.6% (3/114) for Zilver PTX control subjects, 95% CI for the difference, 0.8% [-2.9%, 4.6%], p=1.000 There were no amputations in the LL sub-study subjects 0.0% (0/35) through 60 months. Target lesion revascularization (TLR) rate for RCT Eluvia subjects was 30.6% (71/232) versus 35.1% (40/114) for Zilver PTX control subjects, 95%CI for the difference, 95% CI for the difference -4.5% [-15.1%, 6.1%], p 0.4000. Target lesion revascularization rate for LL sub-study subjects was 45.7% (16/35) with 95% CI 28.8%, 63.4%. At 60 months tent thrombosis rate in the RCT Eluvia treatment subjects was 7.3% (20/273) versus 6.5% (9/139) in Zilver PTX control subjects with 95% confidence interval for the difference 0.9% [-4.3%, 6.0%], p = 0.7495. Stent thrombosis rate in LL subjects at 60 months was 2.2% (1/46) with 95% CI: 0.1%, 11.5%. A total of 9 stent fractures were reported for the RCT Eluvia subjects, 4 fractures for the LL subjects and 1 fracture for PK subjects. One fracture was reported for Zilver PTX subjects of the RCT substudy. A total of 172 RCT subjects had evaluable diagnostic 60-month imaging with 59 subject imaging studies presenting with a halo. Of these, 40 subjects in the treatment group (Eluvia) and 19 in the control group (Zilver PTX) had a halo present, with no statistically significant differences between the groups (p-value =0.3264.
Final Effect Findings	The primary patency rate at 60 months was 53.6% (98/183) in the Eluvia treatment group and 57.7% (60/104) in the Zilver PTX control group. Assisted primary patency showed a 60-month patency rate of 91.2% (125/137) in the Eluvia treatment group and 94.1% (80/85) in the Zilver PTX control group, p=0.4333. The primary patency and primary assisted patency rate at 60 months in the LL substudy were 35.5% (11/31) and 73.7% (14/19), respectively. At the 60-month, 79.7% (145/182) RCT Eluvia subjects and 83.9% (78/93) of Zilver PTX subjects presented with Rutherford Category 0 or I (asymptomatic or had very mild symptoms). At 60 months primary sustained clinical improvement was achieved in 66.5% (121/182) and 65.6% (61/93) in RCT Eluvia and Zilver PTX subjects, respectively with no statistically significant difference between the two subgroups, p=0.8824. Secondary sustained clinical improvement was achieved in 87.4% (159/182) and 93.5% (87/93) in RCT Eluvia and Zilver PTX subjects, respectively, p= 0.1114. At the 60-month, 77.3% (17/22) of LL subjects presented with Rutherford Category 0 or I (asymptomatic or had very mild symptoms). At 60 months primary sustained clinical improvement was achieved in 59.1% (13/22) of LL subjects. When considering subjects with repeat TLR, secondary sustained clinical improvement was achieved by 77.3% (17/22) of subjects. For ankle brachial index (ABI) assessment at 60 months, hemodynamics improvement was achieved by 52.6% (100/190) of RCT Eluvia subjects and 46.6% (48/103) of Zilver PTX subjects, p= 0.3243. For ABI assessment at 60 months, hemodynamic improvement was achieved by 37.5% (12/32) of LL subjects.
Study Strengths & Weaknesses	The Imperial trial included a randomized control substudy that compared performance of the Eluvia drug eluting stent system with the Zilver PTX stent system and therefore had inherent properties of an RCT. However, the continued follow-up results were not evaluated with formal hypothesis testing.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the continued post approval study. The labeling change should include a new section in the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P180011 / PAS002
Date Original Protocol Accepted	09/18/2018
Date Current Protocol Accepted	09/21/2023
Study Name	REGAL and EMINENT Long Term f/u studies
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To confirm the effectiveness of the ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 210 mm in length when compared against bare metal stents, and collect additional data including health economics data. This is a European Study. A prospective, multi-center, randomized 2:1 (ELUVIA vs Self-Expanding Bare Nitinol Stents), controlled, single-blind, superiority trial (RCT). Randomization will be stratified to ensure equal distribution of ELUVIA and Self-Expanding Bare Nitinol Stents in different lesion length subsets.
Study Population	All comers; Eluvia DES only EMINENT: Subjects presenting with lesions 30-210 mm long located in the femoropopliteal arteries with symptoms classified as Rutherford categories 2-4. Eluvia DES vs Bare metal Nitinol treated groups
Sample Size	500 patients EMINENT: - Up to 75 study centers in up to 15 European countries may enroll subjects. 750 subjects including 500 ELUVIA subjects and 250 Control subjects treated with Self-Expanding Bare Nitinol Stents.
Key Study Endpoints	Health economics, technical/procedural success, MAEs, primary patency, CD-TLR EMINENT: Primary Effectiveness - Primary patency at 12 months post-procedure; defined as a binary endpoint and will be determined to be a success when the duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) is = 2.4 at 12- months Secondary Endpoints: - Walking Improvement at 12 months assessed by change in Six Minute Hall Walk (6MHW) / treadmill test from baseline, or preceding any Target Vessel Revascularization -Quality of Life Improvement at 12 months assessed by change in EQ-5D-5L from baseline, or preceding any target vessel revascularization -Major Adverse Event (MAE) rate (and individual components) at each time point, defined as all causes of death, target limb major amputation and/or Target Lesion Revascularization (TLR) -Primary Patency and Assisted Primary Patency at 6 months, 12 months, 24 months and 36 months using different DUS PSVRs -Clinically-driven Target Lesion Revascularization (TLR) and clinically-driven Target Vessel Revascularization (TVR) Rate at each time point - Adverse Event Rates (unanticipated, major, serious, device/procedure-related) at each time point - Number of Stent Fractures reported at 12 months and 24 months utilizing VIVA definitions - Distribution of Rutherford Class during follow-up as compared to baseline at 1 month, 6 months, 12 months, 24 months and 36 months -Walking Improvement at 1 month, 6 months, 12 months, 24 months and 36 months assessed by change in Walking Impairment Questionnaire (WIQ) from baseline -Quality of Life Improvement at 1 month, 6 months, 24 months and 36 months assessed by change in EQ-5D-5L™ from baseline -Rate of Primary and Secondary Sustained Clinical Improvement as assessed by changes in Rutherford Classification from baseline at 1 month, 6 months, 24 months and 36 months -Rate of Hemodynamic Improvement as assessed by changes in Ankle-Brachial Index (ABI) from baseline at 1 month, 6 months, 24 months and 36 months
Follow-up Visits and Length of Follow-up	24 months EMINENT: 6-, 12-, 24-, 36 post index procedure. Subjects will be evaluated at 1 (30 days -7 days to + 14 days) month if visit is local standard of care or if an ELUVIA stent or Self Expanding Bare Nitinol stent was not successfully implanted during the Index Procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	REGAL Study A total of two hundred and ninety-one (291) patients were enrolled. EMINENT Study 775 subjects were enrolled of which 765 received treatment with either investigational device or control device, Eluvia (N=508 subjects) and Control (N=267 subjects) i.e., 2:1 randomization.
Actual Number of Sites Enrolled	REGAL Study Twenty-three (23) sites were enrolled in 4 European countries. EMINENT Study 68 sites were activated in Europe
Patient Follow-up Rate	REGAL Study 82.7% (224/271) at 1 year and 80.2% (211/263) at 2 years EMINENT Study Of the 775 enrolled study subjects: 702 (96.8%) subjects completed the 12-month follow-up visit 649 (94.1%) subjects completed the 24-month follow-up visit 624 (96.6%) subjects completed the 36-month follow-up visit. 36- month duplex ultrasound follow-up compliance was 75.8% (547/722) overall, 73.8% (347/470) for Eluvia group and 79.4% (200/252) for Control group.
Final Safety Findings	REGAL Study Major adverse events (defined as all cause death, major amputation, and target lesion revascularization) rate at 12 months and 24 months post index procedure was 22.5% (63/280) and 27.0% (72/267), respectively. Clinically driven target lesion revascularization (CD-TLR) rate at 12 months and 24 months post index procedure was 8.6% (24/280) and 10.9% (29/267) respectively. Clinically driven target vessel revascularization (CD-TVR) rate at 12 months and 24 months post index procedure was 10.4% (29/280) and 13.1% (35/267) respectively. Amputation rate at 12months and 24 months post index procedure was 8.6% (24/280) and 9.7% (26/267), respectively. All deaths rate at 12 months and 24 months post index procedure was 8.2% (23/280) and 10.5% (28/267) respectively. Stent thrombosis rate at 12 months and 24 months post index procedure was 7.1% (20/280) and 9.7% (26/267) respectively. EMINENT Study CEC adjudicated events through 36 months are as following: TLR rate in Eluvia subjects was 22.1% (100/452) and 20.7% (53/256) in Control subjects, p=0.6590. TVR rate in Eluvia subjects was 23.7% (107/452) and 21.9% (56/256) in Control group, p=0.5851. Amputation rate in Eluvia subjects was 1.1% (5/452) and 0.8% (2/256) in control subjects, p=1.0000 Stent thrombosis rate in Eluvia subjects was 11.9% (54/452) and 6.3% (16/256) in Control subjects, p=0.0147. Major Adverse Events Major Adverse Events (All cause death, Target limb major amputation, and TLR) through 36-month: MAE rate at 36-months for Eluvia subjects was 30.2% (136/451)] and control subjects was 26.3% (67/255), p=0.2738. All-cause death rate at 36 months for Eluvia subjects was 8.4% (38/451) and Control subjects was 5.9% (15/255), p=0.2180. A total of 73 deaths were reported. Of the 73 deaths, forty-two (42; 57.5%) were adjudicated as non-cardiovascular, twenty-six (26; 35.6%) events were adjudicated as cardiac, and five (5; 6.8%) events were adjudicated as vascular. Stent Fractures In total 13 stents were examined for Eluvia subjects and 7 stents were examined for control subjects. One (1) stent fracture was identified for Eluvia subjects and 2 stent fractures were identified for control subjects as assessed by the independent core laboratory.
Final Effect Findings	REGAL Study Primary Patency rate at 12 months and 24 months post index procedure was 79.2% (114/144) and 65.5% (72/110) respectively. Assisted Primary Patency rate at 12 months and 24 months post index procedure was 92.8% (116/125) and 88.2% (75/85) respectively. Primary Sustained Clinical Improvement rate at 12 months and 24 months post index procedure as assessed by changes in Rutherford Classification from baseline was 83.5% (187/224) and 81.7% (165/202) respectively Secondary Clinical Improvement rate at 12 months and 24 months post index procedure as assessed by changes in Rutherford Classification from baseline was 90.6% (203/224) and respectively 91.6% (185/202) respectively. At 12 months and 24 months post index procedure, 80.9% (182/225) and 83.3% (169/203) of patients were asymptomatic or had mild claudication, respectively. Hemodynamic Improvement at 12 months and 24 months post index procedure as assessed by changes in Ankle-Brachial Index (ABI) from baseline without the need for TLR was 80.1% (137/171) and 76.1% (102/134) respectively. Hemodynamic Improvement at 12 months and 24 months post index procedure as assessed by changes in Ankle-Brachial Index (ABI) from baseline including TLR was 85.4% (146/171) and 85.1% (114/134) respectively. Significantly positive results were observed at the time points 1 month through 24 months in each of the three components (p-value<0.0001) of the Walking Impairment Questionnaire (distance, speed and stair climbing). EMINENT Study Primary and Assisted Primary Patency Primary patency rate at 12 months post index procedure was 83.2% in the treatment group (Eluvia) and 74.3% in the control group (BMS), binary rate difference of 8.9%, superiority p-value = 0.0077. Primary patency rate at 24 months post index procedure was 73.4% in the treatment group (Eluvia) and 71.8% in the control group (BMS). Primary patency rate at 36 months post index procedure was 62.7.% in the treatment group (Eluvia) and 66.7% in the control group (BMS). Assisted primary patency at 36-months is 87.7% in the treatment group (Eluvia) and 89.8% in the control group (BMS). Quality of Life Questionnaire: Walking Impairment Questionnaire (WIQ) The WIQ was administered to enrolled subjects at baseline and at 1-month, 6-month, 12-month, 24-month, and 36-month follow-up visits post index procedure. Walking impairment improved significantly as assessed with WIQ through 36 months for both Eluvia and control subjects when compared to baseline measurements, p<0.0001 at each time point. Quality of Life Questionnaire: EQ-5D The EQ-5D Questionnaire was administered to enrolled subjects at baseline and at the 1-month, 6-month, 12-month, 24-month, and 36-month follow-up visits post index procedure. The EQ-5D Index Value increased from 0.7 at baseline to 0.8 at 36-months in the treatment group (Eluvia). The EQ VAS score changed from 64.5 at baseline to 71.5 at 36-months in Eluvia subjects. In the control subjects (BMS) the EQ-5D Index Value increased from 0.7 at baseline to 0.8 at 36-months. The EQ VAS score increased from 66.2 at baseline to 71.4 at 36-months in control subjects. Quality-of-Life improvement: there were no statistically significant differences between Eluvia and control subjects in quality-of-life improvement over 36 months.
Study Strengths & Weaknesses	REGAL Study This was an all-comer, multicenter study in which patients were followed according to standard of care practice. The sample size was not hypothesis driven and study endpoint results were not evaluated by formal hypothesis testing. The study faced enrollment challenges and patient enrollment had to be terminated earlier than planned while all enrolled patients continued through 2 years of follow-up. EMINENT Study This was a randomized, multicenter study that met the primary endpoint of primary patency a 12- months post index procedure.
Recommendations for Labeling Changes	REGAL Study Labeling change is recommended to reflect the long-term results of the post approval study. The labeling change should include a new section in the label showing a summary of the study objective, design, patient population, data source, sample size including number of sites, endpoints, length of follow-up and frequency of follow-up, final results (final endpoint results, follow-up rate etc.), strengths and limitations of the surveillance project. EMINENT Study Labeling updates is recommended with the final study results to include: Long-term patency including K-M curves; and MAEs and their components including K-M curves.
General
Study Status	Completed
Application Number / Requirement Number	P170018 / PAS001
Date Original Protocol Accepted	12/21/2018
Date Current Protocol Accepted
Study Name	OUS Post Market Evaluation Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objectives of the LIFEPAK CR2 defibrillator PAS are: 1. Characterize the performance of the cprINSIGHT algorithm 2. Identify any unanticipated use issues or performance concerns directly attributable to the cprINSIGHT algorithm 3. Evaluate general device usability data collected from LIFEPAK CR2 defibrillator users
Study Population	The study population is prehospital patients in Amsterdam, The Netherlands, who are presumed to be possible victims of cardiac arrest and who are connected to a LIFEPAK CR2 either at Schiphol International Airport, by Amsterdam Police, or by Amsterdam Fire.
Sample Size	The minimum sample size is based on collecting at least 100 cases with coarse VF. It is estimated that about 20% of the cases will have at least one analysis of coarse VF, so the minimum sample size will be 500 patients. It is estimated that in approximately half of the cases with coarse VF, Analysis 1 by the SAS algorithm will reach a Shock Advised decision and there will be no VF after Shock 1, meaning that the cprINSIGHT algorithm will not see VF during the case. In the other approximately half of the cases, cprINSIGHT will analyze VF unless the patient is disconnected from the LIFEPAK CR2 defibrillator before an analysis of VF is completed. Therefore, it is expected that a minimum of 50 cases will have at least one analysis of VF by the cprINSIGHT algorithm. The plan is to collect cases through the end of 2019 to comfortably exceed the above minimum sample sizes. The plan is to collect device use survey forms for cases through the end of 2018.
Key Study Endpoints	Study endpoints are accuracy of the LIFEPAK CR2 shock advisory decisions (made by the SAS algorithm or the cprINSIGHT algorithm), accuracy of just the SAS decisions, and accuracy of just the cprINSIGHT decisions, per the following table: Rhythm Accuracy 90% Lower Confidence Limit Shockable Coarse VF Sensitivity Rapid pulseless VT Sensitivity Nonshockable NSR Specificity Other QRS rhythm Specificity Asystole Specificity Intermediate Fine VF % shocked Other VT % shocked For the device use survey forms, the endpoint is a tabulation of survey answers.
Follow-up Visits and Length of Follow-up	no follow-up
Interim or Final Data Summary
Actual Number of Patients Enrolled	790 cases ((33 airport cases, 555 police cases, 201 fire cases, and 1 case using a privately owned device)
Actual Number of Sites Enrolled	3
Patient Follow-up Rate	no follow-up, as the device recording and device use survey forms contain the data needed for the study.
Final Safety Findings	Overall sensitivity for shockable rhythms was 315/324 = 97.2% [90% LCL 95.6%]. Overall specificity was 1833/1856 = 98.8% [LCL 98.4%]. • The overall proportion of cprINSIGHT analyses that reached a decision with no Pause for SAS was 960/1360 = 70.7%. When the rhythm was coarse VF, 93.1% of cprINSIGHT analyses reached a decision with no Pause for SAS. • No issues or performance concerns attributable to the cprINSIGHT algorithm were reported.
Final Effect Findings	Overall, the usuability gathered through LIFEPAK CR2 Use survey rate was 74%. • In cases for which the voice prompts were reported to be annoying, distracting, or too verbose, there was no substantial adverse effect on the rescuers’ performance of the clinically important resuscitation tasks. • The reported difficulty hearing the voice prompts or the metronome did not appear to adversely affect the rescuers’ performance of the clinically important resuscitation tasks, which are delivering CPR and delivering defibrillation shocks when needed.
Study Strengths & Weaknesses	Study Strength include large sample size. There are no weaknesses.
Recommendations for Labeling Changes	none
General
Study Status	Completed
Application Number / Requirement Number	P160013 S002/ PAS001
Date Original Protocol Accepted	05/31/2019
Date Current Protocol Accepted
Study Name	EXPAND Continuation PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm, prospective, observational post-approval data collection for subjects enrolled and transplanted in the Lung EXPAND clinical trial. 5- Year follow-up data will be collected from UNOS for US transplanted patients and directly from the clinical sites in OUS patients
Sample Size	All 79 subjects in the Lung EXPAND trial will be re-consented for permission to access to their follow-up data. Only patients who provide informed consent are enrolled in the Continuation PAS.
Key Study Endpoints	The primary effectiveness endpoint is Bronchiolitis Obliterans Syndrome (BOS)-free survival (freedom from BOS and mortality) through 5 years after transplantation. Other study endpoints include: Survival (freedom from mortality) through 5 years after transplantation Freedom from BOS through 5 years after transplantation
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	79 patients from the EXPAND pivotal trial
Actual Number of Sites Enrolled	8 sites
Patient Follow-up Rate	5-year follow-up rate: 98% (53/54)
Final Safety Findings	There were 26 deaths and 1 retransplantation over 5 years post initial lung transplant.
Final Effect Findings	5-year rate of BOS-free survival is 55% (BOS defined as grade 1, 2, or 3) 5-year rate of patient survival is 68% 5-year rate of freedom from BOS is 76% (BOS defined as grade 1, 2, or 3)
Study Strengths & Weaknesses	Despite the small sample size in this study, the long-term follow-up was high, with 5-year data collected in 53 of the 54 patients (98%) who were eligible for follow-up. These results need to be replicated in larger studies.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P180013 / PAS001
Date Original Protocol Accepted	05/02/2019
Date Current Protocol Accepted	05/29/2020
Study Name	VIRTUS Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to evaluate the long-term safety and effectiveness of the VICI VENOUS STENT System.
Study Population	Subjects considered for enrollment were 18 years of age or older and had the presence of unilateral, clinically significant, chronic non-malignant obstruction of the common femoral vein, external iliac vein, common iliac vein, or any combination thereof, where obstruction is defined as a greater than or equal to50% reduction in the target vessel lumen diameter as measured by venography during the index procedure. A total of 127 subjects had prior venous obstruction associated with thromboembolic disease and were referred to as post-thrombotic (PT) subjects. A total of 43 subjects had iliofemoral venous segment obstruction without previous thromboembolic or intraluminal disease and were referred to as non-thrombotic (NT) subjects.
Sample Size	The continued follow-up study will evaluate all 163 remaining subjects who were active at the end of the 12-month evaluation.
Key Study Endpoints	Primary endpoint: primary patency by duplex ultrasound (DUS) at 3 years. Secondary endpoints: Overall rate and incidence of major adverse events through 3 years Overall rate and incidence of serious adverse events through 3 years Freedom from target vessel revascularization (TVR) at 2 years and 3 years, defined as freedom from any re-intervention in the target vessel segment and freedom from thrombosis/stenosis > 50% as measured by DUS Primary assisted stent patency rate at 2 years and 3 years, defined as patency regardless of whether an intervention (subsequent to the index procedure) was performed to maintain patency Secondary stent patency rate at 2 years and 3 years, defined as freedom from permanent loss of patency determined through last follow-up (regardless of the number of interventions)
Follow-up Visits and Length of Follow-up	The follow-up period is 36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 200 subjects were enrolled in the VIRTUS Trial, including 30 subjects in the feasibility cohort and 170 subjects in the pivotal cohort.
Actual Number of Sites Enrolled	Total of 31 sites: 9 sites in the U.S. and Europe enrolled subjects for the feasibility study, and 22 sites in the U.S. and Europe enrolled subjects for the pivotal study.
Patient Follow-up Rate	79.0% (158/200) and 72.5% (145/200) at 24 and 36 months, respectively for the total cohort.
Final Safety Findings	Overall rate of major adverse events at 24 and 36 months was 3.2% (6/187) and 5.2% (9/172) respectively Death rate at 24 and 36 months was 0.5% (1/187) and 2.3% (4/172) respectively. Device or procedure related death through 36 months was 0% (0/200). Deep venous thrombosis rate at 24 and 36 months was 0.5% (1/187) and 1.7% (3/172) respectively. Suspected or confirmed pulmonary embolism rate at 24 and 36 months was 0.5% (1/187) and 1.7% (3/172) respectively. Stent movement (dislodgement and migration) as adjudicated by the Clinical Event Committee through 36 months was 0% (0/200). A total of 344 serious adverse events were reported. The reported of rate of subjects with a serious adverse event was 50% (100/200). Overall stent fracture rate was 3.3% (11/332) for the total implanted stents. Ten (10) of the 11 fractures occurred in the common femoral vein and one fracture occurred in the common iliac vein. One subjects with stent fracture underwent a target vessel revascularization. There were no clinical complications associated with any of the fractures.
Final Effect Findings	Primary patency assessed by duplex ultrasound (DUS) at 24 and 36 months was 79.7% (110/138) and 71.7% (86/120) respectively. Freedom from target vessel revascularization rate at 24 and 36 months was 89.2% (166/186) and 87.0% (147/169) respectively. Primary assisted patency rate by DUS at 24 and 36 months was 94.8% (128/135) and 93.8% (105/112) respectively. Secondary patency rate by DUS at 24 and 36 months was 97.0% (130/134) and 96.4% (106/110) respectively.
Study Strengths & Weaknesses	Study Strength: This study is a multicenter study that enrolled 31 investigational sites (22 pivotal and 9 feasibility sites) in the US and Europe. The study met the primary effectiveness endpoint (primary patency rate of 84% at 12 months compared to the performance goal (PG) of 72.1%, p<0.0001). Similarly, the primary safety endpoint of freedom from major adverse event rate within 30 days was met (98.8% freedom from MAE with lower 95% confidence limit of 95% compared to PG of 94%). Clinical Follow-up was completed for nearly 80% of overall subjects at 24 months and over 70% at 36 months. Weakness: This is a non-randomized study with inherent biases.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study (pivotal and feasibility cohorts). The labeling change should include a new section on the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Ongoing
Application Number / Requirement Number	P180014 / PAS002
Date Original Protocol Accepted	10/29/2019
Date Current Protocol Accepted	08/09/2023
Study Name	Long Term Eval PAS of XPS System
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The XVIVO Registry will collect standard-of-care outcome data and device-related safety data from transplant to one-year post-transplant, followed by standard of care and OPTN data collection at years 2, 3, 4, and 5. In addition, 4 and 5-year UNOS registry data of the 126 subjects who received an EVLP transplant under the NOVEL and NOVEL Extension studies are provided as part of the long-term safety and quality of life data. Registry Objectives The purpose of the Registry is to monitor the real-world performance and safety of the XPS™ with STEEN Solution™ procedure for ex vivo lung perfusion (EVLP) of donor lungs for transplant.
Study Population	All comers (all patients receiving donor lungs treated with the XPS System)
Sample Size	An EVLP lung could be transplanted at any of the centers in the United States and will be identified through the OPTN perfusion and solution data fields. In addition, 4 and 5-year UNOS registry data of the 126 subjects who received an EVLP transplant under the NOVEL and NOVEL Extension studies are provided as part of the long-term safety and quality of life data.
Key Study Endpoints	Primary Endpoints The co-primary endpoints are to be compared to control data: Survival at 1 year post-transplant. Rate of Grade 3 primary graft dysfunction (PGD) at 72 hours post-transplant Secondary Endpoints via UNOS The secondary endpoints are: Survival at 2, 3, 4 and 5 years post-transplant for registry and control patients Remaining endpoints to be summarized for registry patients only FEV1 from at 1, 2, 3, 4, and 5 years per UNOS data collection, (obtained from routine PFT closest to anniversary date). Incidence of Bronchiolitis Obliterans Syndrome (BOS) or CLAD at 1, 2, 3, 4 and 5 years post- transplant. If subject was hospitalized from transplant to 1, 2, 3, 4 and 5 years post-transplant. If subject had rejection from transplant to 1, 2, 3, 4 and 5 years post-transplant. Quality of Life based on OPTN data at 1, 2, 3, 4 and 5 years post-transplant. Safety Endpoints The Registry will collect all device-related serious adverse events from transplant to through 30 days post-transplant or initial hospital stay, whichever is longer. All data collected for the registry is to be obtained from normal standard-of-care clinical practices and documentation. Registry and Control data will be provided to the sponsor from UNOS through a data use agreement. This data does not capture BOS, therefore XVIVO will request BOS evaluations and FEV1 (L) for CLAD evaluation and any other data clarifications with the transplant center or hospitals
Follow-up Visits and Length of Follow-up	Functional status and survival at 1,2,3,4 and 5 years will be obtained for all patients transplanted during the same time frame and from the same sites as the EVLP registry patients.
General
Study Status	Ongoing
Application Number / Requirement Number	P180014 / PAS001
Date Original Protocol Accepted	10/29/2019
Date Current Protocol Accepted	11/03/2021
Study Name	NOVEL/NOVEL Ext Cont Long Term PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent & Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the XVIVO Registry is to collect standard of care clinical data from all comers who are transplanted with an EVLP lung treated with the XVIVO Perfusion System™ in order to assess the long-term performance of the device and monitor device-related serious adverse events. At the same time, a continuation study for the study subjects previously enrolled in the NOVEL and NOVEL Extension studies will be conducted to continue to capture long-term data on patients transplanted with donor lungs treated with the XPS System. These are single arm studies and the collected data will be compared to UNOS data on survival and primary graft dysfunction (PGD) at 72 hours post-transplantation, Bronchiolitis Obliterans Syndrome (BOS), FEV1, functional status and survival at 1, 2, 3, 4, and 5 years. The comparator data will be collected for all patients transplanted during the same time frame and from the same sites as the XVIVO Registry patients.
Study Population	All comers (all patients receiving donor lungs treated with the XPS System)
Sample Size	All comers Primary Effectiveness Endpoint: Co-primary endpoints to be compared to control data: Survival at 1 year post-transplantation; Rate of Grade 3 PGD at 72 hours post-transplantation. Secondary Effectiveness Endpoints: Survival at 2, 3, 4, and 5 years post-transplantation for registry and control patients; FEV1 at 1, 2, 3, 4, and 5 years post-transplantation per UNOS data collection (obtained from routine pulmonary function test performed closest to their anniversary); Incidence of Bronchiolitis Obliterans Syndrome (BOS) at 1, 2, 3, 4, and 5 years post-transplantation; Hospitalizations from transplant to 1, 2, 3, 4, and 5 years post-transplantation; Rejection episodes from transplant to 1, 2, 3, 4, and 5 years post-transplantation; Quality of life at 1, 2, 3, 4, and 5 years post-transplantation: Karnovsky Score; Employment for income
Key Study Endpoints	Device-related serious adverse events from transplantation through 30 days post-transplantation, or initial hospital stay, whichever is longer. Co-primary endpoints to be compared to control data: Survival at 1 year post-transplantation; Rate of Grade 3 PGD at 72 hours post-transplantation. Secondary Effectiveness Endpoints Survival at 2, 3, 4, and 5 years post-transplantation for registry and control patients; FEV1 at 1, 2, 3, 4, and 5 years post-transplantation per UNOS data collection (obtained from routine pulmonary function test performed closest to their anniversary); Incidence of Bronchiolitis Obliterans Syndrome (BOS) at 1, 2, 3, 4, and 5 years post-transplantation; Number of hospitalizations from transplant to 1, 2, 3, 4, and 5 years post-transplantation; Number of rejection episodes from transplant to 1, 2, 3, 4, and 5 years post-transplantation; Quality of life at 1, 2, 3, 4, and 5 years post-transplantation: Functional status; Physical capacity.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S112/ PAS001
Date Original Protocol Accepted	09/09/2020
Date Current Protocol Accepted	09/09/2020
Study Name	SAPIEN 3 and SAPIEN 3 Ultra Aortic THV-in-THV Surv
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Characterize long-term clinical outcomes for the SAPIEN 3 and SAPIEN 3 Ultra THV Systems in patients with a failing aortic transcatheter bioprosthetic valve after PMA approval through the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) registry-based surveillance.
Study Population	All patients entered into the TVT Registry database and treated with the SAPIEN 3 or SAPIEN 3 Ultra System for the first 3 years after PMA approval will be included as part of this registry-based post-approval surveillance.
Sample Size	All consecutive patients treated within the first 3 years after the PMA approval that are entered into the TVT Registry (enrollment period).
Key Study Endpoints	For aortic THV-in-THV patients, the surveillance is monitoring the following outcomes: Procedural: Device implanted successfully 30 Days: Myocardial infarction 30 Days, 12 months, and annually for 10 years: all-cause mortality, all stroke, and valve reintervention 30 Days & 1 year: TIA, life-threatening/major bleeding, vascular complications, new requirement for dialysis, KCCQ, mean gradient, and paravalvular leak
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Endpoints: All-cause death: 4.5% (30 Days); 18.9% (1Y) Cardiac death: 2.6% (30 Days); 7.6% (1Y) All strokes: 1.7% (30 Days); 2.5% (1Y) Aortic Valve reintervention: 0.2% (30 Days); 0.2% (1Y) Life threatening/major bleeding: 1.5% (30 Days); 4.2% (1Y) Myocardial infarction: 0.5% (30 Days); N/A (1Y) New requirement for dialysis: 0.5% (30 Days); 0.5% (1Y) TIA: 0.2% (30 Days); 0.2% (1Y) Vascular Complications: 4.0% (30 Days); 4.0% (1Y) Major vascular complications: 0.7% (30 Days); 0.7% (1Y) Minor vascular complication: 3.3% (30 Days); 3.3% (1Y) Paravalvular Leak: 30-days: >= Moderate – 1.4% (4/283) 1-year: >= Moderate – 0.8% (1/125) KCCQ: Baseline: 37.1; 30-day: 73.9; 1-year: 78.6; Mean Gradient: Baseline: 39.8mmHg; 30-day: 16.4mmHg; 1-year: 15.5mmHg Effectiveness Endpoints: Paravalvular Leak: 30-days: > Moderate – 1.4% (4/283) 1-year: > Moderate – 0.6% (1/168) KCCQ: Baseline: 37.0; 30-day: 73.7; 1-year: 79.4; Mean Gradient: Baseline: 39.7mmHg; 30-day: 16.4mmHg; 1-year: 15.5mmHg
Actual Number of Patients Enrolled	434 attempted; 432 implanted with the valve
Actual Number of Sites Enrolled	216
Patient Follow-up Rate	30 Days: 96.1% (417/434); 1 year: 81.1% (352/434) 30 Days: 5 lost to follow-up; 12 missed visits 1 year: 17 lost to follow-up; 65 missed visits
General
Study Status	Ongoing
Application Number / Requirement Number	P180051 / PAS001
Date Original Protocol Accepted	09/03/2021
Date Current Protocol Accepted
Study Name	OCS Heart EXPAND+CAP Continued f/u PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects enrolled under IDE G140111, including the Continued Access Protocol subjects. The objective of this study is to characterize the clinical outcomes of these subjects annually through 5 years post-transplant.
Study Population	All living subjects enrolled under IDE G140111, including the Continued Access Protocol subjects.
Sample Size	All living subjects.
Key Study Endpoints	patient survival, cardiac-related patient survival, and heart graft survival through 5 years post-transplan.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	75 in the pivotal cohort and 75 in the CAP cohort
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	Pivotal: 93.3% at 5 years (all patients have reached 5 years) CAP: 98.7% at 2 years (all patients have reached 2 years)
Final Safety Findings	See effectiveness results.
Final Effect Findings	Patient survival: 76.7% at 5 years (pivotal); 89.2% at 2 years (CAP) Cardiac-related patient survival: 94.6% at 5 years (pivotal); 98.5% at 2 years (CAP) Graft survival: 93.1% at 5 years (pivotal); 95.6% at 2 years (CAP)
General
Study Status	Ongoing
Application Number / Requirement Number	P180051 / PAS002
Date Original Protocol Accepted	09/03/2021
Date Current Protocol Accepted
Study Name	Post-commercialization DBD New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm new enrollment study. The objective of the study is to characterize the performance of the OCS Heart System in the real-world setting, as compared to concurrent control data obtained from the United Network for Organ Sharing (UNOS) database for recipients of standard criteria donor hearts preserved using cold static cardioplegic storage.
Study Population	Patients needing heart transplant
Sample Size	150 patients that constitute the Primary Analysis Population
Key Study Endpoints	The primary endpoint is patient survival at 1 year post-transplant. Other endpoints include patient/graft survival through 5 years posttransplant, incidence of moderate or severe primary graft dysfunction (PGD; left or right ventricle), and incidence of donor heart turndowns following OCS Heart System perfusion.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Graft survival @ 6 months: 97.6% (OCS DCD cohort) vs. 98.8% (SOC cohort) – Non-inferiority met. Effectiveness Results Patient survival @ 1 year: 91.6% (OCS DCD cohort) vs. 93.9% (SOC cohort) – Non-inferiority met.
Actual Number of Patients Enrolled	Primary Analysis Population: 167 (OCS DCD cohort) and 607 (Standard of Care [SOC] cohort: standard criteria donor hearts preserved using cold static cardioplegic storage)
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	100%; no patients have been lost to follow-up in the OCS DCD cohort.
General
Study Status	Completed
Application Number / Requirement Number	P180029 / PAS001
Date Original Protocol Accepted	07/22/2019
Date Current Protocol Accepted
Study Name	Cont F/u of REPRISE III Trial Premarket Cohorts
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled under the REPRISE III study protocol under IDE G140090. The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects enrolled under the IDE (G140090) as part of the REPRISE III study
Sample Size	All living subjects enrolled under the IDE (G140090) as part of the REPRISE III study
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all-cause and disabling stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, major vascular complications, paravalvular aortic regurgitation, valve performance and durability, myocardial infarction, re-operation for valve-related dysfunction, rehospitalization for valve-related symptoms or worsening congestive heart failure, new permanent pacemaker implantation, new-onset atrial fibrillation, functional status as evaluated by New York Heart Association (NYHA) Class 5-meter gait speed test at 1 year, and health status as evaluated by Kansas City Cardiomyopathy Questionnaire (KCCQ) and SF-12 Quality of Life questionnaire at 1, 3, and 5 years.
Follow-up Visits and Length of Follow-up	Visits will be conducted annually through 5 years post-procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	RCT 912 total; 607 in the Lotus ITT cohort and 305 in the CoreValve ITT cohort Roll-in 102 CAS 295
Actual Number of Sites Enrolled	Randomized controlled trial (RCT) 55 centers Lotus only Roll-In 50 centers Lotus US Continued Access Study (CAS) 34 centers
Patient Follow-up Rate	RCT The overall follow-up rate through 5 years was 84% for Lotus and 80.7% for CoreValve Roll-in The overall follow-up rate through 5 years was 87.3% CAS The overall follow-up rate through 4 years was 80.7%
Final Safety Findings	RCT The CEC-adjudicated safety outcomes at 5 years are summarized as follows: All-cause mortality: 50.9% (Lotus); 52.8% (CoreValve) Cardiovascular mortality: 35.7% (Lotus); 40.7% (CoreValve) All-cause stroke: 14.1% (Lotus); 15.3% (CoreValve) Disabling stroke: 8.3% (Lotus); 12.2% (CoreValve) Major vascular complications: 7.5% (Lotus); 6.4% (CoreValve) Life-threatening/disabling bleeding: 21.2% (Lotus); 21% (CoreValve) Hospitalization for valve-related symptoms or worsening congestive heart failure: 34.7% (Lotus); 31.6% (CoreValve) New permanent pacemaker: 38.9% (Lotus); 27.3% (CoreValve) Valve thrombosis: 5.8% (Lotus); 1.8% (CoreValve) Endocarditis: 1.7% (Lotus); 0.5% (CoreValve) Roll-in The CEC-adjudicated safety outcomes at 5 years are summarized as follows: All-cause mortality: 52.3% Cardiovascular mortality: 37.2% All-cause stroke: 19.8% Disabling stroke: 15.9% Major vascular complications: 8.8% Life-threatening/disabling bleeding: 34.9% Hospitalization for valve-related symptoms or worsened CHF: 41.9% New permanent pacemaker: 42.9% Valve thrombosis: 9.5% Endocarditis: 4.0% CAS The CEC-adjudicated safety outcomes at 4 years are summarized as follows: All-cause mortality: 36.6% Cardiovascular mortality: 18.5% All-cause stroke: 14.4% Disabling stroke rate: 8.7% Major vascular complications: 8.6% Life-threatening/disabling bleeding: 18.5% Hospitalization for valve-related symptoms or worsened CHF: 24.7% New permanent pacemaker: 35.7% Valve thrombosis: 6.6% Endocarditis: 4.0%
Final Effect Findings	RCT Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit: NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 80% of assessed Lotus subjects and 78% of assessed CoreValve subjects; this improvement was sustained for both groups at 5 years (82% for Lotus and 74% for CoreValve) for evaluable subjects. KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects in the Lotus cohort, the overall summary score improved from 51.9 +/-5 at baseline to 73.0+/-3 at 30 days and remained high at 5 years (73.5+/-6). Similar results were seen in the CoreValve cohort. Valve Performance Outcomes: Mean aortic gradient improved in both cohorts from baseline values of 43.85+/-31 mmHg (CoreValve) and 44.64+/-35 mmHg (Lotus) to discharge values of 8.19+/-9 mmHg (CoreValve) and 12.20+/-1 mmHg (Lotus). Values remained low out to 5 years at 7.79+/-0 mmHg (CoreValve) and 12.64+/-8 mmHg (Lotus). Mean EOA improved from 0.70+/-9 cm2 (CoreValve) and 0.69+/-9 cm2 (Lotus) at baseline to 1.96+/-2 cm2 (CoreValve) and 1.65+/-7 cm2 (Lotus) at discharge and remained high out to 5 years at 1.57+/-6 cm2 (CoreValve) and 1.42+/-2 cm2 (Lotus). At 30 days, fewer subjects in the Lotus group compared to the CoreValve group had moderate or greater Paravalvular Regurgitation (0.6% vs. 7.2%). This result was maintained at 1 year (0.9% vs. 6.8%) through 5 years (0% vs. 1.9%). Roll-in NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 82.4% of assessed subjects; this improvement was sustained at 1 year (87.2%) and to 5 years for 73.3% of subjects. KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects, the KCCQ overall summary score improved from 52.7+/-6 at baseline to 69.9+/-0 at 30 days and remained high at 1 year (75.6+/-3), 3 years (71.5+/-5), and 5 years (68.6+/-1). Valve Performance Outcomes: Mean aortic gradient improved from 47.9+/-3 mmHg at baseline to 12.1+/- mmHg at discharge and remained low out to 1 year (12.3+/- mmHg) and 5 years (11.8+/- mmHg). Mean effective orifice area improved from 0.67+/-0 cm2 at baseline to 1.70+/-9 cm2 at discharge and was 1.53+/-9 cm2 at 1 year and 1.830+/-562 at 5 years. At 30 days, 1% had moderate or greater Paravalvular Regurgitation, 0% at 1 year and 5.9% at 5 years. CAS NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 79% of assessed subjects; this improvement was sustained at 1 year (86%), 2 years (82%), 3 years (75%), and 4 years (77.3%). KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects, the KCCQ overall summary score improved from 53.5+/-8 at baseline to 71.8+/-6 at 30 days and remained high at 1 year (74.7+/-6) and 3 years (74.4+/-5). Valve Performance Outcomes: Mean aortic gradient improved from 44.3+/-8 mmHg at baseline to 12.5+/- mmHg at discharge and remained low out to 30 days (12.2+/- mmHg), 1 year (12.7+/- mmHg) and beyond. Mean effective orifice area improved from 0.68+/-9 cm2 at baseline to 1.61+/-2 cm2 at discharge and was sustained at 30 days (1.55+/-1 cm2), 1 year (1.51+/-6 cm2), and beyond. At 30 days, 1.5% had moderate or greater Paravalvular Regurgitation. This result was maintained at 1 year (1.2%) through 4 years (1.1%).
Study Strengths & Weaknesses	These continued follow-up studies provide longer-term data on the safety and effectiveness of the Boston Scientific Corporation Lotus Valve System in patients with symptomatic severe aortic stenosis who are at extreme or high risk for standard surgical valve replacement. These studies were intended to evaluate the longer-term safety and effectiveness of the Lotus and LOTUS Edge Valve Systems (through 5 years). Due to voluntary recall and discontinuation of the LOTUS Edge system, the study timeline was truncated for the CAS and LOTUS Edge Nested Registry studies and safety and effectiveness data is collected through 4-year and 30-day follow-up, respectively. For the Randomized controlled trial, generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvements shown for key effectiveness endpoints from baseline to 5 years. Across all studies, it should be noted that some subjects did not complete all visit assessments (e.g., echocardiographic imaging, NYHA, KCCQ). Incomplete data may introduce bias to study outcomes.
Recommendations for Labeling Changes	No labeling changes recommended. The device has been recalled and discontinued, and is no longer commercially available.
General
Study Status	Completed
Application Number / Requirement Number	P180029 / PAS002
Date Original Protocol Accepted	12/06/2019
Date Current Protocol Accepted	03/30/2021
Study Name	RWU of LOTUS Edge Valve System
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To monitor device performance and assess safety and effectiveness outcomes associated with use of the LOTUS Edge™ Valve System (LOTUS Edge) for transcatheter aortic valve replacement (TAVR) in routine clinical practice using data collected in the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapy Registry (TVT Registry™). Additionally, longer-term safety and effectiveness will be monitored using linkage to CMS claims data for outcomes and adverse events starting with the end of one-year post-implant through five years post-implant.
Study Population	All patients with an attempted LOTUS Edge valve implant in the aortic position, and entered into the TVT Registry, from the date of PMA approval (April 23, 2019) through June 30, 2021.
Sample Size	There is no minimum sample size. It is anticipated that approximately 2000 patients will receive an attempted LOTUS Edge implant during this time period and will be entered into the TVT Registry.
Key Study Endpoints	This surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-5 year post implantation.
Follow-up Visits and Length of Follow-up	Successfully implanted patients will be followed through the registry for one year, and patients who can be linked to CMS claims data will be followed through five years. Patients with attempted but unsuccessful implants will be followed through discharge.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1685 (Attempted implant - ITT) 1661 (Implanted)
Actual Number of Sites Enrolled	161 participating centers
Patient Follow-up Rate	97.5% overall follow-up rate for both ITT & Implanted at 30 days
Final Safety Findings	Site-reported Safety Outcomes at 30 Days – Implanted Patients: All-cause mortality: 3.8% (61/1592) Stroke: 4.1% (66/1592) Aortic valve reintervention: 0.1% (1/1592) Major bleeding event: 1.2% (19/1592) Myocardial infarction: 0.4% (6/1592) New permanent pacemaker: 28.5% (453/1592) Atrial fibrillation: 1.6% (25/1592) The average morbidity and mortality (STS) risk score in this population at baseline was 4.8%+/-3.8 compared to 6.7%+/-4.0 in the RCT. This may indicate that the average operative risk in the TVT population was lower than the average operative risk for patients in the RCT.
Final Effect Findings	Implanted Patients: From baseline to 30 days, 79% of patients improved by at least one NYHA functional class and 36.3% improved by at least 2 NYHA functional classes. KCCQ overall summary score change from baseline at 30 days: 22.6 +/- 27.12 Mean Gradient at 30 days: 12.88 /-+ 6.56 mmHg Aortic valve area post procedure: 1.85 +/- 0.58 cm2 At 30 days, paravalvular aortic regurgitation was graded: 80.3% none, 11.8% mild, 1% moderate, 0.1% severe, and 6.8% not documented.
Study Strengths & Weaknesses	This study was intended to evaluate the longer-term safety and effectiveness of the LOTUS Edge Valve System (through 5 years). Due to voluntary recall and discontinuation of the LOTUS Edge system, the study timeline was truncated and safety and effectiveness data is presented through 30 day follow-up only; thus, long-term outcomes are not available from this study. The overall follow-up rate at 30 days was 97.5% for both ITT & implanted populations, and acute outcomes continue to support early safety and performance of the device. It should be noted that some subjects did not complete all visit assessments (e.g., echocardiographic imaging) and/or withdrew or were lost to follow-up. Incomplete data may introduce bias to study outcomes.
Recommendations for Labeling Changes	No labeling changes recommended. The device has been recalled and discontinued, and is no longer commercially available.
General
Study Status	Completed
Application Number / Requirement Number	P180031 / PAS001
Date Original Protocol Accepted	05/16/2019
Date Current Protocol Accepted	01/18/2020
Study Name	ATLAS Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Objective: Data collected through the 12-month follow-up visit are intended to support Premarket Approval (PMA) application to the Food and Drug Administration (FDA). Long-term follow-up data collected through 3 years postoperative are intended to support postapproval study (PAS) requirements. Study Design: This study is designed as a prospective, multicenter, open-label, single-arm 2-cohort (anterior and posterior circulation) study. Eligible subjects presenting with a wide neck (neck greater than or equal to 4mm or a dome-to-neck ratio <2), intracranial, saccular aneurysm arising from a parent vessel with a diameter of greater than or equal to 2mm and less than or equal to 4.5 mm will receive stent-assisted coiling with the Neuroform Atlas™ Stent System and any approved bare metal embolic coils currently on the market.
Study Population	Subjects invited to participate in this study will be those who have an aneurysm arising from a parent vessel with a diameter of 2.0 - 4.5 mm in either the distal anterior or posterior intracranial circulation that is accessible for endovascular treatment. Anterior Circulation (AC) Cohort: Up to 180 subjects with intracranial aneurysms in the anterior circulation (excluding the petrous ICA to superior hypophyseal ICA region) may be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. These data will be used to support a safety and effectiveness analysis for an indication for use of the Neuroform Atlas™ Stent System in the anterior circulation. Posterior Circulation (PC) Cohort: Up to 180 subjects with intracranial aneurysms in the posterior circulation (including vertebral, basilar and posterior cerebral arteries) may be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. These data will be analyzed separately from the AC Cohort data and will be used to support an indication for use of the Neuroform Atlas™ Stent System in the posterior circulation.
Sample Size	Anterior Circulation Cohort: A sample size of up to 180 subjects with intracranial aneurysms in the distal anterior circulation has been selected for this study in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. Assuming an effectiveness primary endpoint response rate of 62% (per the findings of a meta-analysis of Neuroform stent literature as performed by King et al[59]), the expected lower bound of the exact binomial two-sided 95% confidence interval around the success rate is greater than 50%. Assuming a safety primary endpoint rate of 8%, the expected upper bound of the exact binomial two sided 95% confidence interval around the success rate is less than 20%. A sample size of 153 evaluable subjects provides 85% power to demonstrate the effectiveness endpoint, and a power of approximately 99% to successfully demonstrate the safety endpoint given the observed rates stated above. The combined probability of the two endpoints is (.85) x (.99) = .842. Posterior Circulation Cohort: Separate analyses of these cohort data will be performed to support an indication for use in the posterior circulation. A sample size of up to 180 subjects with intracranial aneurysms in the posterior circulation (including vertebral, basilar and posterior cerebral arteries) will also be enrolled in order to provide 153 evaluable subjects at 12 months, with an estimated 15% attrition rate. While the safety endpoint rate for posterior circulation subjects may be higher than that for the anterior circulation subjects, that rate is not expected to exceed 12%. Assuming a safety primary endpoint rate of 12%, the expected upper bound of the exact binomial two-sided 95% confidence interval around the success rate is less than 25%. A sample size of 153 evaluable subjects provides a power of approximately 99% to successfully demonstrate the safety endpoint given the observed rates stated above. Based on outcomes in the MAPS study, the effectiveness rate for posterior circulation subjects is expected to be very close to that of anterior circulation subjects. Therefore, the statement of power to demonstrate effectiveness for a sample size of 153 evaluable anterior circulation subjects also holds for a sample size of 153 evaluable posterior circulation subjects. For the posterior circulation cohort, a Bayesian adaptive study design (“Goldilocks” approach) providing for interim analyses of accumulated data will be used to select the final sample-size. The first interim data analysis will occur once 100 posterior circulation subjects have been enrolled. Based on enrollment rates and the frequency of disease in the posterior circulation, at the time this interim analysis is performed it is estimated that primary endpoint data will be available for approximately 39 – 63 posterior circulation subjects. If, at an interim analysis, there is at least a 95% predictive probability of observing a true rate of complete occlusion that is higher than 50%, enrollment in the posterior circulation cohort will be stopped early for success. The maximum sample-size for the posterior circulation cohort will be no more than 180 subjects.
Key Study Endpoints	The primary effectiveness endpoint of the study is: Complete aneurysm occlusion (100% occlusion – Raymond Class 1) of the treated target lesion on 12 month angiography, in the absence of retreatment, or parent artery stenosis (> 50%) at the target location. The primary safety endpoint of the study is: Any major ipsilateral stroke or neurological death within 12 months. The secondary safety endpoint is: the percent of subjects experiencing one or more serious adverse events (SAEs) through 12 months post-index procedure within the following categories: New or worsening major ipsilateral stroke as measured by the National Institute of Health Stroke Scale (NIHSS) Device-related SAEs Subarachnoid hemorrhage (SAH) Aneurysm rupture The secondary effectiveness endpoints are: identified below will be assessed post-index procedure through 12 months per the schedule requirements: Procedural technical success Incidence of retreatment Incidence of recanalization Incidence of parent artery stenosis at the target aneurysm location (>50% stenosis) Incidence of stent migration based on follow-up angiogram Proportion of aneurysms with occlusion of Raymond Class 1, 2, or 3 Proportion of aneurysms with occlusion of Raymond Class 1 and 2 combined Incidence of progressive occlusion at the target aneurysm location The long-term follow-up endpoints: The pre-specified safety endpoint is neurological death or major ipsilateral stroke at 12 months as adjudicated by the Clinical Events Committee (CEC). Long-term data on this pre-specified safety endpoint will continue to be collected. For the duration of the PAS study, all new or ongoing adverse events will be collected, reported, reviewed, and adjudicated per the CEC charter. Long-term safety events of interest will be grouped into the following combined categories for FDA reporting purposes: Any ischemic or hemorrhagic adverse event of any severity or duration (including transient ischemic attacks [TIAs], subarachnoid hemorrhage [SAH], and aneurysm rupture) Device-related SAEs For imaging performed per standard of care, the long-term effectiveness outcomes identified below will be assessed from 12 months through 3 years (+/- 6 months) postindex procedure per the long-term follow-up schedule requirements: Retreatment Parent artery stenosis at the target aneurysm location (>50% stenosis) Composite effectiveness measure (complete aneurysm occlusion [Raymond Class 1] without significant parent artery stenosis at the target aneurysm location (>50% stenosis) or retreatment) Recanalization Stent migration based on follow-up angiogram Aneurysm occlusion of Raymond Class 1, 2, or 3 Aneurysm occlusion of Raymond Class 1 and 2 combined Progressive occlusion of the target aneurysm
Follow-up Visits and Length of Follow-up	3-year (+/- 6 months) follow-up.
Interim or Final Data Summary
Actual Number of Patients Enrolled	PAS mITT anterior cohort: 146 PAS mITT posterior cohort: 101
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	PAS mITT anterior cohort: 24-months: clinical follow-up rate: 61.6%, imaging follow-up rate: 32.9% 36-months: clinical follow-up rate: 52.7%, imaging follow-up rate: 21.9% PAS mITT posterior cohort: 24-months: clinical follow-up rate: 61.4%, imaging follow-up rate: 36.6% 36-months: clinical follow-up rate: 43.4%, imaging follow-up rate: 18.2%
Final Safety Findings	In the PAS mITT anterior cohort at 24-month follow-up, the at-visit and cumulative rates of primary safety outcome incidence were 1.1% (1/90) and 0.7% (1/146) including 1 new or worsening major ipsilateral stroke, respectively. The at-visit and cumulative primary safety event rates at 36-month follow-up were 0.0% (0/77) and 0.7% (1/146), respectively. One additional new or worsening major ipsilateral stroke was reported in the post-36-month follow-up period bringing the at-visit and cumulative rates to 1.3% (1/80) and 1.4% (2/146), respectively. There were no reported neurological deaths occurring during the PAS period and two subjects were retreated (1.4%; 2/146). In the PAS mITT posterior cohort at 24-month follow-up, the at-visit and cumulative rates of primary safety outcome incidence were 1.6% (1/64) and 1.0% (1/101) including 1 new or worsening major ipsilateral stroke, respectively. The at-visit and cumulative primary safety event rate at 36-month follow-up were 0.0% (0/55) and 1.0% (1/101), respectively. At the post-36-month follow-up, the at-visit and cumulative rates were 0.0% (0/43) and 1.0% (1/101), respectively. There were no reported neurological deaths occurring during the PAS period and two subjects were retreated (2.0%; 2/101).
Final Effect Findings	Anterior cohort: The primary effectiveness outcome rate of Grade 1 Raymond class in the absence of retreatment, or parent artery stenosis (>50%) at the target aneurysm was 77.3% (34/44) at 24 months, 92.3% (24/26) at 36 months, and 80.8% (21/26) at post-36 months. The overall incidence rate of stent migration per subject person years was 0.000 (0/207.6). Posterior cohort: The primary effectiveness outcome rate of Grade 1 Raymond class in the absence of retreatment, or parent artery stenosis (>50%) at the target aneurysm was 65.5% (19/29) at 24 months, 75.0% (18/24) at 36 months, and 71.4% (10/14) at post-36 months. The overall incidence rate of stent migration per subject person years was 0.000 (0/152.5).
Study Strengths & Weaknesses	Strength: A prospective and long-term study. Weaknesses: Single arm study not controlling for confounding factors. Low clinical follow-up rate and low imaging follow-up rate.
Recommendations for Labeling Changes	Yes
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P170027 / PAS001
Date Original Protocol Accepted	11/20/2020
Date Current Protocol Accepted	04/10/2026
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To confirm the safety and effectiveness of SSO2 Therapy. This is a prospective, open-label, randomized (1:1) study. Subjects who present with anterior STEMI requiring stent placement in the proximal and/or mid LAD who meet all eligibility criteria and provide informed consent will be treated with PCI with stenting, and if successful and uncomplicated then immediately randomized to post-procedure infusion of SSO2 Therapy for a duration of 60 minutes or standard of care.
Study Population	Qualifying anterior STEMI patients (1 mm or greater of ST elevation in 2 or more contiguous leads in V1-V4) successfully treated with PCI and stenting within 6 hours from time of symptom onset.
Sample Size	Up to sixty (60) centers including up to 45 centers in the U.S. and no more than 15 centers outside the U.S. A total of 434 patients randomized (1:1) to SSO2 Therapy (Treatment group) or Standard of Care (Control group) i.e., 217 SSO2 Therapy: 217 Control. A minimum of 50% of study subjects will be enrolled in the US and the maximum per site enrollment is 40 subjects. The safety sample size is based on the following assumptions: 1:1 randomization between SSO2 Therapy and control arms, 1-year NACE of 18% in SS02 and control patients, 5% loss to follow-up at 1-year, 1-sided non-inferiority test (Farrington-Manning), Non-inferiority margin of 9.5%, 5% type I error and 80% power Based on the assumptions above, a total sample size of 412 subjects (206 per group) will provide 80% power to evaluate primary safety, which is increased to 434 subjects (217 per group to account for 5% loss to follow-up. The effectiveness assumptions are as follows: 27.1% infarct size at 2-7 days in the standard therapy group. SSO2 Therapy group effect size = 25% relative reduction in 2-7day infarct size Standard deviation of 16.1% in both treatment arms Loss to follow-up or missing measurements = 25% Type I Error = 5% (two-sided) A total of 324 subjects (162 per group) are needed to achieve 96.6% power for testing the superiority of the SSO2 arm compared to the control arm using a two- sample t-test.
Key Study Endpoints	Primary Safety endpoint is the 1-year rate of Net Adverse Clinical Events (NACE). The composite NACE endpoint includes hierarchical total of death (all-cause), reinfarction, target vessel revascularization (ischemia driven), TIMI major bleeding or minor bleeding, New onset heart failure or re-hospitalization for heart failure and Stent thrombosis (ARC definite or probable). The safety endpoint events will be adjudicated and classified by an independent Clinical Events Committee (CEC). Primary effectiveness endpoint is the cardiac MRI endpoint of median infarct size (% of total left ventricle (LV) mass) at 2-7 days. The major powered secondary endpoint is a hierarchical composite of all-cause mortality within 1 year, rehospitalization for heart failure within 1 year, and infarct size measured by cardiac MRI within 2-7 days after PCI. Additional Non-Powered Endpoints: MRI Endpoints- Microvascular obstruction (2-7 days) Left ventricular ejection fraction (2-7days, and 6 months) Left ventricular end diastolic volume and volume index (2-7 days, and 6 months) Left ventricular end systolic volume and volume index (2-7 days, and 6 months) Change from 2-7 days to 6 months in MRI endpoints: Infarct size Left ventricular ejection fraction Left ventricular end diastolic volume and volume index Left ventricular end systolic volume and volume index 30-day, 6-month, and 1-year clinical endpoints Death Rehospitalization Reinfarction Revascularization Target Lesion Failure Stent Thrombosis
Follow-up Visits and Length of Follow-up	12 months
General
Study Status	Completed
Application Number / Requirement Number	P180034 / PAS001
Date Original Protocol Accepted	04/11/2019
Date Current Protocol Accepted
Study Name	TOBA II Continued f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, single arm follow-up of the TOBA II pivotal study cohort studied under IDE G150029
Study Population	Continued follow-up of the IDE cohort
Sample Size	204 remaining IDE subjects, active at the end of the 1-year evaluation
Key Study Endpoints	Safety: Freedom from MAE at 30days compared to PG Effectiveness: Primary patency at 12months compared to PG
Follow-up Visits and Length of Follow-up	3 years post-procedure
Interim or Final Data Summary
Interim Results	24 months follow-up compliance does not raise concerns regarding study conduct and there are no major clinical concerns with the Post Approval Study data reported to date.
Actual Number of Patients Enrolled	A total of 213 subjects were enrolled for the study.
Actual Number of Sites Enrolled	Thirty-three (33) enrolling study sites in the United States and Austria
Patient Follow-up Rate	78.4% (167/213) at 24 months and 71.8% (153/213) at 36 months.
Final Safety Findings	The primary safety endpoint (freedom from occurrence of any new-onset MAEs defined as index limb major amputation (above the ankle), clinically driven TLR, or all-cause death at 30 days) was 100% in both ITT and PP groups (95% lower CI: 98.6% (ITT), 98.5% (PP)), which met the 88% performance goal (p<0.0001). Secondary Safety Results A total of 15 deaths occurred. All deaths were adjudicated by the Clinical Events Committee (CEC) as unrelated to the study device or procedure. The Kaplan-Meier estimate of survival rate at 12, 24 and 36 months was 98.1%, 95.0% and 92.3% (95% CI: 87.5%, 95.3%), respectively. There were 51 clinically driven target lesion revascularizations (CD-TLR) as adjudicated by the CEC. The KM estimate of freedom from CD-TLR at the end of the 12-, 24- and 36-month windows was 84.5%, 78.2%, and 73.6%, respectively. The KM estimate of freedom from any TVR at the end 12-, 24- and 36 months was 83.0%, 74.1% and 69.5%, respectively in the ITT population. KM estimate of freedom from major amputations through 36 months was 100% No Unanticipated major adverse events (UMAEs) occurred within the study.
Final Effect Findings	The primary efficacy endpoint (12- month primary patency) was 65.2% (95% lower CI: 57.9%) in the intent to treat (ITT) group and 65.9% (95% lower CI: 58.0%) in the per protocol (PP) group which were greater than the 52.7% performance goal (0.0008). Secondary Effectiveness Results Significant positive changes in Rutherford class occurred from baseline to 12, 24, and 36 months (p<0.0001). Significant positive changes in measured ABI occurred from baseline to 12, 24, and 36 months (p<0.0001). Significant (p<0.05) positive changes in the Peripheral Artery Questionnaire, EQVAS and Walking Impairment Questionnaire occurred from baseline to 12, 24, and 36 months. No fracture or embolization was observed through 12 months post-procedure. One migration was reported in 730 Tacks implanted in 184 subjects with 12-month x-ray data and was limited to 2.6 mm of movement; through 12 months this subject had no reported adverse events and the artery was patent.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post approval study. The labeling change should include a new section in the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P180032 / PAS001
Date Original Protocol Accepted	03/28/2019
Date Current Protocol Accepted
Study Name	CLARITY Clinical Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is continued follow-up of the premarket cohort (i.e., continued enrollment). The study was an international, prospective, multi-center, single-arm, open label, non-randomized clinical study. The objective of the study was to evaluate the safety and effectiveness of the Cerene Cryotherapy Device in premenopausal women with heavy menstrual bleeding due to benign causes for whom childbearing was complete. There were 12 investigational sites that enrolled subjects and 11 that performed treatments, located in the United States, Mexico, and Canada. Treatments took place between June 2016 and March 2017.
Study Population	Premenopausal women with heavy menstrual bleeding due to benign causes for whom childbearing was complete.
Sample Size	Five hundred and fifty-four (554) subjects were enrolled in the study, with 242 proceeding to treatment and comprising the Intent-to-Treat (ITT) population. The primary safety and effectiveness outcomes were analyzed based on the ITT population.
Key Study Endpoints	The primary safety endpoint was incidence of serious adverse events and serious device-related adverse events at 12 months. The primary effectiveness endpoint was reduction in menstrual bleeding at 12 months; success was defined as a PBLAC score of = 75. The PBLAC is a self-administered instrument that allows the subject to record the number of menstrual products she used during her menstrual period. A PBLAC score is calculated from the number, type, and saturation level of menstrual products recorded on the diary. Additional evaluations included amenorrhea rate at Month 12, subject-reported peri-procedural pain experience, evaluation of dysmenorrhea at Month 12, Quality of Life outcomes at Month 3, 6, and 12 using the Menorrhagia Impact Questionnaire (MIQ) and the Premenstrual Symptoms Impact Survey (PMSIS™), evaluation of uterine access and healing at 12 months post-procedure, and additional medical or surgical interventions for continued heavy menstrual bleeding through Month 36.
Follow-up Visits and Length of Follow-up	36 months (3 years)
Interim or Final Data Summary
Interim Results	Safety – after the Month 12 visit: Eight (8) subjects exited due to additional interventions for menstrual bleeding. Three (3) subjects exited due to uterine pregnancy. Four (4) subjects voluntarily exited. One (1) subject exited prior to hysterectomy for pelvic pain. There are 31 subjects reported gynecologic adverse events after the Month 12 follow-up visit none of which were related to the device and/or procedure. Two (2) events were serious adverse events as a result of hospitalization for hysterectomy. At Month 12, the number of patients reported menorrhagia, dysmenorrhea, uterine fibroids, vaginal infection, and pregnancy was 9, 7, 2, 2, and 1, respectively. Effectiveness – The outcomes at 24-month follow-up are: Regarding quality of life (MIQ survey), 84 % subjects reported to experience limitation in their life at screening and this decreased to 10 % and 6% at the Month 12 and Month 24 respectively. On the PMSIS, 75 % of subjects reported PMS symptoms at the screening and this decreased to 17 % and 19 % at the Month 12 and Month 24 respectively. 89.7 % of the subjects were satisfied or very satisfied with the procedure at Month 12 and 82.9 % at Month 24.
Actual Number of Patients Enrolled	242
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	12-month: 95.0% (230/242) 24-month: 90.5% (210/232) 36-month: 86.6% (201/232)
Final Safety Findings	There were 49 gynecologic adverse events from 12 months to 36 months. There were no unanticipated device-related adverse events in the study through the 3-year follow-up. One (1) event, postcoital bleeding, was recorded as related to the procedure.
Final Effect Findings	Premarket effectiveness endpoints: The overall success rate based on PBLAC results was 76.9% (186/242) at 12 months. The amenorrhea (no menses) rate was 10.3% (25/242). Postmarket effectiveness endpoints: Need for surgical or medical intervention to treat abnormal bleeding: From 12 to 36 months, 5.6% subjects (13/232) had medical or surgical intervention to treat abnormal menstrual bleeding. Subject self-report of pregnancy: Three (3) subjects exited due to ongoing pregnancy. One (1) subject continued in the study following termination of her pregnancy. Quality of Life: The Menorrhagia Impact Questionnaire (MIQ) that subjects experienced moderate, quite a bit, or extreme limitations in their social-leisure and/or physical activities and/or their ability to work is stablized from 10% (23/23) at Month 12 to 4.9% (8/163) at Month 24 and 9.5% (19/201) at the Month 36 follow-up visit. Patient Satisfaction: The percentages of patients reporting very satisfied or satisfied were 84% (121/144) at 24 months and 84.5% (153/181) at 36 months. The percentages of patients who would recommend the procedure to a friend were 90% (135/150) at 24 months and 90.6% (175/193) at 36 months. Contraception Status: Method of Contraception 36 Month (N=201) Surgical Tubal Ligation 90 (44.8%) Vasectomy 69 (34.3%) Condoms 20 (10%) Abstinence 10 (5%) Other 5 (2.5%) IUD 3 (1.5%) Same sec partner 3 (1.5%) Rhythm or fertility awareness method 1 (0.5%)
Study Strengths & Weaknesses	n/a
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S074/ PAS001
Date Original Protocol Accepted	12/27/2018
Date Current Protocol Accepted
Study Name	SAPIEN 3 Ultra Novel Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objective of the surveillance is to assess the real-world use of the commercial SAPIEN 3 Ultra Transcatheter Heart Valve System for native aortic valve replacement in patients at intermediate and above surgical risk and for aortic and mitral valve-in-valve in patients at high and above surgical risk.
Study Population	The surveillance will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry; and the follow-up data from year 2 through year 5 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database. The surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening /major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-5 year post-implantation.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Native: 1 year (TVT-R): all-cause death: 13.1%; all stroke: 3.3%; valve reintervention: 0.2%; KCCQ (mean change in summary score from baseline): 30.3 ± 0.33; NYHA (% in Class I/II): 91.6%; PVL = moderate: 1.5%; mean aortic gradient: 12.7 mmHg (compared to baseline mean gradient of 41.5 mmHg) 2-years (CMS-linked): all-cause death: 24.8%; all-stroke: 6.7%; valve re-intervention: 0.4% Aortic THV-in-SV: 1 year (TVT-R): all-cause death: 14.6%; all stroke: 3.1%; valve reintervention: 2.9%; KCCQ (mean change in summary score from baseline): 37.9 ± 2.15; NYHA (% in Class I/II): 90.7%; PVL = moderate: 1.0%; mean aortic gradient: 18.8 mmHg (compared to baseline mean gradient of 36.6 mmHg) 2-years (CMS-linked): all-cause death: 23.5%; all-stroke: 6.6%; valve re-intervention: counts too small to report per data use agreement Mitral THV-in-SV: 1 year (TVT-R): all-cause death: 18.9%; all stroke: 5.3%; valve reintervention: 0.6%; KCCQ (mean change in summary score from baseline): 40.5 ± 3.34; NYHA (% in Class I/II): 86.8%; PVL = moderate: 2.3%; mean mitral gradient: 8.0 mmHg (compared to baseline mean gradient of 14.2 mmHg) 2-years (CMS-linked): all-cause death: 28.6%; all-stroke and valve re-intervention: counts too small to report per data use agreement
Actual Number of Patients Enrolled	Native: 14,226 patients (attempted); 14,096 patients implanted Aortic THV-in-Surgical Valve: 492 patients (attempted); 486 patients were implanted Mitral THV-in-Surgical Valve: 172 patients (attempted); 164 implanted
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	Native: 30 Days: Patient status known: 96.4%; 1 Year: Patient status known: 80.4%; 2 Years: 85.6% of eligible patients (11,608/13,562) matched within the CMS database. CMS data was available for 100% of matched patients at 2 years. Aortic THV-in-SV: 30 Day: Patient status known: 96.3%; 1 Year: Patient status known: 79.7%; 2 Years: 84.8% of eligible patients (362/427) matched within the CMS database. CMS data was available for 100% of matched patients at 2 years. Mitral THV-in-SV: 30 Day: Patient status known: 94.2%; 1 Year: Patient status known: 70.9%; 2 Years: 77.2% of eligible patients (112/145) matched within the CMS database. CMS data was available for 100% of matched patients at 2 years.
General
Study Status	Ongoing
Application Number / Requirement Number	P180035 / PAS002
Date Original Protocol Accepted	07/12/2021
Date Current Protocol Accepted	07/10/2024
Study Name	MiSight 1 Day Safety PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	PAS002 is a cohort study nested within integrated (optometry / ophthalmology) eyecare practices or integrated health care and coverage organization systems. Consecutive subjects who are fitted in the MiSight1 Day lens, and who meet the product indication inclusion criteria, will be prospectively offered to participate in the study. Subsequent occurrence of the outcomes of interest will be identified via active adverse event reporting via Case Report Forms from investigative sites, an on-site survey at routine biannual visits, and release of medical records from all medical practitioners associated with management of any adverse event. The primary objectives of this study is to confirm that the incidence of Microbial Keratitis (MK) is lower than 0.002/patient-year among the intended patient population in the US. The secondary objective of this study is to determine the incidence rate of the following safety data among the intended patient population of the MiSight 1-Day lens in the US: (1) the incidence of peripheral infiltrative keratitis/non-infectious ulcers, (2) the incidence of non-infectious infiltrative keratitis, (3) the incidence of loss of best-corrected visual acuity greater than or equal to 2 lines for any adjudicated adverse event.
Study Population	The eligible study population will be children ages of 8-12, who have best corrected visual acuity of at least 20/25 bilaterally with refractive error between -0.75 D to – 4.00D spherical equivalent and less than or equal to 0.75 D of astigmatism at the initiation of treatment, who are free of ocular disease or abnormalities (including any corneal scar), who are not under medication that would interfere with contact lens wear or are using or have used any pharmaceuticals or other methods for control of myopia, and who have no other contraindications per product labeling. Only children first fitted in MiSight 1 Day lenses after the date of study initiation at the clinical site are eligible to participate in the study.
Sample Size	To estimate the microbial keratitis rate, accrual of 8,500 patient-years is needed. A minimum of 6,000 patient-years, from approximately 2,000 prospectively identified subjects will be accumulated from this safety PAS, and a minimum of 2,500 patient-years will be accumulated from the subjects enrolled in PAS001 protocol (MiSight 1 Day Post-Approval Study for Effectiveness and Visual Symptoms).
Key Study Endpoints	The primary endpoint for the study is: the incidence rate of contact lens-related microbial keratitis based on the number of adjudicated cases of “Probable microbial keratitis” related to contact lens wear. Secondary endpoints for the study are: the incidence rate of peripheral infiltrative keratitis/non-infectious ulcers based on the number of adjudicated cases of “Peripheral infiltrative keratitis/ Probable non-infectious ulcer”. the incidence rate of non-infectious infiltrative keratitis based on the number of adjudicated cases of “Probable non-infectious infiltrative keratitis”. the incidence rate of loss of best-corrected visual acuity of greater than or equal to 2 lines for any adjudicated adverse event. These additional endpoints will also be ascertained: Patient/Parent/Guardian declining participation in the study and reasons for declining Percentage of subjects discontinuing lens wear and reasons Percentage subjects lost-to-follow-up. An Endpoint Adjudication Committee (EAC) will be formed in association with this study to adjudicate diagnosis of adverse events. The EAC will include five (5) ophthalmologist clinicians/researchers experienced in the diagnosis and management of contact lens-related microbial keratitis, 3 active members and 2 alternates to assure continuity over the multi-year progress of the study.
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1041
Actual Number of Sites Enrolled	50
Patient Follow-up Rate	A total of 1041 children have been consented, enrolled and completed demographic information in the study to date. 81 subjects exited early (34 before 1 year. 47 at or after 1 year) due to discontinuation of lens wear, change in myopia management, no longer receiving eye care at the practice, relocation, lost to follow-up, or other reasons. Six subjects exited after completing all study visits (3 years).
General
Study Status	Completed
Application Number / Requirement Number	P180037 / PAS001
Date Original Protocol Accepted	03/13/2019
Date Current Protocol Accepted
Study Name	VERNACULAR Cont F/u PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (VERNACULAR Continued Follow-Up Study) is to evaluate the long term safety and effectiveness of the VENOVO Venous Stent System for the treatment of symptomatic iliofemoral venous outflow obstruction. This study is a prospective, multi-center follow-up of the VERNACULAR pivotal study (G150248).
Study Population	The study population included patients with symptomatic (non-malignant) venous outflow obstruction in iliofemoral venous segments of greater than or equal to 50% as determined by catheter contrast venography.
Sample Size	All 160 remaining subjects (10 subjects have discontinued the study) of the 170 original study subjects enrolled from 22 investigational sites.
Key Study Endpoints	Primary Endpoint: Freedom from target lesion revascularization (TLR) at 36 months. Secondary Endpoints: Overall rate and incidence of type of serious adverse events from Day 0 through completion of Study follow-up at Month 36. Primary stent patency rate: determined at Month 24 and Month 36 per protocol definition of primary stent patency. Freedom from target lesion revascularization (TLR) at Month 24 and Month 36, as defined by the protocol. Freedom from target vessel revascularization (TVR) at Month 24 and Month 36, as defined by the protocol. Comparison of VCSS Scores measured at Baseline, Month 12, Month 24 and Month 36. Comparison of Quality of Life Questionnaire (QOL) Scores measured at Baseline, Month 12, Month 24 and Month 36. Comparison of CEAP Scores measured at Baseline, Month 12, Month 24 and Month 36. Stent integrity measured as freedom from stent fracture, defined as clear interruption of a stent strut observed in a minimum of two projections, determined by core lab examination of X-rays at 24 and 36 Months.
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	One hundred and seventy (170) subjects were enrolled and treated with the study device
Actual Number of Sites Enrolled	Twenty-two (22) investigational sites enrolled and treated subjects.
Patient Follow-up Rate	75.3% (128/170) of subjects completed follow-up at 36 months
Final Safety Findings	The primary safety endpoint was freedom from MAEs through 30 days (defined as target vessel revascularization, device and/or procedure related death, major amputation of target limb, pulmonary embolism, vascular injury, embolization/migration of stent and device or procedure related DVT of treated limb). The proportion of subjects free from MAE was 93.5% [90% CI: 89.5%,96.3%] compared to literature-derived PG of 89% (1-sided p-value = 0.0322). Key Secondary Endpoints with Hypothesis Testing At 12 month the Venous Clinical Severity Score (VCSS) pain score change from baseline in the total study population was -1.7 [95% CI: -1.81 to -1.49 (P < .0001). At 36 month the VCSS pain score change from baseline in the total study population was -1.8 [95% CI: - 1.95 to -1.66]. At 12-month Quality of Life (QoL) assessment of Chronic Venous Insufficiency Questionnaire (CIVIQ-20) change from baseline in the total study population was -15.7 [ 95% CI: -18.41 to -12.96] (P < .0001). At 36 months total CIVIQ-20 Score change from baseline in the total study population was – 16.8 [95% CI: -20.07 to -13.54]. Secondary Endpoints Without Hypothesis Testing Freedom from TLR rates for the study population at 24 and 36 months was 89.4% and 88.1% respectively. The freedom from TVR rates for study population at 24 and 36 months was 89.4% and 88.1%, respectively. Freedom from TLR and freedom from TVR results are the same through the 36-month analysis as all TLRs were also TVRs. Freedom from stent fracture from Xray analysis by the Core Lab through 36 months was 100%. There was one (1) reported device deficiency that was not associated with an adverse event. This was resolved by post-dilatation inside the stent and the subject did not experience any adverse events through the 36-month follow-up period. A total of 6 deaths were reported. All deaths were adjudicated by the CEC to be not related to the study device or procedure. One (1) subject underwent a planned target limb amputation (1/170, 0.6%). The amputation was adjudicated by the CEC to be not related to the study device or procedure.
Final Effect Findings	The primary effectiveness endpoint was primary patency at 12 months post-index procedure (defined as freedom from TVR and freedom from thrombus occlusion and stenosis > 50% as measured by DUS). The 12-month weighted primary patency rate for the Stent group was 88.6%, 90% CI [82.8%, 94.4%], compared to a literature derived PG of 74% (1-sided p-value <0.0001). Primary endpoint for the post approval study was freedom from target lesion revascularization (TLR) at 36 months per protocol definition. Freedom from TLR at 36 months (unweighted) was 84.0% [90% CI:78.2%, 88.3%]
Study Strengths & Weaknesses	This was a multicenter study that enrolled 22 investigational sites in the US, Europe and Australia. The study met the primary effectiveness endpoint (primary patency rate of 88.6% at 12 months compared to the performance goal (PG) of 74%%, one-sided p<0.0001). Similarly, the primary safety endpoint of freedom from major adverse event rate at 30 days was met (freedom from MAE rate of 93.5% with 90% CI of 89.5% to 96.3% compared to PG of 89%). Follow-up was completed for 75.3% of subjects at 36 months.
Recommendations for Labeling Changes	Labeling change is recommended to update the labeling with the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the postapproval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S085/ PAS001
Date Original Protocol Accepted	08/16/2019
Date Current Protocol Accepted
Study Name	Cont f/u of SAPIEN 3 Low Risk cohort PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the pivotal cohort under the IDE. The objective of this study is to characterize the clinical outcomes annually through 10 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE pivotal cohort.
Sample Size	All living subjects.
Key Study Endpoints	All-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, requirement for renal replacement, coronary artery obstruction requiring intervention, major vascular complication, valve-related dysfunction requiring repeat procedure, new permanent pacemaker implantation, prosthetic valve endocarditis, prosthetic valve thrombosis, New York Heart Association (NYHA) classification, 6-Minute Walk Test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and hemodynamic performance metrics by Doppler echocardiography.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	At 8 years: All-cause mortality (including vital status check): 26.5% [22.8, 30.8]* (TAVR); 22.2% [18.5, 26.5]* (SAVR) - KM Stroke: 9.4% [7.0, 12.6]* (TAVR); 8.2% [5.9, 11.4]* (SAVR) - KM Aortic valve reintervention: 7.3% [5.2, 9.9]* (TAVR); 6.8% [4.6, 9.6]* (SAVR) - CIF NYHA (% in class I/II): 95.1% (TAVR); 95.4% (SAVR) KCCQ (Mean Change from Baseline): 12.3 (TAVR); 13.9 (SAVR) At 7 years: Bioprosthetic valve failure: 6.9% [4.8, 9.4]* (TAVR); 7.5% (SAVR) [5.2, 10.4]* - CIF Transvalvular mean gradient: 13.3 (TAVR); 12.1 (SAVR) Effective orifice area: 1.9 (TAVR); 1.8 (SAVR) Greater than or equal to moderate total aortic regurgitation: 2.4% (TAVR); 1.6% (SAVR) Greater than or equal to moderate PVL: 1.0% (TAVR); 0.4% (SAVR) *Confidence Interval
Actual Number of Patients Enrolled	1,000 randomized subjects; 948 implanted (495 TAVR & 453 SAVR)
Actual Number of Sites Enrolled	71
Patient Follow-up Rate	At 8 years (patient status known): 89.7% (TAVR); 80.4% (SAVR)
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S085/ PAS002
Date Original Protocol Accepted	08/16/2019
Date Current Protocol Accepted
Study Name	SAPIEN 3 Registry-Based Cont Access & Low Risk RWU
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objectives of the surveillance are to characterize the clinical outcomes of the CAP cohort annually through 10 years post implantation and to assess the real-world use of the commercial SAPIEN 3 Transcatheter Heart Valve System and SAPIEN 3 Ultra Transcatheter Heart Valve System to ensure that the device is used in appropriate circumstances.
Study Population	The surveillance of the CAP cohort will consist of all living CAP patients who were enrolled at participating institutions, and the surveillance of the real-world use will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All living CAP subjects and all consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry; and the follow-up data from year 2 through year 10 post procedure will be obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database. The surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 2-10 year post implantation.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Tricuspid Low Risk TVTR CAP at 1 Year: All-cause death: 0.9% All stroke: 2.3% Transient ischemic attack: 0.8% Rehospitalization (Device or procedural related or heart failure): 4.8% Aortic valve re-intervention (site reported): 0.9% Life-threatening/major bleeding (site reported): 1.6% Major vascular complications (site reported): 0.9% New requirement for dialysis (site reported): 0% NYHA (% in class I/II): 99.4% KCCQ (Mean Change from Baseline): 24.6 Transvalvular mean gradient: 13.3 Greater than or equal to Moderate PVL: 3.6% Tricuspid Low Risk TVTR CAP (CMS-linked) at 3 years: All-cause death: 6.0% Stroke: 5.2% Aortic valve reintervention: 1.6% TVTR Low Risk Tricuspid Cohort at 1 Year: All-cause death: 4.4% All stroke: 2.1% Life-threatening bleeding: 1.4% Myocardial infarction: 0.7% New requirement for dialysis: 0.2% Transient ischemic attack (TIA): 0.7% Major Vascular Complications: 0.9% Aortic valve reintervention: 0.4% New permanent pacemaker implantation (site reported): 8.2% Prosthetic valve endocarditis (site reported): 0.4% Prosthetic valve thrombosis (site reported): 0.2% NYHA (% in class I/II): 95.7% KCCQ (Mean Change from Baseline): 27.5 Transvalvular mean gradient: 13.1 Greater than or equal to Moderate PVL: 1.5%
Actual Number of Patients Enrolled	CAP Cohort: Tricuspid: A total of 893 subjects were enrolled, of which 889 were included in the valve implant population. TVTR Low Risk Tricuspid Cohort: A total of 24,262 subjects were treated. Of these, 24,064 subjects were included in the VI population.
Actual Number of Sites Enrolled	Tricuspid Low Risk TVTR CAP: 43 sites TVTR Low Risk Tricuspid Cohort: 703 sites
Patient Follow-up Rate	Tricuspid Low Risk TVTR CAP: Patient status known at 1 year: 90.3% TVTR Low Risk Tricuspid Cohort: Patient status known at 1 year: 83.7%
General
Study Status	Ongoing
Application Number / Requirement Number	P180051 S001/ PAS002
Date Original Protocol Accepted	04/27/2022
Date Current Protocol Accepted
Study Name	Post-commercialization DCD New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm new enrollment study. The objective of the study is to characterize the performance of the OCS Heart System in the real-world setting, as compared to concurrent control data obtained from the United Network for Organ Sharing (UNOS) database for recipients of standard criteria donor hearts preserved using cold static cardioplegic storage.
Study Population	Patients needing heart transplant.
Sample Size	150 patients that constitute the Primary Analysis Population.
Key Study Endpoints	The primary endpoint is patient survival at 1 year post-transplant. Other endpoints include patient/graft survival through 5 years posttransplant, incidence of moderate or severe primary graft dysfunction (PGD; left or right ventricle), and incidence of donor heart turndowns following OCS Heart System perfusion.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Graft survival @ 6 months: 97.6% (OCS DCD cohort) vs. 98.8% (SOC cohort) – Non-inferiority met. Effectiveness Results Patient survival @ 1 year: 91.6% (OCS DCD cohort) vs. 93.9% (SOC cohort) – Non-inferiority met.
Actual Number of Patients Enrolled	Primary Analysis Population: 167 (OCS DCD cohort) and 607 (Standard of Care [SOC] cohort: standard criteria donor hearts preserved using cold static cardioplegic storage)
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	100%; no patients have been lost to follow-up in the OCS DCD cohort.
General
Study Status	Ongoing
Application Number / Requirement Number	P210032 / PAS001
Date Original Protocol Accepted	05/13/2022
Date Current Protocol Accepted
Study Name	Continued Follow-up of the IDE Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of the study was to determine whether the GORE® TAG® Thoracic Branch Endoprosthesis (TBE device) is safe and effective in treating thoracic aortic pathologies while maintaining blood flow to the LSA. Specifically, the objective was to perform hypothesis-driven analysis of the device’s safety and effectiveness in the treatment of aortic aneurysms requiring proximal device placement in Zone 2 of the thoracic aorta.
Sample Size	The IDE allowed for a minimum of 115 and up to a total of 315 Subjects
Key Study Endpoints	Endpoints: The Zone 2 study had a composite primary endpoint design, of eight overall components (one of the components ‘Device Technical Success’ has three further subcomponents). The composite can be considered a mixture of effectiveness and safety variables. The Primary Endpoints for the Zone 2 Aneurysm hypothesis-driven study cohort are described below. A complete listing of these endpoint definitions and relevant assessment scales (Modified Rankin Scale (mRS), Spinal Cord Ischemia (SCI) scale and NIH Stroke Scake (NIHSS)). The primary endpoint for the Zone 2 Aneurysm cohort was a composite of the following events through 12 months: Device Technical Success Successful access and delivery to the intended implantation site, and retrieval of the device delivery system, and; Patency of the graft, and; The absence of unanticipated additional procedure related to the device, procedure, or withdrawal of the delivery system Absence of the following: Aortic rupture Lesion-related mortality Disabling stroke Permanent paraplegia Permanent paraparesis New onset renal failure requiring permanent dialysis Additional unanticipated post-procedural surgical or interventional procedure related to the device, procedure, or withdrawal of the delivery system In addition to the Primary Endpoints noted above, Procedural and Treatment Success data (aggregate and components) were collected and analyzed for all Zone 2 cohorts. Procedural Success was defined as Device Technical Success (defined in Section 7.4.1), with absence of the following events occurring from the initiation of the index endovascular procedure through 1 month: Death (Through 30 days only) Aortic rupture (Through 30 days only) Disabling stroke Paraplegia (Through 30 days only) Paraparesis (Through 30 days only) New onset renal failure requiring permanent dialysis Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system New ischemia Distal device-related thromboembolic adverse event requiring intervention or surgery Extension of a dissection (proximally or distally) (Dissection cohort only) New dissection Life-threatening bleed Myocardial infarction Prolonged intubation Laryngeal or Phrenic Nerve injury Renal dysfunction or volume overload requiring ultrafiltration Severe Heart Failure/Hypotension Treatment Success was defined as Device Technical Success, with absence of the following events occurring from the initiation of the index endovascular procedure and at all appropriate follow-up windows: Aortic enlargement in the region encompassed by the initial lesion Aortic rupture Extension of a dissection (proximally or distally) (Dissection cohort only) New dissection False lumen perfusion through the primary entry tear (Dissection cohort only) False lumen perfusion through an aortic arch branch vessel (Dissection cohort only) Type I or III endoleak Fistula formation Lesion-related mortality Loss of device integrity Loss of aortic or aortic branch patency Migration Disabling stroke within 30 days of the index endovascular procedure only Paraplegia within 30 days of the index endovascular procedure only Paraparesis within 30 days of the index endovascular procedure only New ischemia Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system
Follow-up Visits and Length of Follow-up	5-years, 60 months follow-up
Interim or Final Data Summary
Interim Results	The Zone 2 study had a composite primary endpoint design, of eight overall components (one of the components ‘Device Technical Success’ has three further subcomponents). The composite can be considered a mixture of effectiveness and safety variables. The Primary Endpoints for the Zone 2 Aneurysm hypothesis-driven study cohort are described below. A complete listing of these endpoint definitions and relevant assessment scales (Modified Rankin Scale (mRS), Spinal Cord Ischemia (SCI) scale and NIH Stroke Scake (NIHSS)). The primary endpoint for the Zone 2 Aneurysm cohort was a composite of the following events through 12 months: Device Technical Success Successful access and delivery to the intended implantation site, and retrieval of the device delivery system, and; Patency of the graft, and; The absence of unanticipated additional procedure related to the device, procedure, or withdrawal of the delivery system Absence of the following: Aortic rupture Lesion-related mortality Disabling stroke Permanent paraplegia Permanent paraparesis New onset renal failure requiring permanent dialysis Additional unanticipated post-procedural surgical or interventional procedure related to the device, procedure, or withdrawal of the delivery system In addition to the Primary Endpoints noted above, Procedural and Treatment Success data (aggregate and components) were collected and analyzed for all Zone 2 cohorts. Procedural Success was defined as Device Technical Success (defined in Section 7.4.1), with absence of the following events occurring from the initiation of the index endovascular procedure through 1 month: Death (Through 30 days only) Aortic rupture (Through 30 days only) Disabling stroke Paraplegia (Through 30 days only) Paraparesis (Through 30 days only) New onset renal failure requiring permanent dialysis Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system New ischemia Distal device-related thromboembolic adverse event requiring intervention or surgery Extension of a dissection (proximally or distally) (Dissection cohort only) New dissection Life-threatening bleed Myocardial infarction Prolonged intubation Laryngeal or Phrenic Nerve injury Renal dysfunction or volume overload requiring ultrafiltration Severe Heart Failure/Hypotension Treatment Success was defined as Device Technical Success, with absence of the following events occurring from the initiation of the index endovascular procedure and at all appropriate follow-up windows: Aortic enlargement in the region encompassed by the initial lesion Aortic rupture Extension of a dissection (proximally or distally) (Dissection cohort only) New dissection False lumen perfusion through the primary entry tear (Dissection cohort only) False lumen perfusion through an aortic arch branch vessel (Dissection cohort only) Type I or III endoleak Fistula formation Lesion-related mortality Loss of device integrity Loss of aortic or aortic branch patency Migration Disabling stroke within 30 days of the index endovascular procedure only Paraplegia within 30 days of the index endovascular procedure only Paraparesis within 30 days of the index endovascular procedure only New ischemia Additional unanticipated post-procedural surgical (including conversion to open surgery) or interventional (placement of additional unanticipated endovascular devices) procedure related to the device, procedure, or withdrawal of the delivery system
Actual Number of Patients Enrolled	The IDE allowed for a minimum of 115 and up to a total of 315 Subjects
General
Study Status	Ongoing
Application Number / Requirement Number	P180027 S002/ PAS001
Date Original Protocol Accepted	04/26/2022
Date Current Protocol Accepted	08/21/2024
Study Name	FRED X PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, adaptive design, multi-center, single arm study. The objective of this study is to generate contemporaneous clinical data to facilitate a reasonable comparison of the performance of the FRED™ X™ device with the performance of the FRED™ device. To achieve the objective, this study will evaluate the safety and effectiveness outcomes of FRED™ X™ device in a population of patients that aligns with the indications for use of the FRED™ device. The data generated from this study will be compared to the safety and effectiveness of the FRED™ device by meeting the same performance goals (PGs) established for the FRED™ pivotal study.
Study Population	Patients that aligns with the indications for use of the FRED™ device (See inclusion/exclusion criteria in protocol for detail)
Sample Size	The proposed enrollment target is 154 subjects at a maximum of 30 sites in the United States.
Key Study Endpoints	The primary safety endpoint is the proportion of subjects that experience either- 12 Death or major stroke within 30 days post-procedure. 13 Neurological death or major ipsilateral stroke within 12 months post-procedure. o A major stroke is defined as a new neurological event that persists for >24 hours and results in a =4-point increase in the NIHSS score compared to baseline or compared to any subsequent lower score. o A minor stroke is defined as a new neurological event that persists for >24 hours and results in an increase of <4 points in the NIHSS score compared to baseline or compared to any subsequent lower score. o A major ipsilateral stroke is defined as that occurring within the vascular distribution of the stented artery. o Neurological death is defined as a death which has been adjudicated by the independent clinical events committee to have directly resulted from a neurologic cause. Primary Effectiveness Endpoint: 1 The primary effectiveness endpoint is the percent of subjects with successful aneurysm treatment as defined by complete occlusion (100%) of the target aneurysm and =50% stenosis of the parent artery at the target IA at 12 months and in whom an alternative treatment of the target IA had not been performed within 12 months post-FRED™ X™ Device placement. An alternative treatment is defined as re-treatment of the target aneurysm with an alternative treatment modality including open repair, endovascular placement of an additional stent or treatment of in-stent stenosis observed at the 6-month or 12-month follow-up time points or at an unscheduled follow- up visit.
Follow-up Visits and Length of Follow-up	at discharge, 30 days (±7 days), 6 months (±30 days), 12 months (+60 days/-30 days), 2 years (±60 days), 3 years (±60 days), and 5 years (±60 days).
Interim or Final Data Summary
Interim Results	29 adverse events
Actual Number of Patients Enrolled	29
Actual Number of Sites Enrolled	18
Final Effect Findings	N/A
General
Study Status	Completed
Application Number / Requirement Number	P190008 / PAS001
Date Original Protocol Accepted	11/14/2019
Date Current Protocol Accepted	03/04/2022
Study Name	IN.PACT AV Access IDE Cohort PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The IN.PACT AV Access IDE Cohort Post Approval Study is a study that was initiated prior to device approval. It was designed as a prospective, global, randomized (1:1), multi-center clinical study that is ongoing at sites in the United States, New Zealand, and Japan.
Study Population	Subjects with a de novo or non-stented restenotic obstructive lesion up to 100 mm in length, located in the native arteriovenous dialysis fistulae.
Sample Size	330 subjects randomized in a ratio of 1:1 to either the IN.PACT AV Access DCB (study arm) or a standard PTA balloon (control arm).
Key Study Endpoints	The primary safety endpoint is defined as the serious adverse event (SAE) rate involving the AV access circuit through 30 days post-procedure. The primary effectiveness endpoint is defined as freedom from clinically-driven target lesion revascularization (CD-TLR) or access circuit thrombosis measured through 6 months post-index procedure.
Follow-up Visits and Length of Follow-up	Patients will be followed up to 60 months post-index procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	330
Actual Number of Sites Enrolled	16
Patient Follow-up Rate	As of the data cut-off on June 2, 2023: 96.6% (313/324) of eligible subjects completed the 30-day visit; 99.0% (309/312) of eligible subjects completed the 3 month visit; 96.7% (289/299) of eligible subjects completed the 6 month visit; 97.2% (276/284) of eligible subjects completed the 9 month visit; 94.4% (252/267) of eligible subjects completed the 12 month visit; 96.7% (236/244) of eligible subjects completed the 18 month visit; 95.5% (211/221) of eligible subjects completed the 24 month visit; 98.5% (133/135) of eligible subjects completed the 36 month visit; 89.7% (96/107) of eligible subjects completed the 48 month visit and 100% (98/98) of eligible subjects completed the 60 month visit.
Final Safety Findings	The primary safety endpoint was Serious Adverse Event (SAE) rate involving the AV access circuit through 30 days post-procedure. The 30-day SAE rate involving the AV access circuit was 4.2% in the IN.PACT AV DCB study group and 4.4% in the PTA control group. (unchanged from PMA). New Data Through 60 months, 35.9% (or 61 subjects) of subjects reported infections and infestations System Order Class (SOC) in the IN.PACT AV DCB study group and 27.5% (44 subjects) of subjects reported infections and infestations SOC in the standard PTA control group. In total, there were fifty-nine (59) deaths in the IN.PACT AV DCB study group and sixty (60) deaths in the Standard PTA control group.
Final Effect Findings	The primary effectiveness endpoint was target lesion primary patency through 6 months post-procedure. The 6-month target lesion primary patency rate was 82.2% in the IN.PACT AV DCB study group and 59.5% in the PTA control group (p<0.001). (data unchanged from PMA). New Data Abandonment of the Target AVF through 36 Months: There were a total of 14.5% (48/330) of AV Circuits abandoned through 36 months, 13.5% (23/170) in the IN.PACT AV DCB group, and 15.6% (25/160) in the Standard PTA group. Number of Interventions required to maintain target lesion patency through 36 months: 254 for the IN.PACT AV DCB group and 289 in the Standard PTA group. Subjects with at least one intervention is 49.4% (84/170) for the IN.PACT AV DCB group and 66.3% (106/160) for the Standard PTA group (p=0.002). Number of Interventions required to maintain access circuit patency through 36 months: 307 for the IN.PACT AV DCB group and 345 in the Standard PTA group. Subjects with at least one intervention is 57.1% (97/170) for the IN.PACT AV DCB group and 70.6% (113/160) for the Standard PTA group (p=0.010).
Study Strengths & Weaknesses	Strengths: This study was a prospective, global, multicenter, single blinded, randomized clinical study. The sample size of 330 subjects provided adequate statistical power to achieve the primary objectives planned for the study. In order to provide a high-quality dataset that allows for a confident interpretation of the results, the overall data in this study was 90% monitored. Additional processes were employed to ensure the data quality and to minimize the reporting bias - the imaging data was adjudicated by independent imaging core laboratories. The study endpoint related major events including re-interventions, access circuit thrombosis, and all-cause deaths were adjudicated by an independent clinical event committee (CEC). Considering the additional efforts in collecting the subject’s vital status for those exited the study early, it provides an improved estimate in all-cause mortality through 60 months in this study cohort. The study met the primary effectiveness endpoint for target lesion primary patency at 6-month, demonstrating superiority in the IN.PACT AV DCB study group compared to the PTA control group. The study also met the primary safety endpoint through 30-days with the pre-specified non-inferiority margin of 7.5%. No statistical difference in mortality was observed between the IN.PACT AV DCB and PTA control group through 60 months. The results continue to demonstrate the long-term safety and effectiveness of the IN.PACT AV DCB. Weaknesses: The study was originally designed for 24 months of follow-up. With the study extension to 60 months, a total of 16.4% (54/330) subjects declined consent beyond 24 months. In addition, due to the nature of the end stage renal disease (ESRD) condition in this study cohort, high proportions of the subjects exited the study before the 60-month study follow-up period mainly due to AV fistula abandonment, and withdrawal by subject. The other limitation was the sample size, that presented challenges in the subgroup analyses, such as the estimate of the safety and effectiveness outcomes by lesion type, AV type, lesion location, etc
Recommendations for Labeling Changes	Labeling changes will be recommended
General
Study Status	Ongoing
Application Number / Requirement Number	P190008 / PAS002
Date Original Protocol Accepted	04/10/2020
Date Current Protocol Accepted	09/14/2023
Study Name	New Enrollment IN.PACT AV Access PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The new enrollment IN.PACT AV Access Post Approval Study is a Condition of Approval for the IN.PACT AV device. It is a prospective, non-randomized, multi-center, single-arm post-approval study in the United States. that is intended to assess the long term safety and performance of the IN.PACT AV DCB in a U.S. population. There are two cohorts. The objectives of the primary cohort is to demonstrate the 1-year infection and infestation rate and the mortality rate out to 5 years. An extended cohort will also be enrolled to obtain real-world experience regarding the rates of infection/infestation and mortality.
Study Population	Subjects with a de novo or non-stented restenotic obstructive lesion up to 100 mm in length, located in the native arteriovenous dialysis fistulae with reference vessel diameters of 4 to 12 mm.
Sample Size	240 subjects will be enrolled at up to 20 clinical sites in the US, with an expected enrollment period of 18-24 months. In the primary cohort, a sample size of up to 160 patients will be enrolled to ensure 125 patients complete follow-up through 1-year. Up to 80 patients will be evaluated in the extended cohort.
Key Study Endpoints	Primary Cohort: The primary cohort is designed to meet a performance goal of 30% for Serious Adverse Events defined as site reported serious adverse events MedDRA coded to the “infection and infestations” SOC through 1-year post-index procedure. The study will also collect information on the mortality rate out to 5 years. The mortality rate through 1 and 2 years post-index procedure will include and exclude COVID-19 related deaths. The mortality rate through 3, 4, and 5 years post-index procedure will use vital status data. Extended Cohort: An extended cohort will also be enrolled to obtain real-world experience regarding the rates of infection/infestation and mortality out to 5 years. The mortality rate through 1 and 2 years post-index procedure will include and exclude COVID-19 related deaths. The mortality rate through 3, 4, and 5 years post-index procedure will use vital status data.
Follow-up Visits and Length of Follow-up	Patients will be followed up to 60 months post-index procedure.
Interim or Final Data Summary
Interim Results	Safety Results The following results are based on available data and are subject to change as new data becomes available. These results are cumulative over the total study duration so far. One-hundred thirteen (113) patients (70.2%) in the Primary Cohort experienced one or more SAE through the data cutoff date. Arteriovenous fistula site complications were experienced by forty-two (42) patients (26.1%). Sixty- five (65) patients (79.3%) in the Extended Cohort experienced one or more SAE through the data cutoff date. The most frequent reported SAEs were Injury, poisoning and procedural complications (48.8%). A total of seventy-two (72) deaths were reported as of the data cutoff date. Forty-seven (47) of the deaths were in the Primary Cohort and twenty- five (25) of the deaths were in the Extended Cohort. Effectiveness Results: The following effectiveness results are from the primary cohort. Follow-up was completed on 78.7% (126/160) of the primary cohort study subjects out to 12 months. Preliminary estimates of the effectiveness results are provided based upon available data; updates will be made as additional data is available. Target Lesion Primary Patency KM Estimate at 12 Months: 70.2% (42 events) Access Circuit Primary Patency KM Estimate at 12 Months: 52.6% (68 events) Cumulative Target Lesion Revascularizations KM Estimate at 12 Months: 38.9% (56 events) Cumulative Access Circuit Thromboses KM Estimate at 12 Months: 7.8% (11 events) Number of Interventions Required to Maintain Target Lesion Patency: 0.6 -/+ 1.0 (159 subjects) Number of Interventions Required to Maintain Access Circuit Patency: 0.7 -/+ 1.1 (159 subjects)
Actual Number of Patients Enrolled	254 (160 in primary cohort, 80 in extended cohort, 14 exited)
Actual Number of Sites Enrolled	17
Patient Follow-up Rate	Primary Cohort | Extended Cohort 6 Months: 93.6% (132/141) | 97.4% (74/76) 12 Months: 98.4% (126/128) | 100% (70/70) 24 Months: 100% (48/48) | 100% (34/34) 36 Months: 100% (12/12) | 90% (9/10)
Final Effect Findings	N/A
General
Study Status	Completed
Application Number / Requirement Number	P190009 / PAS001
Date Original Protocol Accepted	02/12/2021
Date Current Protocol Accepted
Study Name	TFAOS PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Other Data Source
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Transfemoral Amputation Osseointegration Study (TFAOS) initiated on November 11, 2017 and is sponsored by the Henry Jackson Foundation. The sponsor of TFAOS has agreed to provide the data to Integrum, who will analyze the data consistent with FDA’s requested endpoints and then submit reports to the agency. The TFAOS is a prospective, multicenter, cohort study to provide an ongoing assessment of the short-term (2 years) safety and effectiveness outcomes of the updated version of the OPRATM Implant system (e.g., improvements with components, AxorTM II, and instrumentation since the H080004 pivotal study).
Study Population	Patients who have the OPRATM implant procedure performed at Walter Reed or Univeristy of California San Francisco (UCSF) and meet the eligibility criteria established in the study protocol.
Sample Size	The sample size of 50 patients in the TFAOS study was calculated to power the primary endpoint in the study, i.e., the change in prosthetic use score. A sample size of 50 patients is also sufficient for the primary endpoints in the PAS analysis. With an alpha of 0.05, 50 subjects have >80% power to demonstrate that each primary endpoint result will be greater than 50%, assuming 70% success.
Key Study Endpoints	Primary Endpoints 1. Rate of overall success at 2 years. The overall success is the composite primary safety and effectiveness endpoint. a. Primary safety endpoint: Proportion of patients with no subsequent secondary surgical interventions and, at most, 2 superficial infections, at 2 years. b. Primary effectiveness endpoint: Proportion of patients who achieve the minimally clinically important difference (MCID) for the total Q-TFA score (mean of all subscores, i.e., prosthetic use score, prosthetic mobility score, problem score, and global score) of 20.25 points, and radiographic success, defined as no radiographic loosening of the implant with a radiolucent zone wider than the thread depth surrounding the entire implant. 2. Proportion of patients who achieved either/or/none of primary safety endpoint or primary effectiveness endpoint at 2 years. Secondary Endpoints Proportion of patients who achieved the MCID for the Q-TFA prosthetic use score (19 points), prosthetic mobility score (11 points), problem score (-23 points), and global score (33 points), individually at 2 years after stage-2 surgery. Change in each of total Q-TFA score, Q-TFA prosthetic use score, prosthetic mobility score, problem score and global score from baseline to 2 years after stage-2 surgery.
Follow-up Visits and Length of Follow-up	2 years after Stage 2 Surgery
Interim or Final Data Summary
Actual Number of Patients Enrolled	50, with 41 at Walter Reed and 9 at UCSF.
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	The follow-up rates at 2 years were 90.2% (37/41) (Enrolled: 41, no deaths, 4 subjects withdrawn) for Walter Reed patients and 33.3% (3/9) (9 enrolled, 1 death, 1 lost to follow-up, 7 remaining subjects, for whom 3 have data) for UCSF patients.
Final Safety Findings	The proportion of subjects with no subsequent secondary surgical interventions (SSI) and at most 2 superficial infections at 2 years was 65% (24/37) in the Walter Reed cohort subjects and 77.8% (7/9) in the UCSF cohort subjects.
Final Effect Findings	Effectiveness Results Walter Reed Cohort: Primary Effectiveness Endpoint: The MCID >= 20.25 of the Q-TFA score and Radiological Success was met by 33/37 (89%) subjects, MCID >= 20.25 of the Q-TFA was met by 31/37 subjects (84%) and Radiologic success was met by 36/37 (97%) patients. (1 subject had implant loosening). Secondary Effectiveness Endpoint: Proportion of subjects who achieved the MCID for the Q-TFA individually at 2 years after stage-2 surgery. It is noted between 76% and 95% of subjects (these percentages represent each of the four subsections of the Q-TFA) had an improvement at 2 years post OPRA implantation, meeting the MCID of the Q-TFA scores. UCSF Cohort: Effectiveness data was obtained for three (3) of 9 enrolled subjects at the USCF at 2-year follow up , due to the limited data made available to Integrum by the study sponsor and the clinical site. 9. The effectiveness data is difficult to interpret and not conclusive, as there is a significant amount of missing data.
Study Strengths & Weaknesses	Study Strengths and Weaknesses Strengths: The study was a prospective enrollment US cohort study with the intent to follow 50 patients for 2 years post-surgery. The study utilized the Q-TFA (Questionnaire for Persons with a Transfemoral Amputation), which is a validated patient-reported outcome measure with established minimal clinically important differences (MCIDs) for assessing prosthetic function. Weaknesses: The study has substantial missing data from UCSF (6 of 9 enrolled subjects), reducing the analyzable population from 50 to 40 subjects. This represents a 20% data loss that compromises the study's statistical power and may introduce potential selection bias. The study enrolled 50 transfemoral amputees across two US sites, representing a subset of the intended use population with appropriate demographics (86% male, 58% blast injuries) particularly for military personnel. The study results may not be generalizable to other US patients Due to Integrum does not have access to per patient data or line data, the objective of using hypothesis testing to evaluate device performance using the composite endpoint comparing to a control (performance goal) could not be performed as required in the P190009 study protocol. Hence, the change to the PAS study design (from hypothesis testing to descriptive analysis) was the most appropriate way to evaluate the final results.
Recommendations for Labeling Changes	Yes, a labeling change is recommended to update the device labeling with the final study results.
General
Study Status	Delayed
Application Number / Requirement Number	P190009 / PAS002
Date Original Protocol Accepted	02/12/2021
Date Current Protocol Accepted	08/14/2025
Study Name	Osseointegration Quality Registry PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A multicenter, prospective, observational cohort Registry to investigate 2-year and 5-year safety and effective outcomes of the OPRATM Implant System when used for transfemoral implantation in amputee patients. The Osseointegration Quality Registry is a prospective registry sponsored by Walter Reed and conducted at all sites that consent to collect data for the registry. The registry study initiated on February 11, 2019 and is sponsored by Walter Reed. WRNMMC will provide patient level study data and results to FDA per FDA requirements and guidance and in accordance with objectives, endpoints and sample size in this protocol and will provide aggregated data bi-annual reports to Integrum AB for the OI Registry OPRA Post- Approval Study. Integrum is the sponsor of the PMA (P190009) and will provide funding to WRNMMC for data entry into OI Registry database (IQAROS) and analysis of data and is responsible for Submission of aggregated data Annual Reports and final report to FDA.
Study Population	Patients at sites that choose to take part in this investigation who have the OPRA implant procedure and meet the eligibility criteria will be offered to prospectively participate in the registry. The study is being offered to all US sites that perform the OPRA implant procedure. Only OPRA patients treated transfemorally with problems using a conventional socket prosthesis OR patients anticipated to experience significant problems with socket use will be included for the registry. In addition, patients from the 2-year TFAOS study who consent to be followed long term in the registry will be included in this study.
Sample Size	85 subjects will be enrolled in the PAS registry. Up to 50 subjects will be from the other PAS study, TFAOS.
Key Study Endpoints	Endpoints Primary Endpoints: 1. Rate of overall success at 2 and 5 years. The overall success is the composite primary safety and effectiveness endpoint. a. Primary safety endpoint: Proportion of subjects with no subsequent secondary surgical interventions and, at most, 2 superficial infections, at 2 years; and no subsequent secondary surgical interventions and at most 3 superficial infections at 5 years. b. Primary effectiveness endpoint: Proportion of patients who achieve the minimally clinically important difference (MCID) from baseline to 2 and 5 years after the stage-2 surgery for the total Q-TFA score (mean of all subscores, i.e., prosthetic use score, prosthetic mobility score, problem score, and global score) of 20.25 points, and radiographic success, defined as no radiographic loosening of the implant with a radiolucent zone wider than the thread depth surrounding the entire implant. 2. Proportion of subjects who achieved either/or/none of primary safety endpoint or primary effectiveness endpoint at 2 and 5 years. Secondary Endpoints: -Proportion of subjects who achieved a significant increase in prosthetic use, individually at 2 years after the stage-2 surgery. -Change in each of total Q-TFA score, Q-TFA prosthetic use score, prosthetic mobility score, problem score and global score from baseline to 2 and 5 years after the stage-2 surgery.
Follow-up Visits and Length of Follow-up	5 years after stage-2 surgery
Interim or Final Data Summary
Interim Results	The study is not yet completed and therefore, there are no results available to date.
Actual Number of Patients Enrolled	96 (Walter Reed n=63; Atrium Health n=24, and UCSF n=9)
Actual Number of Sites Enrolled	Per R019, seven sites were enrolled. Due to the difficulty with data sharing, only one site will provide data, and that is WRNMMC.
Patient Follow-up Rate	66% (63/96)
General
Study Status	Ongoing
Application Number / Requirement Number	P190015 / PAS001
Date Original Protocol Accepted	05/04/2020
Date Current Protocol Accepted
Study Name	Cont F/u of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post approval study is to evaluate the long-term safety and effectiveness of the TREO® Abdominal Stent-Graft System. It is a prospective, multi-center, single-arm clinical study. It involves the long-term follow-up of the premarket cohort.
Study Population	The study population is patients with an infrarenal abdominal aortic aneurysm who met the study selection criteria.
Sample Size	A total of 158 subjects were enrolled in IDE Pivotal and Continued Access studies.
Key Study Endpoints	Major adverse events, all-cause mortality, aneurysm-related mortality, aneurysm rupture, secondary interventions, conversion to open surgery, losses of device integrity, device occlusions, stenosis or kink, aneurysm enlargement (> 5 mm), stent graft migration (> 10 mm), all types of endoleaks, and other device-related events.
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years, with the exception of subjects identified with fracture(s) within the first 5 years who will be offered follow-up for an additional 5 years (total of 10 years of follow-up).
Interim or Final Data Summary
Interim Results	Safety Results: Primary safety: Composite MAE* rate at 30 days: 0.7% (1/150) *Composite major adverse events: all-cause mortality, myocardial infarction, stroke, renal failure requiring renal replacement therapy, respiratory failure, paraplegia, bowel ischemia, procedural blood loss =1000cc Secondary safety: 30 days | 6 months | 1 years Death: 0% (0/150) | 1.3% (2/150) | 1.4% (2/148) Stroke: 0% (0/150) | 1.3% (2/150) | 0.7% (1/148) MI: 0.7% (1/150) | 0% (0/150) | 1.4% (2/148) Bowel ischemia: 0% (0/150) | 0.7% (1/150) | 0% (0/148) Respiratory failure: 0% (0/150) | 0% (0/150) | 0.7% (1/148) Procedural blood loss: 0% (0/150) | 0% (0/150) | 0% (0/148) Paraplegia: 0% (0/150) | 0% (0/150) | 0% (0/148) Renal Failure: 0% (0/150) | 0% (0/150) | 0% (0/148) Composite MAE* rate 6 months: 2.7% (4/150) 1 year: 2.7% (4/148) 2 years: 6.4% (9/148) 3 years: 5.7% (7/128) 4 years: 5.0% (6/119) 5 years: 9.5% (10/105) Effectiveness Results: Primary effectiveness: Treatment success* at 12 months: 93.2% (123/132) *Composite of technical success (At conclusion of index procedure, graft is patent with absence of Type I/III endoleak or aneurysm rupture), absence of aneurysm enlargement >5mm, stent-graft migration >10mm, absence of fracture conversion, rupture, Type I/III endoleak, or stent-graft occlusion Secondary effectiveness: Technical success through 30 days: 98.1% (144/147) - Endograft occlusion through 30 days: 1.3% (2/150) - Type I or III endoleak through 30 days: 0.7% (1/147) Aneurysm rupture: none Conversion to open surgery: 0 at all timepoints Stent graft migration: 1.3% (1/79) at 4 years, 0 at all other timepoints Aneurysm size change (1 year | 3 years | 5 years): No change: 53.7% (73/136) | 39.2% (40/102) | 30.0% (21/70) Decrease: 46.3% (63/136) | 55.9% (57/102) | 61.4% (43/70) Increase (total): 0% (0/136) | 4.9% (5/102) | 8.6% (6/70) Endoleaks, new and persistent (Type Ia | Type Ib | Type III) 30 days: 0.7% (1/147) | 0% | 0% 6 months: 1.5% (2/134) | 0.7% (1/134) | 0% 1 year: 0.8% (1/133) | 0% | 0% 2 years: 0.9% (1/113) | 0% | 0% 3 years: 1.0% (1/100) | 0% | 0% 4 years: 1.3% (1/79) | 0% | 0% 5 years: 1.5% (1/67) | 0% | 0% Device integrity incidence (Strut fracture | Barb fracture) Cumulative # of patients with event at 5 years: 10 | 4 Cumulative # of events at 5 years: 14 | 4 Stent-graft patency (# new occlusions) 30 days: 2 6 months: 1 All other timepoints: 0 Secondary interventions (number of interventions | subjects with any intervention) 30 days: 8 | 4.7% (7/150) 6 months: 4 | 2.0% (3/149) 1 year: 1 | 0.7% (1/144) 2 years: 3 | 2.3% (3/131) 3 years: 3 | 1.7% (2/119) 4 years: 1 | 0.9% (1/111) 5 years: 1 | 1.1% (1/92)
Actual Number of Patients Enrolled	Pivotal cohort: 150 subjects Continued access cohort: 8 subjects (not reported below)
Actual Number of Sites Enrolled	29 sites enrolled at least one subject
Patient Follow-up Rate	Clinical follow-up | Imaging follow-up of any modality 1 month: 100% (150/150) | 100% (150/150) 6 months: 93.3% (139/149) | 93.3% (139/149) 1 year: 95.1% (137/144) | 95.1% (137/144) 2 years: 90.8% (119/131) | 90.8% (119/131) 3 years: 90.8% (108/119) | 95.7% (102/119) 4 years: 86.5% (96/111) | 75.7% (84/111) 5 years: 90.2% (83/92) | 77.2% (71/92) Throughout the study, 11 subjects were lost to follow-up, 25 subjects died, and 31 subjects withdrew early.
Study Strengths & Weaknesses	Strengths: This was a prospective, consecutively enrolling study. Imaging was analyzed by a Core Lab, and a Clinical Events Committee adjudicated procedure- and device-relatedness of events. Clinical and imaging follow-up compliance were high (>86% and >75% respectively at all timepoints). Weaknesses: The study is a non-randomized study with inherent biases. The patient population enrolled was heavily represented by white (98.0%) and male (88.0%) subjects. Limited data is available for other populations.
General
Study Status	Ongoing
Application Number / Requirement Number	P190015 / PAS002
Date Original Protocol Accepted	07/31/2020
Date Current Protocol Accepted	10/30/2020
Study Name	TREO Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The TREO Post Approval Study is a multi-center, open label, single arm, prospective post approval study. The objective of the study is to collect real world safety and effectiveness outcomes of the TREO Abdominal Stent-Graft System in an all-comers population eligible for the endovascular treatment of AAA in routine clinical practice, with emphasis on subjects that experience a device stent-strut or barb fracture.
Study Population	All-comers population
Sample Size	A minimum of 300 subjects will be enrolled.
Key Study Endpoints	The primary endpoints are stent fracture, barb separation, and secondary intervention for adverse events related to stent fracture or barb separation. Additional endpoints will be collected and reported at each follow-up point through 5 years post procedure, including but not limited to the following: technical success, major adverse events, all-cause mortality, aneurysm-related mortality, aneurysm rupture, secondary interventions, conversion to open surgery, losses of device integrity, device occlusions, stenosis or kink, aneurysm enlargement (> 5 mm), stent graft migration (> 10 mm), all types of endoleaks, and other device-related events.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: Note that data is reflective of the most recent interim report inclusive of events at all available follow-up timepoints. All-Cause Mortality* 53 deaths Aneurysm-Related Mortality (CEC)* 2 events reported. These occurred within 30 days of the procedure and were adjudicated by the CEC as related to the procedure but not related to the device. Rupture (CEC)* 2 events reported *Through 5-year follow-up available to date. Effectiveness Results: Note that data is reflective of the most recent interim report. Subjects are still in follow-up and data will be updated as longer-term follow-up is available. Aneurysm Enlargement >5 mm (New + Persistent)** 1 Year: 4.5% (12/267) 2 Year: 7.6% (17/223) 3 Year: 9.6% (15/157) 4 Year: 14.3% (7/49) 5 Year: 25.0% (1/4) Type Ia | Type Ib | Type III Endoleak (New + Persistent)** 30 Day: 0.6% (2/311) | 0.6% (2/311) | 0.6% (2/311) 1 Year: 0.0% (0/263) | 0.0% (0/263) | 0.0% (0/263) 2 Year: 1.0% (2/209) | 0.0% (0/209) | 0.5% (1/209) 3 Year: 0.0% (0/149) | 0.0% (0/149) | 0.0% (1/149) 4 Year: 0.0% (0/41) | 0.0% (0/41) | 0.0% (0/41) 5 Year: 0.0% (0/4) | 0.0% (0/4) | 0.0% (0/4) Stent-Graft Migration > 10mm** 1 observation reported Stent-strut Fracture or Barb Break** 30 Day: 0.0% (0/261) 1 Year: 1.3% (3/223) 2 Year: 1.5% (3/203) 3 Year: 4.1% (6/145) 4 Year: 4.3% (2/47) 5 Year: 0.0% (0/2) Stent-strut fractures and barb breaks have not been associated with any clinical sequelae. Stent-graft Occlusion (New + Persistent)** 30 Day: 2.9% (9/314) 1 Year: 3.8% (10/263) 2 Year: 1.0% (2/207) 3 Year: 1.3% (2/149) 4 Year: 2.3% (1/43) 5 Year: 0.0% (0/4) **Core Laboratory reported observations. Denominator is number of subjects with adequate imaging to assess the event in the given time window, per Core Laboratory determination.
Actual Number of Patients Enrolled	337 Subjects
Actual Number of Sites Enrolled	41 sites enrolled subjects
Patient Follow-up Rate	Note that data is reflective of the most recent interim report (data cut of January 30, 2026). Many subjects are still in follow-up windows for 3-years and beyond; and data will be updated as longer-term follow-up is available. Clinical Visit Performed 30 Day: 95.0% (320/337) 1 Year: 83.6% (266/318) 2 Year: 79.4% (227/286) 3 Year: 69.9% (165/236) 4 Year: 41.3% (57/138) 5 Year: 8.0% (2/25) Imaging Adequate to Assess Key Parameters: Diameter | Endoleak | Migration | Fracture or Barb Break 30 Day: 94.1% (317/337) | 92.3% (311/337) | 91.7% (309/337) | 77.4% (261/337) 1 Year: 83.6% (266/318) | 81.8% (260/318) | 80.8% (257/318) | 70.1% (223/318) 2 Year: 78.7% (225/286) | 72.0% (206/286) | 78.0% (223/286) | 71.0% (203/286) 3 Year: 66.9% (158/236) | 62.7% (148/236) | 66.1% (156/236) | 61.4% (145/236) 4 Year: 34.8% (48/138) | 29.7% (41/138) | 37.0% (51/138) | 34.1% (47/138) 5 Year: 8.0% (2/25) | 8.0% (2/25) | 8.0% (2/25) | 8.0% (2/25)
General
Study Status	Completed
Application Number / Requirement Number	P190019 / PAS002
Date Original Protocol Accepted	12/16/2020
Date Current Protocol Accepted	09/22/2023
Study Name	Range Long Balloon, Ranger China & COMPARE I f/u
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) Ranger™ Paclitaxel Coated Balloon in the 120, 150 and 200 mm lengths for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions. COMPARE I Study: To compare two different Paclitaxel coated balloons in the treatment of high grade stenotic or occluded lesions in SFA and/or PPA in PAD patients with Rutherford class 2-4. The trial is to investigate the safety and efficacy of the Ranger™ Drug Coated Balloon in comparison to the IN.PACT™ Drug Coated Balloon in patients with symptomatic femoropopliteal artery disease.
Study Population	Ranger DCB COMPARE I Study: Subjects with peripheral artery disease (PAD) ranging from intermittent claudication to critical limb ischemia (Rutherford Category 2-4).
Sample Size	Long Balloon Study: 50 China Study: 123 COMPARE I Study: 414 Total 207: Ranger DCB
Key Study Endpoints	Long Balloon Study: The primary safety endpoint assesses the occurrence of Major Adverse Events (MAE) defined as all-cause death through 1 month, target limb major amputation and/or target lesion revascularization (TLR) at 6 and 12 months post-index procedure. The primary effectiveness endpoint assesses primary lesion patency at 6 months as determined by duplex ultrasound (DUS). Mortality Status Annually China Study: The primary safety endpoint is the rate of following major adverse events through 30 days post-procedure: all device and/or procedure related mortality target limb major amputation at Clinically-driven Target Lesion Revascularization (TLR) The primary efficacy endpoint is primary lesion patency of the treated segment(s) as assessed by computed tomography angiography (CTA) at 12 months post-procedure without clinically-driven TLR. Mortality Status Annually COMPARE I Study: Primary Efficacy: patency rate after one year defined as absence of clinically driven TLR (due to symptoms and drop of ABI of greater than or equal to 20% or > 0.15 when compared to post-procedure) or restenosis with PVR > 2.4 evaluated by Duplex Ultrasound. Primary Safety: Composite of freedom from device and procedure-related death through 12 months post procedure as well as freedom from both target limb major amputation and clinically-driven target vessel revascularization. Mortality Status Annually
Follow-up Visits and Length of Follow-up	1 year COMPARE I Study: 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Long Balloon Substudy: 52 enrolled. Ranger China Study: 123 enrolled. COMPARE I Study: 414 enrolled (Ranger DCB – 207 / In.Pact DCB – 207).
Actual Number of Sites Enrolled	Long Balloon Substudy: 7 sites enrolled. Ranger China Study: 10 sites enrolled. COMPARE I Study: 15 sites enrolled.
Patient Follow-up Rate	Long Balloon Substudy: 92.3% Ranger China Study: 89.4% COMPARE I Study: Ranger DCB – 74.9% / In.Pact DCB – 67.6%
Final Safety Findings	Long Balloon Substudy: 12 Months MAE Free-Ranger DCB was 94.0% (47/50). Mortality at 12 month follow up was 5.8% (3/52). One additional death was reported after the 12 month follow up window (4 deaths total). Ranger China Study: 12 Months MAE Free-Ranger DCB for the ITT and PP set was 96.6% (115/119). Mortality at 12 month follow up was 2.5% (3/122). COMPARE I Study: 36 Months MAE Free-Ranger DCB (72.5%) and In.Pact DCB (78.6%). Mortality at 36 month follow up: 7.7% (13/168) for Ranger DCB and 6.0% (9/149) for In.PACT Admiral.
Final Effect Findings	Long Balloon Substudy: Primary Patency Rate was 83.0% (39/47). Ranger China Study: Initial vascular patency for the Ranger DCB ITT and PP set was 61.5% (64/104). COMPARE I Study: Primary patency rate for the Ranger DCB was 83.0% (156/188) and 65.6% (116/177) at 12 and 24 months, respectively.
Study Strengths & Weaknesses	Long Balloon Substudy: Strength – Includes data for worst case drug usage / Weakness - Low sample size, non-blinded. Ranger China Study: Strength – Prospective and multi-center study / Weakness – Only one country. COMPARE I Study: Strength – Large Sample Size, Prospective and multi-center study, 1:1 randomized clinical trial / Weakness – Only conducted in EU.
Recommendations for Labeling Changes	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S125/ PAS001
Date Original Protocol Accepted	05/13/2021
Date Current Protocol Accepted	05/13/2021
Study Name	SAPIEN 3 & SAPIEN 3 Ultra Mitral ValveInRing Surv
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objective of the surveillance is to continue to monitor the performance of the Edwards SAPIEN 3 and SAPIEN 3 Ultra THV System in the real-world setting.
Study Population	Patients with symptomatic heart disease due to failing of a native mitral valve with an annuloplasty ring who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality greater than or equal to 8% at 30 days, based on the Society of Thoracic Surgeons (STS) risk score and other clinical co-morbidities unmeasured by the STS risk calculator).
Sample Size	All consecutive patients treated within the first 5 years after the PMA approval that are entered into the TVT Registry.
Key Study Endpoints	(1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; and (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months.
Follow-up Visits and Length of Follow-up	1 year
Interim or Final Data Summary
Interim Results	Safety Results: Procedural Outcomes: Device implanted successfully: 91.2% (343/376) Safety outcomes at 1 Year: All-cause death: 30.8% Cardiac death: 14.5% All stroke: 2.6% Mitral valve reintervention: 8.0% Life threatening/major bleeding: 6.9% New requirement for dialysis: 5.6% Vascular complications: 5.6% Effectiveness outcomes at 1 Year: Improvement from baseline in NYHA function classification: 70.3% KCCQ Overall Summary Score change from baseline: 28.4 Effective Orifice Area: 1.82 cm2 Mean Gradient: 7.8 mmHg Moderate or greater total mitral regurgitation: 2.3% Moderate or greater paravalvular mitral regurgitation: 3.0%
Actual Number of Patients Enrolled	376 patients (Attempted Implant); 373 patients (valve implanted)
Actual Number of Sites Enrolled	183
Patient Follow-up Rate	At 1 year, subject status was known in 76.9% of subjects (188 visits completed, 96 dead, 5 visit not completed but alive)
General
Study Status	Terminated
Application Number / Requirement Number	P190020 / PAS001
Date Original Protocol Accepted	04/14/2022
Date Current Protocol Accepted
Study Name	LEADERS FREE II (LFII) Clinical Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objectives of the LFII study were to confirm the reproducibility and the generalizability of the primary findings of the prospective, double blind, randomized LEADERS FREE Study in an independent clinical cohort with substantial North American enrollment.
Study Population	patients with coronary artery disease at high risk for bleeding for the treatment of de novo lesions in native coronary arteries with a reference diameter ranging between 2.25 mm and 4.0 mm
Sample Size	2449 patients were consented for the LEADERS FREE II study. Among these, 1246 were screen failures, leaving 1203 patients included in the study. The most common reason for screen failure was the failure to meet one or more inclusion criteria, occurring in 92.5% (1153/1246) screen failed patients.
Key Study Endpoints	Safety The composite of cardiac death and myocardial infarction at six months. Efficacy The incidence of clinically driven target lesion revascularization at six months.
Follow-up Visits and Length of Follow-up	36 months
General
Study Status	Ongoing
Application Number / Requirement Number	P180051 S001/ PAS001
Date Original Protocol Accepted	04/27/2022
Date Current Protocol Accepted
Study Name	Continued FU of the DCD Heart Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects enrolled under IDE G180272, including the Continued Access Protocol subjects. The objective of this study is to characterize the clinical outcomes of these subjects annually through 5 years post-transplant.
Study Population	All living subjects enrolled under IDE G180272, including the Continued Access Protocol subjects.
Sample Size	All living subjects
Key Study Endpoints	patient survival, cardiac-related patient survival, and heart graft survival through 5 years post-transplan.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: see effectiveness results Effectiveness Results: Patient survival: 80.6%% at 4 years (pivotal DCD) vs. 75.8%% at 4 years (pivotal SOC); 80.3% at 3 years (CAP DCD) Cardiac-related patient survival: 95.1% at 4 years (pivotal DCD) vs. 95.7% at 4 years (pivotal SOC); 93.8% at 3 years (CAP DCD) Graft survival 96.4% at 4 years (pivotal DCD) vs. 96.7% at 4 years (pivotal SOC); 94.3% at 3 years (CAP DCD) Patient and graft survival: 79.5% at 4 years (pivotal DCD) vs. 74.2% at 4 years (pivotal SOC); 77.5% at 3 years (CAP DCD)
Actual Number of Patients Enrolled	270 (including 90 DCD patients and 90 SOC patients in the pivotal trial as well as 90 DCD patients in the CAP investigation)
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	Pivotal: 98.9% at 4 years CAP: 98.9% at 3 years
General
Study Status	Delayed
Application Number / Requirement Number	P130008 S089/ PAS001
Date Original Protocol Accepted	05/19/2023
Date Current Protocol Accepted	10/22/2025
Study Name	Inspire UAS New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multi-center, single-arm study of pediatric subjects (age 13-18) with Down syndrome who are undergoing implant of the Inspire Upper Airway Stimulation (UAS) system for the treatment of severe obstructive sleep apnea (OSA). Subjects will be followed for five (5) years post-implant. The objective of the study is to provide an ongoing safety and effectiveness assessment of the Inspire UAS System in the Pediatric Down syndrome population.
Study Population	Study Population Patients with Severe OSA with Down syndrome who are implanted with Inspire UAS Prospective Participants: In Lab PSG annually. Roll-over participants: Any data reported as an interim data in IDE 200322 will be utilized in the study.
Sample Size	Number of subjects: 60
Key Study Endpoints	Endpoints Safety : device and procedure related events Effectiveness: AHI change ODI Change Change ESS-CHAD
Follow-up Visits and Length of Follow-up	Follow-up Prospective participants will be enrolled in the study prior to implant. Data for each implanted subject will be collected at the following timepoints: • Baseline • Implant • 1 Week Post-op • Activation (1 Month Post-Implant) • 2 Months Post-Implant • 3 Months Post-Implant • 4 Months Post-Implant • 6 Months Post-Implant • 1, 2, 3, 4, 5 Years Post-Implant • Interim Visits (if applicable) Roll-over Participants will undergo prospective study visits depending on the timing of their enrollment into this post-approval study and the length of time since they’ve been implanted with the Inspire System. Baseline, Implant and follow-up data through 1 year will be rolled over from the IDE (G200322) study. Retrospective data will be collected (as available) from the time of study exit (from IDE G200322) until enrollment into this PAS. Once the patient is enrolled into the PAS, prospective study visits will begin according to where the patient is at in the visit schedule.
General
Study Status	Delayed
Application Number / Requirement Number	P160017 S091/ PAS001
Date Original Protocol Accepted	06/15/2023
Date Current Protocol Accepted	09/29/2026
Study Name	MiniMed 780G New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	Safety Results: The sponsor reported that there were 24 severe hypoglycemia, 13 diabetic ketoacidosis (DKA), and 55 hospitalization events related to the use of the MiniMed 780G system collected via biweekly surveys and/or Technical Support during the analysis period. A total of 2,212 adverse events (AE) were reported through surveys or Technical Support during the analysis period, including 7 deaths, 77 occurrences of inflammation and/or blister formation affecting the skin, 2,009 occurrences of hematoma/hemorrhage/bleeding, 429 hypoglycemia events, and 3 absence seizure event. Effectiveness Results: Participants demonstrated time in the target range (TIR) of 78.4±11.3% and a maximum mean TIR of 78.8±11.2% with use of the pump system 99.8±2.3% to 99.8±2.9%, and SmartGuard use 91.4±15.4% to 91.8±15.0% across the four 3-month periods observed after completion of the first survey. Participants reported a mean HbA1c of 6.9±0.7% across all four of the 3-month periods observed after completion of the first survey.
Actual Number of Patients Enrolled	2619
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	The sponsor reported that the biweekly survey return rate is 89.02%. The sponsor did not provide return rates for each age cohort or report whether any participants have been lost to follow-up.
General
Study Status	Ongoing
Application Number / Requirement Number	P190023 S002/ PAS002
Date Original Protocol Accepted	01/13/2023
Date Current Protocol Accepted	01/13/2023
Study Name	Registry-Based Real-World Use Surveillance Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of this PAS is to confirm the long-term safety and effectiveness of the Navitor valve for patients at high or greater surgical risk, undergoing TAVR with the Navitor valve and FlexNav delivery system (DS) in a contemporary real-world setting. The study is an observational real-world surveillance study
Study Population	All patients that have undergone attempted TAVR with Navitor valve (23, 25, 27, or 29-mm sizes) using FlexNav Delivery System at a TVT Registry participating site, from the date of PMA approval (January 13, 2023) through January 13, 2025, who are at “high or greater risk” of mortality with open surgery.
Sample Size	There is no minimum sample size. The PAS will include all consecutive patients who have a Navitor valve with FlexNav Delivery System implant attempt at institutions participating in the STS/ACC TVT Registry within the first 2 years following PAS start date.
Key Study Endpoints	This surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, new pacemaker implant, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually at 2-5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Interim Results	Safety Results • 30-days endpoints: o All-cause mortality = 2.9% o All stroke = 2.7% o Life threatening or major bleeding = 0.6% o New requirement for dialysis = 0.4% o New permanent pacemaker implantation = 17.2% o Peri-procedural myocardial infarction = 0.4% o Reintervention – Aortic valve related = 0.3% o Neurological (TIA / non-stroke) events = 0.3% o Major vascular complications = 1.8% o Minor vascular complications = 4.0% o Kansas City Cardiomyopathy Questionnaire (KCCQ) – 75.9 (51.8 pre-procedure) • 1-year endpoints: o All-cause mortality = 12.6% o All stroke = 4.5% o Life threatening or major bleeding = 2.8% o New requirement for dialysis = 0.9% o New permanent pacemaker implantation = 19% o Peri-procedural myocardial infarction = 1.9% o Reintervention – Aortic valve related = 0.6% o Neurological (TIA / non-stroke) events = 0.9% o Major vascular complications = 1.9% o Minor vascular complications = 4.1% o Kansas City Cardiomyopathy Questionnaire (KCCQ) – 80.6 (51.8 pre-procedure)
Actual Number of Patients Enrolled	3380
Actual Number of Sites Enrolled	203
Patient Follow-up Rate	Of the 3380 patients who underwent a Navitor procedure, 3301 patients (97.7%) had a discharge visit completed. Patients alive that have reached the start of the follow-up window: 3061/3229 patients (94.8%) completed their 30-day visit; and 1513/2946 (51.3%) completed their 1-year visit and 1433 do not have data available yet.
General
Study Status	Ongoing
Application Number / Requirement Number	P200045 S002/ PAS001
Date Original Protocol Accepted	03/07/2023
Date Current Protocol Accepted
Study Name	Cont f/u Dissection Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multicenter, non-blinded, non-randomized study designed to assess the RelayPro thoracic endografts in the treatment of acute, complicated type B aortic dissection that consists of continued follow-up of all available subjects from the IDE Pivotal Study.
Study Population	Subjects with acute, complicated type B aortic dissections.
Sample Size	A total of 56 subjects were enrolled in the IDE Pivotal Study.
Key Study Endpoints	Clinical outcomes will include all-cause mortality, lesion-related mortality, major adverse events, false lumen perfusion, retrograde extension, fistula formation, stent graft kinking or twisting, patency, device misalignment, stent fracture, secondary interventions, conversion to open repair, occlusions, stenosis, all types of endoleaks, stent graft migration (>10 mm), aortic expansion (>5 mm), aortic rupture, loss of device integrity, and other device-related events
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P200045 S002/ PAS002
Date Original Protocol Accepted	03/07/2023
Date Current Protocol Accepted
Study Name	Cont f/u Transection Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multicenter, non-blinded, non-randomized study of the RelayPro Thoracic Stent-Graft in subjects with traumatic injury of the descending thoracic aorta (DTA) in subjects who are candidates for endovascular repair that consists of continued follow-up of all available subjects from the IDE Pivotal Study.
Study Population	Subjects with traumatic injury of the DTA in subjects who are candidates for endovascular repair.
Sample Size	A total of 50 subjects were enrolled in the IDE Pivotal Study.
Key Study Endpoints	Clinical outcomes include all-cause mortality, lesion-related mortality, major adverse events, secondary interventions, conversion to open repair, occlusions, stenosis or kink, all types of endoleaks, stent graft migration (>10 mm), aortic dilatation (>5 mm), aortic rupture, compression, erosion, extrusion, stent-graft infection, stent-graft thrombosis, intra-graft thrombus formation, loss of device integrity, and other device-related events.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P190023 S013/ PAS002
Date Original Protocol Accepted	09/15/2023
Date Current Protocol Accepted
Study Name	Registry-Based Real-World Use Surv Navitor Titan
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of this PAS is to confirm the long-term safety and effectiveness of the Navitor Titan valve for patients at high or greater surgical risk, undergoing TAVR with the Navitor Titan Transcatheter Aortic Valve System in a contemporary real-world setting. The study is an observational real-world surveillance study
Study Population	All patients that have undergone attempted TAVR with Navitor Titan valve at a TVT Registry participating site, from the date of PMA approval (January 13, 2023) through January 13, 2025, who are at “high or greater risk” of mortality with open surgery.
Sample Size	There is no minimum sample size. The PAS will include all consecutive patients who have a Navitor Titan valve implant attempt at institutions participating in the STS/ACC TVT Registry within the first 2 years following PAS start date.
Key Study Endpoints	This surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, new pacemaker implant, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually at 2-5 year post implantation.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Interim Results	Safety Results • 30-days endpoints: o All-cause mortality = 6.3% o All stroke = 3.1% o Life threatening or major bleeding = 0.0% o New requirement for dialysis = 0.6% o New permanent pacemaker implantation = 25.4% o Peri-procedural myocardial infarction = 0.6% o Reintervention – Aortic valve related = 1.3% o Neurological (TIA / non-stroke) events = 1.3% o Major vascular complications = 0.6% o Minor vascular complications = 3.8% o Kansas City Cardiomyopathy Questionnaire (KCCQ) - 78.0 (52.5 pre-procedure)
Actual Number of Patients Enrolled	161
Actual Number of Sites Enrolled	67
Patient Follow-up Rate	Of the 161 patients who underwent a Titan procedure, 153 patients (95%) had a discharge visit completed. Patients alive that have reached the start of the follow-up window: 143/147 patients (97%) completed their 30-day visit.
General
Study Status	Completed
Application Number / Requirement Number	P190023 / PAS001
Date Original Protocol Accepted	09/17/2021
Date Current Protocol Accepted
Study Name	Cont f/u of the PORTICO IDE cohorts
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study objective is to characterize the acute safety and effectiveness of the Portico Transcatheter Aortic Heart Valve through 5 years post procedure in patients with symptomatic, severe aortic stenosis who are considered high or greater surgical risk. The study is a prospective, multi-center, randomized controlled trial (RCT) that also included non-randomized arms: Roll-in Registry, FlexNav Study, Extreme Risk Registry and Valve-in-Valve (ViV) Registry.
Study Population	Patients with symptomatic, severe aortic stenosis who are considered high or extreme surgical risk.
Sample Size	All living subjects enrolled under the IDE Portico approval studies, including all analysis, registry, roll-in, and continued access cohorts
Key Study Endpoints	The safety and effectiveness endpoints include, but are not limited to: · all-cause mortality, · all-cause and disabling stroke, · life-threatening and major bleeding events, · stage 2 or 3 acute kidney injury, · major vascular complications, · paravalvular aortic regurgitation, · myocardial infarction, · re-operation for valve-related dysfunction, · rehospitalization for valve-related symptoms or worsening congestive heart failure, · new permanent pacemaker implantation, · new-onset atrial fibrillation, · functional status as evaluated by New York Heart Association (NYHA), · health status as evaluated by Kansas City Cardiomyopathy Questionnaire (KCCQ), and · hemodynamic performance metrics by echocardiography.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	Total: 1242 subjects enrolled in the pivotal IDE trial: Randomized (RCT) Portico group (n=381), Randomized (RCT) control (CAV) group (n=369) CAP Study (n=148), FlexNav Study (n=134; total includes 34 roll-ins), Roll-In Registry (n=197) Extreme Risk Registry (n=13).
Actual Number of Sites Enrolled	Sites enrolled: 65 US sites, 5 AUS sites
Patient Follow-up Rate	Total Duration (excluding deaths and withdrawals): RCT Portico: 95.7% RCT CAV: 95.8% CAP: 96% FlexNav: 97.5%; Roll-in: 96.8%; Extreme Risk: 80.2%; At 60 months (excluding deaths and withdrawals): RCT Portico: 93.5% RCT CAV: 94.8% CAP: 95.6% FlexNav: 94.1%; Roll-in: 93.8%; Extreme Risk: 0.0%
Final Safety Findings	At 60 months – RCT Portico, RCT CAV, FlexNav, Roll-in and CAP: All-cause mortality: 51.7% (RCT Portico), 48.2% (RCT CAV), 46.4% (FlexNav), 55.4% (Roll-in), 54.6% (CAP) All stroke: 11.5% (RCT Portico), 12.9% (RCT CAV), 10.6% (FlexNav), 18.4% (Roll-in), 19.2% (CAP) Myocardial infarction: 9.7% (RCT Portico), 8.8% (RCT CAV), 10.6% (FlexNav), 11.3% (Roll-in), 9.3% (CAP) Reintervention: 3.8% (RCT Portico), 1.2% (RCT CAV), 1.5% (FlexNav), 1.2% (Roll-in), 1.9% (CAP) Rehospitalization for valve-related symptoms: 13.6% (RCT Portico), 12.0% (RCT CAV), 10.3% (FlexNav), 21.0% (Roll-in), 15.9% (CAP) New permanent pacemaker implantation: 36.3% (RCT Portico), 20.6% (RCT CAV), 19.7% (FlexNav), 29.5% (Roll-in), 36.1% (CAP) New-onset atrial fibrillation: 18.5% (RCT Portico), 15.8% (RCT CAV), 21% (FlexNav), 16.9% (Roll-in), 15.2% (CAP) At 48 months – Extreme Risk: All-cause mortality: 43.4% (100% at 60 months) All stroke: 0.0% Myocardial infarction: 12.5% Reintervention: 0.0% Rehospitalization for valve-related symptoms: 19.2% New permanent pacemaker implantation: 11.1% New-onset atrial fibrillation: 9.1%
Final Effect Findings	At 60 months – RCT Portico, RCT CAV, FlexNav: New York Heart Association (NYHA) functional classification (% in Class III/IV): 6.5% (RCT Portico), 11.4% (RCT CAV), 11.1% (FlexNav) Kansas City Cardiomyopathy Questionnaire (KCCQ) score: 73.2 +/- 21.7 (RCT Portico), 74.5 +/- 23.8 (RCT CAV), 70.2 +/- 21.4 (FlexNav) Transvalvular mean gradient: 7.6 +/- 4.7 mmHg (RCT Portico), 9.3 +/- 6.5 mmHg (RCT CAV), 5.6 +/- 2.6 mmHg (FlexNav) Aortic valve area: 1.79 +/- 0.47 cm2 (RCT Portico), 1.69 +/- 0.50 cm2 (RCT CAV), 1.92 +/- 0.48 cm2 (FlexNav) Greater than or equal to Moderate Paravalvular Leak: 2.4% (RCT Portico), 0.0% (RCT CAV), 3.0% (FlexNav)
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through 5 years) on the safety and effectiveness of the Portico valve in patients with severe symptomatic aortic stenosis at high or greater surgical risk. Generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvement in quality of life outcomes and hemodynamic performance. It should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results.
Recommendations for Labeling Changes	Complete longer-term follow-up data warrants inclusion into the labeling for the device and should be informative to clinicians and patients regarding the longer-term benefit risk profile for the device.
General
Study Status	Ongoing
Application Number / Requirement Number	P190023 / PAS002
Date Original Protocol Accepted	11/12/2021
Date Current Protocol Accepted	01/13/2023
Study Name	Registry-Based Real World use Surv of the Portico
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of this Portico PAS is to confirm the long-term safety and effectiveness of the Portico valve for patients undergoing TAVR with the Portico valve and FlexNav delivery system (DS) in a contemporary real-world setting. The study will be a prospective, single-arm, multi-center, observational real-world surveillance study.
Study Population	All patients that have undergone attempted TAVR with Portico valve (23, 25, 27, or 29-mm sizes) using FlexNav Delivery System at a TVT Registry participating site, from the date of PMA approval (September 17, 2021) through September 24, 2023.
Sample Size	There is no minimum sample size. The PAS will include all consecutive patients who have a Portico valve with FlexNav Delivery System implant attempt at institutions participating in the STS/ACC TVT Registry within the first 2 years following PAS start date.
Key Study Endpoints	This surveillance will monitor the following: (1) device success (intra-procedure); (2) all-cause mortality, all stroke, life-threatening/major bleeding, new requirement for dialysis, new pacemaker implant, peri-procedural myocardial infarction, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) at 30 days and 12 months; (3) neurological (non-stroke), vascular complications, and quality of life (KCCQ) outcomes at 30 days and 12 months; and (4) all-cause mortality, all stroke, and repeat procedure for valve-related dysfunction (surgical or interventional therapy) annually at 2-5 year post implantation.
Follow-up Visits and Length of Follow-up	Successfully implanted patients will be followed through one (1) year via STS/ACC TVT Registry and through five (5) years via CMS claims data linkage. Patients with attempted but unsuccessful implants with the Portico valve will be followed through 30 days post-procedure.
Interim or Final Data Summary
Interim Results	Safety Results TVT Registry: • 30-days endpoints: o All-cause mortality = 3.2% o All stroke = 3.0% o Life threatening or major bleeding = 1.1% o New requirement for dialysis = 0.2% o New permanent pacemaker implantation = 17.0% o Peri-procedural myocardial infarction = 0.0% o Reintervention – Aortic valve related = 0.4% o Neurological (TIA / non-stroke) events = 0.2% o Major vascular complications = 1.2% o Minor vascular complications = 3.8% o Kansas City Cardiomyopathy Questionnaire (KCCQ) - 73.6 (49.7 pre-procedure) • 1-year endpoints: o All-cause mortality = 14.2% o All stroke = 5.4% o Life threatening or major bleeding = 5.7% o New requirement for dialysis = 0.9% o New permanent pacemaker implantation = 19.3% o Peri-procedural myocardial infarction = 1.8% o Reintervention – Aortic valve related = 1.1% o Neurological (TIA / non-stroke) events = 2.0% o Major vascular complications = 1.2% o Minor vascular complications = 4.5% o Kansas City Cardiomyopathy Questionnaire (KCCQ) - 81.6 (49.7 pre-procedure) TVTR-CMS Linked: • 30-days endpoints: o All-cause mortality = 3.1% o All stroke = 2.3% o Reintervention – Aortic valve related = 0.2% • 1-year endpoints: o All-cause mortality = 12.3% o All stroke = 5.1% o Reintervention – Aortic valve related = 1.2%
Actual Number of Patients Enrolled	584 TVTR; 488 TVTR-CMS linked
Actual Number of Sites Enrolled	29
Patient Follow-up Rate	Of the 584 patients who underwent a Portico procedure, 566 patients (96.9%) had a discharge visit completed. Patients alive that have reached the start of the follow-up window: 517/553 patients (93.5%) completed their 30-day visit and 346/511 patients (67.7%) completed their 1-year visit. For 1-year follow-up, of the 584 patients: 69 have died, 4 have not yet reached the start of window, and 165 do not have data available yet.
General
Study Status	Completed
Application Number / Requirement Number	P190027 / PAS001
Date Original Protocol Accepted	04/10/2020
Date Current Protocol Accepted
Study Name	TOBA II BTK Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	TOBA II BTK Continued Follow-Up Study. This study should be conducted per protocol CA 0137, Rev C (dated September 14, 2017). This study is a prospective, multi-center follow up of the TOBA II BTK pivotal study (G160144) that treated 233 subjects from 41 investigational sites. It will evaluate the long-term safety and effectiveness of the Tack Endovascular System® (4F, 1.5-4.5mm). All 205 remaining subjects, active at the end of the 6-month evaluation, will continue to be followed annually through 36 months.
Study Population	Continued follow-up of the IDE cohort
Sample Size	205 remaining IDE subjects, active at the end of the 6-month evaluation
Key Study Endpoints	Follow-up at the 1, 2- and 3-year timepoints will include the following: Rutherford Classification Wound, Ischemia, and foot Infection (WIfI) grade wound assessment target limb resting ABI EQ-5D-3L Walking Impairment Questionnaire (WIQ) major adverse event (MAE) occurrence adverse event occurrence review of concomitant medications (antiplatelets/anticoagulants). Follow-up at the 1-year timepoint will also include duplex ultrasound (DUS) and X-ray assessment of implanted Tacks.
Follow-up Visits and Length of Follow-up	3 years post-procedure
Interim or Final Data Summary
Interim Results	Freedom from amputation of the target limb (above the knee), clinically driven TVR, clinically driven TLR and survival at 24 months (750 days) was 94.4%, 73.1%, 73.6% and 78.0% respectively.
Actual Number of Patients Enrolled	A total of 233 subjects were enrolled in the study; 205 subjects were available at 6 months for the continued follow-up study
Actual Number of Sites Enrolled	41 sites across the US and outside the US
Patient Follow-up Rate	83.6% (143/171) at 24months and 91.6% (120/131) at 36 months
Final Safety Findings	Primary Safety and Effectiveness The TOBA II BTK study met both its primary safety and effectiveness endpoints. The primary safety endpoint of major adverse limb events (MALE) plus perioperative death (POD) at 30 days) was 1.3% [95% confidence interval (CI): 0.3%, 3.8%] in the ITT group and 0.9% [95% CI: 0.1%, 3.4%] in the PP group, compared to the 12% performance goal (PG). The primary effectiveness endpoint of freedom from major adverse limb events (MALE) at 6 months + perioperative death (POD) at 30 days) was 95.7% (95% CI: 91.9%,97.8%) in the intent to treat (ITT) group and 95.9% [95% CI:92.0%,98.0%] in the per protocol population compared to 74% PG. Secondary Endpoints Tacked Segment Patency and Assisted Tacked Segment Patency at 12 months in ITT patients was 76.9% [95% CI :71.8%, 81.9%] each. Secondary Tacked Segment Patency and Target Segment PSVR patency at 12 months in ITT patients was 87.6% [95% CI: 83.4%,91.7%) and 63.7% [95% CI: 57.8%,69.6%] respectively. Tack embolization, migration or fracture at 12 months in ITT patients was 0.0% (0/146) [95% CI: 0.0%,2.5%] for each event. The Kaplan Meier (KM) freedom from amputation of the target limb in ITT patients was at 36 months 95% [95% CI: 91.8%, 98.3%]. The KM freedom from survival at 36 months in ITT patients was 66.0% [95% CI: 58.7%, 73.3%]. A total of 64 patients died in the study. Sixty-three (63) of the 64 deaths were adjudicated by the Clinical Events Committee (CEC) to be unrelated to the study procedure and one (1) was adjudicated to be unknown. All 64 deaths were adjudicated by the CEC to be unrelated to the device. Freedom from clinically driven target vessel revascularization in ITT patients at 36 months was 67.4% with 95% confidence interval (59.6%, 75.1%). The KM freedom from clinically driven target lesion revascularization in ITT patients at 36 months was 69.6% [ 95% CI: 62.6%, 76.7%]. Freedom from major adverse limb events (MALE) plus perioperative death (POD) in ITT patients at 36 months was 91.6% [95 % CI: 87.6%, 95.6%]. Significant improvement in measured Rutherford class occurred in ITT patients from baseline to 12, 24, and 36 months (p<0.0001). Significant positive changes in measured ABI and TBI in the target limb occurred in ITT patients from baseline to 12, 24, and 36 months (p<0.0001). Significant improvement in wound grade occurred in ITT patients from baseline to 12, 24 and 36 months (P<0.0001). Significant improvement occurred in foot infection grade in ITT patients from baseline to 12 months (0.0119), 24 months (<0.0001 and 36 months (P=0.0002). Significant positive changes occurred in EQ-VAS score in ITT patients from baseline to 12 months (p=0.0004), 24 months (p=0.0035) and 36 months (p=0.0178) and Walking Impairment Questionnaire (overall) occurred from baseline to 12, 24, and 36 months (p < 0.0001). No unanticipated device effect occurred in the study.
Study Strengths & Weaknesses	The study met both safety and effectiveness endpoints. However, this was not a randomized trial. The continued follow-study results were not evaluated with formal hypothesis testing.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the continued post approval study. The labeling change should include a new section in the label showing a summary of the post- approval study results (final endpoint results, follow-up rate etc.), strengths and limitations of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P170019 S017/ PAS001
Date Original Protocol Accepted	05/06/2022
Date Current Protocol Accepted
Study Name	NTRK Clinical Efficacy PAS for Larotrectinib
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This clinical post-approval study (PAS) is being conducted to confirm the clinical efficacy of F1CDx assay in detecting the NTRK 1/2/3 fusions positive patients for treatment with larotrectinib using solid tumors. This study is intended to fulfill the clinical PAS issued in the approval order for P170019/S017. The objective of this PAS validation protocol is to determine the clinical efficacy of the variant detection component of the F1CDx assay for rearrangements in the NTRK1, NTRK2, and NTRK3 (NTRK1/2/3) genes as compared to the results obtained for the clinical registrational study samples. Samples from the Bayer-sponsored SCOUT and NAVIGATE clinical trials protocols will be used for this confirmation study. Per FDA approved sample criteria, the standard criteria samples for F1CDx are required to meet the range of greater than or equal to 55 ng to less than or equal to 1000 ng and for the conditional criteria samples for F1CDx are required to meet the range of greater than or equal to 27 ng to <55 ng for DNA yield. Formalin-fixed, paraffin-embedded (FFPE) tissue slide samples meeting either approved or conditional sample criteria will be included in this PAS analysis.
Study Population	A total of seventeen (17) samples in the form of FFPE slides will be prospectively obtained from NTRK fusion positive patients enrolled in NAVIGATE and SCOUT (cutoff date July 20th, 2021) that were not included in the F1CDx sPMA. All samples with patient informed consent and sufficient tissue meeting either standard or conditional criteria will be retested using the F1CDx assay. Of the 17 total samples, eight (8) samples are expected to meet the standard criteria (greater than or equal to 55 ng to less than or equal to 1000 ng), and nine (9) samples are expected to meet the conditional criteria (greater than or equal to 27 ng to <55 ng).
Sample Size	A total of 17 samples (8 Standard and 9 Conditional Criteria)
Key Study Endpoints	Primary: The Overall Response Rate (ORR) determined by Independent Review Committee (IRC) using RECIST v1.1 will be the primary efficacy end point Secondary: Duration of Response (DoR), determined with the methods in the drug clinical trials.
Follow-up Visits and Length of Follow-up	2 years for the ORR
Interim or Final Data Summary
Actual Number of Patients Enrolled	Seventeen (17) from NAVIGATE and SCOUT for PAS (QSR-VAL-414) Analysis
Actual Number of Sites Enrolled	Approximately 40 institutions were recruited to enroll patients in SCOUT and NAVIGATE clinical studies.
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	An additional post approval study was conducted to evaluate the clinical effectiveness of F1CDx by testing 17 available remaining formalin fixed paraffin embedded (FFPE) tissues samples from patients with solid tumors enrolled in LOXO-TRK-15002 (NAVIGATE) and LOXO-TRK-15003 (SCOUT) studies (cutoff date July 20, 2021) that had NTRK1/2/3 fusion positive status as determined by multiple local tests (LT). Of the 17 patients, 11 (64.7%) had an NTRK1/2/3 gene fusion detected by F1CDx, while 6 patients (35.3%) were NTRK1/2/3 gene fusion negative by F1CDx. The ORR in the F1CDx NTRK1/2/3 fusion positive population was 63.6% (95% CI: [30.8%, 89.1%]), which is similar to the ORR of the local testing fusion positive population, n=11, from the NAVIGATE and SCOUT clinical studies of 64.7% (95% CI: [38.3%, 85.8%]). The results of the post approval study further confirmed the clinical effectiveness for F1CDx to identify patients with solid tumors with NTRK fusions that may benefit from VITRAKVI therapy.
Study Strengths & Weaknesses	Eight (8) of 17 cases evaluated in the post approval clinical study were pediatric cases from patients that are less than 18 years of age. Of the 6 out of 17 patients that were missed by F1CDx in the PAS study, i.e., had NTRK1/2/3 gene fusions by LT but had [F1CDx negative (-) status, 4 (66.7%) were pediatric cases (ages were less than 18 years of age), 2 were patients with infantile fibrosarcoma (IFS) and 2 were patients with soft tissue sarcoma. Given that these are rare cancers that have high prevalence of NTRK1/2/3 fusions, additional clinical investigation for NTRK1/2/3 fusions determined to be negative by F1CDx is recommended for cancers with high NTRK1/2/3 fusion rates (e.g., soft tissue infantile fibrosarcoma, kidney mesoblastic nephroma, salivary gland secretory carcinoma (MASC), breast secretory carcinoma) such that patients may not forgo a potentially effective therapy. A limitation to address this issue will be added to the device labeling, see above
Recommendations for Labeling Changes	A summary of the PAS study results should be added to the technical information document. The final text will be finalized during the review of the labeling PMA supplement that FMI should submit 30 days after the completion of the review of P170019/R049/A004
General
Study Status	Terminated
Application Number / Requirement Number	P200006 / PAS001
Date Original Protocol Accepted	02/03/2022
Date Current Protocol Accepted	10/28/2022
Study Name	ARIEL2 PAS
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Samples from ARIEL2 (CO-338-017) will be used to support the clinical utility of the F1L CDx assay for selecting ovarian cancer patients with a deleterious BRCA1 or BRCA2 mutation who may benefit from rucaparib treatment. ARIEL2 was a two-part open-label Phase 2 study intended to determine the safety and efficacy of rucaparib in patients with relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Part 1 enrolled patients who received greater than or equal to 1 prior platinum-based regimen and had platinumsensitive disease. Patients in Part 2 must have received 3 to 4 prior chemotherapy regimens and had a documented treatment-free interval of greater than or equal to 6 months following their first chemotherapy regimen. Patients received continuous dosing with oral rucaparib at 600 mg twice daily (BID) in 4-week cycles. Patients enrolled in ARIEL2 were not biomarker selected, although Part 1 was capped at a maximum of 15 patients with prior known gBRCA mutation. A tumor tissue biopsy sample was required to be collected during screening from all patients except for Part 2 patients known to harbor a deleterious gBRCA mutation (for these patients the screening biopsy sample was optional and an archival FFPE tumor tissue sample was mandatory). Tumor samples were retrospectively analyzed for BRCA mutation status by FMI. Up to 9 mL of whole blood was collected for ctDNA analysis was collected at screening or just prior to rucaparib treatment (e.g. Day 1 of Cycle 1). These samples will be used to support the clinical utility of the F1L CDx.
Study Population	Enrollment in ARIEL2 study is complete, and a total of 491 patients (204 patients in Part 1 and 287 in Part 2) were enrolled and treated with at least one dose of rucaparib, including both BRCA positive and BRCA negative patients, and all patients had a known BRCA result from tissue testing using the CTA or local BRCA testing results prior to enrollment. Of the 491 patients, screening plasma with sufficient volume was available for 271 patients, among which, 217 were successfully sequenced using the F1L CDx assay. The proposed analysis population in this protocol (with a sample size of 60) is a subset of these 217 patients. See below for details of the proposed analysis population for this study. Analysis Population Expanded F1L CDx Positive Primary Efficacy Population (PEP) consists of patients (n=60) with ovarian cancer and a BRCA mutation detected by F1L CDx and treated with 600 mg BID rucaparib with 2 or more prior chemotherapy regimens from study ARIEL2. The expanded F1L CDx Positive PEP can be divided into the following two sub-populations: Original NDA PEP sub-population (n=26): patients who were part of the original NDA (209115) population and F1L CDx positive Post NDA PEP sub-population (n=34): patients who were enrolled in the ARIEL2 study after the cutpoint for inclusion in original NDA 209115 and who also fit the clinical characteristics of the Original NDA PEP sub-population. They were additionally included in the Expanded F1L CDx Positive PEP as they represent an expanded population to determine clinical outcome using F1L CDx selection. All demographics and efficacy analyses outlined in this SAP will be performed for the three populations separately: original NDA PEP sub-population (n=26), post NDA PEP sub-population (n=34) and the entire expanded F1L CDx positive PEP (n=60)
Sample Size	Sixty patients with F1L CDx positive status that received 2 or more prior chemotherapy regimens prior to enrollment in ARIEL 2.
Key Study Endpoints	Primary Endpoint: Investigator-assessed Objective Response Rate (ORR) The primary efficacy endpoint is Objective Response Rate (ORR) by RECIST v1.1 as assessed by the investigator. Secondary Endpoints: ORR by Platinum Sensitivity and Number or Prior Chemotherapies Since platinum sensitivity status (i.e., sensitivity, resistant, and refractory) and number of prior number of chemotherapies (2, >=3) are known predictors of response, the ORR rates may be further broken down by platinum status and number of prior chemotherapies. Duration of Response (DOR) Duration of response (DOR) for any confirmed RECIST CR or PR will be measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST.
Follow-up Visits and Length of Follow-up	Patients were required to have measurable disease at baseline. Efficacy was assessed by tumor response at the end of every 8 weeks (± 4 days), and posttreatment (if patient discontinued treatment for any reason other than radiologically confirmed disease progression) until radiologically confirmed disease progression, death or initiation of subsequent treatment) using the Response Evaluation Criteria in Solid Tumors (RECIST)1 Version 1.1. After discontinuing protocol treatment, patients were to attend the safety follow-up visit 28 (± 3) days after the last dose of rucaparib. All patients who discontinued treatment for any reason other than radiologically confirmed disease progression were to continue to have scans every 8 weeks (± 4 days) until radiologically confirmed disease progression, death, or initiation of subsequent treatment. Patients who had been on study at least 18 months could decrease the frequency of disease assessments to every 16 (± 2) weeks.
General
Study Status	Ongoing
Application Number / Requirement Number	P200015 S011/ PAS002
Date Original Protocol Accepted	12/16/2021
Date Current Protocol Accepted	03/03/2023
Study Name	Alterra New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, multi-center, single-arm new enrollment study. The objective of the study is to characterize the real-world performance of the Edwards SAPIEN 3 Transcatheter Pulmonary Valve System with Edwards Alterra Adaptive Prestent through 10 years post implant.
Study Population	Patients with severe pulmonary regurgitation who have a native or surgically-repaired right ventricular outflow tract and are clinically indicated for pulmonary valve replacement.
Sample Size	150
Key Study Endpoints	Acute device success, transcatheter heart valve dysfunction, echocardiographic assessments, New York Heart Association (NYHA) functional class, and adverse events device (including device frame fracture).
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: Freedom from death (with vital status, 1-year): 98.1% Freedom from RVOT/PV reintervention (1-years): 100.0% Alterra pre-stent fracture (1-year Kaplan-Meier rate): 8.6% Sapien 3 valve frame fracture (1-year Kaplan-Meier rate): 0.0% Effectiveness Results: Acute device success Device success: 96.7% (118/122) Single Alterra pre-stent deployed in desired location: 97.8% (134/137) Single Sapien 3 valve implanted in desired location within Alterra 97.1% (133/137) RV-PA peak-to-peak gradient < 35 mmHg post implant: 100% (130/130) Less that moderate PR by discharge TTE: 100% (121/121) Free of explant at 24 hours post-implantation: 100% (134/134) Mean RVOT gradient baseline – 7.3 mmHg; 30 days – 7.6 mmHg Total pulmonic regurgitation 30 days: None – 69.6% (78/112); Trace – 8.9% (10/112); Mild – 21.4% (24/112); Moderate – 0.0% (0/112); Severe – 0.0% (0/112) Paravalvular regurgitation 30 days: None – 95.5% (107/112); Trace - 0.9% (1/112); Mild – 3.6% (4/112); Moderate – 0.0% (0/112); Severe – 0.0% (0/112) Tricuspid regurgitation 30 days: None – 1.8% (2/112); Trace – 23.2% (26/112); Mild – 53.6% (60/112); Moderate – 17% (19/112); Severe – 4.5% (5/112) Change in NYHA from baseline 30 days: Improved – 42.9% (51/119); Same – 52.9% (63/119); Worsened – 4.2% (5/119)
Actual Number of Patients Enrolled	Enrolled: 150; Valve implanted: 134
Actual Number of Sites Enrolled	22
Patient Follow-up Rate	At 30 days, 125 subjects out of 134 subjects with the study devices implanted had known status (93.3%).
General
Study Status	Ongoing
Application Number / Requirement Number	P970051 S205/ PAS001
Date Original Protocol Accepted	03/11/2022
Date Current Protocol Accepted	09/02/2025
Study Name	Cochlear New Enrollment SSD/UHL Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This clinical study will be conducted as a prospective, nonrandomized, single-arm multicenter investigation in which each participant serves as his/her own control.
Study Population	Individuals 18 years or older (Group A) and children 5 years to 17 years 11 months (Group B)
Sample Size	60 subjects at 15 sites 30 subjects aged 18 and above 20 subjects aged 5-11 years; 11 months 10 subjects aged 12-17 years; 11 months
Key Study Endpoints	Primary Effectiveness Endpoints: 1. The improvement in sentences in noise scores obtained at the 12 months post-activation interval in the bimodal (CI + NH) listening condition compared to scores obtained preoperatively in the best listening condition (normal hearing alone or normal hearing + hearing aid) when the speech is presented from the front and noise is presented to the normal hearing ear (SONNH). 2. The improvement in sentences in noise scores obtained at the 12 months post-activation interval in the bimodal (CI + NH) listening condition compared to scores obtained preoperatively in the best listening condition (normal hearing alone or normal hearing + hearing aid) when the speech is presented from the front and noise is presented to the normal hearing ear (SONCI). 3. The improvement in sentences in noise scores obtained at the 12 months post-activation interval in the bimodal (CI + NH) listening condition compared to scores obtained preoperatively in the best listening condition (normal hearing alone or normal hearing + hearing aid) when the speech is presented from the front and noise is presented to the normal hearing ear (SON0). Primary Safety Endpoint 1. Incidence of procedural and device related adverse events reported through the duration of the study Secondary Effectiveness Endpoints 1. Mean improvement in word recognition at 12 months in the CI alone condition compared to preoperative aided performance in the poorer hearing ear alone. 2. Improvement in patient reported spatial hearing at 12 months post-activation compared to the reported outcome preoperatively. Additionally, longitudinal hearing performance, 12-months to 36 months will be analyzed.
Follow-up Visits and Length of Follow-up	36 months
General
Study Status	Completed
Application Number / Requirement Number	P200020 / PAS001
Date Original Protocol Accepted	09/16/2022
Date Current Protocol Accepted	11/17/2022
Study Name	Lenstec SBL-3 PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post approval study (PAS) is to verify the safety of the SBL-3 multifocal IOL and to determine the risk factors that may be associated with the key study endpoint events (MIOL)(P200020) by comparing it to another approved multifocal IOL. The study will be a prospective, randomized, parallel group design. It will compare the SBL-3 MIOL to the Alcon PanOptix® Trifocal Intraocular Lens Model TFAT00 or Model CCWTT0 The study endpoints (discussed below) will be evaluated for each group and a comparison made at the appropriate time points. Subjects enrolled will be newly enrolled. Enrollment will be done so in a 2:1 manner, in which twice as many SBL-3 IOLs subjects will be enrolled as the control MIOL. Enrollment will occur in a single phase (Phase 4).
Study Population	Subjects enrolled will be those that are in good general and ocular health, with age related cataracts requiring extraction and replacement with an IOL. Subjects are eligible for the study if they meet the criteria listed below. greater than or equal to 22 years of age, of any race and either gender Operable, age related cataract grade in both eyes Patients who require an IOL power in the range of 15 D – 30 D only. Able to comprehend and sign a statement of informed consent Planned cataract removal by phacoemulsification Potential postoperative visual acuity of 20/30 Snellen acuity or better in both eyes In good general and ocular health Patients with preoperative astigmatism less than or equal to 1.0 D Clear intraocular media other than cataract in study eyes The subject must be able to undergo second eye surgery between 7 days and 30 days of the first eye surgery. Able to competently complete testing Willing and able to attend study visits The key exclusion criteria will be: Previous intraocular surgery Preoperative distance photopic pupil size of < 3.00 mm Previous corneal refractive surgery Any inflammation or edema (swelling) of the cornea Pterygium with corneal involvement or has the potential of corneal involvement (in the opinion of the Investigator) during the course of the study Subjects with diagnosed degenerative visual disorders (e.g., macular degeneration or other retinal disorders) that are predicted to cause future acuity losses to a level worse than 20/30 Snellen acuity Subjects who may reasonably be expected to require a secondary surgical intervention at any time during the study (other than YAG capsulotomy) Amblyopia Clinically significant ptosis Clinically severe corneal dystrophy (e.g., epithelial, stromal, or endothelial dystrophy), keratitis, keratoconjunctivitis, keratouveitis, keratopathy, or kerectasia Diabetic Retinopathy Extremely shallow anterior chamber, not due to swollen cataract Microphthalmia Previous retinal detachment Previous corneal transplant Severe dry eye Recurrent severe anterior or posterior segment inflammation of unknown etiology Rubella or traumatic cataract Iris neovascularization Glaucoma (medically controlled or uncontrolled) Additionally, subjects with required additional procedures during surgery, forced mechanical or surgical manipulation of the pupil, other than in the bag implantation of the IOL, or other surgical complications that could confound the results of the study or put the subject at risk of ocular system damage or injury will be discontinued from the study during the surgery.
Sample Size	No. of subjects: The test group will enroll up to 330 subjects in order to obtain 300 at the final evaluation. The control group will enroll up to 170 subjects in order to obtain 150 subjects at the final evaluation. No. of sites: 20 Sites location: US
Key Study Endpoints	Safety Endpoints Primary: The primary safety endpoints are as follows: The rates of all implanted eyes (primary eyes + fellow eyes) with secondary surgical interventions (SSI), cumulative over the course of the 6- month study, related to visual symptoms (e.g., glare, halo or starburst or blurred vision) or refractive error. This includes stratified analyses of: i. Secondary surgical interventions related to visual symptoms or any sort, e.g., glare, halo, starbursts, or blurred vision, (excluding those related to refractive error) ii. Secondary surgical interventions related to refractive error 2) Rate of all implanted eyes (primary eyes + fellow eyes) with absolute manifest refraction spherical equivalent (MRSE) greater than or equal to 1 diopter (D) from the intended target starting at any visit at 21 days postoperatively, or required SSI related to refractive error at any time in the study (cumulative over the 6-month study) 3) Rate of all implanted eyes (primary eyes + fellow eyes) with changes between any two postoperative visits of absolute MRSE greater than or equal to 1 D, starting at any visit at 21 days postoperatively (cumulative over the 6-month study) 4) Rate of all implanted eyes (primary eyes + fellow eyes) with changes between any two postoperative visits monocular uncorrected distance visual acuity (UCDVA) greater than or equal to 10 letters (plus or minus) starting at any visit at 21 days post-operatively (cumulative over the 6-month study) 5) Rate of subjects with significant difficulty due to variations in distance vision on a questionnaire (given at every visit, including unscheduled, starting at any visit at 21 days postoperatively over the 6-month study) defined as a "significant (Grade of 5 for either question #1 or question #2*) variation in vision.” *Collected at Questions 1 and 2 of the excerpted NEI RQL-426). 6) Rate of all implanted eyes (primary eyes + fellow eyes) with UCDVA worse than 20/40 at any single visit starting at the 3A visit or later. Secondary: Rate of all implanted eyes (primary eyes + fellow eyes) with other types of serious adverse events (ISO 11979-7 historical grid Table E.2 - Posterior chamber IOL adverse event rates) Non-serious adverse events by comparing the subject incidence of each type of non-serious event between two groups with a Fisher’s exact test.
Follow-up Visits and Length of Follow-up	The scheduled follow up visits will be 1-day post-operative, 1-week post-operative, 1-month post-operative, 3-month post-operative and 6-month post-operative. The 6-month post-operative visit will have a scheduled window of +/-3 weeks from the initial surgical date. The study will run a total of 6 months post-operative.
Interim or Final Data Summary
Actual Number of Patients Enrolled	490 total subjects enrolled, • 320 subjects were enrolled and 319 were bilaterally implanted with the ClearView 3 MIOL • 170 subjects were enrolled and 169 were bilaterally implanted with the control (Alcon PanOptix Trifocal IOL).
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	95% (446/490)
Final Safety Findings	The ClearView 3 demonstrated no statistical differences of secondary surgical interventions (SSI), SSI related to visual symptoms or SSI related to refractive errors. Additionally, there were no statistical differences between manifest refraction spherical equivalent (MRSE) greater than or equal to 1 diopter (D) from the intended target at the study endpoints between the ClearView 3 and the PanOptix. The rate of all implanted eyes with changes of monocular uncorrected distance visual acuity (UCDVA) greater than or equal to 10 letters (plus or minus) did not show any statistical difference between the ClearView 3 and the PanOptix groups. When given the NEI (National Eye Institute) questionnaire asking subjects to report “How much difficulty do you have seeing because of changes in the clarity of your vision over the course of the day?” and “How often are you bothered by changes in the clarity of your vision over the course of the day?”, the ClearView3 showed no statistical difference to the PanOptix control lens. Furthermore, for rates of UCDVA worse than 0.3 LogMAR, the ClearView 3 did not show statistical difference to the PanOptix IOL but the ClearView 3 group did have a lower rate of subjects that experienced worse than 0.3 LogMAR than the PanOptix. Lenstec successfully met each primary endpoint with the exception of endpoint 3; Rate of all implanted eyes (primary eyes + fellow eyes) with changes between any two postoperative visits of absolute MRSE =1 D, starting at any visit 21 days post-operatively or later (cumulative over the 6-month study). The outcomes were significantly different
Final Effect Findings	N/A
Study Strengths & Weaknesses	The study’s design included both strengths and weaknesses. The goal of any clinical trial is to produce reliable and valid data while minimizing bias. Strengths of this study include the prospective, randomized nature of enrollment, including a concurrent control. This ensures that the same population of potential subjects are included in the trial and their data is captured as it is available. The study also had a very high rate of subjects completing the study (>95%), which ensures that those subjects enrolled have their data collected, as it relates to the study endpoints. From a demographic standpoint, there were no differences between the subjects in both groups, which also makes group to group comparison valid. Potential study weaknesses include non-masked participation of its participants. In this study, patients masking. Masking surgical staff would have been very difficult as the two study articles have considerably different optic and haptic designs. This would be noticed from the time of implantation (surgeon, surgical staff) through to the final study visit (surgeon, clinical staff) who necessarily have to visualize the IOL for the purpose of data capture. Another weakness includes the fact that the amount of experience surgeons had with the control article was likely considerably higher than the test group. The control article was designed on an IOL platform that had been in use for more than two decades, by the largest IOL producer in the US. The test article has not been used before the approval of the test IOL (July 2022), which is relevant because of its unique optic and haptic design. The many study strengths outweigh these weaknesses, and therefore, the study results can be considered valid
Recommendations for Labeling Changes	Yes.
General
Study Status	Completed
Application Number / Requirement Number	P200022 / PAS001
Date Original Protocol Accepted	11/05/2020
Date Current Protocol Accepted	05/26/2021
Study Name	Extended Follow-up of IDE Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To evaluate the 5-year long-term safety and effectiveness of the Simplify Cervical Artificial Disc in subjects with symptomatic cervical radiculopathy with or without neck pain or myelopathy due to a single level abnormality localized to the level of the disc space that is unresponsive to conservative management. Design: A continuation of the prospective, multi-center, historically controlled IDE study population to evaluate the long-term safety and effectiveness of the Simplify Cervical Artificial Disc.
Study Population	Investigational Device: Simplify Cervical Artificial Disc Historical Control: Anterior Cervical Discectomy and Fusion (ACDF)
Sample Size	142 Simplify Cervical Artificial Disc IDE subjects and 106 historical ACDF control subjects are elgible for for the PAS study
Key Study Endpoints	Safety Endpoints: • Collection and evaluation of all adverse events for severity and device and/or procedure-relatedness • Evaluation of device failure (device breakage, migration, or mechanical failure) as defined in Radiographic Evaluation Protocol • Subsequent surgical procedures (revision, removal, reoperation, or supplemental fixation) at the index level • Neurologic evaluation – investigational device only • Dysphagia Handicap Index (DHI) – investigational device only Effectiveness Endpoints: • Neck Disability Index (NDI) assessment • Radiographic evaluation • VAS pain assessments (neck and arm; neck, left arm and right arm (investigational device only)) • Treatment satisfaction • SF-12 Health Survey
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	132 investigational device subjects, 106 historical ACDF control subjects enrolled in PAS.
Actual Number of Sites Enrolled	15 of 17 investigational device sites, 21 of 24 historical control sites
Patient Follow-up Rate	At month 60, the follow-up rate is 89% for the investigational device and 61% for the PS selected ACDF control subjects.
Final Safety Findings	In this PAS, the overall AE and SAE rates were comparable between treatment groups. There was no difference between groups with regard to AEs categorized as definitely device- or procedure-related; however, there was a slightly higher rate of device-related spasm AEs in the Simplify group and a slightly higher rate of device-realted pain (narcotic given) in the ACDF control group. There were two instances of secondary surgical interventions (SSIs) in the Simplify group and five SSIs in the ACDF control group after the 24-month timepoint. See tables below.
Final Effect Findings	The composite clinical success for the Simplify Disc group was 91.1% compared to 74.6% for the historical ACDF control group. The study success criteria for non-inferiority as well as for superiority have been met.
Study Strengths & Weaknesses	This 5-year follow-up study had high follow-up rates for the investigational group but lower than the recommended 85% follow-up rate for the historical control group.
Recommendations for Labeling Changes	It is recommended that the labeling be updated with the results of the PAS study (i.e., data at 60-months).
General
Study Status	Completed
Application Number / Requirement Number	P200026 / PAS001
Date Original Protocol Accepted	10/21/2020
Date Current Protocol Accepted
Study Name	ABRE Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the long-term safety and effectiveness of the ABRE Stent System for treatment of symptomatic iliofemoral venous outflow obstruction in patients with venous occlusive disease through 36 months. A prospective, multi-center, follow-up of the ABRE pivotal study
Study Population	Subjects between 18 and 80 years (inclusive) requiring treatment of a non-malignant venous obstruction within the common iliac, external iliac and/or common femoral vein enrolled in the ABRE Study. Subjects were categorized as acute DVT (aDVT), post-thrombotic syndrome (PTS), or non-thrombotic iliac vein lesion (NIVL)).
Sample Size	A total of 200 subjects were enrolled at 24 sites in the U.S. and Europe, 128 (64%) of subjects enrolled at US sites and 72 (36%) subjects at European sites.
Key Study Endpoints	Primary Endpoint Freedom from target lesion revascularization (TLR) at 36 months. Secondary Endpoints The following secondary endpoints will be evaluated annually through 36 months post implant: Primary patency Primary assisted patency Secondary patency Target Lesion Revascularization (TLR) Major Adverse Events (MAE) Delayed Stent Migration Stent Fracture Change in VEINES-QOL/Sym Score Change in VILLALTA Score Change in EQ5D Quality of life Score Change in VCSS Score Major bleeding complication Medical resource utilization
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	200
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	98.9%
Final Safety Findings	Through 1080 days a total of 414 adverse events (non-SAEs) were reported in 144 subjects. Musculoskeletal and connective tissue disorders (23.5%), Vascular Disorders (19.0%), General disorders and administration site conditions (17.5%), and Infections and Infestations (17.0%) were the most reported non-SAE SOCs. Subjects with aDVT mostly reported general disorders and administration site conditions with 24.2%, while 27.4% of subject with PTS reported musculoskeletal and connective tissue disorders, and 25.0% of subjects with NIVL reported vascular disorders.
Final Effect Findings	The 36-month primary patency rate was 80.6%. Among the subjects evaluable for primary patency, the freedom from occlusion rate at 36 months was 98.5%, the freedom from restenosis rate at 36 months was 90.4%, and the freedom from clinically driven TLR through 1110 days was 85.9%. The primary assisted patency rate at 36 months was 86.4%. The secondary patency rate at 36 months was 90.4%.
Study Strengths & Weaknesses	Study strength: good follow up rates were achieved. Weakness: The study was a single-arm study without a control arm.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P200030 / PAS001
Date Original Protocol Accepted	12/22/2020
Date Current Protocol Accepted
Study Name	Cont f/u of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post approval study is to evaluate the long-term safety and effectiveness of the Gore Excluder Conformable AAA Endoprosthesis (EXCC). It is a prospective, multi-center, single-arm clinical study. It involves the long-term follow-up of the premarket cohort.
Study Population	The study population is patients with an infrarenal abdominal aortic aneurysm who met the study selection criteria.
Sample Size	A total of 80 subjects were enrolled in the study and remaining subjects will be followed.
Key Study Endpoints	Serious adverse events, all-cause mortality, aneurysm-related mortality, aneurysm rupture, secondary interventions, conversion to open surgery, losses of device integrity, device occlusions, stenosis or kink, aneurysm enlargement (greater than or equal to 5 mm), stent graft migration (greater than or equal to 10 mm), all types of endoleaks, and other device-related events.
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	80
Actual Number of Sites Enrolled	54
Patient Follow-up Rate	Any data | Imaging Data 60 Months: 88.7% (47/53) | 84.9% (45/53) 48 Months: 82.3% (51/62) | 82.3% (51/62) 36 Months: 85.1% (57/67) | 82.1% (55/67) 24 Months: 78.7% (59/75) | 77.3% (58/75) 12 Months: 94.9% (75/79) | 93.7% (74/79) 6 Months: 97.5% (77/79) | 94.9% (75/79) 1 Month: 98.8% (79/80) | 98.8% (79/80)
Final Safety Findings	Serious Adverse Events: • There were two subjects with device-related SAEs. • There were four subjects with procedure-related SAEs. All-Cause Mortality: • There were 15 subjects who experienced this endpoint event. Aneurysm-Related Mortality: • No subjects experienced this endpoint event. Aneurysm Rupture: • One subject experienced a core lab reported AAA rupture, however, that was not confirmed with assessments from both site and CEC. Secondary Interventions: • Nine (11.3%) subjects required reintervention as adjudicated by the CEC. Five of these subjects required reinterventions on more than one occasion. Conversion to Open Surgery: • No subjects experienced this endpoint event. Loss of Device Integrity: • No subjects experienced this endpoint event. Device Occlusions: • No subjects experienced this endpoint event. Stenosis or Kink: • No subjects experienced this endpoint event. Aneurysm Enlargement (greater than or equal to 5 mm): • Eight (10.3%) subjects experienced this endpoint event as evaluated by core lab. Stent Graft Migration (greater than or equal to 10 mm): • No subjects experienced this endpoint event. All Types of Endoleaks: • There were no site-reported Type III, Type IV or indeterminate endoleaks. Forty-seven (58.8%) subjects were free from any type of site-reported endoleak. One subject (1.3%) experienced a site-reported Type IA endoleak. Thirty-three subjects (41.3%) experienced a site-reported Type II endoleak. As evaluated by the core lab, there were no subjects with Type I endoleaks, there were 36 subjects (45%) who experienced Type II endoleaks, there were no subjects who experienced Type III or Type IV endoleaks and there were nine subjects (56.3%) who experienced indeterminate endoleaks. Other Device-Related Events: • No subjects experienced this endpoint event.
Final Effect Findings	N/A
Study Strengths & Weaknesses	Strengths: The Short Neck Substudy was successful in meeting its performance goal. The follow-up compliance, including for imaging data, was very high. Follow-up assessments through five years post-procedure have shown continued treatment and device durability. Patients also benefitted from complete freedom from aneurysm-related mortality with reasonable rates of endoleak reintervention and rupture in the total absence of device integrity events. Low rates of long-term device complications, coupled with the immediate benefits of endovascular therapy, confirms the value of CEXC device treatment for AAA. Weaknesses: The patient population treated was heavily represented by males (88.8%) and Caucasians (93.8%). Female and African American population representation was very low (11.3% and 3.8% respectively). Limited data was available for other races and ethnicities.
Recommendations for Labeling Changes	Labeling changes are recommended to present the long-term outcomes of this device.
General
Study Status	Ongoing
Application Number / Requirement Number	P100042 S038/ PAS001
Date Original Protocol Accepted	02/03/2026
Date Current Protocol Accepted	02/03/2026
Study Name	CERVIVA Primary Screening Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	Other Data Source
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To collect clinical data evaluating the clinical performance of the Aptima HPV Assay and the Aptima HPV 16 18/45 Genotype Assay compared to an HPV test that is FDA-approved for primary screening in women aged 25-29 years from CERVIVA Primary Screening Study, confirming the safety and effectiveness of the device in this specific age group.
Study Population	All women aged 25 to 29 years presenting for cervical cancer screening.
Sample Size	1800 participants.
Key Study Endpoints	The ratio (Aptima HPV Assay and Aptima HPV 16 18/45 Genotype Assay: FDA-approved HPV test) of clinical sensitivity and false positive rates for detection of CIN2+ and CIN3+.
Follow-up Visits and Length of Follow-up	None
General
Study Status	Delayed
Application Number / Requirement Number	P160053 S009/ PAS001
Date Original Protocol Accepted	06/07/2024
Date Current Protocol Accepted	06/07/2024
Study Name	1ml Magtrace w Sentimag PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Purpose: The purpose of this study is to provide prospective evidence in the US population of the frequency of skin discoloration in patients who have received Magtrace for sentinel lymph node biopsy (SLNB) and to evaluate the impact that skin discoloration has on patients when it does occur using patient reported outcome measures. Design: A prospective, open label study will be conducted to characterize the post-operative skin discoloration that may arise following the use of Magtrace for sentinel lymph node biopsy in breast cancer patients undergoing lumpectomy. Patient perception will be assessed using patient reported outcome measures.
Study Population	Subjects considered for enrollment will be at least 18 years old at the time of consent, and: a) due to undergo planned breast conserving surgery (for example lumpectomy or partial mastectomy) and SLNB with Magtrace, b) meet all other inclusion and no exclusion criteria.
Sample Size	Number of subjects: 184 Assumptions for sample size estimation: A sample of 184 (100 for Subareolar and 84 for peritumoral) is expected to provide a sample of approximately 70 (60 for subareolar and 10 for peritumoral) patients with discoloration. Number of sites: 3-8
Key Study Endpoints	Safety Endpoints Primary: Frequency of Magtrace-related skin discoloration as a proportion of patients receiving Magtrace, overall and by sub-sample. Secondary: A. Change in BREAST-Q score from post-operative visit through to resolution of skin discoloration or through 24 months, whichever is earlier, in the subgroup of patients with discoloration. The following core scales will be used: 1) Psychosocial well-being; 2) Sexual well-being; 3) Cancer worry; 4) Fatigue; 5) Impact on work; 6) Physical well-being: Chest; and 7) Satisfaction with breasts. B. Change in Breast-Q score from pre-operative visit to post-operative visit in patients with and without skin discoloration at the postoperative follow up visit. C. Duration of discoloration over time post-op to resolution of discoloration or 24 month follow up D. Intensity of discoloration (absolute color and contrast to normal breast color) over time post-op to resolution of discoloration or 24mnth follow up E. Severity of discoloration over time post-op to resolution of discoloration or 24mnth follow up as assessed by height and width measurement F. Rates of device-related adverse events and serious device-related adverse events
Follow-up Visits and Length of Follow-up	Frequency (All patients): Visit 1 Pre-op, Visit 2 Post-op. For patients without discoloration: Visit 3 at 12 months. For patients with discoloration: Visit 3-6 every 6 months. Length of Follow up: Up to resolution or up to 2 years, whichever is sooner.
General
Study Status	Ongoing
Application Number / Requirement Number	P200030 S014/ PAS002
Date Original Protocol Accepted	12/04/2024
Date Current Protocol Accepted
Study Name	Gore Together Registry (TGR)
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Primary Data Set: The Long-term EVAR Assessment and Follow-up (LEAF) System is a post-market, observational surveillance effort utilizing an enhanced registry framework and claims-based linkages with targeted clinical and imaging follow-up. The objective of this system is enhanced surveillance of long-term real-world EVAR device outcomes through ten years after implantation. Supplemental Data Set: The TOGETHER Registry is a prospective, observational post-market registry collecting outcomes through a 10-year post procedure follow-up for subjects treated with the EXCC device or the EXCLUDER Iliac Branch Endoprosthesis (IBE device) as a part of routine clinical practice.
Study Population	The LEAF surveillance population will consist of primarily Medicare patients who have undergone or will undergo EVAR at hospitals participating in the SVS-VQI, or patients who have undergone or will undergo EVAR at hospitals in the KP network. The TOGETHER registry will consist of patients presenting with vascular disease who are treated with the applicable endovascular stent grafts.
Sample Size	A minimum of 125 subjects with evaluable imaging at 5 years to support imaging endpoint analysis. Note: No minimum sample size from the Together Registry is required per protocol. Data from the Together Registry is intended to provide supplemental information on subjects from this dataset to support data collection from LEAF Registry.
Key Study Endpoints	LEAF: Clinical endpoints will include the following: • Mortality • Aneurysm-related mortality • Rupture • Reintervention (reason and type) • Conversion to open surgery Imaging endpoints will include the following: • Change in aneurysm size • Endoleak (by type) • Device patency TOGETHER: Gore will summarize Together data with consistent endpoint and definitions as LEAF (summarized above) for both specified subgroups and Together cohort as a whole. Specific sub-group reporting requirements will be addressed with Together until LEAF sub-group reporting is available.
Follow-up Visits and Length of Follow-up	Follow-up to be completed per each participating site’s standard of care (SOC) for 10 years (120 months) post-procedure.
General
Study Status	Ongoing
Application Number / Requirement Number	P230036 / PAS001
Date Original Protocol Accepted	04/26/2024
Date Current Protocol Accepted
Study Name	LIFE-BTK RCT Continued Follow-up Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, randomized (2:1, Esprit BTK:PTA), single-blinded, multi-center follow-up of the pivotal LIFE-BTK RCT trial.
Study Population	Continued follow-up of the Esprit BTK and PTA (control) arm subjects
Sample Size	Total enrolled: 261 subjects. Continued follow-up of all 231 remaining subjects, active at the end of the 1-year evaluation.
Key Study Endpoints	Continued follow-up at the timepoints will include the following assessments: medication review, adverse events review, Ankle-Brachial Index (ABI)/Toe-Brachial Index (TBI) measurements, functional status (Rutherford Becker), new wound assessment, and duplex ultrasound (1-year, 2-year and 3-year follow-ups only).
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Other
Application Number / Requirement Number	P170013 S005/ PAS001
Date Original Protocol Accepted	06/28/2022
Date Current Protocol Accepted	06/28/2022
Study Name	LVIS X PAS
General Study Protocol Parameters
General
Study Status	Completed
Application Number / Requirement Number	P200031 / PAS001
Date Original Protocol Accepted	09/28/2021
Date Current Protocol Accepted
Study Name	PROTECT Continuation PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a continued follow-up of the OCS Liver PROTECT trial (premarket) cohort, designed to evaluate longer-term outcomes after liver transplantation in the OCS and control (cold storage) arms.
Study Population	Patients who were randomized to OCS or control arms and transplanted in the PROTECT trial
Sample Size	300 patients who were randomized to OCS or control arms and transplanted in the PROTECT trial
Key Study Endpoints	Main effectiveness endpoint: Liver graft survival at 24 months post-transplant Other endpoint: patient survival at 24 months post-transplant
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	300
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	93.6%
Final Safety Findings	N/A
Final Effect Findings	The Kaplan-Meier Analysis of Liver Graft Survival rates are 97% in both OCS and SOC arms for mITT & PP analysis groups with a log rank p-value of 0.96. The Kaplan-Meier Analysis of Recipient Survival rates are 93% (OCS) and 92%(SOC) for both the mITT & PP analysis groups with a log rank p-value of 0.88.
Study Strengths & Weaknesses	A strength of this study is that longer term follow-up data is very complete. A weakness of this study is that the 300 liver transplant recipients were enrolled at 20 sites however, 70% of the liver transplant recipients were enrolled at four of the clinical sites, therefore, the results of these four sites are driving the results of the overall PAS and thus the results of this PAS may not be generalizable to the liver transplant population at large.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P200031 / PAS002
Date Original Protocol Accepted	09/28/2021
Date Current Protocol Accepted
Study Name	PROTECT CAP Continuation PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This single-arm study is a continued follow-up of the OCS Liver PROTECT Continued Access Protocol (CAP) cohort (premarket), designed to evaluate longer-term outcomes after transplantation with OCS-perfused livers
Study Population	Patients who were transplanted in the OCS Liver PROTECT CAP study
Sample Size	74 patients who were transplanted in the PROTECT CAP study
Key Study Endpoints	Main effectiveness endpoint: Liver graft survival at 24 months post-transplant Other endpoint: patient survival at 24 months post-transplant
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	The PROTECT CAP trial (premarket) enrolled 74 subjects and these subjects are being followed in this PAS.
Actual Number of Sites Enrolled	The PROTECT CAP trial (premarket) included 11 sites which enrolled patients and all these sites were participating in this PAS.
Patient Follow-up Rate	Month 6 - 93.2%, Month 12 - 90.5, Month 24 - 86.4%
Final Safety Findings	10 deaths have occurred, including one (1) during this reporting period. None of them were procedure or device related. There have been no additional retransplants since PMA approval. No other adverse events were reported.
Final Effect Findings	Kaplan-Meyer (K-M) graft survival for Protect CAP Patients shows the following: Patient’s Non-Survival Events occurred in1.4% (1/69) at 6 months, 1.5% (1/65) at 12 months, and 3.6% (1/28) at 24 months. Graft survival remained high at 96.4% at 24 months (27/28).
Study Strengths & Weaknesses	There have been no additional retransplants since PMA approval.
Recommendations for Labeling Changes	The study elements of this PAS must be included in the labeling, including the study design, specific aims, study outcomes, study population, inclusion and exclusion criteria, statistical analysis, results, and discussion including how the conditions of approval were met
General
Study Status	Completed
Application Number / Requirement Number	P200031 / PAS003
Date Original Protocol Accepted	09/28/2021
Date Current Protocol Accepted
Study Name	OLP New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multi-center, new enrollment PAS designed to evaluate the short- and long-term safety and effectiveness of the OCS Liver System for DBD and DCD donor livers preserved on OCS according to the approved indication, in real-world use. The study will include all liver transplant centers in the U.S. that will commercially use the OCS Liver System, with a minimum of 15 participating sites.
Study Population	Adult primary liver transplant recipients who are transplanted with an OCS Liver-perfused DBD or DCD donor liver according to the approved indication and eligibility criteria
Sample Size	PAS will enroll the initial 160 sequential adult primary liver transplant recipients who are transplanted with an OCS-perfused DBD or DCD donor liver according to the approved indication (primary analysis population). If the initial 160 transplant recipients does not include at least 60 DCD donor liver transplants, PAS will continue to enroll only DCD donor liver recipients until 60 DCD patients have been enrolled. For the primary endpoint (1-year patient and graft survival), a sample size of 107 subjects provides 80% power (with a one-sided alpha of 0.05). For the safety endpoint (6-month graft survival), a sample size of 70 subjects provides 80% power (with a one-sided alpha of 0.05).
Key Study Endpoints	Primary Endpoint: 1-year patient and graft survival post-transplant Safety Endpoint: 6-month liver graft survival post-transplant Other Clinical Endpoints: Incidence of ischemic, non-anastomotic biliary complications through 1-year post-transplant Incidence of non-ischemic, anastomotic biliary complications through 6 months post-transplant Kaplan-Meier patient survival at 1- and 2-years Kaplan-Meier graft survival at 6 months, 1- and 2-years Collection of OCS Liver Related Data: OCS Liver perfusion parameters (hepatic artery flow and pressure, portal vein flow and pressure, perfusate temperature, perfusate hematocrit, perfusate venous saturation) OCS Liver perfusion lactate levels OCS Liver perfusate pH values Total bile volume at end of OCS liver perfusion Incidence of and clinical reasons for donor liver turndown Incidence and reasons for conversion to cold storage Device malfunctions Utilization rate
Follow-up Visits and Length of Follow-up	2 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	As of the date of database closure, 166 patients have been enrolled in the OLP Registry.
Actual Number of Sites Enrolled	Nine sites have been initiated and enrolled patients into the OLP Registry.
Patient Follow-up Rate	Of the 166 subjects enrolled, 158 completed the 24- month visit and are still alive. There were 8 subjects that discontinued the study prior to the 24-month visit. The reason for discontinuation was due to death, retransplantation, and lost to follow-up. There were 5 deaths (3%), 2 retransplantations (1.2%), and 1 subject was lost to follow-up (0.6%).
Final Safety Findings	The safety endpoint of this study is the 6-months liver graft survival post-transplant. This endpoint compares OCS Liver recipients to a pre-specified PG of 85.5%. The 6-month liver graft survival was 162 out of 164 (98.8%).
Final Effect Findings	The primary endpoint was 1-year patient survival with the originally transplanted liver (patient and graft survival) post-liver transplant. This endpoint compares OCS Liver recipients to the pre-specified performance goal (PG) of 83.5%. The endpoint was met as patient and graft survival was 161 out of 166 (97%).
Study Strengths & Weaknesses	All primary endpoints were successfully achieved. Safety profile remains acceptable with low complication rates. Device performance demonstrates continued effectiveness in clinical practice. Longer-term follow-up may be beneficial to capture late biliary complications. Additional data on higher-risk donor populations (macrosteatosis >15%) may be valuable. Continued monitoring of device performance and clinical outcomes in routine practice would be beneficial.
Recommendations for Labeling Changes	The labeling was previously updated following the 1-year Registry follow-up. The OCS Liver system labeling should be updated with the 2-year Registry follow-up data.
General
Study Status	Completed
Application Number / Requirement Number	P190012 / PAS001
Date Original Protocol Accepted	10/15/2021
Date Current Protocol Accepted
Study Name	Spatz3 Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm, multi-center, US-based new enrollment study. The objective is to obtain data regarding the safety and effectiveness of the Spatz3 Adjustable Balloon System in the post-market space. This is an all-comer study.
Study Population	Adults with a Body Mass Index (BMI) of 35.0-40.0 kg/m2 or a BMI of 30.0 to 34.9 kg/m2 with one or more major obesity-related comorbid conditions who have failed to achieve and maintain weight-loss with a supervised weight control program
Sample Size	The sample size is based on the endpoint of deflation with migration. 467 subjects are needed to achieve 80% power with a lower one-sided Z test assuming a Ho rate of 1%, observed rate of 0.03%, and alpha=0.025. Assuming a lost-to-follow-up rate of 15%, 537 subjects will need to be enrolled.
Key Study Endpoints	The primary study endpoint is to demonstrate that the rate of device or procedure related SAEs is less than 8% at 8 months. The secondary study endpoint is to demonstrate that the mean percent TBL in the effectiveness cohort is not less than 14% at eight months. Other study endpoints (through 32 weeks) include: • weight loss measured by percent excess weight loss (%EWL) • device- and/or procedure-related adverse events with respect to severity, relationship to the device and/or procedure, and rate of occurrence • Rates for the following events: o gastric ulcers, o esophageal injury, o spontaneous hyperinflation*, o microorganism growth (inside and outside of the balloon)*, o acute pancreatitis, o aspiration, o esophageal perforation, o gastric perforation, o bowel perforation, o death, o early explants, o deflations, o deflations with migrations, and o deflations that are vomited *Culturing data will be collected for balloon that spontaneously hyperinflate or have microorganism growth inside and/or outside of the balloon Weight maintenance measured by percent excess weight loss (%EWL) and %TBL at 6 months post-explantation will be assessed on an effectiveness cohort - patients who achieved at least 5% TBL at the end of the 8 month treatment period.
Follow-up Visits and Length of Follow-up	8 months or 14 months for patients who achieve at least 5% TBL by the end of the 8 month treatment period
Interim or Final Data Summary
Actual Number of Patients Enrolled	539
Actual Number of Sites Enrolled	23
Patient Follow-up Rate	Follow-up Rate Of the 539, 417 (77.3%) completed the study at week 32 as planned, 76 (14%) had an early balloon removal due to AE and 28 (5.2%) had an early balloon removal due to other causes such as withdraw consent, relocation or reaching goal weight. 18 subjects (3.4%) were lost to follow up before week 52. 2 (0.4%) were unreachable after implantation and 16 subjects (3.0%) had incomplete study data due to site’s (13 and 14) lack of communication and monitoring. Out of 417 subjects completed week 32, 59 (10.9%) did not reach 5 TBL% therefore did not continue to follow up. Out of the 358 (66.4%) who continued to follow up, 151 (42%) completed all 24-week follow-up period. 207 subjects (38.4%) were lost to follow-up after week 32, These subjects had undergone device removal as scheduled and subsequently became non-responsive to follow-up attempts. Because this occurred after device removal, absence of the follow up visits does not impact on the safety or efficacy analysis up to week 32.
Final Safety Findings	Adverse Events (AEs) related to Spatz3 balloon treatment occurred in 17.1% of subjects. Serious AEs (SAEs) occurred in 17 (3.1%) of subjects. Overall, 69.4% of subjects experienced balloon-related AEs; 17.1% experienced severe AEs, and 2.2% experienced SAEs. The most frequent AEs were symptoms of intolerance, including nausea (49.7%), vomiting (39.5%), dyspepsia (36.9%), and abdominal discomfort (35.8%). No deaths occurred in the study. Four hyperinflation events (0.7%) were reported in the study and they occurred several months after implantation.
Final Effect Findings	The mean %TBL for ITT population (n=539) was 13.2% at 32 weeks. Therefore, the study met the pre-specified endpoint of 11%. Across the 23 sites, the %TBL range from 9.2% to 17.4%.The response rate (defined as %TBL greater than or equal to 5%) was more than the 50% goal (TBL greater than or equal to 5% = 97.5% LCB = 80.0%), the observed rate of subjects who maintained 40% of the weight loss with the balloon at six months exceeded the 50% performance goal (Maintained greater than or equal to 40% weight loss = 89.3%), and the response rate (defined as EWL greater than or equal to 25%) exceeded (EWL greater than or equal to 25% = 76.4%).
Study Strengths & Weaknesses	Strength: All “comers study” allows for better reflection of real-world clinical practice and results are more generalizable. Weakness: high number of deviations (missed visits/assessments)
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P160045 S027/ PAS001
Date Original Protocol Accepted	01/21/2022
Date Current Protocol Accepted
Study Name	PAS Clinical Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the clinical validation study is to provide evidence in support of the safety and effectiveness of the ODxT Test when used in accordance with its indications for use and product labeling. The study will support the use of the ODxT Test as an aid to determine EGFR exon 20- insertion mutation status in identifying patients with NSCLC screened and enrolled for treatment with JNJ-372 using multiple Clinical Trial Assays (CTAs) in study JNJ-61186372. The purpose of this PAS is to: 1) Supplement the Olympic clinical study with minimum of approximately 24 additional samples to assess the analytical accuracy of the ODxT Test by evaluating its agreement with an orthogonal test method(s) using EGFR exon 20 insertion-positive clinical samples obtained from the dose expansion cohort of Janssen’s Phase 1/2 clinical trial (Clinical Study Protocol JNJ-61186372); 2) To assess the clinical effectiveness of the ODxT Test in selecting patients for treatment with JNJ-372 administered in subjects with locally advanced or metastatic NSCLC, by evaluating: a. the concordance between the CTA results and the ODxT Test results b. the objective response rate (ORR) based on ODxT Test results; Design: A minimum of approximately 24 EGFR exon 20 insertion mutation-positive NSCLC clinical trial samples collected from the dose expansion Cohort D of Janssen’s clinical study will be tested by both the ODxT Test (CDx) and the TST170 Assay (comparator).
Study Population	The primary analyses population includes specimens with valid ODxT Test results from the efficacy evaluable registrational cohort of Janssen’s clinical study.
Sample Size	A minimum of approximately 24 EGFR exon 20 insertion mutation-positive NSCLC clinical trial samples collected from the dose expansion Cohort D of Janssen’s clinical study will be tested by both the ODxT Test and the TST170 Assay.
Key Study Endpoints	The primary endpoint will be overall response rate (ORR) by RECIST 1.1 as assessed by independent radiologic review and a description of the duration of response (DoR).
Follow-up Visits and Length of Follow-up	The efficacy evaluable analysis set will consist of subjects who received at least one dose of study drug and either had at least 2 post-baseline efficacy disease assessments, or discontinued treatment for any reason, or had disease progression/ death prior to the 2nd post-baseline disease assessment. Moreover, subjects in the efficacy evaluable analysis set for this diagnostic study include only those treated at the recommend phase 2 dose (RP2D) with metastatic NSCLC (metastases within 12 months from last platinum-based chemotherapy use) positive for Exon 20 Insertion whose disease progressed on or after platinum-based chemotherapy. This analysis set will be used for efficacy analysis unless otherwise stated.
Interim or Final Data Summary
Actual Number of Patients Enrolled	24
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	At least 2 post-baseline efficacy disease assessments
Final Safety Findings	The testing for this clinical validation study was conducted retrospectively on archived study specimens. No treatment decisions were made based on any of these test results; therefore, there were no unanticipated adverse device events related to the study products or procedures to subjects or operators.
Final Effect Findings	The Blinded Independent Central Review (BICR)-assessed confirmed overall response rate (confirmed Complete Response + confirmed Partial Response) was 41.7% in the primary efficacy population with EGFR exon 20 insertions detected by the ODxT Test (n=24) versus 41.5% in the primary efficacy population (n-41) based on the Clinical Trial Assays (Local tests).
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Yes. The labeling supplement should include a summary of the post-approval study design and results.
General
Study Status	Terminated
Application Number / Requirement Number	P210014 / PAS001
Date Original Protocol Accepted	12/13/2021
Date Current Protocol Accepted	04/06/2023
Study Name	Cont f/u of OPTIMIZE Clinical Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of the the premarket cohort (OPTIMIZE Clinical Study) Study Objective: To assess the safety and efficacy of the Svelte DES-IDS and the Svelte DES-RX compared to control DES in subjects with = three (3) de novo coronary artery lesions in = two (2) native coronary artery vessels. Study Design: A prospective, single-blind, randomized, active-control, multi-center clinical study comparing the safety and efficacy of the Svelte Sirolimus-Eluting Coronary Stent Integrated Delivery System (Svelte DES-IDS) and Svelte Sirolimus-Eluting Coronary Stent Rapid Exchange Delivery System (Svelte DES-RX) to the commercially available Abbott Vascular XIENCE or Boston Scientific Promus Drug-Eluting Coronary Stents (control DES). In this study, subjects will have stents placed as the primary treatment of symptomatic ischemic heart disease.
Study Population	Single-blind study with Slender IDS and Direct RX Stent Systems
Sample Size	1,645 subjects (already enrolled)
Key Study Endpoints	The study primary endpoint is Target Lesion Failure (TLF) at 12 months post-procedure, defined as cardiac death, Target Vessel Myocardial Infarction (TVMI, including Q wave and non-Q wave) or clinically-driven Target Lesion Revascularization (TLR) by percutaneous or surgical methods. The Svelte DES-IDS and DES-RX investigational group will be considered safe and effective if TLF rates between it and the control DES group are shown to be non-inferior.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Terminated
Application Number / Requirement Number	P210014 / PAS002
Date Original Protocol Accepted	04/08/2022
Date Current Protocol Accepted	04/06/2023
Study Name	DIRECT IV Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Svelte Slender IDS and Direct RX Post-Approval Study
Study Population	A prospective, multicenter, non-randomized post-approval study with Direct Rx and IDS Stent Systems
Sample Size	Approximately 500 subjects
Key Study Endpoints	The primary safety and effectiveness endpoints is percentage of subjects with Target Lesion Failure (TLF) at 12 months post-procedure, defined as cardiac death, non-fatal Target Vessel Myocardial Infarction (TVMI, including Q wave and non-Q wave) or clinically-driven Target Lesion Revascularization (TLR) by percutaneous or surgical methods.
Follow-up Visits and Length of Follow-up	36 months
General
Study Status	Ongoing
Application Number / Requirement Number	P200015 S011/ PAS001
Date Original Protocol Accepted	12/16/2021
Date Current Protocol Accepted
Study Name	Cont f/u of the Alterra IDE Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects enrolled under IDE G170053, including the Continued Access Protocol investigation subjects. The objective of this study is to characterize the clinical outcomes of these subjects annually through 10 years post-procedure.
Study Population	All living subjects enrolled under IDE G170053, including the Continued Access Protocol subjects.
Sample Size	119
Key Study Endpoints	Right ventricular outflow tract/pulmonary valve reintervention, transcatheter heart valve hemodynamic function, and adverse events (including device frame fracture).
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: Freedom from RVOT/PV reintervention (4-years): 97.3% Freedom from death (with vital status, 4-years): 95.7% Alterra Pre-stent fracture (4-year Kaplan-Meier rate): 41.6% Sapien 3 valve frame fracture (4-year Kaplan-Meier rate): 0.0% Site Reported Adverse Events of Interest at 4 years Endocarditis: 0.0% Effectiveness Results: Mean RVOT gradient baseline – 6.7 mmHg; 1 year – 9.8 mmHg; 4 years – 9.3 mmHg Total pulmonic regurgitation 4 years: None – 51.3% (39/76); Trace – 14.5% (11/76); Mild – 28.9% (22/76); Moderate – 3.9% (3/76); Severe – 1.3% (1/76) Paravalvular regurgitation 4 years: None – 98.7% (75/76); Trace – 0.0% (0/76); Mild – 1.3% (1/76); Moderate - 0.0% (0/76); Severe - 0.0% (0/76)
Actual Number of Patients Enrolled	Enrolled: 121; Valve implanted: 118
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	At 4 years, 84 subjects out of 118 subjects with the study devices implanted had known status (71.2%).
General
Study Status	Completed
Application Number / Requirement Number	P200035 / PAS003
Date Original Protocol Accepted	12/09/2021
Date Current Protocol Accepted	10/27/2023
Study Name	New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-site, single arm, unblinded post-approval study comparing prospective recipients of PAS NMP livers versus historical IDE SCS livers with respect to adverse biliary-related events. Primary Objective: To compare the effect of NMP to SCS in the prevention of adverse biliary related events, as measured by biliary complications in subjects that received a liver from a DBD donor or a DCD donor age less than 40y. Secondary Objectives: 1) To assess graft survival in new enrollment NMP livers in subjects that receive a liver from a DBD donor or a DCD donor age less than 40y. 2) To assess subject survival in new enrollment NMP livers in subjects that received a liver from a DBD donor or a DCD donor age less than 40y. 3) To compare the graft survival rate of subjects that received a liver from a DCD donor age 40y-70y to the graft survival rate of subjects that received a liver from a DCD donor age less than 40y.
Study Population	Deceased DBD and DBD donor livers and adult liver transplant recipients more than 40y.
Sample Size	315 transplanted livers, with minimum 40 livers from DCD donors less than 40y and a maximum of 105 livers from DCD donors 40y-70y.
Key Study Endpoints	Primary Effectiveness Endpoint: Adverse biliary-related events as measured by biliary complications at 3-months, 6-months, and 12-months post-transplant. Secondary Effectiveness Endpoints Graft survival rates, subject survival rates at 3-months, 6- months, and 12-months post-transplant
Follow-up Visits and Length of Follow-up	Patients will be followed and evaluated for outcomes at 3, 6, and 12 months. Outcomes will be analyzed and reported after all available transplanted subjects have completed the 12-month post-transplant follow-up visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 315 liver transplant recipients were enrolled, including 210 recipients of livers from DBD donors and 105 recipients of livers from DCD donors.
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	92.4 percent of the patients were followed to 1 year or outcome (retransplant or death). One patient was exited at 6 months by the investigator. One patient was lost to follow-up after the 6-month visit.
Final Safety Findings	Results: Primary Effectiveness Endpoint The overall adverse biliary complication rate at 12 months in the recipients of a liver from a DBD donor or a DCD donor age less than or equal to 40 y was 22.1 percent. The non-anastomotic biliary strictures rate was 2 percent in this group. Secondary Effectiveness Endpoints The death censored graft survival rates at 12 months in recipients of a liver from a DBD donor or a DCD donor age less than or equal to 40 y was 97.9 percent. The patient survival rate at 12 months in the recipients of a liver from a DBD donor or a DCD donor age less than or equal to 40 y was 94.8 percent. The death censored graft survival rates at 6 months in recipients of a liver from a DCD donor age less than or equal to 40 y was 97.6 percent compared to 96.7 percent in recipients of a liver from a DCD donor age greater than 40 y.
General
Study Status	Completed
Application Number / Requirement Number	P200036 / PAS001
Date Original Protocol Accepted	03/01/2022
Date Current Protocol Accepted	07/15/2022
Study Name	Continued Follow-Up of G170301 Clinical Study
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Other Data Source
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort to obtain longer term safety and effectiveness data on the eCoin out to 5 years post-implantation
Study Population	Subjects diagnosed with Urgency Urinary Incontinence (UUI).
Sample Size	Available sample size for longer term follow-up of the original cohort. The original IDE study was designed to enroll and implant between 120 and 135 patients; it enrolled 137 patients with 4 patients exiting prior to implantation (due to ineligibility). Thus, 133 patients were implanted.
Key Study Endpoints	To collect and report clinical outcomes for safety and effectiveness, including 3-day bladder diaries, all device- or procedure-related adverse events, including but not limited to, infections, vasculitis, cellulitis, neuro-sensory and -motor events, device migrations, erosions, unplanned explantations, and re-implantation, to FDA through 5 years post-implantation on patients enrolled in G170301.
Follow-up Visits and Length of Follow-up	5 years, post-implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	31
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	67.7% (21 of 31 at 5 years) The study reconsented 31 subjects for continued follow-up out to 5 years post-implantation. Of those reconsented, 15 subjects consented to re-enroll for follow-up only (no device re-implantation) and 16 subjects consented to be explanted and re-implanted. Prior to the 205 week follow-up, one subject withdrew and 7 subjects were missing at random. Prior to the 257 week follow-up, 2 additional subjects were missing at random.
Final Safety Findings	There were no unanticipated adverse device events. Overall, there were 2 device related adverse events: 1 for incisional site pain and 1 procedure-related adverse event of post-operative infection. These events are anticipated for this type of device.
Final Effect Findings	For subjects who underwent follow up only and were not re-implanted, 75% (9/12 subjects) showed at least a 50% reduction in UUI episodes at 205 weeks, and 58% (7/12 subjects) of subjects experienced at least a 50% reduction in UUI episodes at 257 weeks. Of subjects who were reimplanted, 45% (5/11 subjects) of subjects experienced at least a 50% reduction in UUI episodes at 205 weeks post activation, and 78% (7/9 subjects) experienced at least a 50% reduction in UUI episodes at 257 weeks.
Study Strengths & Weaknesses	Study shows similar results in terms of safety and effectiveness at 4- and 5-years post-implant compared to the pre-market results. However, the results are based upon a very limited number of patients since many subjects did not reconsent and/or were lost to follow-up. Further, the 4- and 5-year data on re-implanted subjects is difficult to interpret as the time elapsed between the explant and re-implant varied among those subjects. Reimplantation of a new eCoin device did not reset their follow-up clock
Recommendations for Labeling Changes	None
General
Study Status	Delayed
Application Number / Requirement Number	P200036 / PAS002
Date Original Protocol Accepted	03/30/2022
Date Current Protocol Accepted	03/03/2026
Study Name	Post-Approval Study of eCoin - RECIPE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This PAS is a prospective, multicenter, single-arm study of the safety and effectiveness of eCoin tibial nerve stimulation in subjects having UUI. Subjects will be screened.
Study Population	The study population will consist of eligible patients (adults above 18 years old) with a diagnosis of UUI. Baseline assessment will include complete medical history, physical examination, and completion of a 3-day voiding diary to quantify voiding behavior, symptoms, and incontinence. Only subjects who meet all the inclusion and exclusion criteria, and have provided informed consent, will be enrolled.
Sample Size	The target enrollment for this study is 200 subjects at 25 sites.
Key Study Endpoints	All study data will be recorded onto electronic Case Report Forms (eCRFs) in an electronic data capture (EDC) system. All eCRFs will be completed using de-identified data. The EDC system will maintain the integrity of patient privacy using a secure server and patient information is still de-identified, using patient numbers only. The protocol identifies measures the sponsor will use to help ensure data reliability and quality control, including training of study personnel responsible for entering all data into the eCRF system, use of a central database (data entered in the eCRF will be immediately saved and changes tracked to provide for an audit trail), Source Data Verification (SDV) performed per the clinical monitoring plan, and locking data upon verification to prevent further editing.
Follow-up Visits and Length of Follow-up	60 months post activation
General
Study Status	Completed
Application Number / Requirement Number	P200037 / PAS001
Date Original Protocol Accepted	07/27/2021
Date Current Protocol Accepted	07/27/2021
Study Name	ACE-PAS
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Active surveillance study using real-world data collected in the ASSURE Registry. Outcome measures are based on analysis of ASSURE Registry data including data recorded by the ASSURE system which has been annotated by clinical experts in electrophysiology.
Study Population	Adult patients prescribed the ASSURE system who have consented to participate in the ASSURE registry
Sample Size	A total of 271 appropriate shock episodes for VT/VF is required to provide the desired level of statistical precision for the primary efficacy endpoint (overall shock conversion rate). It is estimated that a total of 5,179 patients will be required to provide data on 271 appropriate shock episodes. The required sample size is based on the following assumptions: • Performance goal of 89% for overall shock conversion rate • Estimated ASSURE system overall shock conversion rate of 94% • Endpoint will be met if lower bound of a 2-sided 95% exact confidence interval greater than or equal to the performance goal of 89% The estimated number of patients required was derived from a literature review of prospective studies (6) that presented shock data for LifeVest. In these studies, 27/804 (3.36%) patients had a total of 42 appropriate shock episodes, or an average of 1.555 (42/27) shock episodes per patient. It is expected, therefore, that 174 (271/1.555) ASSURE Registry patients will account for the 271 required appropriate shock episodes. If only 3.36% of the ASSURE Registry patients will experience one or more appropriate shock episodes, a total of 5,179 (174/0.0336) patients are required to provide data on 271 appropriate shock episodes for VT/VF.
Key Study Endpoints	Effectiveness Objective: To evaluate shock effectiveness in converting ventricular tachycardia/ventricular fibrillation (VT/VF) Primary Endpoint: Overall shock conversion rate [percent of spontaneous episodes of ventricular tachycardia/ventricular fibrillation (VT/VF) successfully converted with one or more shocks] =89.0% Secondary Endpoint: First shock conversion rate [percent of spontaneous episodes of ventricular tachycardia/ventricular fibrillation (VT/VF) converted with a single shock] (report only) Rationale for Effectiveness Performance Goal: The overall performance goal is based on results from LifeVest German Registry data in which the overall shock conversion rate was 94.0% for 163 appropriate shocks delivered in a population of 6,043 patients. Applying a non-inferiority margin of 5% results in a performance goal of 89%. Safety Objective: To evaluate the prevalence of inappropriate shocks Primary Endpoint: Inappropriate shocks per patient-month of use [total inappropriate shocks/cumulative months of device use for all patients] = 0.0075 Secondary Endpoint: Inappropriate shock rate [percent of patients who experience at least one inappropriate shock] (report only) Rationale for Safety Performance Goal: Based on results from two registry studies and the manufacturer reported rate which cumulatively report 0.0071 inappropriate shocks per patient month (1363 inappropriate shocks/191,743 months of cumulative wear time). The upper bound of a two-sided 95% confidence interval around 0.0071 is 0.0075. Ancillary Effectiveness • Appropriate shock rate per month • Percent of patients who experience at least one appropriate shock • Total shocks delivered • Shocks diverted by Alert Button press Safety • False Positive Shock Alarm rate • True Positive Shock Alarm rate • Adverse Events Compliance • Average Daily Usage (hours) • Device usage in days
Follow-up Visits and Length of Follow-up	The device will be used temporarily (days of use), and the data will be obtained from that period of use. No additional patient follow-up is required.
Interim or Final Data Summary
Actual Number of Patients Enrolled	21,816
Actual Number of Sites Enrolled	N/A since the study uses data from ASSURE Patient Registry
Patient Follow-up Rate	N/A since this uses RWE
Final Safety Findings	The sponsor states that sample size of 271 appropriate shock episodes for VT/VF is required to provide the desired level of statistical precision for the primary effectiveness endpoint (overall shock conversion rate).
Final Effect Findings	The sponsor states the incidence rate of inappropriate shocks was 0.0065 per patient-month with an upper 95% confidence bound of 0.0073 - successfully meeting the prespecified performance goal of 0.0075. Overall, 1.3% of patients experienced inappropriate shocks, while 94% remained free from false-positive shock alarms. The overall shock conversion efficacy for spontaneous VT/VF episodes was 100%, with a lower 95% confidence bound of 98.9%, exceeding the prespecified performance goal of 89%. First-shock conversion efficacy was 97%.
Study Strengths & Weaknesses	ACE-PAS was conducted as a standard of care registry and exhibits real-world performance of the ASSURE WCD in a clinical setting. Prespecified performance goals allowed for assessment of key metrics against established, clinically meaningful benchmarks. Large-scale study enrolling over 20,000 patients exclusively within the United States, making it the largest WCD study conducted to date. However, results may not be generalizable to populations in other geographic regions with differing healthcare systems, clinical practices, and patient demographics. Observational study design did not include longitudinal clinical follow-up, therefore limiting insights into outcomes such as left ventricular ejection fraction improvement, implantable cardioverter defibrillator (ICD) implant, or mortality. Study relied on device-recorded data to evaluate outcomes, which inherently lack comprehensive clinical context, such as patient-reported symptoms or standard 12-lead ECG interpretations. These data are also susceptible to transmission errors and memory corruption, and their accuracy depends on device specific detection algorithms and programming settings, which may vary among patients. To strengthen data validity, all device-detected arrhythmic episodes underwent adjudication by an electrophysiology expert panel.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P200039 / PAS001
Date Original Protocol Accepted	06/04/2021
Date Current Protocol Accepted
Study Name	New Enrollment PAS Registry
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, multicenter, observational, single-arm post-approval study using new data collected in the National Cardiovascular Data Registry (NCDR) CathPCI Registry. The objective of this study is to better understand the utilization, safety, and effectiveness of the Shockwave Coronary IVL System in a real-world setting.
Study Population	Patients with severely calcified, stenotic de novo coronary artery lesions presenting with stable, unstable, or silent ischemia that are suitable for percutaneous coronary intervention (PCI) and with clinical characteristics similar to the Disrupt CAD III IDE study.
Sample Size	Approximately 1000 patients in the CathPCI Registry including a minimum of 30 patients with permanent pacemakers [PPM] or implantable cardioverter defibrillators [ICDs].
Key Study Endpoints	Safety endpoints: Mortality and procedure-related adverse events IVL-specific data reporting IVL-related ventricular arrhythmia IVL balloon loss of pressure and related serious dissections Safety of IVL in patients with PPM/ICD
Follow-up Visits and Length of Follow-up	The timeline and milestones following approval of the protocol.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1212
Actual Number of Sites Enrolled	1700
Patient Follow-up Rate	n/a
Final Safety Findings	1) Procedure related adverse event rate: 2.9% (35/1,212) 2) All cause death rate: 0.2% (3/1,212) 3) Sustained Ventricular Arrhythmia: 0.0% (0/153) 4) Balloon Loss of Pressure/Rupture: 1.3% (2/153) 5) Pacing issues with Cardiac Implantable Electronic Device: 0.0% (0/12)
Final Effect Findings	n/a
Study Strengths & Weaknesses	strengths: real world data, large dataset weaknesses: limited long term data
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P200039 / PAS002
Date Original Protocol Accepted	04/09/2021
Date Current Protocol Accepted
Study Name	DISRUPT CAD III Cont f/u Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design: The overall study design for the CFS is unchanged from the pivotal portion of the IDE study. The study design is a prospective, multicenter, single-arm, global IDE study to evaluate the safety and effectiveness of the Shockwave Coronary IVL System in de novo, calcified, stenotic coronary arteries prior to stenting. Disrupt CAD III will be conducted as a staged pivotal study. During the first stage, up to 25 sites in the United States will be initiated to enroll up to 75 subjects (25 roll-in, 50 pivotal). Sites outside of the US may be initiated during the initial stage and do not count toward the 25 site limit or the 75 subject limit. The first 30 pivotal subjects enrolled in the study will be included in the safety assessment and their data analyzed. Results of this early safety analysis will be sent to the FDA as an IDE supplement with a request to expand the study to 50 sites worldwide. The first 25 US sites will continue to enroll up to a total of 75 subjects during FDA’s review of this IDE Supplement.
Study Population	The study population for the Disrupt CAD III CFS is comprised of the 384 pivotal subjects enrolled in the Disrupt CAD III IDE study. Subjects in the IDE were enrolled per eligibility criteria outlined in Section 7.2. There are no new enrollments in the Disrupt CAD III CFS.
Sample Size	The process for the original sample size determination is outlined in Section 9.2. There are no new enrollments required for the CFS and no new hypothesis testing.
Key Study Endpoints	The primary safety endpoint for the CFS is freedom from MACE at 12 and 24 months, reported descriptively. Other endpoints to be assessed through 2 years post-procedure include the rate of: (1) target lesion failure (TLF) and (2) all death, cardiac death, MI, TV-MI, nonprocedural MI, ID-TVR, ID-TLR, ID-non-TLR ID-non-TVR, all revascularizations (ID and non-ID), and stent thrombosis (ARC definite, probable, definite or probable) at 6, 12 and 24 months. Robust independent adjudication of events (i.e., Clinical Events Committee) will be maintained throughout the CFS, unmodified from the pivotal portion of the study.
Follow-up Visits and Length of Follow-up	Follow-up within 12-24 hours post procedure or at discharge; follow-up at 30 days; follow-up at 6, 12, 24 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	384
Actual Number of Sites Enrolled	47
Patient Follow-up Rate	93.5%
Final Effect Findings	Final Safety and Effectiveness Findings (Combined) The primary endpoint was Major Adverse Cardiac Events (MACE), which was a composite of cardiac death, non-Q-wave myocardial infarction (MI), Q-wave MI, and target vessel revascularization. The MACE rate was 7.0%, 7.8%, 10.2%, 13.6% and 18.9% for the timepoints of in-hospital, 30 days, and 6, 12, and 24 months, respectively, with major contributing components including non-Q-wave myocardial infarction (MI) and target vessel revascularization.
Study Strengths & Weaknesses	Strengths: Study monitoring and adjudication Good follow up compliance to 24 years Weaknesses: Single arm study
Recommendations for Labeling Changes	Yes
General
Study Status	Ongoing
Application Number / Requirement Number	P200045 S002/ PAS003
Date Original Protocol Accepted	08/04/2023
Date Current Protocol Accepted
Study Name	Registry Data Collection for Dissection
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To collect real world, post-approval safety, performance, health economics and patient reported outcomes on patients treated with the RelayPro Thoracic Stent Graft System when used to repair Type B dissections in the descending thoracic aorta. This is a multi-center, prospective observational registry enrolling new patients
Study Population	Patients requiring urgent or elective endovascular treatment of thoracic aortic acute and chronic dissections with the RelayPro Thoracic Stent-Graft System. There is no comparison group for the registry study.
Sample Size	Number of subjects: A minimum of 60 patients with acute dissections and 60 patients with chronic dissections with a minimum of 50% of each indication from the US. Assumptions for sample size estimation: A sample size of 120 provides 80% power (a =0.05) to distinguish an event that occurs with an incidence of 2% or greater from 0. That is, the 95% CI does not include 0. Number of sites: 80 Sites location: US and OUS
Key Study Endpoints	Technical success, defined as: Successful delivery of the device through the vasculature (i.e. ability to deliver the implant to the intended location without the need for unanticipated corrective intervention related to delivery) • Deployment of the endovascular stent-graft in the planned location with coverage of the target lesion (or entry tear in the case of dissection); • Absence of unplanned coverage or aortic branch vessels; • Patency of the endovascular stent-graft, absence of device deformations (e.g. kinks, stent eversion, maldeployment, misaligned deployment) requiring unplanned placement of an additional device within the endovascular stentgraft, and; • Successful withdrawal (i.e. successful withdrawal of the delivery system, without the need for unanticipated corrective intervention related to withdrawal) • Absence of Type Ia, Type Ib, Type IIIa and IIIb endoleak that extends beyond 30 days by confirmatory imaging (CTA, magnetic resonance angiography [MRA], or duplex ultrasound) Clinical success, defined as the absence of: • Target lesion related mortality • Type Ia, Ib, IIIa and IIIb endoleak • Graft infection • Stent patency <50% • Target lesion aortic rupture • Conversion to open repair • Arrest of the original pathological process (e.g., total aortic diameter expansion >5 mm in the aorta that has a study endograft, embolization from penetrating ulcer, extension of dissection, false lumen perfusion) or a new aortic pathology as a result of the intervention (e.g., pseudoaneurysm, dissection, intramural hematoma, unintentional adverse dissection septum rupture, stent-graft induced aortic wall injury, new aortobronchial/tracheal or aortoenteric fistula formation) Additional endpoints: • All-cause mortality • Safety (MAEs, all related adverse events) • Target lesion reintervention, all secondary interventions • Device performance based on imaging assessments of all morphological variables (aortic remodeling, all endoleaks, any loss of patency, stent-graft migration, device integrity, etc.) Patient outcome measures: • Post-operative return to normal activities – employment, household activities, social life and hobbies (return to normal activities will be recorded at one year visit only)
Follow-up Visits and Length of Follow-up	30 days, 6 months, 1 year and annually thereafter through five years
General
Study Status	Ongoing
Application Number / Requirement Number	P200045 / PAS001
Date Original Protocol Accepted	08/05/2021
Date Current Protocol Accepted
Study Name	Continued f/u of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, single-arm, multicenter study that consists of continued follow-up of all available subjects from the IDE Pivotal Study and the Continued Access Study
Study Population	Subjects with TAAs and PAUs eligible for treatment with the RelayPro Thoracic Stent-Grafts
Sample Size	A total of 110 subjects were enrolled in IDE Pivotal Study and 5 subjects were enrolled in the Continued Access Study
Key Study Endpoints	Clinical outcomes will include all-cause mortality, lesion-related mortality, major adverse events, secondary interventions, conversion to open repair, occlusions, stenosis or kink, all types of endoleaks, stent graft migration (>10 mm), aneurysm expansion (>5 mm), aortic rupture, loss of device integrity, and other device-related events.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P200045 / PAS002
Date Original Protocol Accepted	11/16/2021
Date Current Protocol Accepted
Study Name	RelayPro Post-Approval Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To collect real world, post-approval safety, performance, patient reported outcomes and health economic data on patients treated with Terumo Aortic endovascular stent-grafts in standard clinical practice. This is a multi-center, open label, prospective observational registry enrolling new patients to obtain safety and performance data for the RelayPro Thoracic Stent-Graft System.
Study Population	Patients requiring urgent or elective endovascular treatment of thoracic aortic aneurysm, pseudoaneurysm, dissection, penetrating aortic ulcer or intramural hematoma treated with the RelayPro Thoracic Stent-Graft System There is no comparison group for the registry study
Sample Size	A minimum of 177 aneurysm subjects treated with the RelayPro Thoracic Stent-Graft System will be enrolled. Of these a minimum of 88 patients will be enrolled in the U.S. A sample size of 161 subjects provides 80% power (a =0.05) to distinguish any event that occurs at 1% or greater from 0. To allow for 10% attrition at 1 year, a minimum of 177 patients will be enrolled and analyzed. Up to 80 global sites, including up to 40 US sites will be enrolled.
Key Study Endpoints	Primary Outcome The primary outcome is Aortic-related mortality, defined as any death due to aortic rupture, malperfusion or aortic dissection. Secondary Outcomes All-cause mortality Technical Success Clinical Success Serious Adverse Events Major Adverse Events Patient Outcomes (Post-operative return to normal activities – employment, household activities, social life and hobbies) Procedure related health Economics (e.g., total procedure time, blood loss, volume of contrast used etc.) Summary data to be posted on FDA website for interim and final reports include: Aortic-related mortality All-cause mortality Aneurysm rupture Aneurysm enlargement (>5mm) Major Adverse Events All types of endoleaks Graft migration (>10mm) Stent fracture and graft occlusion (including stenosis and kink) Conversion to open surgery Secondary interventions Technical Success
Follow-up Visits and Length of Follow-up	A minimum of 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P200046 / PAS001
Date Original Protocol Accepted	03/26/2021
Date Current Protocol Accepted	03/06/2026
Study Name	Continued Follow-up of the Harmony TPV IDE Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all patients enrolled under IDE G120175, including the Continued Access Protocol investigation patients. The objective of the study is to characterize the clinical outcomes annually, unless otherwise specified, through 10 years post implant.
Study Population	All patients enrolled under IDE G120175, including the Continued Access Protocol investigation patients.
Sample Size	82
Key Study Endpoints	Device success, freedom from TPV dysfunction, freedom from all-cause mortality, serious device-related adverse events, quality of life score (SF-36; 6 months, 2 years, 5 years and 10 years), and reoperation.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results Known device- or procedure-related mortality at 5 years: 0% Freedom from stent fracture at 5 years: 99.0% Effectiveness Results Device success at 5 years: 73.1% Freedom from TPV dysfunction at 5 years: 77.7% Freedom from reoperation at 5 years: 95.1% Freedom from catheter reintervention at 5 years: 91.8%
Actual Number of Patients Enrolled	108 (catheterized)
Actual Number of Sites Enrolled	10 (global)
Patient Follow-up Rate	93.4% at 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P200046 / PAS002
Date Original Protocol Accepted	03/26/2021
Date Current Protocol Accepted	03/06/2026
Study Name	Harmony TPV New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multi-center study. The objective of the study is to characterize the real-world performance of the Harmony TPV through 10 years post implant.
Study Population	Patients with severe pulmonary regurgitation (i.e., severe pulmonary regurgitation as determined by echocardiography and/or pulmonary regurgitant fraction greater than or equal to 30% as determined by cardiac magnetic resonance imaging) who have a native or surgically-repaired right ventricular outflow tract and are clinically indicated for surgical pulmonary valve replacement.
Sample Size	150
Key Study Endpoints	Proportion of patients without valve intervention and with acceptable hemodynamic function at 6 months, procedure success at 30 days, as well as freedom from all-cause mortality, freedom from reoperation, freedom from catheter reintervention, freedom from TPV dysfunction, and serious procedure- and device-related adverse events at 6 months and annually through 10 years.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results Number of Subjects with CEC Adjudicated Adverse Events (Serious Device- or Serious Procedure-Related AEs): CVA: 0.7% (1); Congestive heart failure: 1.3% (2); Erosion: 0.7% (1); Heart block, 3rd degree: 0.7% (1); Hemorrhage: major, life threatening: 1.3% (2); Thrombosis of the TPV: 0.7% (1); Ventricular premature beats 0.7% (1); Ventricular tachycardia, sustained: 1.3% (2) Effectiveness Results There have been 2 surgical reoperations and 3 catheter reinterventions reported. There has been 1 event of major stent fracture and 16 minor stent fractures have been reported by the Radiography core laboratory.
Actual Number of Patients Enrolled	150 (implanted)
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	91.7% at 6 months
General
Study Status	Terminated
Application Number / Requirement Number	P170019 S016/ PAS001
Study Name	Post-Approval Study
General Study Protocol Parameters
General
Study Status	Ongoing
Application Number / Requirement Number	P200002 / PAS001
Date Original Protocol Accepted	04/28/2021
Date Current Protocol Accepted	10/07/2025
Study Name	CONVERGE Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of CONVERGE PAS is to evaluate clinical outcomes (peri-procedural and long-term) in a cohort of patients treated during commercial use of the EPi-Sense and Epi-Sense ST Guided Coagulation System to treat symptomatic long-standing persistent atrial fibrillation (AF) patients who are refractory or intolerant to at least one Class I and/or III AAD. The study is a prospective single arm study with safety and effectiveness compared to performance goals which are based upon published literature.
Study Population	Patients diagnosed with long-standing persistent AF defined in accordance with the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement. Long-standing Persistent: Continuous AF of greater than 12-months duration.
Sample Size	52 Subjects were enrolled at 23 sites including sites in US, UK and EU
Key Study Endpoints	The primary effectiveness endpoint is defined as freedom from AF/AT/AFL absent class I and III AADs except for a previously failed or intolerant class I or III AAD with no increase in dosage following the 3-month blanking period through the 12-months post procedure follow-up visit The Primary Safety Endpoint is the severe adverse event rate through 12-months post-procedure. The primary safety endpoint for the study includes major adverse events (MAEs): The incidence of MAEs through 30-days post Hybrid Convergent procedure The incidence of MAEs related to Hybrid Convergent procedure The incidence of MAEs related to Hybrid Convergent devices Additional endpoints: Clinically significant pericardial effusion; Device and procedure related serious adverse events through 12-months post-procedure; Change in AF symptoms from baseline to 12-, 18-, 24-, and 36-months post-procedure; Freedom from AF/AT/AFL >30 seconds duration absent class I and III AADs except for a previously failed or intolerant class I or III AAD with no increase in dosage following the 3-month blanking period through the 12-months post procedure follow-up visit. Evaluated based on the first 24 hours of the 7-days Holter monitoring and symptom-driven event monitoring; Freedom from any AF/AFL/AT >30 seconds duration without a Class I/III AAD prescribed for AF following the 3-month blanking period through 12- 18-, 24- and 36- months post-procedure; Freedom from any AF/AFL/AT >30 seconds duration with or without an AAD prescribed for AF following the 3-month blanking period through 12-, 18-, 24- and 36- months post -procedure; Residual AF burden / reduction in overall AF burden at 12-, 18-, 24- and 36-months post procedure when compared to baseline; and Change in AF-specific Quality of Life (QoL) score(s) at 12-, 18-, 24- and 36- months post-index procedure when compared to baseline score.
Follow-up Visits and Length of Follow-up	All treated subjects will be followed for a total of 36-months.
Interim or Final Data Summary
Interim Results	Safety Results As of March 20, 2026, 63 adverse events were reported in 29 treated subjects, including 26 SAEs in 16 subjects, 5 primary safety endpoint events, and no deaths or UADEs. Effectiveness Results The document states that no data analysis has been performed to date (Section C.16 – Interpretation of Study Results). Effectiveness findings are therefore not yet available. Final analyses will be conducted following completion of 36-month follow-up for all treated subjects, with a Clinical Study Report subsequently submitted to FDA.
Actual Number of Patients Enrolled	53
Actual Number of Sites Enrolled	11
Patient Follow-up Rate	Subject Progress by Visit Visit Timepoint Number of Subjects Visit 1 Baseline 53 Visit 2 Pre-Procedure 43 Visit 3 Procedure 43 Visit 4 7-Day 43 Visit 5 14-Day42 Visit 6 21-Day43 Visit 7 28-Day43 Visit 7.1 (Staged) Pre-Procedure 19 Visit 7.2 (Staged) Endocardial Procedure 19 Visit 7.3 (Staged) 7-Day Post Endocardial 19 Visit 8 1-Month 39 Visit 9 3-Months 38 Visit 10 6-Months 38 Visit 11 12-Months 23 Visit 12 18-Months 16 Visit 13 24-Months 10 Visit 14 36-Months 5 Early Termination — 17 Study Complete — 5
General
Study Status	Ongoing
Application Number / Requirement Number	P200049 / PAS002
Date Original Protocol Accepted	12/09/2021
Date Current Protocol Accepted
Study Name	Amulet Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/Linked/Registry Based Surveillance
Study Population	Patients with attempted implant of the Amulet device enrolled at sites participating in the LAAO registry.
Sample Size	All consecutive patients treated within the first 2 years that are entered into the LAAO Registry.
Key Study Endpoints	Primary endpoints include the following: 1. Primary safety: composite of procedure-related complications, or all-cause death, or major bleeding (defined as Type 3 or greater based on the Bleeding Academic Research Consortium (BARC) definition) through 12 months 2. Primary effectiveness: composite of ischemic stroke or systemic embolism through 18 months 3. Device closure: device closure rate at the 45-day visit 4. Pericardial effusion: rate of pericardial effusion events requiring intervention through 2 years
Follow-up Visits and Length of Follow-up	The applicant has agreed to link the data to the Centers for Medicare and Medicaid Services (CMS) claims database for long-term surveillance of these patients through 5 years post implantation (follow-up duration).
Interim or Final Data Summary
Interim Results	Safety Results: Adverse Events (AEs): AE counts reported in-hospital: • 631 patients (5.18%) had an in-hospital AE. • The most frequently reported AEs by preferred term included pericardial effusion with no intervention (1.55%), pericardial effusion with tamponade (requiring percutaneous drainage) (0.90%), without tamponade requiring percutaneous drainage (0.39%), and requiring open cardiac surgery (0.21%). • The rate of early pericardial effusion (in-hospital) that required intervention was similar in the registry (n=167 for 1.4%) compared to the rate of early pericardial effusion (0-2 days post procedure) that required intervention in the Amulet IDE trial (1.3%). • AEs related to the device included device explant (0.21%), device migration (0.15%), device thrombus (0.15%), device system embolization (catheter retrieval) (0.11%) and device system embolization (surgical retrieval) (0.13%). AE counts reported at 45 days: • A total of 3,594 patients (37.94%) that have crossed the 45-day visit had an AE. • The most frequently reported AEs by preferred term included non-device-related readmission (30.62%), GI bleeding (4.43%), and pericardial effusion with tamponade (requiring percutaneous drainage) (1.53%). • AEs related to the device included device explant (0.38%), device systemic embolization (0.24%), and device migration (0.23%). AE counts reported at 6 months: • A total of 3290 patients (39.12%) that have crossed the 6-month visit had an AE. • The most frequently reported AEs by preferred term included non-device related readmission (32.12%), GI bleeding (4.45%), and pericardial effusion (no intervention required) (1.56%). • Device thrombus occurred in 93 patients (1.11%). AE counts reported through 1-year: • A total of 2751 patients (40.06%) that crossed the 1-year visit have had an AE. • At 1-year, the most frequently reported AEs by preferred term included non-device related readmission (33.24%), GI bleeding (4.44%), and pericardial effusion with tamponade (requiring percutaneous drainage) (1.56%). • Ischemic stroke occurred in 1.47% and device thrombus in 1.19% of patients. Deaths: • A total of 908 deaths were reported as of the cut-off date. • 29 deaths occurred in-hospital with most (879) occurring during follow-up. • The primary causes of death as reported by the sites in the LAAO registry through the cut-off date were non-cardiovascular reasons (303), pulmonary (76), other cardiovascular reasons (68), and heart failure (64). Effectiveness Results: Procedural Outcomes: • 485 (4.0%) procedures were aborted with the most common reason for aborting the procedure as the anatomy was not conducive for an implant (n=383). • 15 (0.1%) procedures led to a conversion to an open-heart surgery. Residual leaks after implant: • 97.6% had complete closure (0mm) • 2.4% had a small leak (0-5mm) • 5 patients (0.04%) had a large leak (>5mm). Follow-up Assessments: • Of the 5204 patients that have had device closure assessed at 45 days, the 4445 (85.4%) patients had complete closure, 731 (14.0%) had a small leak (0-5mm), and 28 patients (0.5%) had a large leak (>5mm). • Of the 1029 patients that have had device closure assessed at 1 year, 849 (82.5%) patients had complete closure, 172 (16.7%) patients had a small leak (0-5mm), and 8 (0.8%) patients had a large leak (>5mm).
Actual Number of Patients Enrolled	From August 14, 2021, through March 28, 2025, 12,180 patients were enrolled
Actual Number of Sites Enrolled	350 sites have enrolled subjects as of the cut-off date
Patient Follow-up Rate	Of the 12,180 patients with an Amulet attempted procedure: • 12,151 (99.8%) patients were documented as completing the hospitalization visit (discharge visit) • 9,474 (of the 9,783 alive and reached visit window) patients completed their 45-day visit (96.8%) • 8,409 (of the 8,876 alive and reached the visit window) patients completed their 6-month visit (94.7%) • 6,868 (of the 7,340 alive and reached the visit window) patients completed their 1-year visit (93.6%) • 2,341 (of the 2,604 alive and reached the visit window) patients completed their 2-year visit (89.9%) as of the data call date
General
Study Status	Delayed
Application Number / Requirement Number	P210005 / PAS002
Date Original Protocol Accepted	09/20/2022
Date Current Protocol Accepted	12/02/2022
Study Name	New Enrollment Study-IC-8 Apthera IOL
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: To verify the post-market safety of the IC-8 Apthera IOL after the treatment of posterior capsular opacification (PCO), an expected complication related to IC-8 IOL implantation. Design: Prospective, multicenter, single-group, non-randomized new enrollment post approval study to assess the post-market safety of the IC-8 Apthera IOL after Nd:YAG laser capsulotomy following sufficient surgeon training of the sponsor-recommended standardized Nd:YAG laser capsulotomy technique. The study will be conducted in two phases, Phase A and Phase B. Phase A will occur prior to initiating enrollment for Phase B. The objective of Phase A is to develop a clinician-focused training program that ensures proper training for the treatment of PCO, an expected complication related to IC-8 Apthera IOL implantation. Phase A consists of non-interventional, qualitative research to create the clinician-focused training program. Phase B, which this protocol outlines, will begin after development of the surgical training plan in Phase A is completed and has been accepted by FDA. The objective of Phase B will be to assess the safety of the IC-8 Apthera IOL after the treatment of posterior capsular opacification (PCO) with Nd:YAG laser
Study Population	The study population will include subjects previously implanted with the IC-8 Apthera IOL in one eye and a monofocal/monofocal toric IOL in the fellow eye in accordance with the Directions for Use (DFU) for the IC-8 Apthera IOL, who meet all inclusion/exclusion criteria, and who have developed posterior capsular opacification (PCO) following IC-8 Apthera IOL implantation that requires treatment. A total of 483 subjects will be consented and enrolled in the study to ensure 435 subjects are available to complete the two-year (up to 25-months) follow-up. Each investigator should enroll approximately 20-30 subjects, and no investigator may enroll more than 25% of the intended total enrollment.
Sample Size	No. of subjects: 435 The sample size calculation for the study is based on a desired precision around the point estimate for the explant rate. Assuming an explant rate of 0.5%, a 95% exact (Clopper-Pearson) upper confidence limit with precision of 1.0% (i.e., an upper CL of 1.5%) would require 435 subjects. Taking into account 10% attrition rate over 24 months, the study should enroll 483 subjects that have developed PCO and require treatment to ensure a minimum of 435 subjects are available to complete the 2-year (approximately 24-months) follow-up. No. of sites: 15 – 20 Sites location: US
Key Study Endpoints	Co-Primary Safety Endpoints: The co-primary safety endpoints and/or parameters include the following: the rate of any additional Nd:YAG treatments beyond the initial Nd:YAG treatment, Nd:YAG outcome and/or complications, IOL-related assessments (including IC-8 Apthera IOL mask appearance and indication of any Nd:YAG damage), rates of secondary surgical interventions (SSI), rates of other serious ocular adverse events (as described in ISO 11979-7 historical grid), rate of each ocular adverse event (including but not limited to the adverse events described in the ISO 11979-7 historical grd), and rates of subjective visual disturbances. Additional Endpoints: Other parameters that will be collected in the study include but are not limited to the following: Nd:YAG laser technique details and/or settings, Nd:YAG difficulty; monocular and binocular best-corrected visual acuities; uncorrected visual acuities; rates of device deficiencies. Patient-reported outcomes (PROs) will be assessed with the Quality of Vision (QoV) instrument (McAlinden 2010) and the Small Aperture Patient Questionnaire (SAPQ).
Follow-up Visits and Length of Follow-up	Baseline PCO evaluation visit PCO treatment (Nd:YAG laser) 1-week post Nd:YAG laser visit 1-month post Nd:YAG laser visit* 12 Months (330 - 420 days following IC-8 Apthera IOL implantation) 24 Months (630 - 780 days following IC-8 Apthera IOL implantation)
Interim or Final Data Summary
Interim Results	Safety Results: One (1) new adverse event (AE) was reported during the period of this report. In total, there have been 12 AEs reported during this study. No protocol deviations have been reported during this period of the report. In total, there have been 7 protocol deviations. 1 SSI has been reported this period, with a total of 2 SSI during the entire study.
Actual Number of Patients Enrolled	23
Actual Number of Sites Enrolled	21
Patient Follow-up Rate	23 enrolled, 3 failed screening or discontinued, 1 lost to follow-up, 12 in process, 7 completed
General
Study Status	Completed
Application Number / Requirement Number	P210001 S001/ PAS001
Date Original Protocol Accepted	05/20/2022
Date Current Protocol Accepted
Study Name	KEYTRUDA PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to confirm in a post marketing setting the clinical effectiveness of the MMR RxDx as a companion diagnostic in identifying dMMR solid tumor patients for treatment with pembrolizumab. The primary objective of this study is to estimate the objective response rate (ORR) for pembrolizumab treatment among clinical study subjects whose archived solid tumor specimens are dMMR as determined by retrospective testing with the MMR RxDx (CDx). The study design includes two cohorts of patients with solid tumors treated with pembrolizumab: - 34 patients from the original approval cohort (KEYNOTE-158, Cohort K) which previously did not have a full 26-weeks of follow-up, were not included in the original data set, had archival tissue available for CDx testing - Up to 30 patients prospectively enrolled in the ongoing Cohort L underway in China that have been tested with the CDx
Study Population	The study consists of 34 participants from KN-158 Cohort K and 30 participants from KN-158 Cohort K in KN158 is an ongoing multicenter, global, open-label, single-arm cohort of pembrolizumab in participants with any advanced MSI-H/dMMR solid tumor (except CRC) that was incurable and for which prior standard first-line treatment had failed. Participants were eligible for enrollment into Cohort K based on local testing for dMMR/MSI-H status (referred to as the clinical trial assay (CTA). The sPMA dataset (P210001/S001, approved on March 21, 2022) included data from 321 KEYNOTE-158 Cohort K participants with at least 26 weeks of follow-up by the data cutoff date on October 5, 2020. Since then, an additional 34 participants enrolled in that cohort now have 26 weeks of follow-up. Data from these 34 participants are part of this proposed study. Samples from these participants have been tested with the CDx. The proposed study will evaluate the response to pembrolizumab treatment in these 34 participants based on their CDx MMR status. The tumor types represented in these 34 participants include anal (1), breast (2), cervical (1), endometrial, gastric (9), glioma (4), ovarian (1), and small intestine (1). Among these 34 participants, enrolled based on dMMR/MSI-H status per the CTA, whose samples were tested by the CDx, 26 had CDx-positive status and 8 had CDx-negative status. Cohort L in KN158 is an ongoing study cohort enrolling 30 participants who are from mainland China and are of Chinese descent with any advanced solid tumor (including CRC) that is dMMR/MSI-H determined by the CDx (VENTANA MMR RxDx) and Promega PCR, respectively. KN-158 Cohort L is still enrolling, and the tumor types will be included in the report.
Sample Size	34 patients from KEYNOTE-158 Cohort K will be included, 26 of which are CDx positive and 8 are CDx negative. The sample size is limited by the subjects available for inclusion. Up to 30 additional patients from KEYNOTE-158 Cohort L will be evaluated. The sample size is limited by the subjects available for inclusion.
Key Study Endpoints	The primary study endpoint is the objective response rate (ORR) based on partial or complete response among patients whose tumors are dMMR by the CDx. Duration of response (DOR) will be reported as an additional endpoint. For Cohort K, the ORR observed in CDx-negative patients will also be reported
Follow-up Visits and Length of Follow-up	Patients with 26-weeks of follow-up are included in the study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	34 patients in Cohort K, 30 patients in Cohort L
Actual Number of Sites Enrolled	Cohort K: 20 sites across 11 countries; Cohort L: 18 sites in China
Patient Follow-up Rate	100% in Cohort K and Cohort L
Final Safety Findings	No new safety findings were observed.
Final Effect Findings	For the 34 additional Cohort K patients, 26 pooled CDx-positive patients were reported to have an ORR of 50% (95% CI: 29.9, 70.1%), and the 8 pooled CDx-negative patients were reported to have an ORR of 12.5% (95% CI: 0.3-52.7%). For the 30 Cohort L patients, 21 CDx-positive patients were reported to have an ORR of 66.7% (95% CI: 43.0, 85.4%).
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	N/A
General
Study Status	Completed
Application Number / Requirement Number	P200035 / PAS001
Date Original Protocol Accepted	12/09/2021
Date Current Protocol Accepted	04/12/2022
Study Name	WP01 Long-Term Follow-up PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a continued follow-up of patients from the premarket WP01 clinical trial. Outcomes will be evaluated using data from the United Network of Organ Sharing (UNOS) database.
Study Population	The subjects of this study will be all the subjects receiving transplants in the WP01 IDE study where UNOS IDs were provided by the site and where subjects have consented to have their information sent to UNOS.
Sample Size	Up to 136 of 136 NMP transplants performed and up to 129 of 130 SCS transplants performed (final sample size pending evaluation of the number of patients that have consented to have their information sent to UNOS).
Key Study Endpoints	Primary objectives: To assess graft and subject survival in identified subjects To assess evidence of biliary complications in identified subjects Secondary objectives: To report post-transplant malignancy in identified subjects To report viral detection in identified subjects
Follow-up Visits and Length of Follow-up	Data will be collected on subjects through 36 months post-transplant procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	265 (133 NMP and 132 SCS)
Actual Number of Sites Enrolled	Not applicable as patients’ data was provided by UNOS
Patient Follow-up Rate	Crude Follow-up Rates: 81% NMP and 80% SCS
Final Safety Findings	• Causes of subject death were related to malignancies in 6 of the deaths and were presented between 476 and 901 days after transplant. Three cases in the NMP and 3 cases in the SCS arms were reported. • The bilirubin levels were acceptable because they ranged between 0.240 to 3.500 mg/dL thus not reaching critical values. • There was one positive result for HBV Core Antibody 381 days post-transplant. This subject was not reported as experiencing graft failure or death in the data provided. All other reported results for post-transplant malignancy and viral detection were negative, not done, or unknown.
Final Effect Findings	• No graft failures reported in either arm between 12 and 24 months. • Four (4) graft failures reported in the NMP arm 3 graft failure reported in the SCS arm from 24 to 36 months • Kaplan Meier Estimates of Graft Survival – Transplanted and Consented to UNOS Data Collection (As Treated) showed comparable results between arms at 36-month follow-up (96.9% NMP and 96.8% SCS arms). • The Kaplan-Meier Estimates of Subject Survival showed higher events free rates in the SCS arm at 36-month follow-up (88.2% NMP and 90.9% SCS arms).
Study Strengths & Weaknesses	Strengths: Randomization, Kaplan-Meier Estimates of Subject Survival and Graft Survival show comparable results between the two arms of the study. Weaknesses: Although the results indicate no concerns related to safety or effectiveness, the sample size was not large enough to detect enough events to evaluate conclusively if there are safety and effectiveness differences between NMP and SCS.
Recommendations for Labeling Changes	The study elements and results need to be included in the labeling.
General
Study Status	Terminated
Application Number / Requirement Number	P200035 / PAS002
Date Original Protocol Accepted	12/09/2021
Date Current Protocol Accepted
Study Name	WP02 Cont Access Long-Term F/u PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The WP02 CAP Long-Term Follow-Up PAS is an observational study designed to evaluate the long-term outcomes of patients from the WP02 trial. Outcomes will be evaluated using data from the United Network of Organ Sharing (UNOS) database.
Study Population	The subjects of this study will be all of the subjects receiving transplants in the IDE CAP study where UNOS IDs were provided by the site and where subjects have consented to have their information sent to UNOS.
Sample Size	Up to 105 of 105 NMP transplants performed (final sample size pending evaluation of the number of patients that have consented to have their information sent to UNOS).
Key Study Endpoints	Primary objectives: To assess graft and subject survival in identified subjects To assess evidence of biliary complications in identified subjects Secondary objectives: To report post-transplant malignancy in identified subjects To report viral detection in identified subjects
Follow-up Visits and Length of Follow-up	Data will be collected on subjects through 36 months post-transplant procedure.
General
Study Status	Ongoing
Application Number / Requirement Number	P210020 / PAS002
Date Original Protocol Accepted	02/03/2022
Date Current Protocol Accepted	06/10/2022
Study Name	URINATE PAS (PR1276)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The “Post-market Registry Evaluating the Safety and Effectiveness of the Optilume® DCB in a Real-World Setting” study (PR1276-001 Rev A) is a prospective, single arm, multi-center, non-interventional post market registry evaluating the Optilume DCB in a real-world setting. The objective of this study is to verify the continued safety and effectiveness for the Optilume® Urethral Drug-Coated Balloon (DCB) in real-world clinical use. The study duration is anticipated to be up to 7 years from first enrollment. including 2 years for subject recruitment and 5 years for clinical follow-up.
Study Population	The study will enroll up to 150 patients at up to 15 sites in the European Union and will be open to male subjects 18 years of age or older who meet the selection criteria, as shown below. Inclusion Criteria 1. Male subjects greater than or equal to 18 years old. 2. Subject diagnosed with a recurrent stricture in the anterior urethra that is able to be treated with Optilume DCB in accordance with the approved Instructions for Use. 3. Subject is willing to provide informed consent and comply with standard follow-up assessments. Exclusion Criteria 1. Subjects with a known hypersensitivity to paclitaxel or structurally related compounds. 2. Subject is unwilling to abstain or use a condom for 30 days after the procedure. 3. Subject is unwilling to use highly effective contraception for 6 months after the procedure if partner is of childbearing potential. Subjects with a history of carcinoma of the genitourinary system (kidney, bladder, prostate, urethra, testes) that is not considered in complete remission.
Sample Size	Number of subjects: up to 150 subjects Sample size was estimated based on a performance goal of 60% and an expected responder rate of 73% at 12 months for the Optilume Urethral DCB. Calculation based on one-sided alpha of 0.025 and 90% power, which results in a minimum required sample size of 139. Accounting for approximately 10% loss to follow-up at 12 months gives a total sample size of 150 subjects. A total of up to 15 sites was chosen to allow for an average of approximately 10 subjects per site, which will allow for an appropriate sample size to conduct site poolability assessments.
Key Study Endpoints	Efficacy Endpoints Primary Efficacy Endpoint The responder rate, defined as the proportion of subjects experiencing a greater than or equal to 30% improvement in International Prostate Symptom Scores (IPSS) without repeat intervention, will be compared against a performance goal of 60% at 1 year. Ancillary Efficacy Endpoints Freedom from repeat intervention including repeat dilation (rods/bougies/dilators/balloons), urethrotomy, urethroplasty, or intermittent self-dilation by Kaplan-Meier analysis. Symptom improvement measured by the IPSS questionnaire and USS PROM questionnaires will be summarized by descriptive statistics at each follow-up timepoint. Functional improvement measured by peak urinary flow rate (Qmax). Safety Endpoints Primary Safety Endpoint The rate of treatment related serious adverse events (SAEs) through 3 months post-treatment will be summarized with descriptive statistics. Ancillary Safety Endpoint Frequency and severity of treatment related complications graded by Clavien-Dindo severity scores (Dindo D, 2004).
Follow-up Visits and Length of Follow-up	Clinical follow-up is anticipated to be conducted at 3 months, 6 months, and 1 year post-procedure, and annually thereafter through 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P210020 / PAS003
Date Original Protocol Accepted	01/27/2022
Date Current Protocol Accepted	09/29/2022
Study Name	STREAM PAS (PR1275)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The “Evaluation of the Impact of the Optilume® Urethral Drug Coated Balloon (DCB) on Semen Characteristics Post-Treatment” study (PR1275 Rev A) is a single-arm, prospective study assessing semen quality after treatment with the Optilume® Urethral DCB in men younger than 55 years of age with a stricture in the anterior urethra that can be treated with the Optilume®. The objective of the study is to determine if treatment with the Optilume® Urethral DCB negatively impacts semen characteristics in men with normal baseline semen characteristics. The study duration is anticipated to be up to 3 years.
Study Population	The study will enroll 34 patients at up to 5 sites in the United States and will be open to male subjects between 22 and 55 years of age who meet the selection criteria, as shown below. Inclusion Criteria 1. Male subjects between 22 and 55 years of age 2. Subject diagnosed with a stricture in the anterior urethra that is able to be treated with the Optilume Urethral DCB in accordance with the approved Instructions for Use. 3. Subject is willing to provide written informed consent and comply with study required follow-up assessments. 4. Subject able to provide viable semen samples and baseline semen quality characteristics are above reference values based on WHO criteria (average of 2 samples): ejaculate volume greater than or equal to 1.5mL total sperm greater than or equal to 39 million sperm concentration greater than or equal to 15 million/mL total motility greater than or equal to 40% morphology greater than or equal to 4% Exclusion Criteria 1. Subjects with a known hypersensitivity to paclitaxel or structurally related compounds. 2. Subjects with a history of vasectomy or other condition that may inhibit semen/sperm production or ejaculatory function. 3. Subjects currently taking 5-alpha reductase inhibitors, alpha-blockers, selective serotonin reuptake inhibitors, or hormone replacement therapy. 4. Subject is unwilling to abstain or utilize a condom for 30 days after the procedure. 5. Subject is unwilling to utilize highly effective contraception for 6 months after the procedure if partner is of childbearing potential. 6. History of cancer in any body system that is not considered in complete remission.
Sample Size	Number of subjects: 34 subjects The sample size for the study is based on the primary effectiveness endpoint using the following assumptions: An anticipated standard deviation of 60% Estimated based on a performance goal of not more than a 30% decrease from baseline Statistical power of approximately 80% A sample size of 34 subjects was estimated based on a performance goal of not more than a 30% decrease from baseline, with an anticipated standard deviation of 60%, and an estimate of a 0% decrease from baseline after treatment with the Optilume Urethral DCB, and 80% power. NOTE: Median change from baseline at 3 months in ROBUST III was +/- 8% (-2% for those with ‘normal’ baseline sperm concentration values). Calculations are based on a one-sided 0.025 alpha level t-test for a mean. No. of Sites: 5 sites Sites location: United States
Key Study Endpoints	Efficacy Endpoints Primary Efficacy Endpoints There are no hypothesis tested efficacy endpoints Ancillary Efficacy Endpoints Improvement in IPSS Over Time Improvement in Qmax and PVR Over Time Safety Endpoints Primary Safety Endpoint Average Change in Sperm Concentration from Baseline Secondary Safety Endpoint Proportion of Subjects Experiencing greater than or equal to 50% Decrease in Sperm Concentration from Baseline Ancillary Safety Endpoint Change in Semen Characteristics from Baseline Change in Erectile Function & Overall Satisfaction IIEF Sub-Scores Device and Procedure Related Adverse Events
Follow-up Visits and Length of Follow-up	Semen quality parameters will be assessed at Baseline, 3 months, and 6 months post-treatment. Parameters will include ejaculate volume (mL), sperm concentration (million/mL), total sperm per ejaculate (million), motility (% of sperm that is motile), progressive motility (%), and morphology (% normal). Values at each timepoint will be the average of two samples collected within 1-2 weeks of each other. Clinical follow-up will be conducted at 30 days, 3 months, 6 months, and 12 months posttreatment evaluating Lower Urinary Tract Symptoms (LUTS), sexual function, and voiding function. The total length of follow-up for each subject is one year.
General
Study Status	Ongoing
Application Number / Requirement Number	P190023 S002/ PAS001
Date Original Protocol Accepted	01/13/2023
Date Current Protocol Accepted	07/09/2026
Study Name	Continued F/U of the IDE Portico NG Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study objective is to characterize the acute safety and effectiveness of the Navitor Transcatheter Aortic Heart Valve through 5 years post procedure in patients with symptomatic, severe aortic stenosis who are considered high or greater surgical risk. The study is a prospective, multi-center, single-arm study.
Study Population	Patients with symptomatic, severe aortic stenosis who are considered high or extreme surgical risk.
Sample Size	All living subjects enrolled under the IDE Portico NG Approval study, including all analysis, roll-in, and continued access cohorts
Key Study Endpoints	The safety and effectiveness endpoints include, but are not limited to: all-cause mortality, all-cause and disabling stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, major vascular complications, paravalvular aortic regurgitation, myocardial infarction, re-operation for valve-related dysfunction, rehospitalization for valve-related symptoms or worsening congestive heart failure, new permanent pacemaker implantation, new-onset atrial fibrillation, functional status as evaluated by New York Heart Association (NYHA), health status as evaluated by Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) through 1 year, and hemodynamic performance metrics by echocardiography.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results; Site-reported K-M rates at 3 Years: All-cause mortality: 23.9% All-cause stroke: 9.0% Myocardial infarction: 6.2% Re-operation for valve-related dysfunction: 0.8% Rehospitalization for valve-related symptoms: 3.2% New permanent pacemaker implantation: 24.8% New-onset atrial fibrillation: 10.6% Effectiveness Results: Mean aortic valve gradient: 7.3±3.3mmHg [24 months] Effective orifice area (EOA): 2.0±0.5 cm2 [24 months] Paravalvular Leak (moderate/severe): 0.6% [24 months] New York Heart Association (NYHA) functional class (Class III/IV): 4.8% [36 months]
Actual Number of Patients Enrolled	Total: n = 260 implanted with the Navitor valve
Actual Number of Sites Enrolled	26 sites in the United States, Australia, Denmark, Italy, and the United Kingdom (19 US, 7 OUS)
Patient Follow-up Rate	Patient status known at 3Y = 86.5% ((167 visits completed + 58 deaths) / 260 implanted)
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S182/ PAS001
Date Original Protocol Accepted	04/30/2025
Date Current Protocol Accepted	10/10/2025
Study Name	Cont F/u of EARLY TAVR Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the pivotal cohort under the IDE. The objective of this study is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE pivotal cohort.
Sample Size	All living subjects
Key Study Endpoints	All-cause death, all stroke, death or disabling stroke, hospitalization, new onset atrial fibrillation, New York Heart Association (NYHA) Functional Class, health status as evaluated by Kansas City Cardiomyopathy Questionnaire (KCCQ) score, hemodynamic valve performance and other echocardiographic parameters, and aortic valve intervention.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P210032 S015/ PAS002
Date Original Protocol Accepted	08/21/2025
Date Current Protocol Accepted	07/13/2026
Study Name	GORE TAG TBE Zone 0/1 New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective multi-center post-market study collecting outcomes through at least 5-years and up to 10-years post procedure follow-up for subjects treated with the TBE Device in Zone 0/1 as a part of routine clinical practice.
Study Population	Patients presenting with thoracic aortic disease who may benefit from the placement of the GORE® TAG® Thoracic Branch Endoprosthesis (TBE Device) in Zone 0 or Zone 1.
Sample Size	Number of subjects: Minimum of 125 subjects Assumptions for sample size estimation: A minimum sample size of 125 subjects with at least 50 subjects evaluable at 5 years post implantation. Number of sites: 50 Sites location: USA
Key Study Endpoints	Primary: -Initiation of the index endovascular procedures following the surgical revascularization procedure -Device technical success (index endvascular procedure only) -Absence of the following through all follow-up windows (unless indicated): -lesion-related mortality -Disabling Stroke (within 30 days) -Permanent Paraplegia (within 30 days) -Permanent Paraparesis (within 30 days) -New onset renal failure (within 30 days) requiring ongoing analysis - Lesion rupture (treated area) - Loss of aortic or branch patency -Endoleaks -Reintervention Secondary: The following endpoints will be assessed through all follow-up windows (unless indicated) -Access-related complications (index endovascular procedure only) -Life threatening bleed (index endovascular procedure only) -All-cause mortality -Stroke -Transient ischemic attach (TIA) - Paraplegia (within 30 days) -Paraparesis (within 30 days) - Myocardial infarction (within 30 days) - Laryngeal or Phrenic nerve injury (within 30 days) - Distal device-related thromboembolic adverse event requiring intervention or surgery (through 1-month) -Fistula formation - Upper extremity ischemia - Lesion enlargement (treated area) - Device migration - New dissection (with / without treatment) - Device and treatment-related Adverse Events (AEs) - Serious Adverse Events (SAEs) - Device integrity events (e.g., fracture, kinking, compression) - False lumen status (dissection pathology) -False lumen perfusion (dissection pathology)
Follow-up Visits and Length of Follow-up	Frequency of Follow-up: Pre-treatment (Screening), Treatment, Discharge, and Follow-up (1 Month, 6 Month, 1 Year, and Annually Thereafter for a minimum of 5-years and up to a maximum of 10 years) Length of Follow-up: Minimum of 5 years and Maximum of 10 years
General
Study Status	Ongoing
Application Number / Requirement Number	P240036 / PAS001
Date Original Protocol Accepted	04/22/2025
Date Current Protocol Accepted	04/24/2026
Study Name	LEADR PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to characterize the long-term safety and estimate the lead-related complication-free survival of the Model 3930M Lead using registry data (Product Surveillance Registry)
Study Population	Adolescent pediatric (>12 years old) and adults.
Sample Size	Approximately up to 2000 patients will be enrolled into LEADR PAS across an estimated 250 active PSR global sites where the Model 3930M is commercially available. Dependent on market approval, participating geographies may include, but are not limited to, US/Canada, EMEA, APAC, SEA, and Greater China. 125 adolescent pediatric patients will be enrolled and included within the total patient enrollment count. Approximately 5 pediatric specific sites are planned to be added to the PSR to support enrollment of this population. A minimum of 339 patients with LBBA placement will be included in the total patients enrollment count who have completed 5 years of follow up at the time of final analysis.
Key Study Endpoints	Primary Objective: Estimate Model 3930M Lead-related complication-free survival through five (5) years post implant. For an adverse event to meet the endpoint, defined as a first occurrence of a complication related to the Model 3930M Lead of an enrolled patient as determined by the CEC, the event must have occurred within five (5) years post-lead implant and be adjudicated by the CEC as being a complication related to the lead. a. The following complications will be included in the analysis: i. Failure to capture ii. Failure to sense/undersensing iii. Oversensing iv. Elevated threshold v. Abnormal pacing/defibrillation impedance vi. Lead insulation breach vii. Lead conductor fracture viii. Extracardiac Stimulation ix. Lead migration/dislodgement x. Cardiac perforation xi. Lead structural failure xii. Erosion/extrusion xiii. Infection xiv. Transvenous lead-related thrombosis Ancillary objectives will include the following: 1. Summarize patient demographics 2. Summarize Model 3930M Lead-related adverse events 3. Summarize patient deaths 4. Summarize all Model 3930M Lead system modifications 5. Summarize Model 3930M Lead electrical performance
Follow-up Visits and Length of Follow-up	The study will complete when approximately 500 patients have completed 5 years of follow-up. The total estimated PAS duration is 7 years.
General
Study Status	Ongoing
Application Number / Requirement Number	P210032 / PAS002
Date Original Protocol Accepted	07/08/2022
Date Current Protocol Accepted
Study Name	Post-Market Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The GORE® TAG® Thoracic Branch Endoprosthesis Zone 2 Post-Market Surveillance is a single-arm, non-randomized, multicenter registry collecting data from consecutively treated Patients. The objective is to ensure that the clinical outcomes during the commercial use of the GORE® TAG® Thoracic Branch Endoprosthesis are as anticipated.
Study Population	Patients who undergo treatment with the GORE® TAG® Thoracic Branch Endoprosthesis at Sites participating in the SVS VQI.
Sample Size	Max number of Patients: 350 Proximal Landing Zone: Zone 2 (per Study protocol) Min number of Patients: 250 Min number of Patients enrolled by new Sites*: 60 Min number of Patients for specific pathologies: • Acute Type B Dissection: 45 • Other Isolated Lesions (including PAU and IMH): 20 • Traumatic Transections: 25 A minimum of 100 evaluable Patients in Zone 2 will be available at 5-years. The minimum number of evaluable Patients at 5-years for specific pathologies will be: • Acute Type B Dissection: 13 • Other Isolated Lesions (including PAU and IMH): 6 Traumatic Transections: 7
Key Study Endpoints	Procedural Success: Device Technical Success and the absence of the following through the 1-Month follow-up window (181 days): • Mortality (device- and disease or treatment-related) • Stroke (mRS = 2) (through 30-days) • Paraplegia / Paraparesis (through 30-days) • Aortic rupture • Type I/III endoleak • Branch vessel occlusion requiring reintervention • Additional surgical or interventional procedure related to the device or treatment (Reintervention) Treatment Success: Device Technical Success and absence of the following through all follow-up windows (unless indicated) • Mortality (device- and disease or treatment-related) • Stroke (mRS = 2) (through 30-days only) • Paraplegia / Paraparesis (through 30-days only) • Aortic enlargement in the region encompassed by the initial lesion • Aortic rupture • Type I/III endoleak • New dissections • Loss of device integrity • Device migration • Loss of aortic/aortic branch patency • Additional surgical or interventional procedure related to the device or procedure (Reintervention) Additional endpoints of interest through all follow-up windows unless indicated: • Access complications requiring additional intervention (procedural / periprocedural only) • Stroke (mRS = 2) • All-cause mortality • New dissections requiring additional intervention / reintervention • All endoleaks • Branch vessel occlusion requiring reintervention • False lumen status (dissection pathology only) False lumen perfusion source (dissection pathology only)
Follow-up Visits and Length of Follow-up	120 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	90
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	53/73 (72.6%) of subjects with clinical data at 1-month, 3/55 (5.5%) of subjects with calinical data at 1-year. 47/73 (64.4%) subjects with CT imaging at 1-month, 2/55 (3.6%) with CT imaging at 1-year. No subjects lost to follow-up and withdrawals. 52/555 (94.5%) subjects with follow-up pending at 1-year.
Final Safety Findings	n/a: Insufficient information available for any safety conclusions
Final Effect Findings	n/a: Insufficient information available for any effectiveness conclusions
General
Study Status	Completed
Application Number / Requirement Number	P210034 / PAS001
Date Original Protocol Accepted	03/29/2022
Date Current Protocol Accepted
Study Name	Extended Follow-up of the Premarket Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multicenter, open-label, randomized 2:1, and controlled trial of Agili-C™ vs. SSOC for the repair of joint surface lesions.
Study Population	Patients with joint surface lesions of the knee
Sample Size	Up to 251 subjects (167 Agili-C™ subjects and 84 SSOC subjects) who were enrolled into the Pivotal study and are continuing follow up.
Key Study Endpoints	Primary Endpoint: Change from baseline to 60 months in the average overall KOOS score (Pain, Symptoms, QOL, ADL & Sports) Safety Endpoint: Adverse events, including serious adverse events, reoperations and revisions, up to 60 months Confirmatory Secondary endpoints: This trial will have one primary endpoint and 6 confirmatory secondary endpoints for labeling purposes. These will be tested sequentially, and Type I Error controlled hierarchically. Trial success will be declared if the primary endpoint has been met. Additional labeling claims will be made for confirmatory secondary endpoints met in sequence following success on the primary endpoint: Change from baseline to 60 months in the average overall KOOS score (Pain, Symptoms, QOL, ADL & Sports) Additional Secondary endpoints: KOOS subscores, MRI defect fill %, IKDC, SF-12, Tegner, Lysolm, subgroup analyses.
Follow-up Visits and Length of Follow-up	60 months (5 years) post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	251 subjects (167 investigational and 84 control)
Actual Number of Sites Enrolled	26 sites (11 US and 15 OUS)
Patient Follow-up Rate	At 60 months, the total follow-up rate was 83.7 %
Final Safety Findings	When comparing the safety results from baseline up through the end of study at 60 months, the group differences are all reflecting a favorable safety profile for the Agili-C implant and its related procedure. Throughout the course of the study, there was no evidence of any increase in treatment-emergent events, serious events, or device-related/procedure-related events for Agili-C compared to the SSOC control and the rate of injection use, overall failure, and conversion to total knee arthroplasty were all lower for Agili-C.
Final Effect Findings	Primary Endpoint: Agili-C was demonstrated to be superior over the SSOC control in change from baseline to 60 months in the average KOOS Overall Score (posterior probability of superiority = 1.000). The robustness of this outcome was confirmed through observed and change from baseline KOOS Overall Score over time. On both assessments, Agili-C outperformed the SSOC control at each timepoint, and the LB of the 95% confidence interval of between group differences at each timepoint did not contain zero, demonstrating statistical significance.
Study Strengths & Weaknesses	The study described the longer-term effectiveness and safety performance of the Agili-C for the treatment of an ICRS grade III or above knee-joint surface lesion(s), with a total treatable area of 1-7cm2, without severe osteoarthritis (Kellgren-Lawrence grade 0-3). The population consisted of continued follow-up of the original IDE study subjects. No new subjects were enrolled. Subjects and evaluators remained blinded. Subjects were informed of their treatment after the last evaluation. The follow-up rates at the longer timepoints were slightly lower than those that would be excepted for ongoing follow-up during the course of an IDE and for filing a PMA (83.7% compared to 85%), they are reasonable rates for a post-approval study collecting data out to 6 years post-op.
Recommendations for Labeling Changes	There are no new safety or efficacy findings that alter the conclusions that led to PMA approval, or would require addition to labeling. The sponsor has been instructed to submit a modified package insert containing the updated timecourse distributions of AEs and clinical and radiographic outcome out to 60 months post-op.
General
Study Status	Completed
Application Number / Requirement Number	P210025 / PAS001
Date Original Protocol Accepted	06/16/2023
Date Current Protocol Accepted
Study Name	TRANSCEND Continued Follow-up Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To show sufficient long term safety and effectiveness of the SurVeil DCB for use in superficial femoral or popliteal arteries. The study was designed as a global, multicenter, single blind, randomized trial. This study is continued follow-up of premarket cohorts.
Study Population	Adult patients with PAD
Sample Size	N=446 (n=222 Surveil DCB; n=224 IN.PACT Admiral DCB)
Key Study Endpoints	The primary safety endpoint was a composite of freedom from device- and procedure-related death through 30 days post-index procedure and freedom from major target limb amputation (above the ankle) and clinically-driven target vessel revascularization (TVR) through 12 months post-index procedure. The primary effectiveness endpoint was primary patency, defined as a composite of freedom from clinically-driven TLR and binary restenosis (restenosis defined as DUS peak systolic velocity ratio [PSVR] greater than or equal to 2.4 or greater than or equal to 50% stenosis as assessed by independent angiographic and DUS core labs) through 12 months post-index procedure.
Follow-up Visits and Length of Follow-up	5 years annually
Interim or Final Data Summary
Actual Number of Patients Enrolled	446
Actual Number of Sites Enrolled	79
Patient Follow-up Rate	Approximately 85-92%
Final Safety Findings	91.8% Surveil vs 89.8% for the IN.PACT
Final Effect Findings	82.2% Surveil vs 85.9% for the IN.PACT
Study Strengths & Weaknesses	Strengths: RCT, long term follow up Weaknesses: Follow up complacence (withdrawals) in the test arm
Recommendations for Labeling Changes	Update to reflect the new data at 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P220002 / PAS001
Date Original Protocol Accepted	08/11/2023
Date Current Protocol Accepted
Study Name	The TOPS System Continued F/U Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this prospective, randomized, concurrently controlled, multi-center study is to evaluate the safety and effectiveness of the TOPS™ System versus to lumbar spinal fusion control.
Study Population	Participants in the IDE study who failed at least 6 months of conservative therapy for treatment of leg pain with or without back pain at one vertebral level between L2 and L5 stemming from (1) moderate to severe central, foraminal, and/or subarticular recess lumbar spinal stenosis (LSS) and (2) up to Grade I degenerative spondylolisthesis or equivalent retrolisthesis and (3) thickening of the ligamentum flavum or scaring facet joint capsule.
Sample Size	A total of 299 subjects in the Per Protocol analysis set (206 TOPS, 93 fusion control) who were enrolled into the Pivotal study and are continuing follow up to 5 years. Assuming 85% compliance, it implies 175 TOPS subjects and 79 Fusion controls. If compliance in controls is only 80%, this implies a control sample size of 74.
Key Study Endpoints	Primary Effectiveness Endpoint: The primary effectiveness endpoint is a composite clinical success (CCS) responder endpoint based on clinical status at Month 60. An individual subject will be regarded as achieving Month 60 CCS only if s/he meets all of the following criteria at 60-months compared to baseline: A reduction of 15 points or more in the 60-month Oswestry Disability Index (ODI) compared to baseline; No new or worsening, persistent neurologic deficit; No epidural steroid injection, facet joint injections, nerve block procedures or implantable spinal cord stimulator to treat back or leg pain symptoms at any lumbar level; Any TOPS subject will be considered a failure if fusion occurs as defined in the radiographic protocol. Any Fusion subject will be considered a failure if fusion (as defined in the radiographic protocol) does not occur. This assessment will be made by a core lab; No revision or removal of implants; No supplemental fixation at the index level or at the immediately adjacent levels; No occurrence of a major device related adverse event. Secondary Endpoints: Individual components of 60-month composite clinical success (CCS); CCS at Months 36 and 48; ODI, changes from baseline in ODI, and 15 point improvement in ODI; Visual analog scale (VAS) for back pain and worse leg pain, changes from baseline in VAS, and 20 mm improvement in VAS; for VAS, the higher of the two leg scores at baseline will be used for analysis purposes. ZCQ findings; o Improvement of greater than or equal to 0.5in ZCQ physical symptom score and symptom severity and less than or equal to 2.5 on ZCQ subject satisfaction over time. o Overall ZCQ success defined as meeting all 2 of 3 individual ZCQ success criteria. o Overall ZCQ success defined as meeting all three individual ZCQ success criteria. Reduction in physical component score on SF-12; Time to revision or removal, or supplemental fixation at index or adjacent level; Narcotics use for lower back pain and leg pain; Range of motion in flexion/extension at the index and immediately adjacent levels Safety Endpoint: Evaluation of the incidence and severity of complications and adverse reactions associated with the treatment. The following AE listings will be constructed: All AEs Sorted by Group and Event Type All AEs Sorted by Group and Subject Serious AEs Severe AEs Device Related AEs Serious Device Related AEs Severe Device Related AEs Severe Life-Threatening AEs Procedure Related AEs Other AEs AEs among subjects discontinued early AEs among subjects who died.
Follow-up Visits and Length of Follow-up	After 24-month follow-up visit, the subject will continue to be followed long term annual post 24 months, at 36, 48, until patient reaches 60 months. 60 months (5 years) post-implant
Interim or Final Data Summary
Interim Results	Safety Results In the mITT population (211 TOPS™, 98 Fusion): Overall AEs: 83.4% TOPS™ vs 78.6% Fusion (difference: 4.8%, 95% CI: -4.7% to 14.4%) Device-related AEs: 28.9% TOPS™ vs 34.7% Fusion (difference: -5.8%, 95% CI: -17.0% to 5.5%) SAEs: 41.2% TOPS™ vs 34.7% Fusion, but device-related SAEs were lower in TOPS™ (6.2% vs 7.1%) Reoperations: 8.6% TOPS™ vs 14.6% Fusion through 24 months Note: Most common AE categories were musculoskeletal/connective tissue disorders and injury/procedural complications in both groups. Effectiveness Results: 24-Month CCS Results (final data): TOPS™ demonstrated superiority with 79.1% success (159/201) vs 27.5% Fusion success (25/91), difference of 51.6% (p<0.0000001). Key secondary outcomes favor TOPS™: ODI improvement greater than or equal to 15 points: 95.5% TOPS™ vs 84.7% Fusion Motion preservation: TOPS™ maintained baseline range of motion while Fusion lost ~3° flexion-extension Fusion status success: 98.4% TOPS™ (no fusion) vs 46.4% Fusion (achieved fusion) 36/48/60-month CCS data: Not yet available as insufficient subjects have reached these timepoints. While some individual patient data may be available for subjects who have reached these timepoints, the CCS analysis requires sufficient numbers of subjects to have completed each timepoint before the composite endpoint can be meaningfully analyzed and reported.
Actual Number of Patients Enrolled	309 mITT subjects who underwent surgery (211 TOPS™, 98 Fusion)
Actual Number of Sites Enrolled	37 (34 active and 3 closed due to subject completion)
Patient Follow-up Rate	Month 6: 97.0% TOPS™, 93.3% Fusion Month 12: 97.8% TOPS™, 92.1% Fusion Month 24: 91.6% TOPS™, 77% Fusion Month 36: 90% TOPS™, 77% Fusion Month 48: 86.8% TOPS™, 76.0% Fusion Month 60: Limited data (ongoing follow-up) Loss to Follow-up (7 total subjects) TOPS™ Group: 3 subjects Subject 09-012: Lost to follow-up after 24-month visit Subject 34-004: Lost to follow-up after 12-month visit Subject 43-001: Lost to follow-up after 36-month visit (subject is incarcerated) Fusion Group: 4 subjects Subject 09-021: Lost to follow-up Subject 19-038: Lost to follow-up after 6-month visit Subject 24-003: Lost to follow-up after 6-month visit Subject 34-005: Lost to follow-up after 24-month visit The sponsor noted that among the 309 mITT patients taken to surgery as part of the IDE, 28 patients have terminated early, including 4 patients (2 TOPS, 2 Fusion) that were considered withdrawn from the study intraoperatively due to the operating surgeon’s decision to intraoperatively change to a non-study treatment (row “A3aii” in the above table), as well as 24 subjects who were withdrawn following the index surgery (row “A3bi” in the above table), 3 of which (2 TOPS, 1 Fusion) are newly reported since the 12 month PAS report. See Table 2: Subject Accounting at the Time of Database Lock for more information. Additionally, see the 24 month PAS progress report for more information on the specific subjects withdrawn intraoperatively, and of those that were withdrawn following both TOPS™ and Fusion treatment.
General
Study Status	Ongoing
Application Number / Requirement Number	P220003 / PAS001
Date Original Protocol Accepted	09/14/2022
Date Current Protocol Accepted
Study Name	Continued Follow-up of the CLASP III Trial Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled in the pivotal cohort under the IDE. The objective of this study is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE pivotal cohort.
Sample Size	All living subjects.
Key Study Endpoints	Major adverse events (MAEs), all-cause mortality, non-elective mitral valve re-intervention (either percutaneous or surgical), stroke, transient ischemic attack (TIA), major vascular events, renal complications, residual atrial septal defect (ASD), MR grade, 6-minute walk test (6MWT) distance, and quality of life (QoL) measures.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: Pascal Roll-in safety results at 3-years: Composite MAEs: 34.2% All-cause mortality: 29.7% Cardiovascular death: 19.5% Non-elective mitral valve re-intervention: 1.1% Stroke: 6.4% Transient ischemic attack (TIA): 3.3% Severe Bleeding: 20.2% Major vascular events: 1.1% New Need for Renal Replacement Therapy: 4.1% Residual atrial septal defect: 48.3% Randomized safety results at 3-years: PASCAL: Composite MAEs: 36.2% All-cause mortality: 28.1% Cardiovascular death: 19.8% Non-elective mitral valve re-intervention: 2.1% Stroke: 6.8% Transient ischemic attack (TIA): 1.5% Severe Bleeding: 15.6% Major vascular events: 0% New Need for Renal Replacement Therapy: 1.9% Residual atrial septal defect: 56.8% MitraClip: Composite MAEs: 25.1% All-cause mortality: 21.1% Cardiovascular death: 16.5% Non-elective mitral valve re-intervention: 2.1% Stroke: 2.4% Transient ischemic attack (TIA): 1.1% Severe Bleeding: 10.5% Major vascular events: 0% New Need for Renal Replacement Therapy: 1.1% Residual atrial septal defect: 42.9% Pascal Registry safety results at 3-years: Composite MAEs: 39.5% All-cause mortality: 31.5% Cardiovascular death: 23.8% Non-elective mitral valve re-intervention: 1% Stroke: 6.8% Transient ischemic attack (TIA): 1% Severe Bleeding: 16.3% Major vascular events: 1% New Need for Renal Replacement Therapy: 5.1% Residual atrial septal defect: 68.2% Effectiveness Results: Mitral Regurgitation (Greater than Moderate-Severe): Roll-in: 98.8% (Baseline); 8.9% (3Y); Randomized: PASCAL - 97.4% (Baseline); 4.2% (3Y); MitraClip - 100% (Baseline); 1.7% (3Y); Registry: 99% (Baseline); 4.8% (3Y) 6-minute walk test (6MWD): Roll-in: The median improvement in 6MWD compared to baseline was 23.0 m at 1 year. Randomized (PASCAL): The median 6MWD distance increased by 15.9 m at 1 year. Randomized (MitraClip): The median 6MWD distance increased by 22.2 m at 1 year. Registry: The median 6MWD distance increased by 7.3 m at 1 year. KCCQ (Overall Score): Roll-in: An increase in the median score was observed at 2 years (19.3 points). Randomized (PASCAL): An increase in the median score was observed at 2 years (15.8 points). Randomized (MitraClip): An increase in the median score was observed at 2 years (13.7 points). Registry: An increase in the median score was observed at 2 years (10.7 points).
Actual Number of Patients Enrolled	Roll-In: 91; Randomized: 300; Registry: 98
Actual Number of Sites Enrolled	Roll-In: 51; Randomized: 54 sites; Registry: 35
Patient Follow-up Rate	Roll-In (visits completed+deaths / subjects enrolled): 3-year: 77/91 (85%) Randomized: PASCAL: 3-year: 170/199 (85%); MitraClip: 3-year: 90/95 (95%) Registry: 3-year: 79/98 (81%)
General
Study Status	Ongoing
Application Number / Requirement Number	P220003 / PAS002
Date Original Protocol Accepted	09/14/2022
Date Current Protocol Accepted
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive/linked/registry-based surveillance. The objective of the surveillance is to assess the real-world performance of the PASCAL Precision system.
Study Population	The surveillance will involve all consecutive patients treated within the first 2 years that are entered into the TVT Registry (enrollment period)
Sample Size	All consecutive patients treated within the first 2 years in the commercial setting that are entered into the TVT Registry.
Key Study Endpoints	The clinical data through one (1) year are collected through the TVT Registry. The follow-up data (including all-cause mortality, stroke, repeat procedure for mitral valve-related dysfunction, and hospitalization) from year 2 through year 5 post procedure are obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: TVT registry: Device implanted successfully: 97.6% At 30 Days: All-cause death: 2.3% All stroke: 1.3% Mitral valve re-intervention: 0.3% All-cause hospitalization: 8.9% Heart failure hospitalization: 2.6% Single leaflet device attachment: 0.5% Major or life-threatening bleed: 1.4% At 1 Year: All-cause death: 9.7% All stroke: 2.1% Mitral valve re-intervention: 1.8% All-cause hospitalization: 24.5% Heart failure hospitalization: 7.6% Medicare-Linked TVT registry: Device implanted successfully: 99.8% At 1 Year: All-cause death: 17.5% All stroke: 2.4% Mitral valve re-intervention: 3.7% All-cause hospitalization: 44.7% Heart failure hospitalization: 11.9% Effectiveness Results: TVT registry: Mitral Regurgitation (Greater than Moderate): 100% (Baseline); 6.4% (30 Days) KCCQ (Overall Score): Change from baseline to 30-day visit: 21.6 Change from baseline to 1-year visit: 23.8 NYHA Class: Improved or stayed the same at 30-day visit: 96.7% Improved or stayed the same at 1-year visit: 96.9%
Actual Number of Patients Enrolled	2411 patients (TVT registry) 524 (Medicare-linked TVT registry)
Actual Number of Sites Enrolled	199 sites
Patient Follow-up Rate	Patient status known (TVT registry): At 30 days: 92.6% At 1 year: 52.2% Patient status known (Medicare-linked TVT registry): At 1 year: 14.7%
General
Study Status	Ongoing
Application Number / Requirement Number	P190023 S013/ PAS001
Date Original Protocol Accepted	09/15/2023
Date Current Protocol Accepted
Study Name	Cont f/u of the IDE Portico NG Titan Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The study objective is to characterize the acute safety and effectiveness of the Navitor Titan Transcatheter Aortic Heart Valve through 5 years post procedure in patients with symptomatic, severe aortic stenosis who are considered high or greater surgical risk. The study is a prospective, multi-center, single-arm study.
Study Population	Patients with symptomatic, severe aortic stenosis who are considered high or extreme surgical risk.
Sample Size	All living subjects enrolled under the IDE Portico NG Approval study – Titan cohort, including all analysis and roll-in subjects.
Key Study Endpoints	The safety and effectiveness endpoints include, but are not limited to: all-cause mortality, all-cause and disabling stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, major vascular complications, paravalvular aortic regurgitation, myocardial infarction, re-operation for valve-related dysfunction, rehospitalization for valve-related symptoms or worsening congestive heart failure, new permanent pacemaker implantation, new-onset atrial fibrillation, functional status as evaluated by New York Heart Association (NYHA), health status as evaluated by Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) through 1 year, and hemodynamic performance metrics by echocardiography.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: At 24 months: All-cause mortality: 14.1% All-cause and disabling stroke: 10% (all); 2.9% (disabling) Re-operation for valve-related dysfunction: 1.4% Rehospitalization for valve-related symptoms: 2.8% New-onset atrial fibrillation: 5.7% At 12 months: Life-threatening and Major bleeding events: 2.9% (life-threatening); 9.9% (major) Stage 2 or 3 acute kidney injury (AKI): 0.0% Major vascular complications: 4.1% Myocardial infarction: 4.3% New permanent pacemaker implantation: 38.6% Effectiveness Results: At 24 months: Mean aortic valve gradient: 4.5±1.9mmHg Effective orifice area (EOA): 2.6±0.6 Paravalvular Leak (moderate/severe): 0.0% New York Heart Association (NYHA) functional class (Class III/IV): 3.8% At 12 months: Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36): 42.4±9.4 (Physical, PCS), 55.1±7.3 (Mental, MCS)
Actual Number of Patients Enrolled	73 subjects implanted with the Navitor Titan valve
Actual Number of Sites Enrolled	18 sites in the United States, Australia, Denmark, Italy, and United Kingdom (12 US, 6 OUS)
Patient Follow-up Rate	96% (12 months); 88% (24 months).
General
Study Status	Study Pending
Application Number / Requirement Number	P220013 / PAS001
Date Original Protocol Accepted	06/25/2024
Date Current Protocol Accepted
Study Name	TactiFlex SE PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center clinical investigation with no continued follow-up of IDE study subjects.
Study Population	Subjects at least 18 years of age with paroxysmal atrial fibrillation (AF) that have tried and are refractory or intolerant to at least one Class I or III antiarrhythmic medication.
Key Study Endpoints	Primary Effectiveness: Freedom from AF recurrence post 90-day blanking period at 12 months. Primary Safety: Rate of device and/or procedure-related serious adverse events (SAE) within 3 months of the index ablation procedure.
Follow-up Visits and Length of Follow-up	12 months
General
Study Status	Completed
Application Number / Requirement Number	P220021 / PAS001
Date Original Protocol Accepted	06/07/2023
Date Current Protocol Accepted
Study Name	DETOUR2 Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	DETOUR 2 To evaluate the long-term safety and effectiveness of the DETOUR System. The study is continued follow-up of the pivotal DETOUR 2 trial cohort (G170083). The premarket was a prospective, single arm, multicenter study that treated 220 subjects at 36 investigation sites.
Study Population	DETOUR2 All remaining subjects treated with the DETOUR System in the DETOUR 2 trial active at the time of 12 months evaluation. There is no comparator group.
Sample Size	DETOUR 2 -All 197 subjects remaining in the DETOUR 2 trial study at 12 months will be enrolled.
Key Study Endpoints	DETOUR 2 Endpoints to be assessed at 24 and 36 months include Major Adverse Events (MAE) Symptomatic Deep Vein Thrombosis (DVT) on ipsilateral limb Pulmonary embolism Stent graft separation and migration identified via ultrasound imaging Clinical Success defined as limb ischemia improvement as assessed by Rutherford Clinical Classification (improvement in scale by =1) Limb ischemia by Rutherford Clinical - Classification Primary Patency Primary assisted patency Secondary patency Target Vessel Revascularization Ankle-Brachial Index (ABI) or Toe Brachial Index (TBI) of both the index limb and contralateral limb Major index limb amputations Venous Clinical Severity Score and Villalta Scale
Follow-up Visits and Length of Follow-up	DETOUR 2 - 3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	DETOUR2: 220 subjects (202 enrolled subjects plus18 roll-in subjects) Continued Access: 11 subjects were enrolled with intention to treat at 5 sites, and 10 subjects were treated with the device in the U.S.
Actual Number of Sites Enrolled	DETOUR2: 32 US and 4 OUS Continued Access: 8
Patient Follow-up Rate	DETOUR2: Enrolled Subjects All Subjects: 96.6% (169/175) at 24 months and 98.7% (153/155) at 36 months. Roll-in Subjects: 100% (13/13) at 24 months and 100% (11/11) at 36 months. Continued Access: 30 days - 100% (10) 6 months -100% (9) 12 months - 100% (8/8) 24- months - 100% (6/6)
Final Safety Findings	DETOUR2: Major Adverse Events (MAE): MAE were defined as any of the following: all-cause mortality, clinically-driven target lesion revascularization (CD-TLR), major amputation of the treated limb, symptomatic deep vein thrombosis, pulmonary embolism, or procedure-related bleeding requiring any transfusion of packed red blood cells or surgery. Through 24 months the Kaplan Meier (KM) estimate for MAE was 33.1%, with 24.8% of subjects experiencing clinically driven target lesion revascularization (CD-TLR). At 36 months the KM estimate for MAE was 42.3% with 32.7% of subjects experiencing CD-TLR. The KM estimate for death was 4.8% at 24-months, and 8.9% at 36-months. In all subjects, the amputation rate (within the treated limb) remained at 2.1% from 12 through 36 months. In roll-in subjects, through 24 months the KM estimate for MAE was 46.7%, with 42.9% of subjects experiencing CD-TLR. Through 36 months the KM estimate for MAE was 46.7% and 42.9% of subjects experienced CD-TLR. No stent fractures were reported by the Core Lab on X-ray (evaluated only at the 12-month follow-up visit). One (1) stent graft separation and one (1) stent migration >1cm were observed (0.6% each; 1/180 and 1/180 respectively) at 12-month follow-up. There were no fractures, stent graft separations or migrations at 24 or 36 months. There were no fractures, stent graft separations or migrations in the roll-in population at any timepoint. Continued Access: The MAE rate was 9.1% (1/11) through 30-days, with symptomatic deep vein thrombosis as the only occurring MAE component. The MAE rate through 12-months was 45.5% (5/11). At 24-months, the cumulative MAE rate was 87.5% (7/8). All-Cause Mortality was the most common MAE component, occurring in 50.0% (4/8) of subjects. Clinically driven TLR rate at 24 months was 37.5 % (3/8). Serious Adverse Events (SAEs) Through 12-months, SAEs were adjudicated by the clinical event committee in 54.5% (6/11) subjects, with subjects experiencing one or more SAEs. The most commonly reported SAE was Vascular Disorders (27.3%, 3/11). From 12 through 24-months, there was 37.5% (3/8) subjects with SAEs adjudicated by the CEC.
Final Effect Findings	DETOUR2: At 24 months, the KM estimate for primary patency was 59.5% and at 36 months the KM patency rate was 49.8%. At 24 months and 36 months the KM estimate for primary patency in the roll-in subjects was 57.1% and 42.9% respectively. At 24 months, secondary patency rate was 85.3% and 84.6% for enrolled cohort and roll-in subjects respectively. At 36 months, secondary patency was 76.2% for enrolled group and remained at 84.6% for the roll-in group. Rutherford Assessment: A negative value for change from baselines indicates an improvement in Rutherford class. At 24- and 36-months post-procedure, the Rutherford class improved by an average score of - 2.7. ABI (Ankle Brachial Index): At 24- and 36-month post-procedure, the mean change in ABI from baseline in the target limb was 0.37 and 0.35 respectively. Villalta Scale: A negative change from baseline indicates improvement in the parameter assessed. At 24- and 36-months post-procedure, the overall Villalta score showed an improvement from baseline with -0.8 and -0.5 respectively. Target Vessel Revascularization (TVR): At 24 months post-procedure, the KM estimate for TVR was 32.9%, and at 36-months post-procedure the KM estimate was 41.4%. Venous Clinical Severity Score (VCSS): A negative change from baseline indicates improvement in the parameter assessed. At 24-and 36-months post-procedure, the approximate overall change in VCSS from baseline was 0.3 and 0.6 respectively. Continued Access: Rutherford Assessment As of the final data cut at 24-months post-procedure, the most common Rutherford score was 0 (66.7%). ABI (Ankle Brachial Index) At 24-months post-procedure, the mean change in ABI from baseline was 0.50. Villalta Scale As of the final data cut, at 24-months post-procedure, showed follow-up score mean of 0.2 +/- 0.4 (6) and median of 0.0 (0.0, 1.0). Venous Clinical Severity Score (VCSS) At 24-months post-procedure, the approximate overall change in VCSS from baseline was 0.0 +/- 0.0 (6). Stent Graft Patency At 12- and 24-months post-procedure, stent graft patency rate was 85.7% (6/7) and 83.3% (5/6) respectively. Secondary Patency Secondary patency rate was 88.9% at 12 and 24-months by Kaplan-Meier method.
Study Strengths & Weaknesses	DETOUR2 Strengths This was a prospective multicenter study that compared safety and effectiveness of the DETOUR System to a performance goal (PG). Both primary safety and effectiveness endpoints were met (for primary safety the lower bound of the exact sided 97.5% confidence interval for MAE was 88.5% versus PG of 84%; for primary effectiveness endpoint or patency, the lower bound was 60.9% versus 60.4% PG. Weaknesses Subjects were non-randomized. Approximately 75.7% (153/202) enrolled subjects and 61.1% (11/18) roll-in subjects completed. Continued Access: This study had a very small sample size. No subject was lost to follow-up. The main reason for premature discontinuation among subjects was death
Recommendations for Labeling Changes	DETOUR2: Labeling change is recommended with the final long-term follow-up results. Continued Access: Labeling updates are under review.
General
Study Status	Delayed
Application Number / Requirement Number	P220021 / PAS002
Date Original Protocol Accepted	08/09/2023
Date Current Protocol Accepted	08/09/2023
Study Name	PTAB1 New Enrollment Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single arm, registry-based study to evaluate the real-world use of the DETOUR System
Study Population	Patients with symptomatic femoropopliteal lesions from 200 mm to 460 mm in length with chronic total occlusions (100 mm to 425 mm) or diffuse stenosis > 70% who may be considered suboptimal candidates for surgical or alternative endovascular treatments. Inclusion Criteria Participants should be a candidate for the DETOUR System as assessed by the treating physician after review of the clinical and anatomic Indications for Use. Exclusion Criteria There are no exclusion criteria. All cases entered in the registry at participating centers will be included up through the targeted goals per the enrollment plan.
Sample Size	Number of subjects: A maximum of 450 subjects will be enrolled with at least 200 evaluable female and 200 evaluable male subjects at the 12-month post-procedure follow up. Assumptions for sample size estimation: With an assumed 12% drop-out rate through 1 year, a sample size of 400 patients will provide sufficient precision in 1-year estimates, and the subgroup sample size of 200 females allows precision of the KM estimate in line with the DETOUR2 study. Duplex Imaging Cohort Sites that are performing (arterial and venous) duplex ultrasound assessments according to the institution’s standard practice will be asked to participate in the DUS imaging cohort. A vascular imaging sub-study of the first 55 females and 55 males enrolled will be completed. The sample size used for imaging cohort (n=110) will provide approximately 60 patients evaluable at year 5 for imaging-driven outcomes. This is a sufficient sample size to evaluate the outcomes as they are not extremely rare (<1%). Number of sites: 200 clinical sites. Sites location: United States
Key Study Endpoints	Primary Safety Endpoints Freedom from a major adverse event (MAE) at 30 days post-procedure defined as any occurrence of the following events: death, clinically-driven target lesion revascularization (CD-TLR), and/or major amputation of the treated Limb. Primary Effectiveness Endpoints Patency as defined as Freedom from clinical driven target lesion revascularization (CD-TLR) through 1 year. Secondary Endpoints: 1. Major Amputation of the Treated Limb 2. All-Cause Mortality 3. Major Adverse Limb Event (MALE) defined as above-ankle amputation or major reintervention including placement of a new bypass graft, interposition graft, thrombectomy, or thrombolysis 4. Symptomatic Deep Vein Thrombosis (DVT) on ipsilateral limb: Clinical symptoms (including, but are not limited to: pain, swelling, warmth, redness, tenderness, cramps, pale/bluish decolorization of the skin of the affected extremity) and evidence of occlusive thrombus within a deep vein. 5. Incidental Venous Thrombus 6. Pulmonary embolism (PE) 7. Procedure-related myocardial infarction 8. Patency defined as flow within the stent graft without reintervention 9. Primary assisted patency defined as: revascularization of non-occlusive (<99%) stenosis within the stent graft or immediately above or below the treated arterial segment with less than 50% residual stenosis 10. Secondary patency defined as: revascularization of occlusion (100%) within the stent graft or immediately above or below the treated arterial segment with less than 50% residual stenosis 11. Amputation-free survival 12. Procedure-related infections 13. Procedure duration 14. Length of stay (from Index procedure to discharge) 15. Discharge status (from Index procedure) Imaging Sub-study Endpoints Imaging-driven graft patency defined as the absence of clinically driven target lesion revascularization (CD-TLR) and absence of recurrent target lesion diameter stenosis >50% by imaging (e.g., duplex ultrasound peak systolic velocity ratio peak systolic velocity ratio [PSVR] of >2.5 or as measured by invasive angiography) within the stent or immediately 1cm above or below the treated segment. Venous thrombus within the vein containing the graft (i.e thrombus or fibrin within the vein containing the graft as observed on imaging without symptoms) Symptomatic DVT: Clinical symptoms (including, but are not limited to: pain, swelling, warmth, redness, tenderness, cramps, pale/bluish decolorization of the skin of the affected extremity) and evidence of occlusive thrombus within a deep vein. Occlusive DVT Non-occlusive DVT
Follow-up Visits and Length of Follow-up	1, 12, 24-, 36-, 48- and 60-months post-procedure. Follow-up assessments at 48 and 60 months may be conducted via a telephone call. The sub-study will include Duplex imaging at 1-, 12-, 24-, and 36-months post-procedure to assess the endpoints of graft patency and venous thrombus within the vein containing the graft.
Interim or Final Data Summary
Interim Results	Safety Results: The Kaplan Meier (KM) estimate of freedom from all-cause mortality was 99.4% at 30 days, 89.3% at 1 year, and 86.3% at 2 years. The KM estimate of freedom from Major Adverse Limb Event (MALE) was 97% at 30 days, 77.3% at 1 year and 72.7% at 2 years. The KM estimate of freedom from major amputation was 99.4% at 30 days and 91.7% through both 1- and 2-year follow-up. The KM estimate of freedom from symptomatic deep vein thrombosis (DVT) was 99.2% at 30 days, 88.0% at 1 year and 70.4% at 2 years. The KM estimate of freedom from pulmonary embolus was 100% at 30 days and 98.9% through both 1- and 2-year follow-up. The KM analysis of amputation free survival rate was 94.8% at 30 days, 80.2% at 1 year and 77.8% at 2 years. Effectiveness Results: The KM analysis of freedom from TLR (primary patency) was 97.6% at 30 days, 82.7% at 1 year and 77.9% at 2 years. The KM analysis of primary assisted patency was 97.9% at 30 days, 83.3% at 1 year, and 68.5% at 2 years. The KM analysis of secondary patency rate was 97.6% at 30 days, 90.4% at 1 year, and 85.8% at 2 years.
Actual Number of Patients Enrolled	177 Subjects
Actual Number of Sites Enrolled	26
Patient Follow-up Rate	96.6% at 30 days, 74.7% at 1 year (1 year follow-up i incomplete)
General
Study Status	Delayed
Application Number / Requirement Number	P220023 / PAS002
Date Original Protocol Accepted	02/05/2024
Date Current Protocol Accepted	08/13/2026
Study Name	US Arm of the Global Paradise System Registry PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Global GPS Registry is designed to evaluate real- world use of the Paradise System in up to 3000 patients at up to 300 clinical centers worldwide. The US GPS Study is the independently powered arm of the GPS Registry. The US GPS study is a multi-center, single-arm post market study and US GPS is designed with similarities in safety reporting and data collection to the overall Global GPS study, which facilitates potential pooling of safety and efficacy data. The US GPS study will include two cohorts: 3. Approximately 30 subjects currently enrolled in the RADIANCE Continued Access Protocol (CAP). 4. Prospective patients treated as per the approved labeling; There is no randomization for prospectively treated patients. The objective of the Global GPS Registry, including the US arm of the Global Paradise System Post Approval Study (US GPS) is to evaluate the real-world use of the Paradise System as per approved labeling. In addition, US GPS will collect data in patient populations underrepresented within the RADIANCE clinical program.
Study Population	Hypertension patients in whom lifestyle modifications and antihypertensive medications do not adequately control BP identified from the general population by the enrolling center. Patients must meet all inclusion criteria and none of the contraindications for use of the Paradise System, per the Instructions for Use (IFU). Subjects enrolled in the RADIANCE CAP study will be transferred to the US GPS study after completion of their 12-month follow-up visit in the RADIANCE CAP study, to complete the remainder of the long-term annual follow-up visits under the post approval study protocol. Inclusion criteria Patients who meet all of the following inclusion criteria and non of the exclusion criteria should be given consideration • Signed and dated study informed consent • Documented history of hypertension • Documented history of current or prior antihypertensive medication(s) • Mean seated office systolic BP at screening greater than or equal to 140 mmHg • Mean pre-procedure home systolic BP of greater than or equal to 135 mmHg • Estimated glomerular filtration rate (eGFR) of greater than or equal to 30 mL/min/m2 RADIANCE CAP patients must provide signed and dated informed consent for inclusion in long-term follow-up. No other criteria are required for inclusion. Exclusion Criteria Exclusion from the US GPS study will follow the contraindications documented in the approved IFU. The following contraindications listed in the IFU may be determined at the time of procedure prior to treatment: • Renal arteries with diameter < 3mm and > 8mm • Renal artery with fibromuscular dysplasia (FMD) • Stented renal artery • Renal artery aneurysm • Renal artery diameter stenosis >30% • Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter Additional exclusion criteria are: • Patient lacks appropriate renal anatomy for any treatment with the Paradise Catheter • Patient under the age of 18 years old at the time of consent • Patient is pregnant • Patients with transplanted kidney • Presence of abnormal kidney (or secreting adrenal) tumors
Sample Size	Number of subjects: The US GPS will enroll a total of 1000 subjects. Study Sites Up to 100 clinical sites in the USA will be enrolled. A minimum of 20% and a maximum of 40% of the total sites will have prior ultrasound RDN experience. The total number of treated patients at a single center will be limited to a maximum of 20% of the total study sample size to prevent any single center from unduly influencing study outcomes. The US GPS will enroll patients within the following subgroups, at least . • 250 evaluable female • 150 evaluable Black/African Americans • 100 evaluable Hispanic • 50 evaluable Asian (or other) In addition, enrollment of at least 50 subjects will also be targeted • Elderly (persons = 65yrs old) • Heart failure (NYHA Class II-IV with any ejection fraction) Number of subjects: The US GPS will enroll a total of 1000 subjects. Study Sites Up to 100 clinical sites in the USA will be enrolled. A minimum of 20% and a maximum of 40% of the total sites will have prior ultrasound RDN experience. The total number of treated patients at a single center will be limited to a maximum of 20% of the total study sample size to prevent any single center from unduly influencing study outcomes. The US GPS will enroll patients within the following subgroups, at least . • 250 evaluable female • 150 evaluable Black/African Americans • 100 evaluable Hispanic • 50 evaluable Asian (or other) In addition, enrollment of at least 50 subjects will also be targeted • Elderly (persons = 65yrs old) • Heart failure (NYHA Class II-IV with any ejection fraction) • Type 2 Diabetes • Stage 3 chronic kidney disease (eGFR<60; but >30) • Atrial arrhythmias (documented history of AT/AF) • Orthostatic hypertension at screening (increase in office BP when standing as compared with sitting of =20 mmHg systolic and/or =10 mmHg diastolic) Effectiveness Assumptions Effectiveness: BP reduction. A total sample size of 1000 patients, with up to approximately 15% attrition for an evaluable sample size of 850 patients, will provide adequate power for a range of plausible effect sizes of interest for the BP reduction endpoint. With a -5 mmHg lower confidence bound, the minimum mean difference required would be -6.9 mmHg assuming an enrolled sample size of 1,000 patients and a standard deviation of 20. Effectiveness: Subject Responder For the responder co-primary endpoint, assuming a true responder rate of 57%, an evaluable sample size will also provide approximately 82% power. The assumed responder rate of 55% is based on the expectation that response in a real-world patient population may be lower than the response rate observed in the controlled clinical study population. Safety Assumptions The proposed sample size of 1000 enrolled patients would allow 95% probability of detecting clinical events with an occurrence rate as low as 0.3%.
Key Study Endpoints	Primary Effectiveness Endpoints Two co-primary endpoints will be evaluated for primary effectiveness. Co-Primary Endpoint #1: Group mean home Systolic BP reduction at 3 months Co-Primary Endpoint #2: Subject Responder at 3 months A subject will be defined as a responder if they achieve any of the following: • Control in home BP (defined as systolic BP <130 mmHg) at 3 months and/or • Absolute reduction in home systolic BP fall = 5 mmHg at 3 months and/or • Reduction in medication burden measured using defined daily dose (DDD)* *Where a meaningful outcome will be considered a change in the cumulative medication burden (DDD) of at least 0.3 Durability of Effectiveness To evaluate the durability of effectiveness of the Paradise system, both endpoints above will be evaluated at 12 months post procedure. Secondary Effectiveness Assessments from [baseline to 1, 3, 6, 12, 24, 36, 48 & 60 months] include - Change in mean home systolic/diastolic blood pressure in mmHg - Change in mean office systolic/diastolic blood pressure in mmHg - Change in home and office heart rate - Change in home and office pules pressure - Change in the number and/ or dosage and/or type of antihypertensive medications taken - Change in patient reported outcomes Other Secondary Effectiveness Assessments - Percentage of patients who are controlled as measured by various cut points of home BP (control to be assessed as both < 130 mmHg systolic and <135 mmHg systolic) office BP (control to also be assessed as <130 mmHg and <140 mmHg systolic) - Percentage of patients who demonstrate a reduction in home systolic BP of = 5mmHg, = 10 mmHg and = 15 mmHg at 3, 6, 12, 24, 36, 48 and 60 months compared to baseline - Percentage of patients who demonstrate a reduction in office systolic BP of = 5mmHg, = 10 mmHg and = 15 mmHg at 3, 6, 12, 24, 36, 48 and 60 months compared to baseline - Change in home and office heart rate at 1, 3, 6, 12, 24, 36, 48 and 60 months compared to baseline Safety Endpoints (Secondary Endpoints) Data to be presented as an incidence rate from > 30 days post procedure and annually: - Death from any cause - Hospitalization for o Major cardiovascular or hemodynamic events o Hypertensive crisis or symptomatic hypotension - New onset stroke; TIA, CVA or other major cerebrovascular event - Acute myocardial infarction - Coronary revascularization - Major vascular complications - Kidney-related adverse events - Adverse drug reaction due to antihypertensive medication
Follow-up Visits and Length of Follow-up	Prospectively enrolled patients will be followed at 1, 3, 6, 12, 24-, 36-, 48- and 60-months post procedure. Screening, treatment, 1-, 3- & 12-month follow-up visits will be done in office. Six (6), 24-, 36-, 48- and 60-month visits may be conducted remotely.
Interim or Final Data Summary
Actual Number of Patients Enrolled	390 patients have been enrolled (consented) and 172 treated with the device (including 17 RADIANCE CAP patients).
Actual Number of Sites Enrolled	42
General
Study Status	Ongoing
Application Number / Requirement Number	P220025 / PAS002
Date Original Protocol Accepted	10/12/2023
Date Current Protocol Accepted
Study Name	PROMISE III Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, single-arm, multi-center study. To provide additional information on the LimFlow System for creating an AV connection in the below the knee (BTK) vascular system using an endovascular, minimally invasive approach to arterialize the pedal veins for the treatment of chronic limb-threatening ischemia in subjects ineligible for conventional endovascular or surgical limb salvage procedures.
Study Population	Subjects who are confirmed as “no option” (ineligible for conventional endovascular or surgical limb salvage procedures) by the treating physician. “No option” is defined as either a) absence of a usable pedal artery target (endovascular or surgical approach), or b) the presence of a pedal artery target with absence of a viable single-segment vein in either lower extremity or either arm that could be used for autogenous vein conduit.
Sample Size	The study will enroll up to 100 subjects. Assumptions for sample size estimation: A sample size of 100 subjects with an estimated proportion of 54% success would provide a sufficiently precise estimate with a two-sided 95% confidence interval half-width of 0.0977 or +/- 10%. Up to 25 sites will be enrolled in the United Sates. Individual site enrollment is capped at 20% of total enrollment. It is estimated that the overall general loss to follow-up will be 10% at the time of primary analysis, and a true loss to follow up rate <10% will incur censoring while a loss > 10% will require sensitivity analyses.
Key Study Endpoints	Primary Endpoints Amputation Free Survival (AFS) defined as freedom from major amputation (defined as above-ankle amputation of the index limb) and death (all-cause mortality) at 6 months. Secondary Endpoints: Secondary endpoints to be evaluated at 30days, then 6 months through 36 months • Primary patency • Primary Assisted Patency • Secondary Patency • Limb Salvage • Change in Rutherford Classification • Technical Success • Procedure Success • Target wound Healing • All Wound Area Reduction • Freedom from Contrast Induced Nephropathy • Procedure Time • Radiation Exposure • Contrast Volume
Follow-up Visits and Length of Follow-up	Hospital discharge, 14 days, 30 days, 3 and 6 months, at 1 year 2 years and 3 years. Subjects will be followed for 3 years
Interim or Final Data Summary
Interim Results	Safety Results: All-cause mortality at 6 months was 8.9% (7/79). Target limb major amputation at 6 months was 14.8% (13/88). Amputation free survival at 6 months was 80.7% for the modified ITT population and 83.2% for per protocol population. Effectiveness Results: Technical Success rate was 100/103 (97.1%) Procedure Success rate was 81/103 (78.6%). At 6 months 78.3% (54/69) of primary wound status were reported as healed or healing and 10.1% (7/69) as stable; Another 10.1% (7/69) of primary wounds were reported as worsening.
Actual Number of Patients Enrolled	One hundred (100) subjects were enrolled in the PROMISE III PAS as of August 29, 2025. Twelve (12) additional subjects were enrolled in the PROMISE III sub-study. A total of 103 Limbs were treated.
Actual Number of Sites Enrolled	24
Patient Follow-up Rate	Follow-up visit completed at 1, 3 and 6 months was 97.9% (92/94), 95.5% (85/89) and 100% (80/80) respectively.
General
Study Status	Completed
Application Number / Requirement Number	P220026 / PAS001
Date Original Protocol Accepted	11/17/2023
Date Current Protocol Accepted
Study Name	SPYRAL HTN-OFF MED and HTN-ON MED Cont f/u studies
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Population	Device only
Sample Size	up to 200
Key Study Endpoints	• Office and ambulatory blood pressure • Renal imaging • Adverse events
Follow-up Visits and Length of Follow-up	5 years post procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	337 randomized subjects (206 to Denervation group and 131 to Sham Control group)
Actual Number of Sites Enrolled	56
Patient Follow-up Rate	In the RDN group through 36 months, there were 9 withdrawals and 2 deaths. Of the 195 RDN subjects eligible at 36 months, 79% (155/195) completed 24-hour BP measurement and 90% (175/195) completed Office BP measurement. In the Sham Control group, through 36 months there was a total of 85 subject crossovers, 6 withdrawals and 1 death. Of the remaining 39 subjects eligible at 36 months, 77% (30/39) completed 24-hour BP measurement and 82% (32/39) completed Office BP measurement. Twelve (12) additional subjects from the Sham Control arm crossed over after 36 months for a total 97 crossover subjects.
Final Safety Findings	Composite Safety Endpoint is defined as a composite of the following events at 3, 6, 12, 24 and 36 months post -procedure: -All-cause mortality -End-stage renal disease (ESRD) -Significant embolic event resulting in end-organ damage -Renal artery perforation requiring intervention -Renal artery dissection requiring intervention -Vascular complications -Hospitalization for hypertensive crisis/emergency -New renal artery stenosis > 70% The study met the composite primary safety endpoint at 1 month with a composite event rate of 1.0% (2/206) in the Denervation group 1-sided Upper 95 CI of 3.0% compared to the performance goal of 7.1%, p<0.001. There were 2 vascular complications requiring surgical repair, intervention, thrombin of injection or blood transfusion. At 36 months, the composite safety endpoint rate was 3.3% (6/184) and 2.7% (3/113) (p=1.000) in the Denervation and Control groups, respectively. The CEC adjudicated five events as procedure related but not catheter, generator or therapy related all of which were associated with vascular access site complications. There were 3 reported deaths in the SPYRAL HTN-ON MED study. All deaths were adjudicated by the CEC as cardiovascular deaths and not related to the study catheter, generator or procedure. Follow-up imaging determined that 10 of 15 cases (67%) were false positives, resulting in RAS >50% in 5 of 557 patients (0.9%) based on noninvasive imaging. However, the RAS was determined to be <60% in 4 of these 5 patients. A potential stenosis >70% was identified in the left renal artery in one patient via MRA at 3 years post-procedure. Renal Function The mean change in serum creatinine at 36 months was 0.04 +/-0.14 mg/dL (p= <0.001 for change from baseline in the RDN group and 0.05 +/-0.15 mg/dL (p= 0.060 for change from baseline) in the Control group. The mean change in eGFR at 36 months was -2.86 +/-12.01 mL/min/1.73 m2 (p= 0.002 for change from baseline) in the RDN group and -3.71 +/-12.06 mL/min/1.73 m2 (p= 0.091 for change from baseline) in the Control group.
Final Effect Findings	Primary Efficacy Endpoint Analysis (ITT Population) The primary effectiveness endpoint was the baseline-adjusted change (using Analysis of Covariance) in 24- hour systolic blood pressure from baseline to 6-months. This analysis used a Bayesian design incorporating the Pilot data as an informative prior which was then discounted independently for each group in the ITT population. The treatment difference between the Denervation and Control groups was -0.030 mmHg (Bayesian 95% credible interval: -2.82 to 2.77) in 24-hour systolic blood pressure. The primary effectiveness endpoint was not met in the ITT population at 6 months. At 6 months, the change from baseline for office systolic BP for the RDN group was -9.9 mmHg compared to Control group change of -5.1 mmHg (ANCOVA difference -4.9 mmHg; p=0.001). Thus, the study met the secondary endpoint of office systolic BP reduction compared to control at 6 months. 24-hour Systolic Blood Pressure At 24 months the average 24-hour systolic blood pressure between the RDN (137.3 +/- 14.9 mmHg) and control groups (143.5 +/- 13.2 mmHg) showed statistically significant differences in favor of the RDN group, p=0.028. At 24 months, the average 24-hour SBP difference between the RDN and Control groups (-12.1 vs -7.0 mmHg) was a statistically significant (adjusted for baseline and change in medication burden) difference of -5.4 mmHg (p=0.042). At the 36 months, the RDN group had an average 24-hour systolic blood pressure of 135.4 +/- 13.2 mmHg, versus 139.2 +/- 12.2 mmHg in the Control group (p=0.150). There was an average change of -14.0 +/- 14.0 mmHg in the RDN group compared to -10.7 +/- 14.1 mmHg in the control group. At 36 months, the average 24-hour SBP difference between the RDN and Control groups (-14.0 vs -10.7 mmHg) was a statistically significant (adjusted for baseline and change in medication burden) difference of -5.8 mmHg (p=0.02). Office Systolic Blood Pressure (office SBP) At the 24-months, the RDN group had an average office SBP of 145.5 +/- 15.9 mmHg, compared to 154.3 +/- 17.0 mmHg in the Control group (p=0.003). The changes from baseline were statistically significant, with the RDN group showing a change of -17.4 +/- 16.1 mmHg compared to the Control group's change of -9.0 +/- 19.4 mmHg (p=0.007) At the 36-months, the RDN group had an average office SBP of 144.2 +/- 17.1 mmHg, compared to 143.9 +/- 14.6 mmHg (p=0.905) in the Control group. The RDN group showed a change of -18.5 +/- 17.8 mmHg compared to the Control group's change of -18.7 +/- 16.7 mmHg (p=0.948). Target Blood Pressure At 24 months, the percentage that achieved target office systolic BP<140 mmHg in the RDN group was 35.3% compared to Control 17.1% (p=0.048). At the 12-month, 29.1% of RDN patients achieved target office BP <140 mmHg compared to 19.7% in the Control group (p=0.159), and at 36 months, this was 46.9% vs 43.8% in the Control group (p=0.848). Prescribed Anti-Hypertensive Medication to 36 months At 12 months, the mean medication burden score, as measured by Index 2A, was higher in the Control group compared to the RDN group with mean scores of 5.34 vs. 4.06, respectively, p = 0.035. At the 36- months, the mean medication burden scores (measured by Index 2A) were 5.73 for the RDN group and 9.70 for the Control group (p=0.122).
Study Strengths & Weaknesses	This was a randomized, multicenter, international study. The study did not meet the primary effectiveness endpoint of baseline-adjusted change in 24- hour systolic blood pressure from baseline to 6-months.
Recommendations for Labeling Changes	Labeling update is recommended
General
Study Status	Ongoing
Application Number / Requirement Number	P220026 / PAS002
Date Original Protocol Accepted	02/15/2024
Date Current Protocol Accepted	04/10/2025
Study Name	SPYRAL AFFIRM PAS: New Enrollment Registry Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The SPYRAL AFFIRM study is a multi-center, international, prospective, interventional, single arm study designed to investigate renal denervation in a real-world population with a focus on the safety, efficacy, and durability of the procedure in subjects with varying severity of hypertension and associated comorbidities. The SPYRAL AFFIRM study will evaluate the long-term safety, efficacy, and durability of the Symplicity Spyral system in the full population and several subgroups. The data will be used to complement data from the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED trial, SPYRAL HTN-ON MED trial, as well as the Global SYMPLICITY Registry
Study Population	The study population will consist of two cohorts: a) Main Cohort: The SPYRAL AFFIRM Main Cohort will consist of all subjects consented to the AFFIRM study who undergo the renal denervation procedure once enrolled. • ABPM Subset: The SPYRAL AFFIRM study will also collect ABPM data for the first 250 Main Cohort subjects who have a initial valid ABPM at baseline. b) Continuation Cohort: SPYRAL AFFIRM sites that also participate in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and/or SPYRAL HTN-ON MED studies can enroll subjects initially randomized to the treatment arm and successfully treated via the renal denervation procedure for continued follow up through 60 months after the renal denervation procedure they received in the aforementioned studies. All subjects that meet the criteria above are eligible to be consented for continued follow up in the SPYRAL AFFIRM study within one week (+ or -) of exit from the prior study. All subjects in the Main Cohort, must meet all Inclusion and no Exclusion criteria prior to undergoing the RDN procedure. For subjects in the Continuation Cohort, all Inclusion/Exclusion criteria will need to have been met at the time of their initial procedure in the SPYRAL PIVOTAL- SPYRAL-HTN OFF MED or SPYRAL HTN-ON MED study participation. Intent-to-Treat (ITT): all subjects who signed and dated informed consent form, met the enrollment criteria and the renal denervation therapy is delivered (i.e., the catheter is delivered through the guide catheter with the intention to provide the renal denervation treatment). This will be the primary analysis set for this study. Per-Protocol (PP): The ITT population excluding subjects who do not meet certain key entry criteria. The analysis of the primary endpoint will be repeated for PP set as a secondary analysis.
Sample Size	Number of subjects: A total of 1100 subjects (US and OUS) will be treated in the study, with a minimum of 700 subjects from the US. A minimum number of subjects (US & Non-US) will be enrolled in the following key subgroups: 300 females, 200 Black Americans (US only), 150 age >65, 50 subjects with Type 2 diabetes, 75 subjects with eGFR<60 ml/min/1.73m2 and approximately 80 subjects of Hispanic ethnicity. Continuation Cohort: Up to 100 eligible RDN treated subjects who participated in the SPYRAL PIVOTAL-SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED clinical trials, at sites that are participating in the AFFIRM study, will continue to be followed through 60 months post RDN procedure. Assumptions for sample size estimation: The change in office SBP at 6 months is expected to be -8.7 mmHg (US IDE studies) with a standard deviation of 20 mmHg. The performance goal is set at -6.0 mmHg, which represents 69% of the expected reduction of the primary endpoint in this subgroup (US cohort) and is chosen to represent a clinically meaningful blood pressure reduction. A one-sided Alpha = 0.025 level of significance, an evaluable sample size of 550 treated subjects yields 88% power to reject the null hypothesis in favor of the alternative. Approximately 1300 subjects will be treated in the study of which a minimum of 700 will be from the US. The total study sample size will be up to 1400 (including 100 Continuation cohort). PASS 2021 one sample t-test was used for the sample size calculation. Number of sites: Main Cohort: The study is expected to be conducted at approximately 100 study sites. Sites location: Greater than 50% of sites will be in the United Sates with additional sites in OUS. To ensure distribution of subjects across sites and geographies, an investigative site may enroll up to 10% of the total study sample.
Key Study Endpoints	Effectiveness Endpoints Primary: Office Systolic Blood Pressure (SBP) change at 6 months The primary endpoint will be compared to the prespecified performance goal at 6 months for the subjects treated in the US. Efficacy objectives will be evaluated for all Main Cohort subjects and for US subjects in the Main Cohort at each follow up visit based on subject cohort assignment. Secondary Endpoints: • Change in OBP from baseline at 3, 12, 24, 36, 48 and 60-months post-procedure • Change in home blood pressure (HBP) from baseline at 3, 6, 12, 24, 36 months post-procedure (Main Cohort only) • Change in 24-hour blood pressure from baseline including day and night independently (ABPM Subset & Continuation Cohort) at 3, 6, 12, 24, 36, 48 and 60-months post-procedure • Change in OBP, HBP and 24-hour blood pressure from baseline will be assessed in each of the subgroups as applicable: • Percent of subjects achieving blood pressure target reduction and control of =140 mmHg as measured by OBP, HBP and ABPM • Time subject’s blood pressure is controlled through 36-month follow-up or study exit • Characterization of anti-hypertensive medication burden over time • Change from baseline in quality of life as measured by the EQ-5D instrument, and change in patients’ HTN health status measures • Evaluation of laboratory and clinical characteristics for predictors of response to renal denervation • Percent of subjects requiring repeat renal denervation • Evaluation of blood pressure as measured by OBP, HBP and ABPM, adjusting for anti-hypertensive medication burden through 36- months Safety Endpoints (Secondary Endpoints) Secondary: (for all Main Cohort subjects and the Continuation Cohort • Incidence of major adverse events (MAE) at 3, 6, 12, 24, 36, 48 and 60-months post procedure: • Composite safety objective (All-cause mortality, End-stage renal disease, Significant embolic event, Renal artery perforation requiring intervention etc.) • greater than or equal to 40% decline in eGFR from baseline • Incidence of increase in serum creatinine >50% from baseline • Incidence of myocardial infarction • Incidence of stroke • Renal artery re-intervention • Major bleeding according to TIMI definition (i.e. intracranial hemorrhage, greater than or equal to5g/dl decrease in hemoglobin concentration, a greater than or equal to 15% absolute decrease in hematocrit, or death due to bleeding within 7 days of the procedure) • Slope of eGFR
Follow-up Visits and Length of Follow-up	3 years post procedure
Interim or Final Data Summary
Interim Results	Safety Results Serious Adverse Events As of this report, SAEs have been reported for a total of 19% (130/684) of subjects treated in the Main Cohort of the SPYRAL AFFIRM study. The most frequently reported SAEs were for vascular disorders (6.7%). Twenty-six (26) events from the ITT population were adjudicated in the Main Cohort of which 16 were adjudicated as No Event. Two cardiovascular deaths have been adjudicated by the CEC in the Main cohort. The deaths occurred on 197- and 275- day post procedure. Continuation Cohort A total of 14.7% (5/34) subjects reported SAEs in the Continuation Cohort. The most frequently reported SAEs were for injury, poisoning, and procedural complications 5.9% (2/34). No events were adjudicated in the Continuation Cohort. US Main Cohort As of this report, SAEs have been reported for 18.8% (110/586) of subjects treated in the US Main Cohort. The most frequently reported SAEs were for vascular disorders (6.8%). Twenty- three (23) events from the Intent-to-treat (ITT) population US Main Cohort were adjudicated by the CEC. The CEC adjudicated 1 renal artery re-intervention due to dissection on day 0 (zero) of procedure, 1 major bleeding event on day 1 post-procedure and 1 other vascular complication event on day 0 (zero) of procedure.
Actual Number of Patients Enrolled	Main Cohort A total of 1217 subjects have been enrolled in the Main Cohort of the SPYRAL AFFIRM and 684 subjects have been treated with the device. Of the 684 subjects treated in the Main Cohort, 586 were enrolled and treated in the US and 98 OUS. A total of 34 additional subjects (11 US, and 23 OUS) have been enrolled in the Continuation Cohort. Twenty-seven (27) SPYRAL AFFIRM Main Cohort subjects have been enrolled and treated in the low eGFR subgroup (30 and 45 ml/min/1.73m2). US Main Cohort As of database snapshot date, a total of 1049 subjects have been enrolled in the US Main Cohort and 586 have been treated with the renal denervation in the SPYRAL AFFIRM study.
Actual Number of Sites Enrolled	71 sites in the US, 20 sites OUS
Patient Follow-up Rate	Main Cohort As of this report, 432 subjects in the Main Cohort, had reached their primary endpoint visit window, with 404 subjects completing the primary endpoint visit (94%). US Main Cohort Of 373 subjects treated after PMA approval, 110 (of 122 with open visit windows) have completed their 6-month visit resulting in a 90.2% compliance rate. Of 210 subjects treated on or before PMA approval 203 completed the 6-month follow-up (96.7%).
General
Study Status	Ongoing
Application Number / Requirement Number	P220029 / PAS001
Date Original Protocol Accepted	06/30/2023
Date Current Protocol Accepted
Study Name	PINNACLE Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multicenter, double blind, randomized, sham-controlled study with a non-randomized, Pharmacokinetics (PK) study arm To evaluate the safety and efficacy of Optilume™ BPH Catheter System in the treatment of benign prostatic hyperplasia (BPH).
Study Population	Male subject 50-80 years old who has symptomatic BPH
Sample Size	162 subjects (98 Test arm, 49 Control arm, 15 PK arm) Statistical power of 90%, one-sided 0.025 alpha, common standard deviation of 7, mean improvement in the Control arm of 6 points and mean improvement in the Test arm of 12.5 points, and 10% loss of follow-up rate
Key Study Endpoints	Primary Effectiveness Endpoint: Observed improvement in IPSS at 12 months post-treatment in the Test arm at least 25% greater than that of the Control arm at 3 months. Primary Safety Endpoint: Major Device-Related Serious Complications Secondary Effectiveness Endpoints: 1) average IPSS improvement in the Test arm from baseline to 12 months must be greater than or equal to 30% 2) Percentage of responders at 3 months 3) Durability – Percentage of responders at 12 months 4) The change or increase in Qmax at 12 months
Follow-up Visits and Length of Follow-up	Through 5 years
General
Study Status	Delayed
Application Number / Requirement Number	P220029 / PAS002
Date Original Protocol Accepted	08/25/2023
Date Current Protocol Accepted	12/15/2025
Study Name	PEAK PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single-arm, multi-center, post market clinical trial to verify the continued safety and effectiveness for the Optilume BPH Catheter System
Study Population	Male subject greater than or equal to 50 years old Diagnosed with lower urinary tract symptoms (LUTS) secondary to obstructive benign prostatic hyperplasia (BPH) Prostate volume < 80 g with a prostatic urethral length between 32-55 mm as determined by trans-rectal ultrasound (TRUS)
Sample Size	Number of subjects: 92, 34 in semen sub-study Assumptions for sample size estimation: One-sided alpha of 0.025 and 80% power, based on performance goal of 30% improvement in International Prostate Symptom Score (IPSS) giving a minimum sample size of 73. Accounting for approximately 20% loss to follow-up through the full duration of the study (5 years) gives a total sample size of 92 subjects. Semen sub-study sample size is based on anticipated standard deviation of 60%, performance goal of not more than 30% decrease from baseline, and statistical power of 80%, based on one-sided 0.025 alpha level t-test for a mean for 34 subjects. Number of sites: 15 Sites location: within the United States
Key Study Endpoints	Safety Endpoints Primary: Freedom from composite treatment-related serious adverse events. Secondary (semen sub-study only): The average change from baseline in sperm concentration at 13 weeks (3 months) post-procedure will be compared against a performance goal of -30% (30% decrease from baseline). Ancillary: Frequency and severity of treatment-related adverse events. Change from baseline in semen characteristics over time (semen sub-study only). Effectiveness Endpoints Primary: Average International Prostate Symptom Score (IPSS) improvement from baseline to 12 months. Ancillary: Improvement in IPSS over time Improvement in Internation Continence Society (ICS) male short form over time Improvement in peak urinary flow (Qmax) over time Improvement in post-void residual volume (PVR) over time Freedom from repeat intervention (time-to-event)
Follow-up Visits and Length of Follow-up	Follow-up visits at 1-, 3-, 6-, and 12-months post-procedure, and annually thereafter through 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	165
Actual Number of Sites Enrolled	7
General
Study Status	Study Pending
Application Number / Requirement Number	P140029 S054/ PAS001
Date Original Protocol Accepted	05/15/2026
Date Current Protocol Accepted	05/15/2026
Study Name	Safety Eval Following Retreatment w Restylane
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A Prospective, Multicenter Study to Evaluate the Safety of Re-treatment with Restylane® Contour in the Treatment of Temple Hollowing
Study Population	Approximately 100 subjects will be enrolled and treated. Investigation sites will be instructed to enroll subjects of race and ethnicity representative to the general population, and to include at least 10% male subjects. At least 20 subjects will be Fitzpatrick skin type (FST) IV through VI, this includes at least 10 subjects with FST V – VI, where at least 5 subjects will be FST V and at least 5 subjects will be FST VI.
Sample Size	Number of subjects: 100 Assumptions for sample size estimation: N/A Number of sites: 8 Sites location: United States of America
Key Study Endpoints	Safety Endpoints Primary: Treatment-emergent adverse events (TEAEs) that are related to the device and/or injection procedure after the optional Month 12 re-treatment. Effectiveness Endpoints Secondary: To evaluate the effectiveness of Restylane Contour in correction of temple hollowing for the defined endpoints: ¿ Proportion of responders (subject has at least 1 grade improvement from baseline in both temples based on the Treating Investigators’ live assessment of the Galderma Temple Volume Deficit Scale [GTVDS]) at 3 and 12 months after initial treatment and 3 months after optional Month 12 re-treatment. ¿ Proportion of subjects having at least “Improved” (improved, much improved, or very much improved) on the Global Aesthetic Improvement Scale (GAIS) on both sides of the face (each temple) as assessed by the Subject and Treating Investigator, separately, at 3 and 12 months after initial treatment and 3 months after optional Month 12 re-treatment. ¿ Proportion of subjects in each response category for every question in the Subject Satisfaction Questionnaire (SSQ) at 3, and 12 months after initial treatment and 3 months after optional Month 12 re-treatment. ¿ Time in hours until the subject felt comfortable returning to social engagement after treatment, based on a follow-up question via telephone at 72 hours after treatment.
Follow-up Visits and Length of Follow-up	Follow-up visits are planned for 3 and 12 months after initial treatment, and 3 months after optional re-treatment at Month 12.
General
Study Status	Study Pending
Application Number / Requirement Number	P220004 / PAS001
Date Original Protocol Accepted	11/02/2023
Date Current Protocol Accepted
Study Name	PALMAZ MULLINS XD Real-World Use PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, single-arm, multi-center, post-approval study of all consecutive subjects treated with the Palmaz Mullins XD Pulmonary Stent. The objective of this study is to characterize clinical outcomes and to assess the real-world use of the commercial Palmaz Mullins XD Pulmonary Stent.
Study Population	The study population will contain all consecutive subjects treated with the commercially available Palmaz Mullins XD Pulmonary Stent. “Consecutive” is defined as a commitment by the participating investigators at each study site to enroll all subjects admitted for non-emergency treatment of pulmonary artery stenosis who meet eligibility criteria per the IFU and are selected to receive the Palmaz Mullins XD Pulmonary Stent.
Sample Size	Number of subjects: The study will enroll a minimum of 35 subjects and a maximum of 75 subjects or until the end of the 2-year enrollment period has been reached, whichever comes first. Assumptions for sample size estimation: Sample size is based on assumed enrollment rate over a two year period. Number of sites: Up to 11 sites Sites location: In the United States
Key Study Endpoints	Safety Endpoints Primary: Device or procedure-related, serious adverse events reported through time of hospital discharge, which meet any of the following criteria: a) Led to a death, b) Led to a serious deterioration in health of the subject, that either resulted in 1. Life-threatening illness or injury, or 2. Hospitalization (initial or prolonged), or 3. Disability or permanent impairment of a body structure or a body function, or 4. Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function c) Other Serious (important) Medical Events Effectiveness Endpoints Primary: Patency defined as an increase in stented vessel minimum pulmonary artery diameter by = 50% of the pre-stent diameter determined by post-implant angiography. Technical Success defined as: 1) Successful access, delivery and retrieval of the device delivery system, 2) Deployment and correct positioning of the device in the intended location, and 3) No need for additional, unplanned surgery or re-intervention related to the device or access procedure.
Follow-up Visits and Length of Follow-up	Length of follow-up is through time of hospital discharge. There will not be follow-up visits after the patient is discharged following the implantation procedure of the Palmaz Mullins Pulmonary Stent
General
Study Status	Ongoing
Application Number / Requirement Number	P220025 / PAS001
Date Original Protocol Accepted	09/11/2023
Date Current Protocol Accepted
Study Name	PROMISE II Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the long-term safety and effectiveness of the LimFlow System. The study is a single-arm, prospective, multi-center follow-up of the pivotal PROMISE II trial (G160156) that treated 105 subjects from 20 investigational sites in the United States.
Study Population	All remaining subjects treated with the LimFlow System in the PROMISE II trial active at the end of 6 months evaluation. The PROMISE II study population comprised of subjects who were confirmed as “no option” (ineligible for conventional endovascular or surgical limb salvage procedures) by the Independent Review Committee. There is no comparator group for the continued follow-up study.
Sample Size	One hundred and two (102) active subjects from the PROMISE II IDE trial.
Key Study Endpoints	Endpoints to be assessed at 9, 12, 24 and 36 months include • Rutherford Classification • Wound, Ischemia, and foot Infection (WIfI) grade • Wound assessment • Amputation and/or reintervention of the stent graft • Device or procedure related adverse events and serious adverse events • Review of concomitant medications (antiplatelets/anticoagulants), • All-cause mortality • Stent graft patency by duplex examination
Follow-up Visits and Length of Follow-up	3 years
General
Study Status	Ongoing
Application Number / Requirement Number	P220032 / PAS001
Date Original Protocol Accepted	11/17/2023
Date Current Protocol Accepted	07/05/2024
Study Name	POLARx PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a Prospective Multi-site safety and efficacy study of the Boston Scientific Cardiac Cryoablation System for drug refractory, recurrent Paroxysmal atrial fibrillation. The objective of the study is to collect clinical data on safety, effectiveness and procedural success of Boston Scientific’s Cardiac Cryoablation System (includes all BSC commercially available POLARx/POLARx Fit catheters) when used to perform pulmonary vein isolation (PVI) in the ablation treatment of de novo Atrial Fibrillation (AF).
Study Population	Patients being treated for paroxysmal atrial fibrillation (PAF). The study will include a diverse (i.e, race, ethnicity, gender) patient population.
Sample Size	Number of subjects: A minimum of 200 de novo treatment subjects with at least 50 US subjects participating in a LUX-Dx Sub-study. Number of sites: Up to 50 centers globally Sites location: At least 50% of study sites will be in the United States.
Key Study Endpoints	The primary safety endpoint at 12 months is defined as the safety event free rate at 12 months post-procedure. Primary safety events at 12 months will consist of a composite of the following procedure-related and/or device-related adverse events. Acute primary safety endpoint events, events occurring up to 7 days post-index procedure or hospital discharge, whichever is later, include: • Death • Myocardial infarction (MI) • Persistent gastroparesis/injury to vagus nerve • Transient ischemic attack (TIA) • Stroke/Cerebrovascular accident (CVA) • Thromboembolism/ Air embolism • Cardiac tamponade/perforation • Pneumothorax • Serious vascular access complications • Pulmonary edema/heart failure • AV block not attributable to medication effect or vasovagal reaction Chronic primary safety endpoint events, events occurring through 12 months post-index procedure, include: • Atrial esophageal fistula • Pulmonary vein stenosis (greater than or equal to 70% reduction of diameter) OR presented by patient’s symptoms at 12-Month follow-up and requiring intervention • Persistent Phrenic nerve injury The primary effectiveness endpoint will be evaluated by the failure-free rate at 12 months post-index procedure. Failure defined as: • Failure to achieve acute procedural success* in the index procedure • Any documented recurrent AF episode(s), or new onset of AFL or AT events: o greater than or equal to 30 seconds in duration from any clinical recording devices considered standard of care at the study center (excluding insertable loop recorders)** or o greater than or equal to 10-second of continuous AF, AFL or AT documented on any 12-lead ECG between Days 91 and 12-Month follow-up • Any of the following interventions for atrial fibrillation, or new onset of atrial flutter or atrial tachycardia between days 91 and 12 Month Follow Up: o Repeat procedure o Electrical and/or pharmacological cardioversion for AF/AFL/AT o Prescribed a higher dose of any AAD*** documented at baseline or a new AAD not documented at baseline. o Hospitalization for AF/AT/AFL *Acute procedural success is defined as isolation of all pulmonary veins or anatomical equivalents achieved with the BSC Cryoablation System at the end of the index procedure and as demonstrated,at minimum, by entrance block (other techniques of assessment are per investigator’s discretion). ** Subjects will be monitored for recurrences/new onset of arrhythmias by means of clinical visits, 12-lead ECG or any clinical recording devices (for example but not limited to, smart watch, 24-hour Holter monitoring, home monitoring systems or implanted devices etc.) that are per standard of care (SOC) used by the hospital/clinic. Documentation of episodes captured by standard of care monitoring methods must be verified by investigator and filed in medical records. Recurrences documented on implantable loop recorders for the treatment of atrial fibrillation will be collected but will not be counted as primary effectiveness endpoint events. ***AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken for control of AF/AT/AFL recurrence.
Follow-up Visits and Length of Follow-up	All subjects treated with the Boston Scientific Cardiac Cryoablation System will be followed for 12 months. Subjects with a pre-existing LUX-Dx or a LUX-Dx inserted within 7 days of the ablation procedure will have arrhythmia recurrence monitored remotely via the LATITUDE Home Monitoring System to assess for arrhythmia recurrence for up to 3 years. Subjects will undergo the index procedure and be followed at pre-discharge, 3 Month, 6 Month and 12 Month visits. Attempt subjects will receive a phone call at 30 days post-procedure to verify adverse events and complications. The total study duration is expected to take 5 years.
Interim or Final Data Summary
Interim Results	Safety Results: Three adverse events (pericarditis, myocardial perforation with tamponade, and atrial fibrillation) in three subjects, two of which were considered serious adverse events. There have been no unanticipated adverse events. Effectiveness Results: Insufficient data to meaningfully assess effectiveness.
Actual Number of Patients Enrolled	21
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	All subjects remain active. One subject withdrew prior to treatment
General
Study Status	Ongoing
Application Number / Requirement Number	P150012 S158/ PAS001
Date Original Protocol Accepted	11/08/2024
Date Current Protocol Accepted
Study Name	INGEVITY + LBBAP Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Real World Evidence (RWE) methodology study to establish the safety and effectiveness of INGEVITY + pacing leads for use in left bundle branch area pacing (LBBAP) for patients with a pacing indication. The study is prospective single-arm, non-randomized, observational cohort using RWE methodologies from the Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION) project.
Study Population	The study will include all patients registered in Boston Scientific’s device tracking database with an INGEVITY+ lead implanted in the LBBA until at least 1,013 leads are followed to 5 years post-implant. The study will also include patients with applicable data from the pre-market cohort.
Sample Size	At least 1,013 implanted leads for chronic safety endpoint. At least 141 implanted leads are required for the acute safety endpoint. At least 137 lead measurements through 60 months are required to evaluated effectiveness endpoints. Chronic safety endpoint drives overall sample size based on the following assumptions: • Expected performance = 95% • Performance goal = 92.5% • One-sided significance level = 2.5% • Power = 90%
Key Study Endpoints	Safety Endpoints Acute: The event-free rate from implant to 1 month. Chronic: The event-free rate from 1 to 60 months. Effectiveness Endpoints Effectiveness 1: Percent of pacing capture threshold (PCT) responders defined as PCT less than or equal to 2 V. Effectiveness 2: Percent of R-wave sensed amplitude responders defined as R-wave sensed amplitude greater than or equal to 5mV.
Follow-up Visits and Length of Follow-up	Visits: N/A Length of F/U: Patients will be followed through at least 5 years following the end of enrollment.
Interim or Final Data Summary
Interim Results	Safety Results: At 30 days of follow-up, an event-free rate of 98.6% has been observed to date. Effectiveness Results: The percentage of responders has been observed to be 97.5% for primary effectiveness endpoint 1 and 95.5% for primary effectiveness endpoint 2 at 12 months post-implant.
Actual Number of Patients Enrolled	Primary Safety Endpoint 1: 3721; Primary Safety Endpoint 2:3156; Primary Effectiveness Endpoint 1: 10273; Primary Effectiveness Endpoint 2: 9877
Actual Number of Sites Enrolled	N/A- Real World Data
Patient Follow-up Rate	N/A - Real World Data
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S162/ PAS002
Date Original Protocol Accepted	05/23/2024
Date Current Protocol Accepted
Study Name	Continued Follow-up of the SAPIEN 3
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The key safety and effectiveness endpoints include all-cause mortality, all stroke, myocardial infarction, valve reintervention, prosthetic valve endocarditis, prosthetic valve thrombosis, structural valve deterioration (SVD), New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, hemodynamic performance metrics by Doppler echocardiography and adverse events.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: At 4-years: All-cause mortality: 6.1% All-stroke: 12.4% Mitral valve reintervention: 2.2% Prosthetic valve endocarditis: 2% Prosthetic valve thrombosis: 8.1% Structural valve deterioration: 0% Effectiveness Results: At 4-years: Improvement from baseline in NYHA functional classification: 80% KCCQ Overall Summary Score change from baseline: 25.2 Mitral valve area: 1.4 cm2 Mean Mitral Gradient: 5.3 mmHg Moderate or greater Paravalvular Mitral Regurgitation: 0%
Actual Number of Patients Enrolled	A total of 53 subjects were enrolled. 50 subjects underwent the procedure.
Actual Number of Sites Enrolled	12
Patient Follow-up Rate	Patient status known at 4 years is 92.0%
General
Study Status	Study Pending
Application Number / Requirement Number	P240013 / PAS001
Date Original Protocol Accepted	02/03/2025
Date Current Protocol Accepted	05/30/2025
Study Name	SPHERE Per-AF Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Evaluate primary safety adverse event (AE) rate for ablation using the Sphere-9™ Catheter and Affera™ Ablation System. Estimate the 36-month freedom from atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) recurrence following ablation procedure using the Sphere-9™ Catheter and Affera™ Ablation System.
Study Population	Subjects greater tha or equal to 18 years of age who have a recommendation for an ablation with the Sphere-9™ Catheter and Affera™ Ablation System. Inclusion Criteria * A diagnosis of recurrent symptomatic persistent AF (continuous AF sustained longer than 7 days but less than 12 months). -Refractory (i.e., not effective, not tolerated, or not desired) to at least one Class I or III antiarrhythmic drug. -Patient is greater than or equal to 18 years of age. -Planned de novo pulmonary vein isolation (PVI) procedure using commercially available Sphere-9™ Catheter and Affera™ Ablation System. -Patient is willing and able to comply with study requirements and give informed consent. Exclusion Criteria * Long-standing persistent AF (continuous AF sustained >12 months). -Prior left atrial catheter or surgical ablation. -Life expectancy <36 months. -Presence of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function). -Current or anticipated participation in any other clinical trial of a drug, device, or biologic during the duration of the study not pre-approved by the sponsor.
Sample Size	Number of subjects: 200 Assumptions for sample size estimation: 175 subjects treated. Number of sites: 15 Sites location: All subjects will be enrolled within the United States of America.
Key Study Endpoints	Safety Endpoints Primary: Estimate the primary safety adverse event rate for ablation using the Sphere-9™ Catheter and Affera Ablation System. The following device- and/or procedure-related serious adverse events (SAEs) following the index ablation procedure will be considered a primary safety event: Within 7 Days: * Death -Myocardial Infarction -Phrenic nerve paralysis (ongoing at 6 months) -Transient ischemic attack (TIA) -Stroke/cerebrovascular accident (CVA) -Thromboembolism -Major vascular access complications/bleeding -Heart block -Gastroparesis -Severe pericarditis -Hospitalization (initial or prolonged) due to cardiovascular or pulmonary AE‡ Within 30 days: * Cardiac Tamponade/perforation Within 90 days: * Atrio-esophageal fistula Within 180 days: * Pulmonary vein stenosis ‡ Excludes hospitalization due to AF/AT/AFL recurrence Effectiveness Endpoints Primary: The primary effectiveness endpoint is defined as freedom from any of the following through 36 months: * Documented recurrent AF/AT/AFL after a 90-day blanking period -Minimum of 10 seconds on 12-lead ECG -Minimum of 30 seconds on 24-hour Holter -Minimum of 30 seconds on other cardiac rhythm monitoring device (e.g. event monitor, TTM) -Repeat ablation for the treatment of AF/AT/AFL after a 90-day blanking period -Cardioversion for the treatment of AF/AT/AFL after a 90-day blanking period Blanking period is defined as the 90 days post study index ablation procedure. Recurrent AF/AT/AFL or treatments for AF/AT/AFL during the 90-day blanking period do not count towards the primary effectiveness endpoint. Subjects may be managed with medications and cardioversions per standard of care (SOC) during the 90-day blanking period. Repeat ablation during the blanking period is discouraged.
Follow-up Visits and Length of Follow-up	Once enrolled, a subject will be assessed at the following visits: * Enrollment/Baseline Ablation procedure 6 months 12 months 24 months 36 months
General
Study Status	Study Pending
Application Number / Requirement Number	P150048 / PAS003
Date Original Protocol Accepted	07/28/2023
Date Current Protocol Accepted
Study Name	Model 11500A Valve-in-Valve PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a single-arm observational study which includes both prospective and retrospective data.
Study Population	Adults age 18 or older at the time of the TAVR ViV treatment, determined to need routine ViV placement of an Edwards transcatheter aortic heart valve (TAVR) FDA-approved for ViV within a dysfunctional 19mm to 25mm Edwards INSPIRIS RESILIA aortic valve.
Sample Size	50 subjects
Key Study Endpoints	Primary effectiveness endpoints (pre-ViV and post-ViV): Quantitative measurements of the inner area of 19mm- 25mm INSPIRIS RESILIA aortic valves post-ViV compared to baseline. Measurements will be taken prior to ViV placement (“pre-ViV” or baseline) and after placement at Day 30 or later (post-ViV). Primary safety endpoints (up to 30 days): A composite of all-cause mortality, all stroke (disabling and non-disabling), life-threatening bleeding, new requirement for dialysis, coronary artery compression or obstruction, major vascular complication, and valve-related dysfunction requiring reintervention, through 30 days following the transcatheter aortic valve implantation. An incidence of valve malpositioning including all instances of ViV-TAVR migration, embolization, and valve recapture or retrieval up to 30 days post-ViV. Additional outcomes (through 1 month): In alignment with the TVT registry data collection, reportable adverse events, readmissions, interventions, and surgical procedures including the following will be assessed up to 30 days: • Myocardial Infraction • Endocarditis • Conduction Disturbance requiring Pacemaker • Atrial Fibrillation • Aortic Dissection • Conduction Disturbance requiring ICD • Cardiac Arrest • Annular Dissection • Perforation with or without Tamponade • Transient Ischemic Attack • Ischemic Stroke • Hemorrhagic Stroke • Undetermined stroke • Device Fracture • Device Thrombosis • New Requirement for Dialysis • Aortic Valve Re-intervention • Unplanned Other Cardiac Surgery or Intervention (excluding AVR or PCI) • Unplanned Vascular Surgery or Intervention (for Bleeding or Access Site Complication) • PCI • Valve Related Readmission • Non-Valve Related Readmission • Major Vascular Complication • Minor Vascular Complication • Transapical Related Event • Major Bleeding Event • Bleeding at Access Site • Retroperitoneal Bleeding • GU Bleed • Device Embolization LV • Device Recapture or Retrieval • Life Threatening Bleeding • Hematoma at Access Site • GI Bleed • Other Bleed • Device Embolization Aorta • Coronary Compression or Obstruction • Other Device Related Event
Follow-up Visits and Length of Follow-up	one month after TAVR ViV treatment
General
Study Status	Delayed
Application Number / Requirement Number	P220014 / PAS001
Date Original Protocol Accepted	12/23/2023
Date Current Protocol Accepted	10/01/2026
Study Name	CraniSeal Registry New Enrollment PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: This is a prospective, multicenter, non-randomized, 2-arm, observational post-approval study designed to evaluate and compare postoperative CSF leakage rates in subjects who receive CraniSeal Dural Sealant and control subjects who receive DuraSeal Dural Sealant as an adjunct to elective infratentorial or supratentorial cranial dural closures. The CraniSeal Dural Sealant arm will consist of subjects who undergo a cranial procedure where CraniSeal hydrogel is administered. The control arm will consist of subjects who undergo a cranial procedure where DuraSeal hydrogel is administered. Sites are not required to enroll in both study arms. Subjects will be followed for 90 days after cranial surgery. Objectives: The objective of this study is to collect post-approval data comparing the safety and effectiveness of the recently FDA-approved CraniSeal Dural Sealant to DuraSeal Dural Sealant when used by a broad group of physicians under commercial use conditions.
Study Population	Patients who are scheduled for elective infratentorial or supratentorial cranial surgery that entails a sutured dural incision that needs to be augmented with a dural sealant.
Sample Size	Number of subjects: 134 Assumptions for sample size estimation: Sample size calculations for the CraniSeal and DuraSeal treatment arms were performed based on the primary effectiveness endpoint, occurrence of CSF leakage or pseudominigocele within 90-days after the cranial surgical procedure. Assuming 95% exact confidence intervals (CI) and true percentages for the primary effectiveness endpoint of 1% for each treatment, a 1:1 ratio of the number of subjects in each arm, and an 80% probability of the CI half-width being less than or equal to 4%, the required sample size per treatment arm is 67 subjects, for a total sample size of 134 subjects. Number of sites: 20 Sites location: US
Key Study Endpoints	Safety Endpoints Primary: None Secondary: None Effectiveness Endpoints Primary: The primary effectiveness endpoint is the occurrence of cerebrospinal fluid (CSF) leakage within 90-days after the cranial surgical procedure. This endpoint will be summarized by treatment group using frequencies and percentages, together with an exact (Clopper-Pearson) confidence interval (CI) for the true percentage. The observed difference in percentages between treatment groups (DuraSeal Dural Sealant - CraniSeal Dural Sealant), together with a 95% normal approximation CI for the true difference, will also be presented. Secondary: The secondary endpoint is occurrence of post-operative surgical site infections through 90 days that are judged to be definitely or probably related to the use of the dural sealant. This endpoint will be summarized in the same manner as the primary effectiveness endpoint
Follow-up Visits and Length of Follow-up	90 days
Interim or Final Data Summary
Interim Results	Safety Results Types and frequency of adverse events: An in-depth review of Adverse Events (AEs) was completed by the Sponsor in June, based on data reported as of May 29, 2026. 151 AEs were reported: o 28 SAEs o 7 Device Related AEs – 3 of which are SAEs ¿ All Device related S/AEs were also related to procedure o 60 Related only to Procedure o 84 Unrelated to Device or Procedure Effectiveness Results: Effectiveness endpoints: No interim analysis completed or planned. Observations and trends: No observable trends to date.
Actual Number of Patients Enrolled	82
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	11 participants have been entered as withdrawn or terminated early
General
Study Status	Completed
Application Number / Requirement Number	P230002 / PAS001
Date Original Protocol Accepted	07/28/2023
Date Current Protocol Accepted
Study Name	EASE Clinical Trial
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the safety and effectiveness of the Minitouch System for treatment of menorrhagia due to benign causes in premenopausal women for whom childbearing is complete. Prospective, single-arm, non-randomized, multi-center clinical trial
Sample Size	114
Key Study Endpoints	At least 85% of the current patient cohort must be followed out to 36 months post procedure. The following outcomes will be provided: Need for surgical or medical intervention to treat abnormal bleeding Subject self-report of pregnancy Contraception status (data to be collected at 3 years only) Menstrual status Gynecologic adverse events Quality of Life Questionnaire Patient Satisfaction
Follow-up Visits and Length of Follow-up	36 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	114
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	93.9% (107/114) through 36 months
Final Safety Findings	There were 22 gynecologic adverse events (AEs) from 12-month to 36-month. There were zero (0) incidences of device or procedure-related serious adverse events (SAEs) or unanticipated adverse device effects (UADEs) through the 36-month follow-up.
Final Effect Findings	PREMARKET EFFECTIVENESS ENDPOINTS At 12-month, the overall success rate based on PBLAC results was 89.5% (102/114), and the amenorrhea rate was 51.8% (59/114). POSTMARKET EFFECTIVENESS ENDPOINTS: Need for surgical or medical intervention to treat abnormal bleeding: From 12-month to 36-month, 2.6% (3/114) of the subjects had medical or surgical intervention to treat abnormal menstrual bleeding. Subject Self-report of Pregnancy: From 12-month to 36-month, there were zero (0) incidences of pregnancy. Menorrhagia Impact Questionnaire (MIQ): From 12-month to 36-month, most of the subjects reported no limitations, due to menstrual bleeding, in work (MIQ 2), physical activity (MIQ 3), and social/leisure (MIQ 4) activities at a rate of 90.2% (102/112), 87.5% (98/112) and 90.2% (101/112), respectively, at 24-month; and most of the subjects also reported no limitations, due to menstrual bleeding, in work (MIQ 2), physical activity (MIQ 3), and social/leisure (MIQ 4) activities at a rate of 93.5% (100/107), 93.5% (100/107), and 95.3% (102/107), respectively, at 36-month. Dysmenorrhea-related Pain: From 12-month to 36-month, 92.0% (103/112) of the subjects reported a reduction in dysmenorrhea symptoms at 24-month; and 91.6% (98/107) of the subjects reported a reduction in dysmenorrhea symptoms at 36-month. Patient Global Evaluation (PGE): From 12-month to 36-month, 90.2% (101/112) of the subjects were very satisfied or satisfied with the treatment received, and 90.2% (101/112) of the subjects would recommend the procedure to friends at 24-month; and 90.7% (97/107) of the subjects were very satisfied or satisfied with the treatment received, and 88.8% (95/107) of the subjects would recommend the procedure to friends at 36-month Investigator Global Evaluation (IGE): From 12-month to 36-month, the investigators assessed the subjects menstrual status as normal (eumenorrhea) or less than normal (hypomenorrhea, spotting and amenorrhea) menstrual blood loss in 96.4% (108/112) of the subjects at 24-month; and the investigators assessed the subjects menstrual status as normal (eumenorrhea) or less than normal (hypomenorrhea, spotting and amenorrhea) menstrual blood loss in 95.3% (102/107) of the subjects at 36-month. Contraception Status: At 36-month, subjects (N=107) reported use of the following contraception methods. Abstinence: 4.7% (5/107) Cervical Cap: 0.0% (0/107) Condom: 19.6% (21/107) Diaphragm: 0.0% (0/107) Partner’s vasectomy: 44.9% (48/107) Tubal sterilization: 28.0% (30/107) Spermicidal vaginal sponge: 0.0% (0/107) Sterile: 0.0% (0/107) Hormonal method (includes pills, injections, patches, rings, implants): 3.7% (4/107) Intrauterine devices: 1.9% (2/107) Other: 4.7% (5/107)
Study Strengths & Weaknesses	N/A
Recommendations for Labeling Changes	Include final PAS data in the physician and patient labeling
General
Study Status	Ongoing
Application Number / Requirement Number	P230005 / PAS001
Date Original Protocol Accepted	09/26/2024
Date Current Protocol Accepted
Study Name	Post-Approval PMA Cohorts Study - PACS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	continued follow-up of premarket cohort
Study Population	Adult (age 22 and over) women who are undergoing primary breast augmentation, primary breast reconstruction or revision breast surgery to correct or improve the results of a primary breast augmentation or reconstruction surgery. There is no control group.
Sample Size	Total subject population 800 subjects (approx. 1,510 implants) in four pivotal cohorts: · 450 subjects: Primary Augmentation cohort · 100 subjects: Revision Augmentation cohort · 200 subjects: Primary Reconstruction · 50 subjects: Revision Reconstruction cohort There will be two sub-study groups for this study: · Magnetic Resonance Imaging (MRI) Sub-Study: This group will be a sub-set of the treated population that will be selected to obtain MRIs at years 1, 2, 3, 5, 7, and 10. These data will be used for the analysis of silent rupture. A total of 250 subjects (approx. 475 implants) will be included in the MRI sub-study. · Radiofrequency Identification Device (RFID) Microtransponder SubStudy Population: This group will be a subset of the treated population who elect to receive an optional RFID microtransponder that is embedded in their Motiva Implants®. A total of approximately 150 subjects will be included in the microtransponder sub-study.
Key Study Endpoints	Effectiveness Endpoints: The primary effectiveness endpoint is the assessment of patient satisfaction on a 5-point Likert scale at 2 years post-implant for all implantation groups. The subject will be considered satisfied if the response to this survey is “satisfied” or “very satisfied.” Secondary effectiveness assessments will include the following analyses · Patient Satisfaction with Breast (BREAST-Q™) Questionnaire by cohort (approximately 300 subjects to participate at baseline). · Physician Satisfaction (5-point Likert scale) at 2 years post-implant [aggregate analysis and by cohort]. · Quality of Life (Rosenberg Self-Esteem Scale, SF-36, Body Esteem Scale) for all cohorts. · Breast Measurements (Net Chest Circumference and HemiCircumference) change from baseline (for Primary Augmentation cohort only). Safety Endpoints: The primary safety endpoint is the total adverse event rate (“any complication)” through two years of follow-up. Kaplan-Meier analysis of adverse events will be conducted by time period for each type of adverse event. Secondary safety assessments will include the following analyses: · Kaplan-Meier analysis of all complications, including reoperation and explantation · Cox regression analyses for the following endpoints: Capsular contracture III/IV, Breast Pain, Infection, and Implant Rupture. · Kaplan-Meier analysis of rupture (based on the MRI sub-study cohort) · Kaplan-Meier analysis of connective tissue disease (CTD) and CTD signs/symptoms · Kaplan-Meier analysis of Cancer (Breast Cancer, Breast ImplantAssociated Anaplastic Large Cell Lymphoma (BIA-ALCL), and others) · Additional events will be included in listings by level of seriousness and device and procedure-relatedness.
Follow-up Visits and Length of Follow-up	10 years
Interim or Final Data Summary
Interim Results	Safety Results: Key adverse events through Year 5 for the primary augmentation cohort include: 8.8% reoperation, 3.1% explantation, 12% any complication, 1.2% breast pain, 0.5% capsular contracture III/IV, 0.9% infections, and 0.6% rupture- suspected/confirmed. Key adverse events through Year 5 for the revision augmentation cohort include: 36.0% reoperation, 22.8% explantation, 39.5% any complication, 2.2% breast pain, 7.9% capsular contracture III/IV, 0.9% infections, and 0% rupture- suspected/confirmed. Effectiveness results: Participant satisfaction by subject at Year 5 for augmentation (N=387) includes 311 (80.4%) very satisfied, 61 (15.8%) satisfied, 8 (2.1%) neither dissatisfied nor satisfied, 6 (1.6%) dissatisfied, and 1 (0.3%) very dissatisfied. Participant satisfaction by subject at Year 5 for revision augmentation (N=80) includes 57 (71.3%) very satisfied, 16 (20.0%) satisfied, 5 (6.3%) neither dissatisfied nor satisfied, 2 (2.5%) dissatisfied, and 0 very dissatisfied.
Actual Number of Patients Enrolled	Primary Augmentation (N=451) Revision Augmentation (N=109)
Actual Number of Sites Enrolled	21 active investigational sites
Patient Follow-up Rate	87.8%
General
Study Status	Ongoing
Application Number / Requirement Number	P230005 / PAS002
Date Original Protocol Accepted	11/22/2024
Date Current Protocol Accepted	11/22/2024
Study Name	New Enrollment Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multicenter study including baseline (preoperative), operative, and postoperative data collection at baseline and annually Years 1-10 The Post Approval Study is a new enrollment study that will examine the general post market use and endpoints not addressed during premarket studies in women who are undergoing primary augmentation and revision augmentation breast surgery to correct or improve the results of a primary breast augmentation, and in a group of control subjects undergoing an aesthetic procedure other than breast implant surgery
Study Population	Subject population of 2,400 subjects in three cohorts: - 1,500 primary augmentation subjects implanted with approved Motiva devices - 500 revision augmentation subjects implanted with approved Motiva devices - 400 control subjects consisting of women undergoing an aesthetic procedure other than breast implant surgery
Sample Size	Number of subjects: 2400 Assumptions for sample size estimation: Sufficient sample size assuming worst-case (40%) loss-to-follow-up to have sufficient power (at least 80%) to detect a 2.0 odds ratio for CTD and systemic signs and symptoms differences between the Motiva group and Control group when the incidence in the control group is at least 10%. Number of sites: 50 Sites location: in the US
Key Study Endpoints	Safety Endpoints Primary: Patient-reported incidence of CTD and systemic signs and symptoms using a questionnaire including the PROMIS-29 Survey, a validated tool that assesses eight health domains: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference and cognitive functions and compare them among study groups (i.e., implanted vs control) Secondary: - Patient-reported incidence of reproductive complications, cancer (including breast cancer), local complications (including suspected rupture), reoperation, implant removal comparing (a) Round to Round Ergonomix devices, (b) Non-White participants to White participants, (c) RFID devices to non-RFID devices, and d) Implanted vs Controls, where data collection allows - Assess the impact of RFID on imaging (MRI or ultrasound) Effectiveness Endpoints Primary: none Secondary: Patient Satisfaction
Follow-up Visits and Length of Follow-up	Annual follow-up visit (questionnaire) administered annually for 10 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	0
Actual Number of Sites Enrolled	One site (Site 101), has completed their IRB enrollment process and is pending IRB Committee approval.
General
Study Status	Ongoing
Application Number / Requirement Number	P240009 / PAS001
Date Original Protocol Accepted	10/11/2024
Date Current Protocol Accepted	10/11/2024
Study Name	Continued Follow-up Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	continued follow-up of premarket cohort
Study Population	subjects at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the criteria outlined below: • Patients with symptomatic stenosis of the common or internal carotid artery with greater than or equal to 50% as determined by angiography using NASCET methodology OR Patients with asymptomatic stenosis of the common or internal carotid artery with greater than or equal to 80% as determined by angiography using NASCET methodology; • Patients with reference vessel diameters 4.0 – 8.0 mm.
Sample Size	305 subjects that were treated in the pivotal IDE study G200007
Key Study Endpoints	N/A
Follow-up Visits and Length of Follow-up	To 3 years post-procedure At 2-years and 3-years
General
Study Status	Ongoing
Application Number / Requirement Number	P200030 S014/ PAS001
Date Original Protocol Accepted	04/05/2024
Date Current Protocol Accepted
Study Name	Continued Follow-up of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the post approval study is to evaluate the long-term safety and effectiveness of the Excluder Conformable AAA Endoprosthesis (EXCC). The study consists of long-term follow-up of the premarket cohort. The study was designed to evaluate the safety and effectiveness of the EXCC device for the treatment of infrarenal AAA including patients with short and/or angulated aortic necks. The pivotal study was comprised of two substudies, the Short Neck (SN) substudy and High Neck Angulation (HNA) substudy. Data from the HNA substudy were the basis for the P200030/S014 approval decision.
Study Population	Patients with abdominal aortic aneurysms having aortic neck angulation up to 90° and infrarenal aortic neck length >10 mm.
Sample Size	A total of 175 subjects were enrolled in the study across the SN and HNA substudies. Ninety-five subjects were enrolled in the HNA substudy and remaining subjects will be followed.
Key Study Endpoints	Major adverse events, all-cause mortality, aneurysm-related mortality, aneurysm rupture, secondary interventions, conversion to open surgery, losses of device integrity, device occlusions, stenosis or kink, aneurysm enlargement (greater than or equal to 5 mm), stent graft migration (greater than or equal to 10 mm), all types of endoleaks, and other device-related events
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: Follow-up is not complete and therefore these rates may change as more data becomes available. Serious Adverse Events: • Device-Related Serious Adverse Events (SAEs): 3 subjects experienced device-related SAEs in the study to date. • Procedure-Related SAEs: 6/95 subjects (6.3%) experienced procedure-related SAEs in the study to date. • SAEs (Any): 67/95 subjects (70.5%) experienced an SAE at any time interval to date. All-Cause Mortality: • 33 subjects experienced all-cause mortality to date. Aneurysm-Related Mortality: • 1/95 subjects (1.1%) experienced aneurysm-related mortality to date. Aneurysm Rupture: • 1/95 subjects (1.1%) experienced an AAA rupture. Secondary Interventions: • 15/95 subjects (15.8%) required reintervention to date, with a total of 27 reinterventions performed. Conversion to Open Surgery: • 4/95 subjects (4.2%) experienced conversion to open repair to date Loss of Device Integrity: • 1 subject experienced lumen obstruction, device compression, and loss of patency. Device Occlusions: • 1 UADE involving device occlusion was reported in the study to date. Stenosis or Kink: • 1 report of stenosis and 1 report of device kinking in the study to date. Aneurysm Enlargement (greater than or equal to 5 mm): • Eighteen (20.5%) subjects experienced this endpoint event as evaluated by core lab. Stent Graft Migration (greater than or equal to 10 mm): • No subjects experienced this endpoint event. All Types of Endoleaks: • 20/94 subjects (21.3%) had an indeterminate endoleak identified by core lab at any time in the study, with 4 of these subjects undergoing reintervention • 4 (4.3%) Type I endoleaks were identified by core lab at any time in the study Effectiveness Results: Procedural technical success for the HNA substudy was 97.9 % (93/95).
Actual Number of Patients Enrolled	175 (80 in short neck substudy and 95 in high neck substudy)
Actual Number of Sites Enrolled	54
Patient Follow-up Rate	1 Month: 87/95 (91.6%) of eligible subjects had any data; 84/95 (88.4%) had CT imaging data. 6 Months: 83/94 (88.3%) of eligible subjects had any data; 81/94 (86.2%) had CT imaging data. 12 Months: 78/91 (85.7%) of eligible subjects had any data; 78/91 (85.7%) had CT imaging data. 24 Months: 63/82 (76.8%) of eligible subjects had any data; 63/82 (76.8%) had CT imaging data. 36 Months: 55/64 (85.9%) of eligible subjects had any data; 52/64 (81.3%) had CT imaging data. 48 Months: 44/54 (81.5%) of eligible subjects had any data; 41/54 (75.9%) had CT imaging data. 60 Months: 35/44 (79.5%) of eligible subjects had any data; 33/44 (75.0%) had CT imaging data.
General
Study Status	Ongoing
Application Number / Requirement Number	P230007 / PAS002
Date Original Protocol Accepted	05/31/2024
Date Current Protocol Accepted	11/13/2024
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: This is a prospective, single-arm, observational, multi-center, post-approval study. Patients in the TriClip PAS will be treated and followed per the hospital standard of care. Objective: The objective of the TriClip PAS is to assess the real-world performance of the TriClip™ System in a contemporary real-world setting as well as to assess clinical outcomes of the device in patient populations underrepresented in the TRILUMINATE Pivotal trial
Study Population	All consecutive patients who are at least 18 years old from the general population who undergo an attempted TriClip procedure and are entered into the TVT Registry
Sample Size	Number of subjects: This study will involve all consecutive patients treated within the first 2 years following the approval of TriClip™ System or a total of 5,000 consecutively treated patients, whichever is greater, who are entered into the TVT Registry. Additionally, this study will enroll a minimum of 100 patients from each of the following racial and ethnic groups (Black/African American, Asian, American Indian/Alaskan Native, Native Hawaiian/Pacific Islander, and Hispanic or Latino ethnicity). If required, enrollment will continue in these racial and ethnic groups (past the 5,000 consecutive patients) until the specific enrollment is met. Assumptions for sample size estimation: N/A Number of sites: A minimum of 50 US commercial sites participating in the TVT registry. Sites location: US commercial sites. Additionally, A representative subset of sites will be selected based on procedural volume/implanter experience and geographical location in order to evaluate outcomes in a cohort of patients that is not overrepresented by a specific type of site. Additionally, at least 50% of the sites included in this representative group will not have participated in the TRILUMINATE Pivotal trial.
Key Study Endpoints	The following endpoints will be collected from the first implant procedure via the TVT Registry Tricuspid Valve Data Collection Form: • All-cause mortality through 1 year • Stroke through 1 year • Hospitalizations through 1 year • Heart failure hospitalizations through 1 year (pending addition to the data collection form) • Tricuspid valve (TV) re-intervention through 1 year • Adverse events (AE) through 1 year • TR grade at baseline, discharge, 30 days, and 1 year • NYHA Class at baseline, 30 days, and 1 year • KCCQ-12 score at baseline, 30 days, and 1 year • Six-Minute Walk Test (6MWT) at baseline, 30 days, and 1 year The following endpoints will be reported from 2 years through 5 years post-procedure annually via linking the TVT Registry data with the CMS claims database: • All-cause mortality • Stroke • Hospitalizations • Heart failure hospitalizations • TV reintervention
Follow-up Visits and Length of Follow-up	Clinical assessment and echocardiographic data at baseline, procedure, discharge, 30 days post-procedure, and 1-year post-procedure will be captured through the TVT Registry Tricuspid Valve Data Collection Form. Long-term endpoints from 2 years through 5 years post-procedure will be reported annually by linking the TVT Registry data with the CMS claims database.
Interim or Final Data Summary
Interim Results	Safety Results 30 days: All-cause mortality: 1.4% Cardiovascular death: 0.8% Stroke: 0.3% Hospitalizations: 8.2% Heart failure hospitalizations: 2.3% Tricuspid valve re-intervention: 0.6% Effectiveness Results: 30 days: Tricuspid Regurgitation Severity: Baseline: 96% severe and 4% moderate. 30 days: 87% moderate or less KCCQ Overall summary score: Baseline: mean of 46.5 +/- 23.8 points. 30 days: mean of 69.6 +/- 24.1 points NYHA: Baseline: 73% classified as NYHA functional class III/IV. 30 days: 21% classified as NYHA class III/IV 6-minute walk test: Mean improvements were 24.4 meters at 30 days
Actual Number of Patients Enrolled	3,035 patients
Actual Number of Sites Enrolled	278 sites
Patient Follow-up Rate	30 days: 2,838 known patient status / 3,035 enrolled patients = 94%
General
Study Status	Delayed
Application Number / Requirement Number	P230001 / PAS001
Date Original Protocol Accepted	05/03/2024
Date Current Protocol Accepted	08/27/2026
Study Name	ColoSense Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study will be a prospective study. Subjects can be enrolled online using decentralized recruitment procedures. The primary objective is to continue to evaluate the clinical effectiveness of ColoSense by obtaining at least 23 CRC cases (23 cases in addition to the 27 obtained in CRC-PREVENT for a total of 50 CRC cases) to have an adequate number of CRC subjects that are part of the intended use population (average risk) to provide more certainty in the test performance. The secondary objective of this PAS is to further define sensitivity for colorectal cancer, advanced adenomas, and serrated precancerous lesions and specificity for negative findings on a colonoscopy for Geneoscopy’s multitarget stool RNA test (ColoSense), using colonoscopy as the reference methods.
Study Population	Subjects aged 45 years or older, who are at typical average-risk of developing colorectal neoplasms and are considered enrolled after understanding and consenting to ICF. Inclusion Criteria: ¿ Subject is male or female, =45 years of age ¿ Subject is able to understand the study procedures, and is able to provide consent to participate in the study and authorizes release of relevant protected health information through reviewing and consenting to a HIPAA medical release form ¿ Subject is able and willing to provide stool samples within the 120 days prior to a colonoscopy procedure. ¿ Subject is able and willing to undergo a colonoscopy after providing a stool sample Exclusion Criteria: Subjects are not permitted to enroll in the PAS study if any of the following exclusion criteria are met: ¿ Subject had any precancerous findings on most recent colonoscopy. This does not include benign, and/or hyperplastic polyps of any size. ¿ Subject has a history or diagnosis of colorectal cancer ¿ Subject has a history of aerodigestive tract cancer ¿ Subject has had a positive non-invasive screening diagnostic within the associated recommended intervals: ¿ Fecal occult blood test or fecal immunochemical test within the previous twelve (12) months ¿ FIT-DNA test within the previous 36 months ¿ Subject has had a colonoscopy in the previous nine (9) years. ¿ Subject has had a prior colorectal resection for any reason other than sigmoid diverticular disease ¿ Indication for colonoscopy was due to overt rectal bleeding, e.g., hematochezia or melena, within the previous 30 days. (Blood on toilet paper, after wiping, does not constitute rectal bleeding) ¿ Subject has a diagnosis or personal history of any of the following high-risk conditions for colorectal cancer: ¿ Inflammatory bowel disease (IBD) including chronic ulcerative colitis (CUC) and Crohn's disease ¿ Familial adenomatous polyposis (also referred to as "FAP", including attenuated FAP) ¿ Hereditary non-polyposis colorectal cancer syndrome (also referred to as "HNPCC" of "Lynch Syndrome") ¿ Other hereditary cancer syndromes including but are not limited to: ¦ Peutz-Jeghers Syndrome, MYH-Associated Polyposis (MAP), Gardner's Syndrome ¦ Turcot's (or Crail's) Syndrome, Cowden's Syndrome, Juvenile Polyposis ¦ Cronkhite-Canada Syndrome, Neurofibromatosis and Familial Hyperplastic Polyposis
Sample Size	Number of subjects: 12,500 subjects Assumptions for sample size estimation: an estimate that 65% of enrolled patients would complete all study requirements, approximately 8,125 viable results. This study size is based on estimated observed in the CRC-PREVENT clinical trial (NCT04739722), a CRC incidence of 0.40% (n = 36) including those with a first-degree relative with CRC; and a CRC incidence of 0.30% (n = 27) excluding those with a first-degree relative with CRC. Therefore, with 12,500 enrolled subjects and 8,125 viable subjects, an additional 33 patients with CRC. Of these 33 subjects with CRC, 23 would have no first-degree relative with CRC.
Key Study Endpoints	The primary endpoints for this study are ColoSense sensitivity for colorectal cancer, ColoSense sensitivity for advanced adenomas, ColoSense sensitivity for serrated precancerous lesions, and ColoSense specificity for all other findings. Criteria for success requires that the combined sensitivity of CRC (CRCs observed in the CRC-PREVENT clinical trial and CRCs observed in the PAS) must be greater than 90% and the lower bound of the 95% two-sided confidence interval must be greater than 80%. The secondary endpoints for this study evaluate ColoSense sensitivity for subsets and supersets of the various histopathological categories.
Follow-up Visits and Length of Follow-up	Subjects will be followed annually for a total of 2 years.
Interim or Final Data Summary
Interim Results	Safety Results: No adverse events reported to date Effectiveness Results: N/A
Actual Number of Patients Enrolled	1181
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P230007 / PAS001
Date Original Protocol Accepted	04/01/2024
Date Current Protocol Accepted	05/31/2024
Study Name	Continued f/u of the Premarket Cohort
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this trial was to evaluate the safety and effectiveness of the TriClip device in symptomatic patients with severe TR who were determined by the site’s local heart team to be at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery. The study includes continued follow-up of patients enrolled under the IDE, including the TRILUMINATE pivotal trial and the Continued Access Protocol (CAP) investigation. The TRILUMINATE pivotal trial was a prospective, multicenter, randomized, controlled, clinical trial to test the superiority of the TriClip device in addition to medical therapy over medical therapy alone. The CAP began once the Randomized and Single-Arm cohorts of the pivotal trial finished enrolling. All subjects enrolled into the CAP received the TriClip device.
Study Population	The study population consists of patients with symptomatic, severe tricuspid valve regurgitation whose symptoms and TR severity persist despite being optimally treated with medical therapy and who are at intermediate or greater risk for tricuspid valve surgery as determined by a heart team.
Sample Size	The study will continue to follow all living patients who were enrolled under the IDE.
Key Study Endpoints	Data will be collected per the study protocol and summarized descriptively, including, but not limited to, adverse event data including deaths, tricuspid valve reintervention, heart failure related hospitalizations, echocardiographic endpoints including tricuspid regurgitation severity grade, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, SF-36 score (1 and 2 years only), New York Heart Association (NYHA) classification, and 6-Minute Walk Test (6MWT) distance. KCCQ score and TR severity grade will be collected with a minimum of 75% completeness rate each year through 5 years.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Randomized cohort, 3-year outcomes: Freedom from all-cause mortality: Device group: 76.1%, Control group: 73.9% Freedom from heart failure related hospitalizations: Device group: 68.7%, Control group: 69% Tricuspid valve intervention: Device group: 4.6%, Control group: 53% (includes crossover events) Single-arm cohort, 3-year outcomes: Freedom from all-cause mortality: 67.7% Freedom from heart failure related hospitalizations: 63.6% Tricuspid valve intervention: 5.3% Continued access cohort, 1-year outcomes: Freedom from all-cause mortality: 90.5% Freedom heart failure related hospitalizations: 82.9% Tricuspid valve intervention: 1.9% Effectiveness Results: Randomized cohort, 3-year outcomes (Device group): TR: Baseline TR was 2% moderate or less. TR severity improved relative to baseline, with 84% moderate or less at 3 years. KCCQ: Mean KCCQ scores increased from 56 at baseline to 72 at 3 years. NYHA: The proportion of subjects in NYHA class I/II increased from 44% to 84%. SF-36 physical and mental component summary scores changed from 35 to 38 and from 48 to 55, respectively. The mean 6MWT distance increased from 241 meters to 259 meters. Single-arm cohort, 3-year outcomes: TR: Baseline TR was 0% moderate or less. TR severity improved relative to baseline, with 66% moderate or less at 3 years. KCCQ: Mean KCCQ scores increased from 53 at baseline to 75 at 3 years. NHYA: The proportion of subjects in NYHA class I/II increased from 40% to 88%. SF-36 physical and mental component summary scores changed from 35 to 34 and from 48 to 50, respectively. The mean 6MWT distance improved from 226 meters at baseline to 255 meters. Continued access cohort, 1-year outcomes: TR: Baseline TR was 3% moderate or less. TR severity improved relative to baseline, with 78% moderate or less at 1 year. KCCQ: Mean KCCQ scores increased from 57 at baseline to 73 at 1 year. NYHA: The proportion of subjects in NYHA class I/II increased from 45% to 84%.
Actual Number of Patients Enrolled	Number of subjects randomized or with attempted procedure (single-arm and CAS cohorts): Randomized cohort: N=572 Single-arm cohort: N=188 Continued access (CAS) cohort: N=378
Actual Number of Sites Enrolled	75
Patient Follow-up Rate	Follow-up Rate At 3-years Randomized cohort: 84% Single-arm cohort: 88% At 1-year Continued access cohort: 93%
General
Study Status	Ongoing
Application Number / Requirement Number	P230013 / PAS001
Date Original Protocol Accepted	02/01/2024
Date Current Protocol Accepted
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry-Based Real-World Use Surveillance. The objective of the surveillance is to assess the real-world performance of the EVOQUE system and the clinical outcomes of the device in patient populations underrepresented in the TRISCEND II pivotal trial.
Study Population	Patients with symptomatic severe tricuspid regurgitation despite optimal medical therapy, for whom tricuspid valve replacement is deemed appropriate by a heart team.
Sample Size	All consecutive patients treated within the first 2 years following device approval or a total of 5,000 consecutively treated patients, whichever is greater, who are entered into the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry (enrollment period). Data collection will continue for underrepresented racial and ethnic groups (Black/African American, Asian, American Indian/Alaskan Native, Native Hawaiian/Pacific Islander, and Hispanic or Latino ethnicity) until each group has enrolled a minimum of 100 patients.
Key Study Endpoints	The clinical data through one (1) year are collected through the TVT Registry. The follow-up data (including all-cause mortality, stroke, tricuspid valve reintervention, and hospitalization) from year 2 through year 5 post procedure are obtained through linking the TVT data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results All-cause death: 30 days, 3.9%; All stroke: 30 days, 0.8%; Tricuspid valve re-intervention (percutaneous or surgical): 30 days, 0.8%; All-cause hospitalization: 30 days, 12.1%; Heart failure hospitalization: 30 days, 4.1%; Life-threatening or major bleeding events: 30 days, 0.0% New conduction disorder/disturbance requiring a permanent pacemaker: 30 days, 7.1% Effectiveness Results Moderate/Severe Tricuspid Regurgitation: baseline, 100%; 30 days, 5.2%; Kansas City Cardiomyopathy Questionnaire Overall Summary score: baseline 41.6 +/- 25.5; 30 days, 67.7 +/- 24.8; New York Heart Association Functional Classification III/IV: baseline, 77%; 30 days, 25.9%
Actual Number of Patients Enrolled	138
Actual Number of Sites Enrolled	27
Patient Follow-up Rate	All 128 patients had a known 30-day follow-up status, including 112 patients with a completed visit (91% of alive patients). At 30-day follow-up, there were 5 reported patient deaths and 11 patients who had not completed a visit but were alive through 30 days. At 1-year follow-up, 8 patients had known status, all of whom died. The remaining 120 patients had pending 1-year visits. Table 3-2 of the report provides the patient disposition data.
General
Study Status	Ongoing
Application Number / Requirement Number	P230023 / PAS001
Date Original Protocol Accepted	01/12/2024
Date Current Protocol Accepted
Study Name	Continued Follow-up of the IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Assess the safety and effectiveness of the TAMBE Device in the treatment of thoracoabdominal aortic aneurysms (TAAA) and pararenal aortic aneurysms. This is continued follow up of the premarket cohort.
Study Population	Subjects with thoracoabdominal or pararenal aortic aneurysms requiring treatment of their adapted Crawford Type IV TAAA and pararenal aneurysms
Sample Size	142
Key Study Endpoints	Clinical endpoints include a composite of Uncomplicated Technical Success and Procedural Safety, as well as a composite of Clinically Significant Reintervention and Lesion-related Mortality
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results Study provided co-primary safety and effective endpoints: Uncomplicated Technical Success/Procedural Safety through 1 Month visit = 76.6% (108/141) Absence of Clinically Significant Reintervention / Lesion related Mortality through 12 Month visit = 72.7% (80/110) - Rupture = 0.8 % (1/123) - Lesion Related Mortality = 0.8% (1/124) Failure of Device Technical Success (SVS Standards) = 0.7% (1/140) Failure of Clinical success through 12 Month visit = 15.6% (17/109) Cumulative Mortality through all follow-up = 16.3% (23/141) Effectiveness Results Cumulative Reinterventions ([Number of events] subjects) Procedure = [2] 1.4% (2/141) 1 mo = [4] 2.8% (4/141) 3 mo = [17] 9.3% (13/140) 6 mo = [17] 9.9% (13/131) 12 mo = [29] 15.0% (19/127) 24 mo = [41] 23.7% (27/114) 36 mo = [53] 34.7% (33/95) 48 mo = [55] 53.2% (33/62) 60 mo = [55] 71.7% (33/46) Aneurysm Growth > 5mm* 1 mo visit = 0.0% (0/131) 3 mo visit = 0.0% (0/19) 6 mo visit = 2.1% (2/97) 12 mo visit = 4.7% (5/106) 24 mo visit = 9.9% (8/81) 36 mo visit = 25.6% (11/43) 48 mo visit = 52.9% (9/17) *Core lab reported outcomes; follow-up is not complete. Endoleak new and persistent (Type I | Type III)** 1 mo visit = 2.3% (3/132) | 1.5% (2/132) 3 mo visit = 2.7% (1/37) | 0.0% (0/37) 6 mo visit = 1.0% (1/103) | 0.0% (0/103) 12 mo visit = 1.8% (2/114) | 1.8% (2/114) 24 mo visit = 4.5% (4/89) | 0.0% (0/89) 36 mo visit = 1.9% (1/52) | 0.0% (0/52) 48 mo visit = 0.0% (0/22) | 0.0% (0/22) 60 mo visit = 0.0% (0/2) | 0.0% (0/2) **site reported outcomes; follow-up is not complete. Loss of patency in Branch components* (Celiac | SMA | Left Renal Artery | Right Renal Artery | [evaluable subjects]) 1 mo visit = 0.0% (0) | 0.0% (0) | 3.0% (4) | 1.5% (2) | [134] 3 mo visit = 0.0% (0) | 0.0% (0) | 4.7 % (5) | 1.9% (2) | [106] 6 mo visit = 0.9% (1) | 0.0% (0) | 4.7% (5) | 4.7% (5) | [106] 12 mo visit = 1.8% (2) | 0.0% (0) | 6.3% (7) | 7.1% (8) | [112] 24 mo visit = 3.4% (3) | 1.1% (1) | 8.0% (7) | 12.6% (11) | [87] 36 mo visit = 5.7% (3) | 3.8% (2) | 15.1% (8) | 24.5% (13) | [53] 48 mo visit = 8.1% (3) | 5.4% (2) | 21.6% (8) | 35.1% (13) | [37] 60 mo visit = 13.6% (3) | 9.1% (2) | 36.4% (8) | 59.1% (13) | [22] *Core lab reported outcomes; follow-up is not complete. Cumulative events* incidence to date through all available follow-up: Wire fractures ([Number of events] subjects) [12] 9 Subjects Device Compression 10.2% (14/137) Device Migration, Device Kink, Component Separation [0], 0 Subjects *Core lab reported outcomes
Actual Number of Patients Enrolled	141 Subjects in the Primary Study Arm / Continued Access
Actual Number of Sites Enrolled	44 Sites
Patient Follow-up Rate	Clinical Follow-up | Follow-up Complete with All Required Imaging 1 mo visit = 95.7% (134/140) | 92.5% (124/134) 3 mo visit = 79.9% (111/139) | 80.2% (89/111) 6 mo visit = 82.6% (109/132) | 78.9% (86/109) 12 mo visit = 90.6% (115/127) | 91.3% (105/115) 24 mo visit = 80.9% (89/110) | 84.3% (75/89) 36 mo visit = 63.5% (54/85) | 79.6% (43/54) 48 mo visit = 53.5% (23/43) | 82.6% (19/23) 60 mo visit = 13.3% (2/15) | 0.0% (0/2) 15 subjects have been lost to follow-up
General
Study Status	Delayed
Application Number / Requirement Number	P230017 / PAS001
Date Original Protocol Accepted	06/18/2024
Date Current Protocol Accepted
Study Name	PULSED AF Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, global, registry-based, observational study
Study Population	Subjects greater than or equal to 18 years of age (or minimum age as required by local regulations) who have a recommendation for an ablation with the PulseSelect™ PFA System may be approached regarding enrollment in this study.
Sample Size	Number of subjects: 580 Assumptions for sample size estimation: ~10% attrition Number of sites: 15 Sites location: US and OUS
Key Study Endpoints	Safety Endpoints Primary: Estimate the rate of major procedural complications for catheter ablation using the PulseSelect™ PFA System. Effectiveness Endpoints Primary: Estimate the 36-month freedom from AF/AFL/AT recurrence following ablation using the PulseSelect™ PFA System. Ancillary Objectives: 1. Characterize the PulseSelect™ PFA System ablation procedure, including but not limited to: o Acute procedural success o Total procedure time o Left Atrial (LA) dwell time o Total Fluoroscopy time o Total PulseSelect™ PFA System ablation time o Number and location of applications 2. Estimate change in quality of life (QoL) through 36 months. 3. Estimate the freedom from symptomatic AF/AFL/AT recurrence through 36 months. 4. Characterize all reported AEs through 36 months. 5. Estimate the rate of procedure-related mortality of the AF ablation procedure using the PulseSelect™ PFA system. 6. Estimate the rate of early mortality after ablation using the PulseSelect™ PFA system through 3 months post-procedure. 7. Estimate the rate of cardiac arrest that occurs during or after the AF ablation procedure (index or repeat) using the PulseSelect™ PFA system through 12 months post-procedure. 8. Estimate the rate of new left ventricular wall motion abnormality seen on echocardiogram at 12 months post-ablation. 9. Estimate the rate of all serious device or serious procedure related adverse events for catheter ablation using the PulseSelect™ PFA System through 12 months post-procedure. 10. Estimate the freedom from AF/AFL/AT recurrence post-90-day blanking period through 12 months post-ablation using the PulseSelect™ PFA System. 11. Estimate the freedom from AF/AFL/AT recurrence post-90-day blanking period through 12, 24, and 36 months post-ablation using the PulseSelect™ PFA System for subjects off all Class I/III AADs.
Follow-up Visits and Length of Follow-up	3-, 6-, 12-, 24-, 36-months
Interim or Final Data Summary
Actual Number of Patients Enrolled	180
Actual Number of Sites Enrolled	14
General
Study Status	Ongoing
Application Number / Requirement Number	P230023 / PAS002
Date Original Protocol Accepted	03/22/2024
Date Current Protocol Accepted	01/15/2025
Study Name	GORE TAMBE Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is prospective, single-arm, multicenter post-market study designed to collect clinical outcomes data from subjects who have been treated with the TAMBE Aortic Component (AC). The objective of the study is to confirm that the benefit-risk assessment of the GORE® EXCLUDER® Thoracoabdominal Branch Endoprosthesis (TAMBE Device) remains positive in real-world use and to ensure the adequacy of the TAMBE Device training program
Study Population	Patients who receive the GORE® EXCLUDER® Thoracoabdominal Branch Endoprosthesis (TAMBE Device) Aortic Component (AC) used in endovascular repair.
Sample Size	Number of subjects: 300 Assumptions for sample size estimation: NA Number of sites: 60; a minimum of 10 new sites (i.e., sites without prior TAMBE implant experience) will contribute to the data collection. Sites location: United States
Key Study Endpoints	Two co-primary endpoints are proposed: 5.4.1 Technical Success Defined utilizing criteria outlined in the SVS reporting standards, in which all of the following qualifying criteria are met (in the absence of surgical conversion or mortality, type I or type III endoleaks, branch occlusion, or graft limb obstruction): Successful access to the arterial system using remote arterial exposure, percutaneous technique, or open surgical conduits at index procedure. Successful delivery and deployment of the aortic stent graft and all modular stent graft components at index procedure. Successful side branch catheterization and placement of bridging stents with restoration and maintenance of flow in all intended target vessels at final completion angiography. Absence of type I or type III endoleaks at final completion angiography. Patency of all aortic modular stent graft components and intended side branch components at final completion angiography. 5.4.2 Clinical Success Defined utilizing criteria outlined in the SVS reporting standards, in which all of the following qualifying criteria are met from the initiation of the TAMBE Device implant procedure through 12 months post-index procedure: Technical success Absence of death from the initial procedure, secondary intervention, or aorta-related cause. Absence of persistent type I or type III endoleak Absence of lesion enlargement > 5 mm Absence of device migration > 10 mm Absence of failure due to device integrity issues Absence of lesion rupture Absence of conversion to open surgical repair Absence of permanent paraplegia Absence of disabling stroke Absence of "loss of function" or "end-stage renal disease" stage according to the RIFLE Classification following the index procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	6
Actual Number of Sites Enrolled	9
General
Study Status	Ongoing
Application Number / Requirement Number	P230035 / PAS001
Date Original Protocol Accepted	04/11/2024
Date Current Protocol Accepted	06/28/2024
Study Name	AGENT Post-Approval Surveillance Analysis
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The AGENT Post-Approval Surveillance Analysis is designed to assess acute and long-term safety and effectiveness outcomes associated with the use of the AGENTTM Paclitaxel Coated Balloon Catheter (AGENT DCB) in a routine clinical setting. This is an observational, prospective, non-randomized, multicenter registry surveillance analysis plan that will use data captured in the CathPCI Registry for AGENT DCB patients.
Study Population	All patients enrolled in the CathPCI Registry who undergo a PCI procedure and are treated with AGENT DCB during the 2-year enrollment period.
Sample Size	Number of subjects: 10,000 Assumptions for sample size estimation: n/a Number of sites/sites location: Data will be captured from all sites in the United States that participate in the CathPCI Registry and use AGENT DCB.
Key Study Endpoints	Safety Endpoints: All cause death, MI Effectiveness Endpoints: Revascularization
Follow-up Visits and Length of Follow-up	The CathPCI Registry collects data at baseline, procedure, and discharge. Event data occurring from years 1 and 2 post-procedure will come from the Centers for Medicare and Medicaid Services (CMS) claims data linkage
Interim or Final Data Summary
Interim Results	Safety Results: N/A Effectiveness Results: N/A
Actual Number of Patients Enrolled	17,850
Actual Number of Sites Enrolled	843
Patient Follow-up Rate	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P230035 / PAS002
Date Original Protocol Accepted	02/29/2024
Date Current Protocol Accepted
Study Name	AGENT IDE Continued Follow-up Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To assess the safety and effectiveness of the AgentTM Paclitaxel Coated PTCA Balloon Catheter compared to balloon angioplasty (POBA) in patients with in-stent restenosis (ISR) of a previously treated lesion of up to 26 mm in length (by visual estimate) in a native coronary artery 2.0 mm to 4.0 mm in diameter. A prospective, multi-center, 2:1 randomized (AGENT to POBA), controlled, single-blind, superiority trial.
Study Population	Subjects meeting the clinical and angiographic inclusion and exclusion criteria for the AGENT IDE trial
Sample Size	600
Key Study Endpoints	The primary endpoint is the 12-month Target Lesion Failure (TLF) rate, defined as any ischemia-driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave and non–Q-wave) related to the target vessel, or cardiac death. The MI events include the Peri-Procedural MI (PPMI) according to the SCAI MI definition and the spontaneous MI according to the 4th Universal MI definition.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Delayed
Application Number / Requirement Number	P230009 / PAS001
Date Original Protocol Accepted	09/20/2024
Date Current Protocol Accepted	09/20/2024
Study Name	Shield Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Shield post-approval study (PAS) is a prospective, longitudinal study supplemented with Real World Evidence (RWE). The study objective is to collect longitudinal data on subjects who receive the Shield test for colorectal cancer screening at two consecutive screening intervals and evaluate performance measures of the test at the second interval using colonoscopy as the reference method.
Study Population	Subjects between the ages of 45 and 81 at average risk of CRC
Sample Size	Number of subjects: 3,375 Assumptions for sample size estimation: Based on the expected prevalence of CRC (0.4%-0.7%) and targeted sample size for CRC established below, a total of at least 3375 subjects confirmed without a CRC diagnosis are expected to be available with a valid negative Shield test result at T0. Assuming T3 AA prevalence is at least 7% and non-AN prevalence is at least 88%, there will be at least 70 T3 AA subjects and at least 880 T3 non-AN subjects. Based on 70 AA subjects and 880 non-AN subjects, the half-width of the two-sided 95% confidence interval of AA sensitivity and AN specificity are expected to be within 8% and 2%, respectively, assuming AA sensitivity is 13%, and AN specificity is 90%. Number of sites: 40 sites Sites location: US.
Key Study Endpoints	Co-Primary performance measures: • Sensitivity for CRC, AA, and specificity for non-advanced neoplasia at T3. • Positive predictive value (PPV) for CRC, AA and advanced neoplasia at T3. • Negative predictive value (NPV) for CRC and advanced neoplasia at T3. Secondary performance measures: • Cumulative risk of false positive result (cFPR) and cumulative risk of a true positive result (cTPR) • Probability that a negative Shield result at baseline remains negative through 3 years • Probability that a negative Shield result at baseline (T0) results in no CRC through 3 years • Distribution of colorectal epithelial lesions (by Category) among positive Shield subjects at T0 and at T3 • Adherence to repeat Shield at T3 • Compliance to colonoscopy following a positive T0 Shield result • Cross-over to alternative screening methodologies (e.g., FOBT, colonoscopy, other) from T0 to T3 • The rate of no Shield result (e.g., invalid result) • Supplemental real world evidence study to evaluate PPV at T0 and T3
Follow-up Visits and Length of Follow-up	Patients will receive Shield test at T0 and T3. Colonoscopy will be performed for patients with positive Shield test and all patients at T3. Real-world evidence will be used to supplement the two years (T1 and T2) between T0 and T3 and the one year directly after T3 (T3-T4). Enrolled participant data will be gathered to not only follow participants between points of care for disease onset and/or progression but also to mitigate for data resulting from lost-to-follow-up or incomplete events using claims history in the T3-T4 period
General
Study Status	Study Pending
Application Number / Requirement Number	P230026 / PAS001
Date Original Protocol Accepted	08/02/2024
Date Current Protocol Accepted
Study Name	NSE Alpha New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This new enrollment study is a prospective, multicenter, single-arm, post-approval study to further evaluate the Lacrosse NSE ALPHA coronary dilation catheter in patients with stenotic coronary artery disease who are suitable candidates for percutaneous transluminal coronary angioplasty. The purpose of the study is to further evaluate the performance of Lacrosse NSE ALPHA for crossing and scoring stenotic lesions in complex lesions, with specific focus on understanding success of lesion crossing after encouraging physicians to plan for the use of extra delivery support in complex (moderate to severely calcified and/or tortuous) lesions. Patients will be consecutively enrolled and at least 30 patients will have both severe calcification and moderate/severe vessel tortuosity. The remaining patients will have lesions with complex characteristics (i.e., lesions characterized on a spectrum of moderate to severe calcification or vessel tortuosity).
Study Population	Patients with stenotic coronary artery disease who are suitable candidates for percutaneous transluminal coronary angioplasty. At least 30 patients with complex lesion characteristics will be enrolled. Outside of the minimum 30 patients enrolled for severe calcification and moderate/severe vessel tortuosity, the remaining patients will maintain complex lesion characteristics i.e., lesions characterized on a spectrum of moderate to severe calcification or vessel tortuosity.
Sample Size	Number of subjects: At least 100 subjects, including at least 30 subjects with complex lesion characteristics (i.e., lesions with both severe calcification and moderate/severe vessel tortuosity), will be consecutively enrolled and followed through discharge. Outside of the minimum 30 subjects with both severe calcification and moderate/severe vessel tortuosity, the remaining patients will have lesions with complex characteristics (i.e., lesions characterized on a spectrum of moderate to severe calcification or vessel tortuosity). Assumptions for sample size estimation: N/A Number of sites: Subjects will be enrolled at up to 10 sites, with no single sire enrolling more than 20% of the total enrollment. Sites location: U.S.
Key Study Endpoints	Primary Endpoints: Device procedural success, defined as: - Successful delivery, inflation, deflation, and withdrawal of the study balloon; and - No evidence of device-related vessel perforation, flow limiting dissection (grade C or higher, per Clinical Events Committee [CEC] adjudication) or reduction in thrombolysis in myocardial infarction (TIMI) flow from baseline (per core laboratory assessment); and - Final TIMI flow grade of 3 at the conclusion of the percutaneous coronary intervention (PCI) procedure (per core laboratory assessment). This endpoint will be presented as the proportion of subjects experiencing device procedural success. The proportion of target lesions meeting the primary endpoint will be concurrently calculated and presented as a secondary endpoint, as noted below. The following Subgroup and Sensitivity Analyses will be performed for the primary outcome: - Lesion complexity (overall); by operator grading and angiography (per core laboratory assessment) - Support catheter use (overall) - Support catheter use in complex lesions Secondary Endpoints: 12. Angiographic procedural success, defined as final diameter stenosis less than or equal to 50% in at least one of the Lacrosse NSE ALPHA attempted lesions following completion of the interventional procedure, including adjunctive stenting (per core laboratory assessment). 13. Major adverse cardiac events (MACE) through hospital discharge (per CEC adjudication). MACE is defined as a composite of: - All-cause death - Myocardial infarction - Clinically indicated target lesion revascularization 14. Stent thrombosis within the target vessel(s) through hospital discharge using ARC-2 definitions for definite and probable (per CEC adjudication). 15. Clinically significant arrhythmia (defined as those requiring intervention) through hospital discharge (per CEC adjudication). 16. Occurrence of Lacrosse NSE ALPHA balloon rupture (per device deficiency electronic case report form [eCRF]). 17. Change in minimum lumen diameter following use of Lacrosse NSE ALPHA catheter, measured by quantitative coronary angiography (per core laboratory assessment). 18. Device procedural success defined as for the primary endpoint, calculated and presented per target lesion. 19. Rate of device success and failure to cross lesions, including how this may relate to specific lesion characteristics (i.e., calcified and/or torturous). 20. Number of crossing attempts with the device, if any complications with crossing are observed. 21. Details regarding the use of support catheters and/or additional devices to enable lesion crossing after failure from use of device. 22. Physician a priori evaluation of crossing complexity. Secondary endpoints 1 through 5 are defined at the subject level and will be presented as the proportion of subjects experiencing the above events. In cases where multiple events per subject may be observed (e.g., adverse events), the main analysis will be at the subject level, but total event counts will also be reported. Secondary endpoints 6 through 11 are defined at the lesion level and statistical analyses of these endpoints will account for within-subject correlation as some subjects will have more than one target lesion, using generalized estimating equations with an exchangeable correlation structure.
Follow-up Visits and Length of Follow-up	The overall study duration, from screening the first patient to the final follow-up visit, data analysis, and final report, is expected to be approximately 27 months.
General
Study Status	Study Pending
Application Number / Requirement Number	P200029 S011/ PAS001
Date Original Protocol Accepted	04/10/2026
Date Current Protocol Accepted	04/10/2026
Study Name	ADVANCE-MCD Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design: Open label, single arm, prospective, US study to evaluate the safety and effectiveness of TheraSphere Microspheres administration using multicompartment dosimetry in patients with unresectable HCC. Primary Objective: To evaluate the safety of TheraSphere Microspheres treatment based on multicompartment dosimetry for pretreatment planning and post-treatment evaluation. Secondary Objective: To evaluate the effectiveness of the treatment procedure.
Study Population	Patients with solitary (1-8 cm diameter) unresectable hepatocellular carcinoma (HCC), Child-Pugh Score A cirrhosis, well-compensated liver function, no macrovascular invasion, and good performance status.
Sample Size	Number of subjects: 140 evaluable patients Assumptions for sample size estimation: A formal sample size computation, based on a pre-defined statistical hypothesis test, will not be performed for this study. However, a minimum of 140 evaluable patients are considered to provide sufficiently narrow 95% confidence intervals (CIs) for the number of patients with REILD Grade greater than or equal to 3 up to 4 months. Assuming an expected REILD Grade greater than or equal to 3 rate of 5%, the two-sided 95% CI would be 2.0% to 10.0% with 140 evaluable patients using the method of Clopper-Pearson. The study will be considered successful if the upper bound of the two-sided 95% CI for the REILD Grade greater than or equal to 3 rate is less than 10% up to month 4 after any TheraSphere Microspheres administration performed before progression. To account for an anticipated dropout rate of 5%, approximately 147 patients will be enrolled to ensure that at least 140 evaluable patients are available for primary safety analysis. Number of sites: 10 sites Sites location: US
Key Study Endpoints	Safety Endpoints Primary: The rate of Radioembolization Induced Liver Disease (REILD) Grade greater than or equal to 3 occurring up to 4 months after any TheraSphere Microspheres treatment administration before progression. Secondary: -Number of device and/or procedure# related Adverse Events (AEs) and Serious Adverse Events (SAEs) -Change from baseline in Albumin Bilirubin (ALBI) score. -The most severe grade of hepatoxicity after RE occurring during the 13-month follow-up period Effectiveness Endpoints Secondary: -Objective Response Rate (ORR) evaluated by localized mRECIST and mRECIST criteria -Duration of Response (DoR) evaluated by localized mRECIST and mRECIST criteria -Number of patients that become eligible for liver transplantation or liver resection -Histopathology evaluation for patients who had surgery -Overall survival
Follow-up Visits and Length of Follow-up	The study duration for each patient is expected to be approximately 14 months (1 month screening and 13 months follow-up).
General
Study Status	Ongoing
Application Number / Requirement Number	P230030 / PAS001
Date Original Protocol Accepted	06/18/2024
Date Current Protocol Accepted
Study Name	ADVENT Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of the ADVENT PAS study is to collect clinical data on safety, effectiveness, and procedural success of Boston Scientific FARAPULSE PFA System when used to perform pulmonary vein isolation (PVI) in the ablative treatment of de novo drug refractory, recurrent, symptomatic, paroxysmal atrial fibrillation (PAF). The study is designed as a prospective, non-randomized, multi-center, global, single arm registry.
Study Population	Patients being treated for paroxysmal atrial fibrillation (PAF). The study will include a diverse (i.e. race ethnicity, gender) patient population.
Sample Size	Number of subjects: A minimum of 220 de novo treatment subjects with at least 100 subjects participating in the LUX-Dx Sub-study Assumptions for sample size estimation: Performance goal of 11% for the primary safety endpoint and a performance goal of 50% for the primary effectiveness endpoint. Power of 0.85 to reject the null hypothesis at an alpha of 0.025. Number of sites: Up to 75 centers globally Sites location: At least 50% of study sites will be in the United States
Key Study Endpoints	Safety Endpoints Primary: Primary safety events will consist of a composite of the following serious procedure-related and device-related adverse events: Early Onset: Acute primary safety endpoint events, events occurring up to 7 days post-Index Procedure or hospital discharge, whichever is later, include: • Death • Myocardial infarction (MI) • Persistent phrenic nerve palsy* • Stroke/Cerebrovascular accident (CVA) • Transient ischemic attack (TIA) • Peripheral or organ thromboembolism • Cardiac tamponade / perforation • Pericarditis • Pulmonary edema • Serious vascular access complications • Heart block • Gastric motility / pyloric spasm disorders • Severe hemolysis with subsequent renal injury * A non-recovered phrenic nerve injury at 12 months post-Index Procedure will count as primary endpoint. The study will collect information on phrenic nerve palsy observed before the end of the Index Procedure, and in case it occurred, will track information for potential recovery during the study visits. Late Onset: Either of the following with an onset date any time through 12-month post-Index Procedure: • Atrial esophageal fistula • Pulmonary vein stenosis (greater than or equal to 70% reduction of diameter) Definition of the safety events can be found in Table 5.2-1. Effectiveness Endpoints Primary: The primary effectiveness endpoint is treatment success in treated subjects, defined as: • Acute Procedural Success* AND • Chronic Success, defined as freedom from the following: o After the Blanking Period up to the 12-Month Follow-up visit: ¿ Occurrence of any Detectable AF, AFL, AT • greater than or equal to 30 seconds in duration from any approved** clinical recording devices considered standard of care at the study center (excluding implantable loop recorders)** or • greater than or equal to 10-second of continuous AF, AFL or AT documented on any 12-lead ECG ¿ Following interventions: • Any cardioversion for AF, AFL or AT • Prescribed a higher dose of any failed Class I or III AAD documented at baseline or any new Class I or III AAD • Re-ablation for AF, AFL or AT (other than for CTI-dependent flutter only)***
Follow-up Visits and Length of Follow-up	All subjects treated with the FARAPULSE PFA System will be followed for 36 months. Subjects with a pre-existing LUX-Dx or a LUX-Dx inserted within 7 days of the ablation procedure will have arrhythmia recurrence monitored remotely via the LATITUDE Clarity System to assess for arrhythmia recurrence for up to 3 years. Subjects will undergo the index procedure and be followed at pre-discharge, 3 Month, 6 Month, 12 Month, 24 Month, and 36 Month visits. Attempt subjects will receive a phone call at 30 days post-procedure to verify adverse events and complications. The total study duration is expected to take 5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	228
Actual Number of Sites Enrolled	309
Patient Follow-up Rate	215 (94.3%) patients in active follow-up
General
Study Status	Completed
Application Number / Requirement Number	P230021 / PAS001
Date Original Protocol Accepted	12/26/2023
Date Current Protocol Accepted
Study Name	VIVID Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To evaluate the long-term safety and effectiveness of the Duo Venous Stent System. The study is a prospective, multi-center follow-up of the VIVID (G190030) that enrolled 162 subjects from 30 investigational sites in the United States and European Union.
Study Population	All remaining subjects treated with Duo Venous Stent System in the VIVID trial active at the end of 12 months evaluation. There is no comparator group for the continued follow-up study.
Sample Size	One hundred and fifty two (152) active subjects from the VIVID IDE trial.
Key Study Endpoints	Endpoints to be assessed at 24 and 36 months include: • Freedom from clinically driven target lesion revascularization (CD-TLR) • Primary patency • Primary assisted patency • Secondary patency • Stent fracture, migration, and embolization • Changes in CEAP, Villalta, VCSS pain score, and VEINES QOL • Venous Ulcer Assessment • Clinically driven target vessel revascularization (CD-TVR) • Adverse Events
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	162 - Non-thrombotic – 104 subjects - Acute thrombotic – 16 subjects - Chronic post-thrombotic– 42 subjects
Actual Number of Sites Enrolled	32
Patient Follow-up Rate	77.2% (125/162) at 24 months 73.5 (119/162) at 36 months
Final Safety Findings	Kaplan Meier (KM) estimate of freedom from MAEs in the ITT population was 89.7% (95% CI: 82.8, 94.0) at 36 months. KM estimate of freedom from CD-TLR and CD-TVR at 36 months in ITT population was 91.1% (95% CI: 84.4, 95.0) and 90.5% (95% CI: 83.7, 94.5) respectively. Venous Ulcer Assessment: For venous ulcers present at baseline or new during follow-up, most improved into the “dressed”, “healed”, or “improved” categories and no wounds were rated at “worsened” and “amputated”. Only two subjects developed new wounds during the 12- month period and two subjects had new wounds develop during the 24- to 36-month follow-up period. There were no unanticipated adverse device events
Final Effect Findings	Primary Effectiveness Endpoint: Primary patency at 24 months and 36 months in the ITT Subjects was 90.0% (108/120) and 86.1% (87/101) respectively. Secondary Effectiveness Endpoints Primary assisted patency in the ITT subjects was 95.8% (113/118) [95% CI:90.4, 98.6] at 24- months and 96.9% (94/97) [95% CI: 91.2, 99.4] at 36 months. Secondary patency in the ITT subjects at 24 and 36 months was 97.5% (115/118) [95% CI: 92.7, 99.5] and 96.9% (94/97) [95% CI: 91.2, 99.4] respectively. Through the 36-month follow-up, there were no stent fractures, migration or embolization. CEAP classification improved from baseline to 12-, 24-, and 36-months. At baseline 97.6% of ITT subjects were scored in the more severe CEAP categories: C3 – Edema; C4 – Change in skin and subcutaneous tissue secondary to chronic venous disease; C5 – Healed; and C6 – Active venous ulcer. At 24 months, 52% (66/126) were in the C0-C2 categories. At 36 months, 59% (68/115) were in the C0-C2 categories ITT subjects showed significant improvement from baseline to 12 months in all five dimensions of the EQ-5D-3L score (p<0.0171) and the EQ-VAS health state score (p<0.0001). Positive changes were sustained through 36-month follow-up. The Villalta score significantly improved (p<0.0001) from a baseline median score of 10 (range 1-23) which was in the mild/moderate PTS severity range to a 12-month median of 2 (range 0-20), which was in the no PTS range. Through 36 months positive changes were sustained (<0.0001). The VEINES SYM scale score in ITT subjects significantly improved (p<0.0001) from a median score at baseline of 51 (range 2-100) to 83 (range 9-100) at 12 months. The VEINES QOL scale in ITT subjects also significantly improved (p<0.0001) from a median baseline score of 52.5 (range 2.1-96.5) to a median score at 12 months of 82.7 (range 12.7-100.0). Positive changes were sustained through 36-month follow-up
Study Strengths & Weaknesses	This was a prospective, multi-center, single-arm study. The study met both primary safety and effectiveness endpoints. The freedom from MAEs (FAS cohort) at 30 days was 98.7% with lower 95% confidence bound of 95.5% versus 89% performance goal, PG (p<0.0001). Primary patency at 12 months (FAS cohort) was 90.2% with a 95% lower confidence bound of 83.1% versus 77.3% PG (p=0.0002).
Recommendations for Labeling Changes	Labeling update is recommended with long-term results of the VIVID Continued Follow-up study.
General
Study Status	Delayed
Application Number / Requirement Number	P230032 / PAS001
Date Original Protocol Accepted	02/16/2024
Date Current Protocol Accepted	05/20/2026
Study Name	AvertD Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS for AvertD is a prospective open-label study intended to assess AvertD performance and achieve the following goals: Goal 1: Assess device performance in the “real world” in the intended use population. Goal 2: Assess device performance across representative demographic subgroups. Goal 3: Assess impact of device results on healthcare provider (HCP) prescribing practices. Goal 4: Assess patient and HCP comprehension of the device labeling.
Study Population	Patients who are prescribed AvertD as part of their clinical care prior to being prescribed a first prescription of oral opioids for 4-30 days for acute pain management.
Sample Size	A minimum of 3000 subjects targeting the identification of a minimum of 50 OUD positive subjects each in White, African-American, Other Racial Subgroups, and Hispanic/Latino racial and ethnic subgroups.
Key Study Endpoints	The Primary Endpoints for the AvertD PAS for each Goal are described below: Goal 1: Sensitivity and specificity of AvertD in the overall study population Goal 2: Sensitivity and specificity of AvertD in the representative demographic subgroups Goal 3: Difference, if any, in HCPs’ opioid prescribing practices for the patient prior to and after receiving AvertD test results Goal 4: The percentage of correct responses for participants and for HCPs on a knowledge test
Follow-up Visits and Length of Follow-up	One virtual study visit is planned for after subject enrollment and baseline assessment, but before the subject’s procedure for which they were provided an opioid prescription. This visit is intended to record the AvertD test results and the details of the planned procedure as well as record the HCP’s Opioid prescription details after receipt of the AvertD test results. One virtual follow-up is planned ~14 days after the patient’s procedure to confirm if the patient filled their opioid prescription and used the opioids as instructed. An optional second follow-up is available ~30 days after the patient’s procedure for subjects who had not fill or take opioids at the time of the first 14 day follow up. For the next 5 years, patients will be assessed annually each year (remotely) using the M.I.N.I. Questionnaire following the DSM 5 criteria to determine if the participant has developed OUD.
General
Study Status	Ongoing
Application Number / Requirement Number	P230036 / PAS002
Date Original Protocol Accepted	06/21/2024
Date Current Protocol Accepted	08/08/2025
Study Name	Esprit BTK-PAS - New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multi-center post approval observational study. To assess the continued safety and effectiveness of the Esprit BTK System under commercial use, in the planned treatment of diseased infrapopliteal lesions in patients with CLTI in a real-world setting.
Study Population	Subjects from all genders with arterial narrowing in infrapopliteal lesions causing critical limb-threatening ischemia. Subjects must meet all eligibility criteria and provide written informed consent prior to discharge. Subjects with Rutherford Becker clinical category 6 can be treated but are not to exceed 10% of the registered population. General Inclusion Criteria 1. Subject must provide written informed consent prior to any study- specific procedures which are not considered standard of care at the site. a. Informed consent can be obtained up to 3 days post- procedure or prior to discharge whichever comes first. b. Subject, or a legally acceptable representative must provide written informed consent per site IRB/EC requirements. 2. Subject must be at least 18 years of age. 3. Subject has evidence of symptomatic Critical Limb-Threatening Ischemia (CLTI) with infrapopliteal lesions. Anatomic Inclusion Criteria 1. Subjects who have lesion(s) in an infrapopliteal vessel with reference vessel diameter greater than or equal to 2.5 mm and less than or equal to 4.0 mm. 2. Target lesion(s) must have greater than or equal to 70% stenosis, per visual assessment at the time of the procedure. If needed, quantitative imaging (angiography and intravascular imaging) can be used to aid accurate sizing of the vessels. General Exclusion Criteria 1. Subjects who have contraindications to the Esprit BTK system per the instructions for use (IFU). 2. Subject is currently participating in another clinical investigation that has not yet completed its primary endpoint. 3. Subject or Legally Acceptable Representative (LAR) is unable or unwilling to provide written consent prior to enrollment. 4. Subject with life expectancy less than or equal to 1 year. 5. Subject with an unsalvageable limb (as per physician assessment at the time of the index procedure), who is likely to get a below-the-knee amputation. Anatomic Exclusion Criteria 1. Subject has in-stent restenosis in the target vessel or requires treatment with a metallic stent in the target vessel during the index procedure. 2. Subject had been previously treated with Esprit BTK scaffold(s) within the past 30 days in the same vessel. Full Analysis Set (FAS) Population is defined as subjects who are registered in the study. Modified Full Analysis Set (mFAS) Population includes subjects in the FAS population with all inflow and outflow lesion(s) treated successfully as well as successful target lesion(s) treatment with the study device at the exit from the procedure room. Per-protocol (PP) Population includes subjects in the FAS population without protocol deviation on anatomic inclusion/exclusion criteria or protocol deviations on informed consent.
Sample Size	Number of subjects: Approximately 200 patients with a minimum of 50% of patients in the US. No site may register more than 20% of the total registered subjects. A total sample size of 200 could provide sufficient accuracy in assessing both the primary effectiveness and safety endpoint. Given a true rate of approximately 93% and 5% for the primary effectiveness endpoint and the primary safety endpoint respectively, the precision (half-width of the 2-sided 95% CI) is approximately 3.3% for both. The study will be conducted at up to 50 sites in the United States (US). Additional sites may be added outside of the US (OUS).
Key Study Endpoints	Primary Effectiveness • Freedom from clinically driven target lesion revascularization (CD-TLR) at 1 year. Primary Safety • Major Adverse Limb Events (MALE) at 6 months + Peri-Operative Death (POD) at 30 days. Secondary Endpoints to be evaluated at each follow-up timepoint • All-cause mortality • Amputation (minor, major) • Amputation-free survival • Ankle-Brachial Index (ABI)/Toe-Brachial Index (TBI) progression over time • Rutherford Becker category evolution over time • Wound healing, as assessed by investigator The following adverse events will be reported in this study. • All serious adverse events regardless of the relationship to the device/procedure. • All non-serious adverse events related to the device/procedure and unknown relationship. • Additional specific adverse events involving the index limb, regardless of seriousness or relationship to device/procedure, through 3- year post-procedure: revascularization; major limb intervention; amputation; stent/scaffold thrombosis; new wound
Follow-up Visits and Length of Follow-up	Discharge, 30 days, 90 days (only for subjects with index wound), 6 months, 1 year, 2 years, 3 years. • Office visits are strongly recommended. Phone call visit is only allowed if all attempts failed and no other options are available. • To aid in follow-up compliance, if necessary, an independent service may be utilized to provide in-home visits for clinical follow-up.
Interim or Final Data Summary
Interim Results	Safety Results: CEC Adjudicated Events The CEC evaluated 52 events in 41 subjects at the time of the data cut-off for this report. There were 15 index Limb reinterventions in 12 subjects, 5.7% (12/210). All of these were revascularizations, 5.7% (12/210). There were no major reinterventions, 0.0% (0/210). There were index limb amputations in 15 subjects, 7.1% (15/210). This includes 6 major amputations in 6 subjects, 2.9% (6/210) and 10 minor amputations in 9 subjects, 4.3% (9/210). Twenty-one (21) of 24 deaths were adjudicated as of this report, 10.0% (21/210).
Actual Number of Patients Enrolled	210
Actual Number of Sites Enrolled	4135
Patient Follow-up Rate	Visit-specific Rate at 6 months: 73.6% (81/110) Population level/Potential rate at 6 months: 86.2% (181/210)
General
Study Status	Ongoing
Application Number / Requirement Number	P240003 / PAS001
Date Original Protocol Accepted	08/28/2024
Date Current Protocol Accepted
Study Name	Continued Follow-up of the Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	Single-arm, prospective, non-randomized, multi-center, open-label, pivotal study Continued follow-up of premarket cohort - Minima Stent System
Study Population	The study population was comprised of subjects with a clinically relevant pulmonary artery or aortic vascular stenosis who were indicated for treatment. For each treatment location (pulmonary artery or aortic vascular), a minimum of 10 subjects was required per the study protocol.
Sample Size	42 subjects enrolled For the study to successfully pass, all both Safety & Efficacy Primary Endpoints must reject their null hypothesizes concurrently, using the appropriate one-sided significance level for each endpoint (2.5% and 2.5% respectively); therefore, power calculations were performed for each hypothesis statement, based on the normal approximation to the binomial distribution, and combined using the Inclusion-Exclusion Rule (shown below), assuming the 2 endpoints are independent, to determine the power of the study at each sample size. P(A U B) = P(A) + P(B) - P(AB) Where: P(A) = ßEfficacy P(B) = ßSafety P(AB) = ßEfficacy x ßSafety P(A U B) = ßEfficacy & Safety Study Power = 1 - ßEfficacy & Safety Using the assumptions above, analysis shows a minimum of 36 subjects will provide 90% power to meet both the primary efficacy and safety performance goals. To account for approximately 15% attrition rate, a maximum of 42 United States subjects (42=36(100%+15%)) were allowed to be implanted, prior to further authorization.
Key Study Endpoints	The primary efficacy endpoint is assessed as the rate of clinical success, with the performance goal defined as a clinical success rate of greater than 77%. Clinical success was defined as: • Stenosis relief, defined by stent outer diameter = 75% o the surrounding vessel immediately after deployment • Freedom from open surgical intervention required to treat Minima Stent dysfunction through 6 months • Maintenance of stented vessel diameter = 50% of post-implant diameter at 6 months; as measured using CT angiography and/or angiography. The primary safety endpoint was assessed as the percentage of cases with freedom from procedure- or device-related SAEs resulting in an event listed below, with the performance goal defined as greater than 78% of cases: • Death • Cardiac arrest and/or emergency ECMO cannulation • Stroke • Limb loss • Vessel dissection of target lesion • Device thrombosis/occlusion • Cardiac perforation requiring percutaneous or open surgical intervention • Persistent cardiac arrhythmia requiring a pacemaker The secondary efficacy endpoints are as follows: • Peak-to-peak pressure gradient (ventricle to arterial or arterial to arterial) < 20 mmHg after stent placement, when applicable. • Successful stent re-dilation (when indicated) at re-catheterization, defined as an increase in the intra stent angiographic luminal diameter of within 2 mm of the adjacent native vessel diameter immediately after re-dilation. The secondary safety endpoints are as follows: • Free from stent embolization or migration through 6 months. • Free from stent fracture that led to reintervention through 6 months • Free from non-elective Minima Stent explant at 90-days post re-dilation • Free from procedure- or device-related SAE during re-dilation that results in the following: o Death o Cardiac arrest and/or emergency ECMO cannulation o Stroke o Limb loss o Vessel dissection of target lesion o Device thrombosis/occlusion o Cardiac perforation requiring percutaneous or open surgical intervention o Persistent cardiac arrhythmia requiring a pacemaker
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P240003 / PAS002
Date Original Protocol Accepted	11/08/2024
Date Current Protocol Accepted
Study Name	New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	Single arm, prospective, non-randomized, multi-center, open-label, post approval study To collect post-market, real-world safety and effectiveness data of the Minima Stent and Minima Pro Stent when used in treatment of native and post-operative congenital vascular stenoses within the aortic and pulmonary circulations, in neonates, infants, and small children.
Study Population	The study population will comprise patients treated with the Minima Stent System and the Minima Pro Stent System.
Sample Size	Minimum 100 patients with minimum of 15 subjects enrolled with the 10mm Minima Pro Stent System Number of sites: N/A Sites location: N/A
Key Study Endpoints	Safety Endpoints Primary: Freedom from procedure- or device-related SAEs resulting in an event listed below: •Death •Cardiac arrest and/or emergency ECMO cannulation •Stroke •Limb loss •Vessel dissection of target lesion •Device thrombosis/occlusion •Cardiac perforation requiring percutaneous or open surgical intervention •Persistent cardiac arrhythmia requiring a pacemaker Secondary: • Freedom from intraprocedural stent movement to non-intended location during the procedure. • Freedom from postprocedural stent embolization or migration • Freedom from stent fracture that led to reintervention • Freedom from non-elective Minima Stent or Minima Pro Stent explant • Freedom from procedure- or device-related SAE during re-dilation that results in the following: o Death o Cardiac arrest and/or emergency ECMO cannulation o Stroke o Limb loss o Vessel dissection of target lesion o Device thrombosis/occlusion o Cardiac perforation requiring percutaneous or open surgical intervention o Persistent cardiac arrhythmia requiring a pacemaker Effectiveness Endpoints Primary: Acute device success as defined by: •Stenosis relief, defined by stent outer diameter = 75% of the normal surrounding vessel immediately after deployment. •Freedom from open surgical intervention required to treat Minima Stent or Minima Pro Stent dysfunction at implantation Secondary: •Peak-to-peak pressure gradient (ventricle to arterial or arterial to arterial) < 20 mmHg after stent placement, in treatment of Aortic Coarctation, when applicable. •Successful stent re-dilation (when indicated) at re-catheterization, defined as angiographic improvement of stenosis to >50% of the normal surrounding vessel. •Maintenance of stented vessel diameter = 50% of post implant diameter at the time of re-dilation (pre re-dilation).
Interim or Final Data Summary
Interim Results	Safety Results: N/A Effectiveness Results: N/A
Actual Number of Patients Enrolled	4
Actual Number of Sites Enrolled	Following protocol approval, 15 sites were recruited to take part in the Minima Post-Approval Study. The first site completed activation activities on April 8, 2025 and there is only one site pending activation as of August 27, 2025. The last site is only pending IRB approval and is anticipating approval within the next week. This site, like the others, began site initiation activities in November of 2024 following Protocol Approval and experienced numerous delays within their site due to new processes and resourcing issues. The 14 other sites have completed IRB Approvals and are able to enroll patients.
Patient Follow-up Rate	N/A
General
Study Status	Study Pending
Application Number / Requirement Number	P240006 / PAS001
Date Original Protocol Accepted	05/09/2025
Date Current Protocol Accepted	02/12/2026
Study Name	VP PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center, observational study of the Biosense Webster VARIPULSE™ Catheter system to evaluate long term safety and effectiveness for the treatment of symptomatic paroxysmal atrial fibrillation (PAF). The study will enroll 276 adult subjects (age = 22 years) who intend to undergo their de novo pulmonary vein isolation (PVI) using the VARIPULSE™ Catheter system. After the study ablation procedure, subjects will enter a 2-month blanking period (Day 0-60) followed by a 36-month evaluation period (Days 61-1095). The primary objective of this clinical investigation is to evaluate the long-term safety and effectiveness of the VARIPULSE™ Catheter system for pulmonary vein isolation (PVI) in the treatment of subjects with symptomatic PAF.
Study Population	Subjects undergoing electrophysiology mapping and pulsed field ablation (PFA) for treatment of symptomatic PAF refractory, intolerant, or contraindicated to at least one Class I or Class III antiarrhythmic drugs (AADs). Of the enrolled subjects, a subset of 40 subjects will undergo echocardiography imaging at baseline and 12 month post index procedure for assessment of ventricular wall motion abnormality. Inclusion Criteria 1. Symptomatic paroxysmal AF (episode terminates spontaneously within 7 days) who, in the opinion of the investigator, are candidates for catheter ablation for AF. 2. Refractory, intolerant, or contraindicated to Class I/III AAD 3. Age = 22 years 4. Willing and capable of providing consent 5. Able and willing to comply with all pre-, post- and follow-up testing and requirements. Exclusion Criteria 1. Previously diagnosed with persistent or long-standing persistent AF (> 7 days in duration) 2. Previous surgical or catheter ablation for AF 3. Significant congenital anomaly or medical problem that in the opinion of the investigator would be a contraindication to catheter ablation for AF. 4. Current enrollment in an investigational study evaluating another device or drug. 5. Life expectancy less than 12 months 6. Any contraindications noted in the clinical investigation protocol.
Sample Size	Number of subjects: 276 Assumptions for sample size estimation: • At least 50% female subjects. • Each site to contribute no more than 15% of target enrollment. Number of sites: Up to 30 Sites’ location: United States Total duration: Approximately 24 months of enrollment and 36 months of follow-up. The targeted enrollment timeline following first site activation is as follows: • First subject enrolled within 6 months. • 20% of subjects enrolled within 12 months. • 50% of subjects enrolled within 18 months. • 1000% of subjects enrolled within 24 months.
Key Study Endpoints	Safety Endpoints Primary: The primary safety endpoint is the occurrence of early onset PAEs (within seven days of the index ablation procedure, unless otherwise indicated using the VARIPULSE™ Catheter system). PAEs include the following: • Esophageal perforating complications (atrio-esophageal fistula, esophago-pericardial fistula). • Cardiac tamponade/perforation. • Death (device or procedure related). • Major vascular access complication/bleeding. • Myocardial infarction (MI). • Pericarditis. • Heart block. • Phrenic nerve paralysis (permanent). • Pulmonary vein stenosis. • Stroke/cerebrovascular accident (CVA). • Thromboembolism. • Transient ischemic attack (TIA). • Pulmonary edema (respiratory insufficiency. • Vagal nerve injury/gastroparesis. Secondary: • Occurrence of the following procedure- and/or device-related safety events: o Cardiac tamponade/perforation in women undergoing PAF ablation using the VARIPULSE™ Catheter system. o Early mortality occurring within 3 months following ablation procedure using the VARIPULSE™ Catheter system. o Cardiac arrest occurring following ablation procedure using the VARIPULSE™ Catheter system. o Renal failure occurring within 30 days following ablation procedure using the VARIPULSE™ Catheter system. o Occurrence of serious device- or serious procedure-related adverse events within 12 months following ablation procedure using the VARIPULSE™ Catheter system. o Occurrence of new ventricular wall motion abnormality seen on echocardiogram within 15 months following index ablation procedure using the VARIPULSE™ Catheter system for subjects in the transthoracic echocardiogram (TTE). o Occurrence of unanticipated adverse device effects (UADEs). Effectiveness Endpoints Primary: The primary effectiveness endpoint is freedom from documented (symptomatic and asymptomatic) atrial tachyarrhythmias (AF, atrial tachycardia (AT), or atrial flutter (AFL) of unknown origin*) episodes during the effectiveness evaluation period (Day 61-1095 post-index procedure). *AFL of unknown origin is defined as all AFL except those cavotricuspid isthmus-dependent AFL as confirmed by 12-lead electrocardiogram (ECG) and entrainment maneuvers in an electrophysiology (EP) study. Secondary: • Occurrence of the following procedure- and/or device-related safety events: o Acute procedural success o 12 month and 24 month effectiveness success o 36 month clinical success o 12 month, 24 month, and 36 month effectiveness success off class I/III AAD o 36 month effectiveness success and freedom from additional failure modes o First Pass Isolation o Non-study Catheter Use o Repeat Ablation Procedures o Procedural efficiency
Follow-up Visits and Length of Follow-up	Study and follow-up visits will be performed at pre-ablation, procedure, pre-discharge, 2 months, 6 months, 12 months, 24 months, and 36 months. Transthoracic echocardiogram will be collected at 12 months.
General
Study Status	Ongoing
Application Number / Requirement Number	P240012 / PAS001
Date Original Protocol Accepted	01/30/2025
Date Current Protocol Accepted	06/22/2026
Study Name	AeroPace Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A single-arm, prospective, multicenter cohort study to assess the 30-day safety and effectiveness of the AeroPace System in patients on mechanical ventilation (MV) at least 96 hours and who have not weaned. This is a study to evaluate the safety and effectiveness of the AeroPace System in the post-market setting. Safety and effectiveness outcomes will be compared to data from historical RESCUE 3 Control group subjects.
Study Population	Patients 18 years or older on mechanical ventilation at least 96 hours and who have not weaned.
Sample Size	Number of subjects: Up to 120 enrolled subjects in order to yield 100 subjects who have been treated with the AeroPace System. Number of sites: Up to 20 centers Sites location: United States
Key Study Endpoints	Safety Endpoints Primary: Incidence of SAEs including but not limited to vascular, infection and cardiac events. Secondary: • Incidence of device/procedure related SAEs (compared to RESCUE 3 Treatment group) • Mortality through Day 30 Effectiveness Endpoints Primary: Proportion of subjects successfully weaned by Day 30. Secondary: - Days on MV from time of initial placement procedure through Day 30 - Incidence of reintubation/reinstatement of MV through Day 30 - Incidence of tracheostomy from enrollment through Day 30 - ICU/hospital days from initial placement procedure to Day 32
Follow-up Visits and Length of Follow-up	Maximum study duration for any subject is 32 days. Follow-up will be through: - Withdrawal or death - Unsuccessful placement of the AeroPace Catheter – 48 hours after initial placement attempt - Successful wean/Unsuccessful wean/Transfer – to Day 32 Successfully weaned is defined as passing an SBT, or removed from MV, and not returned to MV within 48 hours.
General
Study Status	Study Pending
Application Number / Requirement Number	P150048 S092/ PAS001
Date Original Protocol Accepted	02/06/2026
Date Current Protocol Accepted	02/06/2026
Study Name	EHR-Based New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	EHR-Based New Enrollment Study. The objective of this study is to assess the real-world performance of the TRIFORMIS RESILIA Tricuspid Valve, with an emphasis on valve hemodynamic performance
Study Population	Patients implanted with the TRIFORMIS RESILIA Tricuspid Valve.
Sample Size	A minimum of 75 evaluable patients
Key Study Endpoints	Hemodynamics (discharge, 30 days, and 1 year, at a minimum), all-cause mortality, cardiovascular mortality, all-cause readmission (30 days only), valve-related heart failure hospitalization, freedom from tricuspid valve reintervention, and major valve-related events (including valve thrombosis, endocarditis, thromboembolism, and hemorrhage).
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P150048 S092/ PAS002
Date Original Protocol Accepted	02/06/2026
Date Current Protocol Accepted	02/06/2026
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry-Based Real-World Use Surveillance. The surveillance will be carried out to assess the real-world performance of the TRIFORMIS RESILIA Tricuspid Valve.
Study Population	Patients implanted with the TRIFORMIS RESILIA Tricuspid Valve
Sample Size	All consecutive patients implanted with the device up to the first 3 years following commercial distribution of the device, who are entered into the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD; enrollment period).
Key Study Endpoints	The clinical data through 30 days (i.e., tricuspid regurgitation grade, left ventricular ejection fraction, all-cause readmission, and pulmonary embolism) will be collected through the ACSD. The follow-up data (including all-cause mortality, cardiovascular mortality, tricuspid valve reintervention, and all-cause reoperation) from year 1 through year 5 post-procedure will be obtained through the ACSD (for freedom from tricuspid valve reintervention and all-cause reoperation) and linkage with the National Death Index (for all-cause mortality and cardiovascular mortality).
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P240011 / PAS001
Date Original Protocol Accepted	09/18/2025
Date Current Protocol Accepted	09/18/2025
Study Name	TITAN 2 Pivotal Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was initiated prior to device approval and is a single-arm, multi-center clinical study. It was conducted at 25 sites and enrolled 188 subjects. One hundred and twenty-six (126) subjects were implanted in this study. The 12-month outcomes from the study were used to support PMA approval. The 24-months follow-up data from this study must be submitted to assess the continued safety and effectiveness of the Medtronic Altaviva System.
Study Population	Male and Female patients with urge urinary incontinence (UUI)
Sample Size	188 subjects were enrolled, and 126 subjects were implanted
Key Study Endpoints	Effectiveness • Percentage of subjects who experience an improvement in UUI episodes (therapy responders) of at least 50% or more (primary) • Percentage of subjects who experience an improvement in OAB-q HRQL of at least 10 points. • Change from baseline in quality of life as measured and assessed by the total OAB-q HRQL (health related quality of life) score • Change from baseline in mean number of UUI episodes • Subgroup analysis of the UUI responder rate for the patient population 65 and older. Safety • Comprehensive summary of all adverse events (AEs) for the duration of study participation, including all device- or procedure-related AEs and device-, procedure-related serious adverse events. • Revision rates • Explantation rates Device Use ¿ Device parameters including but not limited to voltage, pulse width, frequency, and stimulation duration/day
Follow-up Visits and Length of Follow-up	24-months follow-up of the pivotal study
Interim or Final Data Summary
Actual Number of Patients Enrolled	188
Actual Number of Sites Enrolled	29
Patient Follow-up Rate	55.3% (104/188) through 24 months
Final Safety Findings	Of the 188 subjects enrolled, a total of 126 subjects were implanted during this study. 718 total adverse events (AEs) were reported in 188 subjects from enrollment through study completion (24 months). Following implantation, there were 226 AEs in 71% (90/126) of subjects through 6 months, 439 AEs in 85% (107/126) of subjects through 12 months, and 685 AEs in 91% (115/126) of implanted subjects through 24 months. Device and Procedure-related AEs were reported in 17% (21/126) of subjects at 6 months, 20% (25/126) at 12 months, and 24% (30/126) through study end, with the highest incidence occurring in the first 3 months post-implant. The most common device and procedure-related AEs were implant site infection (4%, 5/126) and device-related pain (4%, 5/126). Two device or procedure related serious adverse events (SAEs) were reported throughout the entire study period (Clostridium difficile colitis, implant wound infection resulting in device explant). All device and procedure-related AEs were classified as mild (grade 1, 9% (11/126) of subjects) or moderate (grade 2, 18% (23/126) of subjects). More severe events (grades 3-5) occurred in 38% (48/126) of subjects but were not device related. Through 24 months, 3 subjects required system modifications due to device and procedure-related AEs, with 18 total explanations performed primarily at the patient’s request.
Final Effect Findings	The urge urinary incontinence (UUI) responder (i.e., more than 50% improvement in daily UUI episodes as compared to baseline) rates decreased from 58.4% (73.5/126) at 6 months to 55.5% (70/126) at 24 months in the 'all implanted' analysis set (N=126). The average change in UUI episodes/day from baseline was 2.7 at 6 and 12 months and 2.6 at 24 months. Results from the Overactive Bladder Questionnaire (OAB-q) scores were overall stable with the average score being 71.1 at 12 months and 72.7 in 24 months The OAB-q responder (i.e., an improvement in OAB-q score of at least 10 points) rate at 24 months decreased to 59% (74/126) from 65.1% (82/126) at 12 months and 70.6% (89/126) at 6 months follow-up. Effectiveness differences were observed between age-related subgroups. At 24 months, patients over 65 years old showed 49% (33.3/68) UUI response rates compared to 63.2% (36.6/58) in younger patients. Additionally, the stimulation amplitude increased over time. The average value of the stimulation amplitude increased from 5.5 mA at 1 month to 8.4 mA at 24 months.
Study Strengths & Weaknesses	Strengths: Prospective, multicenter clinical study. High rate of follow-up at 24 months (104 of 126 (82.5%) implanted subjects completed 24 month followed up). Weaknesses: Single-arm study, therefore, in the absence of a control group, the study endpoints may be subject to placebo effect. Given the UUI responder rate over time and effectiveness differences in subjects >65 years old, longer-term effectiveness data are necessary to determine whether the device’s effectiveness continues to diminish over time and with age.
Recommendations for Labeling Changes	The sponsor should revise the labeling to include the 24-month data from the pivotal study in the labeling.
General
Study Status	Ongoing
Application Number / Requirement Number	P240011 / PAS002
Date Original Protocol Accepted	09/18/2025
Date Current Protocol Accepted	03/26/2026
Study Name	ENDURANCE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary purpose of this prospective, multicenter study is to assess the long-term safety and effectiveness of the Altaviva system for the treatment of UUI.
Study Population	Male and Female patients with urge urinary incontinence (UUI)
Sample Size	Approximately 256 subjects at approximately 30 sites will be enrolled in the study to achieve a minimum of 170 implanted subjects to account for about 33% attrition between enrollment and implant. At least 90 subjects must be followed to 60 months post implant. Additionally, a least 50% of enrolled subjects must be aged 65 years or older. To ensure that a minimum of 50% of enrolled subjects are aged 65 years or older, enrollment may be opened exclusively to individuals within this age group during the study if needed.
Key Study Endpoints	Primary Effectiveness Endpoint: UUI responder rate annually through 60 months after implant. A UUI responder is defined as having at least 50% improvement from baseline in daily UUI episodes. The following additional effectiveness endpoints will be evaluated annually through 60 months: -Change from baseline in daily UUI episodes, -UUI responder rate for subjects aged 65 and older, -Change in OAB-q HRQL, -Other urinary symptoms as measured with voiding diaries: Change from baseline in daily urinary frequency (UF) episodes in subjects with UF at baseline, Change in daily urgent episodes, Change in urinary urgency based on the Indevus Urgency Severity Scale (IUSS), Complete continence rate, Change in nocturia rate, -Change in urinary urgency as measured with the Urgency Perception Scale (UPS), -Change in general mental health as measured with GHQ-12 overall total score (for 6-month, 12-month and 60-month visits only) -Change in sexual matters quality of life as measured with ICIQ-FLUTSsex or ICIQMLUTSsex overall total score (for 6-month, 12-month and 60-month visits only) -Change in work productivity and activity impairment as measured with the WPAI:SHP (for 6-month, 12-month and 60-month visits only) -Patient reported impression of improvement as measured with the Patient Global Impression of Improvement (PGI-I) questionnaire, -Patient satisfaction -Physician/site staff satisfaction (for implant and 12-month visits only) -Device and system usage data Safety Endpoints: Procedure-, device-, and/or therapy-related adverse events through 60 months by reporting the number of events, and number and percentage of subjects with events. Serious adverse events through 60 months by reporting the number of events, and number and percentage of subjects with events
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Delayed
Application Number / Requirement Number	P150038 S037/ PAS001
Date Original Protocol Accepted	03/23/2026
Date Current Protocol Accepted	03/23/2026
Study Name	FREEDOM Study (PD018)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design: An international prospective, multi-center, assessor-blinded, two-stage randomized controlled trial evaluating successive Exablate treatment (first and second side) versus BMT. Primary Objective: To compare the effect of the MDS-UPDRS Part III Upper Lower Extremity (ULE) score in the OFF-medication state for the treated side at Month 3 versus respective baseline for each Exablate PTT Intervention: (1) Active Group 1 (1st Side Exablate) vs. Control Group 1 (BMT) (2) Active Group 2 (2nd Side Exablate) vs. Control Group 2 (1st Side + BMT). These combined comparisons are intended to demonstrate the overall therapeutic impact of Exablate PTT interventions.
Study Population	Patients diagnosed with idiopathic Parkinson’s disease experiencing bilateral motor symptoms and motor complications not adequately controlled by medication therapy.
Sample Size	Minimum 90 and up to 120 subjects treated (1st side) to get to a minimum of 60 subjects in the Exablate Treated Arm at Month 3 post 2nd side (T2-M3) at up to 25 sites worldwide.
Key Study Endpoints	Effectiveness Endpoints Co-Primary Endpoints Formal analyses of Primary Endpoint 1 and Primary Endpoint 2 will be conducted at different timepoints as detailed below and will include the following: Primary Endpoint 1: the between-group difference (Active Group 1 vs. Control Group 1) in the treatment effect (point change) in the MDS-UPRDS Part III ULE score in the OFF-medication state from BL1 to T1-M3. This assessment will be performed by a Movement Disorders neurologist blinded to patient study group allocation. Primary Endpoint 2: the between-group difference (Active Group 2 vs. Control Group 2) in the treatment effect (point change) in the MDS-UPRDS Part III ULE score in the OFF-medication state from BL-2 to T2-M3. This assessment will be performed by a Movement Disorders neurologist blinded to patient study group allocation. Secondary Effectiveness Endpoints Formal analyses of Secondary 1 (1st side treatment) and Secondary 2 (2nd side treatment) Endpoints will be conducted at different timepoints as detailed below and will assess the following: • MDS-UPDRS III Total score in the OFF-medication state • MDS-UPDRS Part III OFF ULE score & % change (on the first side, second side and both sides combined) • MDS-UPDRS Part III ON Total score & % change • MDS-UPDRS Part IV Total score & % change • Number of hours per day in ON time without troublesome dyskinesia- as measured by patient diaries • Number of hours per day in the OFF time as measured by patient diaries • Number of hours per day with troublesome dyskinesia • Quality of Life as measured by PDQ-39 • Daily Medication (L-DOPA equivalents) Secondary 1: 1st side Treatment Endpoints • Between-group comparison (Active Group 1 vs Control Group 1) of the treatment effect at Month 3 following Treatment 1 (T1-M3) compared to baseline (BL-1) for all assessments • Within-group comparison (Active Group 1) of the treatment effect at all study visits (Month 1, 3 and 6) following Treatment 1 compared to baseline (BL-1) for all assessments Secondary 2: 2nd side Treatment Endpoints 6. Between-group comparison (Active Group 2 vs Control Group 2) of the treatment effect at Month 3 post Treatment 2 (T2-M3) compared to re-baseline (BL-2) for all assessments 7. Within-group comparison (Active Group 2) of the treatment effect at all study visits (Month 1, 3, 6 and 12) following Treatment 2 compared to re-baseline (BL-2) for all assessments Safety Analysis Exablate intervention treatments will be summarized alongside those from the control group receiving relevant best medical therapy. The incidence and severity of adverse events (AEs) will be summarized descriptively for each treatment group throughout the comparative part of the study.
Follow-up Visits and Length of Follow-up	Active Group 1: Month 1 -/+ 7 days, Month 3 -/+ 14 days, and Month 6 -/+ 21 day; after the Month 6 visit, subjects will be randomized again into either Active Group 2 or Control Group 2 and will follow that schedule of events. Active Group 2: Month 1 -/+ 7 days, Month 3 -/+ 14 days, and Month 6 -/+ 21 day and Month 12 -/+ 60 day; at the end of their Month 12 visit subjects will be considered as having completed the study and be exited.
General
Study Status	Ongoing
Application Number / Requirement Number	P240020 / PAS001
Date Original Protocol Accepted	09/05/2025
Date Current Protocol Accepted	09/05/2025
Study Name	Continued Long-Term Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design and Objective(s) A descriptive prospective, single-center, single-arm study design. To evaluate the 5-year long-term safety and effectiveness of the TOUCH CMC 1 Prosthesis.
Study Population	Study Population Enrollment of the patients included in the original PMA cohort (Touch Cohort Swiss study), who are evaluable for the long term 5 year follow up, which includes all 103 remaining patients, from the original 149 patients. Supplemental analysis will evaluate: - Retrospective PMCF 5-Year Study: N=74 patients (82 devices) - Published Falaise et al. 2025: N=57 patients (61 devices)
Sample Size	103
Key Study Endpoints	Study Endpoints Primary endpoints: A Year 5 composite clinical success (CCS) primary endpoint will be employed. To be a success, a subject must meet all of the following criteria: • Improvement of pain: A clinically meaningful improvement in pain defined as a decrease in the pain score of = 30% on a 10-point scale. • Maintenance or improvement in function: defined by key pinch strength which is = 85% of the subject’s pre-operative key pinch strength. • Safety: success is defined as freedom from: o Subsequent secondary surgical interventions (SSI) (i.e., reoperation, revision, removal of any study component, or supplemental fixations) on the study carpometacarpal joint, or Serious, device- or procedure-related adverse events. Secondary endpoints: • Pain evolution (% change), as measured by either Numerical Rating Scale (NRS) or Visual Analog Scale (VAS) on a 10-point scale • Key pinch strength (kg) evolution • Kapandji index • Patient satisfaction via brief Michigan Hand Outcomes Questionnaire (bMHQ) • Return to work time • Radiographic success – investigators will make best efforts to obtain 5 years post-operative radiographs for all enrolled subjects: absence of device migration, osteolysis, radiolucencies or fracture Individual components of the CCS including need for revision surgery and serious, device-related adverse events¿
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Delayed
Application Number / Requirement Number	P240020 / PAS002
Date Original Protocol Accepted	09/05/2025
Date Current Protocol Accepted	12/17/2025
Study Name	TOUCH CMC 1 New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, single-arm observational post-approval study (PAS) with hypothesis testing. The purpose of this study is to meet a PMA (P240020) condition of approval of the TOUCH® CMC 1 Prosthesis to evaluate the effectiveness and safety of the prosthesis in the United States (US) population. The device performance in newly enrolled US patients implanted by US surgeons will be compared to device performance observed within the outside the US (OUS) premarket cohort.
Study Population	US Adult patients requiring surgical intervention for treating 1st CMC joint osteoarthritis that are indicated for the device, do not have any contraindications and who have failed non-conservative treatment.
Sample Size	Minimum of 163 subjects Up to 8 US sites, with no single site enrolls greater than 25% of subjects
Key Study Endpoints	A composite clinical success (CSS) endpoint will be evaluated at 24 months/2 years post-implantation. To be considered as a success, a subject must meet all of the following criteria: Improvement of pain: A clinically meaningful improvement in pain during activities defined as a decrease in the Numerical Rating Scale (NRS) pain score of greater than or equal to 30% on a 10-point scale. Maintenance or improvement in function: defined by key pinch strength, which is greater than or equal to 85% of the subject’s pre-operative key pinch strength. Safety: success is defined as freedom from: o Subsequent surgical interventions (SSI) (i.e., reoperation, revision, removal of any study component, or supplemental fixations) on the study carpometacarpal joint, or Serious, device- or procedure-related adverse events Secondary endpoints will be evaluated through 2 years. Secondary endpoints will be evaluated through 2 years. Pain at rest Pain during activities Key pinch (kg) Kapandji index Brief MHQ Range of Motion (ROM): Thumb Metacarpal Flexion Thumb Metacarpal Radial Abduction Thumb Metacarpal Palmar Abduction Thumb length PROMIS® (Patient-Reported Outcomes Measurement Information System) Upper Extremity Computer Adaptive Test (CAT) PROMIS® Pain Interference CAT EQ-5D-5L EQ-5D-VAS Return to work (days) in those working at baseline Patient Satisfaction, including aesthetic Radiographic endpoints: Device migration Osteolysis Radiolucencies Fracture Individual components of the safety endpoint, including SSI(s) and adverse events
Follow-up Visits and Length of Follow-up	Screening/Baseline (within 90 days of surgery) Surgery 6 weeks -/+ 14 days 3 months -/+ 14 days 12 months -/+ 60 days 24 months -/+ 60 days Patients are to be consented to 5-years for additional follow-up and evaluation, if necessary.
Interim or Final Data Summary
Interim Results	Follow-up Rate: N/A Safety Results: N/A
Actual Number of Patients Enrolled	7
Actual Number of Sites Enrolled	4
Patient Follow-up Rate	4.29% (7/163)
General
Study Status	Delayed
Application Number / Requirement Number	P160036 / PAS003
Date Original Protocol Accepted	09/20/2024
Date Current Protocol Accepted	07/31/2026
Study Name	TAR Performance Descriptive Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Objective: The purpose of this multi-center post-approval study is to meet the conditions of the PMA approval for the H3 TAR, to evaluate the trends in performance among implant sizes, and to assess the outcomes of the primary surgeon of the premarket study that supported PMA approval, compared to other surgeons that are less familiar with the device. Design: Prospective multicenter single arm post approval study with data supplementation from the UK National Joint Registry (UK NJR)
Study Population	Patients who have discussed options for management of a painful arthritic ankle joint due to primary osteoarthritis, post-traumatic osteoarthritis, or arthritis secondary to inflammatory disease (e.g., rheumatoid arthritis, hemochromatosis, etc.), and who have decided to undergo total ankle replacement, are candidates for this study.
Sample Size	US Population: 94 subjects/ 10 Clinical Sites UK Population: 407 subjects / 45 Clinical Sites
Key Study Endpoints	Primary Endpoints for US population: • Survivorship (absence of revision to metal components only) • Survivorship (absence of revision to metal and polyethylene components) Additional Endpoints for US population: • American Orthopaedic Foot and Ankle Society (AOFAS) score at 2 years or more • Percentage of subjects with a serious device related adverse event, other than a revision or removal within 2 years • Incidence, occurrence, and types of serious device related adverse events • Nature, onset, duration, severity, relationship to the device, relationship to the operative procedure, and outcome of any adverse event • Visual Analog Scale (VAS) score • Subjects Satisfaction Surverys • SF-36 • Radiographs (loosening, osteolysis, implant migration, other findings) • Explant analysis UK population: • Survivorship (absence of revision to metal components only) • Survivorship (absence of revision to metal and polyethylene components)
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Interim Results	Safety Results: US data: Fourteen (14) Implant-Related Events, representing 15.6% and thirty-nine (39) Procedure-Related Events representing 43.3% were reported. There have been three (3) revisions and nine (9) removals. No deaths have occurred since the study started. UK Registry data: There have been twenty-eight (28) reported revision surgeries in this cohort. Effectiveness Results: US data: At baseline 69.3% (61/88), 6-week rated 26.03% (19/73), 24-week 98.30% (58/59), 1-year 96.22% (51/53), 2-year 93.61% (44/47), and 3-year 100% (5/5).
Actual Number of Patients Enrolled	101 US subjects/ 407 UK subjects
Actual Number of Sites Enrolled	13 US subjects / 45 UK sites
Patient Follow-up Rate	US data: Follow-up rate (All data available per protocol) is 6 weeks: 54.4% (49/90), 24 weeks: 54.2% (46/83), 1-year: 45% (36/80), 2-year: 59.1% (36/66) and 3-year: 83.3% (5/6). UK Registry data: The Kaplan-Meier estimate of survivorship at 5 years is 94.5% with a 95% confidence interval of (91.5%, 96.5%). At 10 years, the Kaplan-Meier estimate of survivorship is 91.3% with a 95% confidence interval of (87.4%, 94.0%).
General
Study Status	Ongoing
Application Number / Requirement Number	P240028 / PAS001
Date Original Protocol Accepted	06/18/2025
Date Current Protocol Accepted	06/18/2025
Study Name	WiSE CRT System Post-Approval Study (PAS)
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The WiSE-UP Registry is a prospective, non-randomized, observational, multi-center study tracking patients implanted with the WiSE System to understand clinical outcomes, CRT response, & long-term product performance. Patients enrolled in the study will be followed per the standard of care practices of their provider.
Study Population	Adults at least 22 years of age
Sample Size	Number of subjects: 320 Assumptions for sample size estimation: • Projected attrition rates of 10% annual mortality and 15% annual loss to follow-up. • Estimate a 1-month 15% event rate based on the observed rate during the SOLVE-CRT Pivotal Study • Estimation that at least 275 patients will complete 1-month follow-up. • Estimation that approximately 240 patients will remain evaluable at 1 year. Number of sites: 50 Sites location: US and OUS
Key Study Endpoints	The rate of serious adverse events (SAEs) at < 30 days post implant related to the WiSE System and/or implant procedure. Secondary Endpoints: The outcome measures for this study include the following evaluations: • Procedural Success • CRT Response Assessment • HF Clinical Composite Score • NYHA Classification • QRS Duration • Minnesota Living with Heart Failure Questionnaire (6 & 12 months only) • Events Assessment • Mortality • Patient Global Assessment • Device Longevity & Battery Performance • Left Ventricular End-Systolic Volume (LVESV)
Follow-up Visits and Length of Follow-up	Baseline visit, 1 month, 6 months, annually for 5 years
Interim or Final Data Summary
Interim Results	Safety Results: No Serious Adverse Events (SAEs) have been reported. Effectiveness Results: Procedural success rate was 100% (17/17). At 1-month follow-up, 12/13 patients had Cardiac Resynchronization Therapy (CRT) data available: 3/12 patients were classified as “Responders”, 7/12 patients were classified as “Likely Responders”. A mean reduction in QRS duration of 14 ms was observed from baseline to 1 month (n=13).
Actual Number of Patients Enrolled	17
Actual Number of Sites Enrolled	5
Patient Follow-up Rate	13 patient had 1-month follow-up data available at the time of data cutoff.
General
Study Status	Study Pending
Application Number / Requirement Number	P210032 S015/ PAS001
Date Original Protocol Accepted	04/11/2025
Date Current Protocol Accepted
Study Name	Cont Follow-up IDE Study Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Assess the safety and effectiveness of the TAMBE Device in the treatment of thoracoabdominal aortic aneurysms (TAAA) and pararenal aortic aneurysms. This is continued follow up of the premarket cohort.
Study Population	Patients with lesions of the aortic arch.
Sample Size	77
Key Study Endpoints	Procedural Success (defined as Device Technical Success with the absence of serious adverse events at 30 days, including: death, disabling stroke, paraplegia, paraparesis, new onset renal failure requiring permanent dialysis, unanticipated reintervention related to the device or the procedure, new ischemia, distal device-related thromboembolic events requiring intervention, life threatening bleed, myocardial infarction, prolonged intubation, laryngeal or phrenic nerve injury, renal dysfunction or volume overload requiring ultrafiltration, severe heart failure or hypotension, aortic rupture, new dissection, or extension of a dissection (Dissection Cohort only)) and Treatment Success (defined as Device Technical Success, with absence of all of the following at all appropriate follow-up windows: lesion-related mortality, disabling stroke, paraplegia and paraparesis, protocol-defined reintervention, new ischemia, aortic rupture, loss of patency, fistula formation, loss of device integrity, device migration, new dissection, Type I/III endoleak, aortic enlargement, extension of dissection (Dissection Cohort only), false lumen perfusion through primary entry tear (Dissection Cohort only), and false lumen perfusion through an aortic arch branch vessel (Dissection Cohort only).
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P240023 / PAS001
Date Original Protocol Accepted	02/12/2025
Date Current Protocol Accepted	02/12/2025
Study Name	Completion of WAVE Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, randomized (AVF cohort only), controlled, multicenter study comparing the Merit WRAPSODY Endovascular Stent Graft to Percutaneous Transluminal Angioplasty for treatment of venous outflow circuit stenosis or occlusion in hemodialysis patients. The objective of this study is to demonstrate the long-term safety and efficacy of the Merit WRAPSODY Endovascular Stent Graft for treatment of stenosis or occlusion within the dialysis access outflow circuit, including: a) AVF Peripheral - the peripheral veins of subjects with an arteriovenous (AV) fistula, and b) AVG Peripheral – at the venous anastomosis of subjects with a synthetic arteriovenous graft access Cohort (a) will be compared to PTA. Cohort (b) will be compared to performance goals.
Study Population	The study comprises two (2) independent cohorts: 1) Subjects with AVF for hemodialysis who have stenosis or occlusion of the peripheral venous outflow circuit, including the cephalic arch; and 2) subjects with AVG for hemodialysis who have stenosis or occlusion at the graft-vein anastomosis or juxta-anastomosis.
Sample Size	Number of subjects: 246 AVF peripheral subjects; 112 AVG Anastomosis Subjects; 16 Central Cohort Number of sites: 43 centers; 10 international Sites location: United States, United Kingdom, and Brazil
Key Study Endpoints	Two primary endpoints are proposed: Primary Safety: Proportion of subjects without any localized or systemic safety events through 30 days that affect the access or venous outflow circuit and result in reintervention, hospitalization, or death Primary Effectiveness: Target Lesion Primary Patency (TLPP) at 6 months Secondary: Key secondary endpoints include: TLPP at months 12 and 24 Access Circuit Primary Patency (ACPP) at months 6, 12, and 24 Rates of procedure- and device- related adverse events Rate of device observations and potential malfunctions or failures Number of reinterventions at months 6, 12, and 24 months
Follow-up Visits and Length of Follow-up	After the index procedure on Day 0, subjects shall be evaluated within the clinic at 30 days, then at months 6, 12 and 24. Telephone follow-up shall be completed at months 3, 9 and 18.
Interim or Final Data Summary
Actual Number of Patients Enrolled	AVF Cohort (Randomized 1:1 WRAPSODY to PTA): 246 AVG Cohort (WRAPSODY only): 112
Actual Number of Sites Enrolled	43 sites; 33 US sites; 4 Brazilian sites; 1 Canadian site; 5 UK sites
Patient Follow-up Rate	Completed the study: Overall: 215/374 (57.5%) AVF: 151/246 (61.4%) AVG: 54/112 (48.2%)
Final Safety Findings	AVF Cohort (WRAPSODY | PTA): Primary Safety: 30-Day Safety*: 96.6% (115/119) | 95.0% (115/121) *defined as freedom from localized or systemic safety events that affect the access or venous outflow circuit and resulted in reintervention, hospitalization, or death (not including stenosis or thrombosis) Secondary Safety: Rates of Procedure-Related Adverse Events 6 Months: 6.1% (7/115) | 17.4% (20/115) 12 Months: 6.6% (7/106) | 21.2% (21/99) 24 Months: 8.4% (7/83) | 26.9% (21/78) Rates of Device-Related Adverse Events 6 Months: 2.6% (3/114) | 8.0% (9/113) 12 Months: 2.9% (3/105) | 9.4% (9/96) 24 Months: 3.7% (3/81) | 12.3% (9/73) Rate of device observations and potential malfunctions or failures: 2.5% (3/122) | N/A AVG Cohort (WRAPSODY only) Primary Safety: 30-Day Safety*: 95.4% (104/109) *defined as freedom from localized or systemic safety events that affect the access or venous outflow circuit and resulted in reintervention, hospitalization, or death (not including stenosis or thrombosis) Secondary Safety: Rates of Procedure-Related Adverse Events: 6 Months: 14.7% (14/95) 12 Months: 17.5% (14/80) 24 Months: 23.3% (14/60) Rates of Device-Related Adverse Events: 6 Months: 8.4% (8/95) 12 Months: 10.1% (8/79) 24 Months: 13.8% (8/58) Rate of device observations and potential malfunctions or failures: 0.0% (0/112)
Final Effect Findings	AVF Cohort (WRAPSODY | PTA): Primary Effectiveness: Target Lesion Primary Patency (TLPP) at 6 Months: 89.6% (103/115) | 62.3% (71/114) Secondary Effectiveness: TLPP: 12 Months: 70.4% (76/108) | 38.5% (40/104) 24 Months: 45.2% (42/93) | 22.3% (21/94) Access Circuit Primary Patency (ACPP): 6 Months: 72.2% (83/115) | 57.0% (65/114) 12 Months: 56.4% (62/110) | 31.1% (33/106) 24 Months: 27.3% (27/99) | 15.2% (15/99) Mean number of target lesion reinterventions (total number): 6 Months: 0.18 (115) | 0.47 (114) 12 Months: 0.49 (108) | 1.08 (104) 24 Months: 1.26 (93) | 1. 80 (94) AVG Cohort (WRAPSODY only) Primary Effectiveness: Target Lesion Primary Patency (TLPP) at 6 Months: 81.4% (79/97) Secondary Effectiveness: TLPP: 12 Months: 58.0% (51/88) 24 Months: 33.8% (26/77) Access Circuit Primary Patency (ACPP): 6 Months: 68.0% (68/100) 12 Months: 33.7% (31/92) 24 Months: 19.8% (17/86) Mean number of target lesion reinterventions (total number): 6 Months: 0.21 (97) 12 Months: 0.66 (88) 24 Months: 1.40 (77)
Study Strengths & Weaknesses	Strengths: This was a prospective, consecutively enrolling study. Imaging was analyzed by a Core Lab, and a Clinical Events Committee adjudicated procedure- and device-relatedness of events. Weaknesses: The AVG Cohort of this study is a non-randomized study with inherent biases. Follow-up was achieved in 57.5% of subjects at 24 months.
Recommendations for Labeling Changes	Labeling change is recommended to reflect the long-term results of the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study results (e.g., final endpoint results, follow-up rates, strengths and limitations of the PAS).
General
Study Status	Ongoing
Application Number / Requirement Number	P240023 / PAS002
Date Original Protocol Accepted	02/12/2025
Date Current Protocol Accepted	12/11/2025
Study Name	WRAP Registry
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multicenter, observational study designed to collect clinical outcomes data from subjects who have been treated with the Merit WRAPSODY® Cell Impermeable Endoprosthesis. The objective of this study is to expand and understand the safety and effectiveness of the Merit WRAPSODY® Cell Impermeable Endoprosthesis in a real-world North American population.
Study Population	Subjects with stenosis or occlusion within the dialysis outflow circuit who meet the inclusion and exclusion criteria are intended to participate in this study. The eligibility criteria are kept to a minimum to better represent the subject profile treated in actual clinical practice without selecting sub-groups of particular low/high risk or excluding certain diseases or anatomies.
Sample Size	Number of subjects: up to 250, with 125 enrolled at United States sites. Number of sites: up to 25, with 15 located in the United States Sites location: United States and Canada
Key Study Endpoints	wo primary endpoints are proposed: Primary Safety: Proportion of subjects without any localized or systemic safety events through 30 days that affect the access or venous outflow circuit and result in reintervention, hospitalization, or death Primary Effectiveness: Target Lesion Primary Patency (TLPP) at 6 months Secondary: Key secondary endpoints include: TLPP at months 12, 24, and 36 Access Circuit Primary Patency (ACPP) at months 6, 12, 24, and 36 Rates of procedure- and device- related adverse events Rate of device observations and potential malfunctions or failures Number of reinterventions at months 6, 12, 24, and 36 months
Follow-up Visits and Length of Follow-up	Data will be collected from available medical records for at 30 days, 6 months, 12 months, 24 months, and 36 months.
General
Study Status	Ongoing
Application Number / Requirement Number	P240024 / PAS001
Date Original Protocol Accepted	11/07/2025
Date Current Protocol Accepted	11/07/2025
Study Name	Ext FU of the premarket cohort (DREAM Study)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Multicenter clinical study design, continued follow-up of premarket cohorts, Single arm trial.
Study Population	Patients who had the Genio system for the treatment of Obstructive sleep apnea with patients as their own controls.
Sample Size	115
Key Study Endpoints	First co-primary endpoint: percentage of responders at 12 months based on AHI4, a responder being defined as a participant who satisfies the following criteria: at least a 50% reduction from the average AHI4 of screening and baseline to 12 months post-surgery and a remaining AHI4 less than 20 at the 12-month visit (aka “Sher Criteria”), as measured with fixed therapeutic settings on full-night PSG (all scored by an independent core laboratory) Second co-primary endpoint: percentage of responders at 12 months based on ODI4, a responder being defined as a participant who satisfies the following criterion: at least a 25% reduction from the average ODI4 of screening and baseline to 12 months post-surgery, as measured with fixed therapeutic settings on full-night PSG (all scored by an independent core laboratory). Secondary Effectiveness Endpoint • Mean change in the sleep-specific function measured by the Functional Outcomes of Sleep Questionnaire (FOSQ-10) at the 12-month visit compared to screening. • Mean change in the OSA-specific quality of life measured by the SNORE-25 instrument at the 12-month visit compared to screening. • Mean change in the sleep propensity measured by the ESS at the 12-month visit compared to screening. • Mean change in the intermittent hypoxia measured by the ODI4 at the 12-month PSG compared to the average of screening and baseline. • Mean change in the hypoxemic burden measured by the percentage of sleep time with oxyhemoglobin saturation < 90% at the 12-month PSG compared to the average of screening and baseline. Mean change in OSA severity measured by the AHI4 at the 12-month PSG compared to the average of screening and baseline. Safety will be evaluated by the incidence of device related serious adverse events recorded during the study for a period of 12 months post-surgery and in the long-term follow-up phase to 60 months post-surgery. Adverse events will be adjudicated by an Independent Clinical Events Committee (CEC). An independent Data & Safety Monitoring Board (DSMB) will be established to review accumulated safety data from the trial.
Follow-up Visits and Length of Follow-up	Upon completion of 12 months post-surgery, participants will be followed up to 5 years post-surgery for safety and efficacy.
Interim or Final Data Summary
Interim Results	Safety Results: NSE: 280 (70.4%) SE:21 (9.6%): Devices or procedure related 79.1% anticipated:6.1% Unanticiapted:0.9% Effectiveness Results: N/A-Interim analysis of secondary endpoints has not been completed
Actual Number of Patients Enrolled	115 Implanted-Screening:687-Eligibile-119
Actual Number of Sites Enrolled	25
Patient Follow-up Rate	48 early exits. No deaths reported. 68 subjects in long term follow up: 28 subjects progressed beyond M48: One reached M60.
General
Study Status	Delayed
Application Number / Requirement Number	P240024 / PAS002
Date Original Protocol Accepted	10/03/2025
Date Current Protocol Accepted	10/03/2025
Study Name	New Enrollment Study (BREATHE Study)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, Single arm, post approval study to demonstrate the long term safety and effectiveness of the device in treating OSA
Study Population	Adult patients 22 years of age and older who have been confirmed to fail, cannot tolerate or are ineligible to be treated with current standard of care treatments including lifestyle modifications, positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP] machines), oral appliances (such as mandibular advancement devices), and pharmacotherapy (such as tirzepatide).
Sample Size	229 patients: 25 Investigational sites: US
Key Study Endpoints	* First co-primary endpoint: percentage of responders at 12 months based on AH14, a responder being defined as a subject who satisfies the following criteria: at least a 50% reduction from the average AH14 of screening to 12 months post-surgery and a remaining AH14 less than 20 at the 12-month visit (aka "Sher Criteria"). * Second co-primary endpoint: percentage of responders at 12 months based on OD14, a responder being defined as a subject who satisfies the following criterion; at least a 25% reduction from the average OD14 of screening to 12 months post-surgery. * Incidence of device-related Serious Adverse Events, as reported by investigator and adjudicated by the CEC, at 12 months post-surgery. * Incidence of device-related (including the incidence rate of migration explants and revisions) and procedure-related Serious Adverse Events at 12 months post-surgery.
Follow-up Visits and Length of Follow-up	Follow up at 12,24,36,48 and 60 months
Interim or Final Data Summary
Interim Results	Safety Results NONE Available Effectiveness Results N/A
Actual Number of Patients Enrolled	None
Actual Number of Sites Enrolled	21 (approved)
Patient Follow-up Rate	N/A
General
Study Status	Ongoing
Application Number / Requirement Number	P990065 S014/ PAS001
Date Original Protocol Accepted	07/01/2025
Date Current Protocol Accepted
Study Name	Continued Follow up of the IDE (DOORwaY) Subjects
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a single arm, multicenter, prospective study that consists of continued follow-up of all available subjects from the IDE Pivotal Study (DOORwaY90, STX2001, revision F). The objective of the DOORwaY90 study is to evaluate the safety and effectiveness of selective internal radiation therapy using SIR-Spheres Y-90 resin microspheres as first-line treatment for local control of hepatocellular carcinoma (HCC) in patients with Barcelona Clinic Liver Cancer (BCLC) stage A, B1, B2, and C.
Study Population	Patients diagnosed with HCC, no macrovascular invasion, Child Pugh-A cirrhosis, BCLC stage A, B1, B2, and C with maximal single lesion size of less than or equal to 8 cm, and who are not considered suitable for treatment by resection or eligible for ablation at time of study entry.
Sample Size	100 subjects treated (up to 150 consented)
Key Study Endpoints	Co-primary Effectiveness Endpoints - Overall response rate (ORR) using a localized version of modified Response Evaluation Criteria in Solid Tumors (“localized mRECIST”) criteria and best response through 9 months. - Duration of response (DoR), defined as the interval from first time of response (partial response (PR) or complete response (CR)) until disease progression (PD), as defined by localized mRECIST criteria Secondar Endpoints - Grade greater than or equal to 3 toxicity (CTCAE v5.0) at 2 months and 6 months - Incidence of liver resection - Incidence of liver transplant - Quality of life metrics: Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire EQ-5D-5L questionnaire
Follow-up Visits and Length of Follow-up	24 months
Interim or Final Data Summary
Interim Results	Safety Results: As of the latest reporting, 667 AEs were reported in 90 out of 100 patients. Five (5) device- or procedure-related serious adverse events (SAEs) were observed among four (4) subjects out of 100 enrolled and treated subjects. None (0) of the 17 deaths reported in the study were related to the device or procedure. Effectiveness Results: Overall Response Rate (ORR): 99% (95/96) of subjects demonstrated response by localized mRECIST as adjudicated by the independent imaging core laboratory. The lone failure of this endpoint was due to unevaluable imaging. Duration of Response (DoR): 74.7% (71/95) showed duration of response (DoR) of at least 6 months as adjudicated by the independent imaging core laboratory, exceeding the 60% threshold for this coprimary endpoint. "
Actual Number of Patients Enrolled	100
Actual Number of Sites Enrolled	18 sites
Patient Follow-up Rate	12-months: 71/100 24-months: 33/100
General
Study Status	Study Pending
Application Number / Requirement Number	P240029 / PAS001
Date Original Protocol Accepted	06/23/2025
Date Current Protocol Accepted	06/23/2025
Study Name	Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective, multicenter follow-up of the pivotal study (G190185) that treated 316 subjects from 24 investigational sites. It will evaluate the long-term safety and effectiveness of the CGuard Prime Carotid Stent System. All 303 remaining subjects active at the end of the 12-month evaluation will continue to be followed annually through 36 months.
Study Population	The study has 303 remaining subjects who will follow-up at 24- and 36-Month time points.
Sample Size	303 subjects
Key Study Endpoints	The following assessments are performed: · Anticoagulant and/or antiplatelet medications (concomitant medications) · Targeted physical exam (can be performed by licensed personnel) · NIH Stroke Scale · Modified Rankin Scale · Carotid Duplex Ultrasound · INR for subjects on long term VKA anticoagulant therapy · Adverse Event Assessment
Follow-up Visits and Length of Follow-up	36 months
General
Study Status	Study Pending
Application Number / Requirement Number	P230030 S007/ PAS001
Date Original Protocol Accepted	08/25/2026
Date Current Protocol Accepted	08/25/2026
Study Name	The ADVANTAGE PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
General
Study Status	Protocol Pending
Application Number / Requirement Number	P030004 S035/ PAS001
Study Name	Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Ongoing
Application Number / Requirement Number	P250011 / PAS001
Date Original Protocol Accepted	12/09/2025
Date Current Protocol Accepted
Study Name	F/u for the ProVIDE Pivotal Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was initiated prior to device approval and is a prospective, multi-center, double-blind, 2:1 randomized, sham controlled clinical study. It was conducted at 17 sites and enrolled 221 subjects. One hundred and fifty (150) subjects were implanted in the study in the treatment arm (71 subjects underwent control). The 12-month outcomes from the study were used to support PMA approval. The 60-months follow-up data from this study must be submitted to assess the continued safety and effectiveness of the ProVee Expander System. No greater than 20% the patients enrolled in the study (i.e., patients enrolled in the treatment arm and patients crossed over from the sham to treatment arm) will be lost to follow up through 60-months. Data must be summarized descriptively, without statistical testing. Patient and physician labeling must be updated annually via a PMA supplement to include the effectiveness and safety outcomes listed above after the patients enrolled in this study complete each annual year of follow up.
Study Population	Male subject greater than or equal to 45 years old who has symptomatic BPH
Sample Size	A total of 221 subjects were enrolled in the ProVIDE study. 150 were randomized to the ProVee Treatment arm and 71 were randomized to the Sham Control Arm.
Key Study Endpoints	Effectiveness • Long term symptom improvement 1 (timeframe: procedure through 60-months) Percent of subjects who experience at least a 30% improvement in IPSS from their baseline pre-treatment score at 1, 3, 6-month and annually post treatment. • Long term symptom improvement 2 (timeframe: procedure through 60-months) Percent change in IPSS in the treatment arm compared to baseline at all timepoints post treatment. • QoL Questionnaire (timeframe: procedure through 60-months) Mean improvement from baseline in QoL questionnaire at 3, 6, 12-month follow-up visits, and annually through 60-months. • Uroflow Metrics 1 (timeframe: 1-month through 60-months) Mean improvement from baseline uroflowmetry measures of peak flow rate (Qmax) as measured at all timepoints. • Uroflow Metrics 2 (timeframe: 1-month through 60-months) Mean improvement from baseline in PVR as measured at all timepoints post treatment. • Re-intervention – device (timeframe: procedure through 60-months) Post-procedure incidence of secondary reintervention using alternate surgical LUTS therapy annually through 60 months. • Re-intervention – drug (timeframe: procedure through 60-months) Post-procedure incidence of secondary reintervention using standard pharmacological agents for LUTS therapy through 60 months. • Post procedure device removal rate (timeframe: 12-months through 60-months) Rate of post procedure incidence of device removal and summary of the reasons for removal. Safety • Adverse Events (procedure through 60-month) Rate of device or procedure related adverse events at all time points. • Sexual Health Questionnaire (timeframe: 3 months post procedure through 60-months post procedure) Change in sexual health characterized by change in International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD) at 3, 6, 12 month and annually post treatment through 60 months. • Adverse Event Classification (timeframe: procedure through 60-months) Proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 60-months. • Device removal related adverse events (timeframe: procedure through 60-months) Assessment of retrieval procedure related adverse events related to implant removal.
Follow-up Visits and Length of Follow-up	Follow-up annually through 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P250011 / PAS002
Date Original Protocol Accepted	12/09/2025
Date Current Protocol Accepted
Study Name	F/u of the ProVIDE II Bridging Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was initiated prior to device approval and is a prospective, multi-center, non-randomized bridging study. It was conducted at 8 sites and enrolled 40 subjects. Forty (40) subjects were implanted in the study. The 3-month outcomes from the study were used to support PMA approval. The 60-months follow-up safety data, and effectiveness data from this study must be submitted to assess the continued safety and effectiveness of the ProVee System for BPH. No greater than 20% of the patients enrolled in the study will be lost to follow up through 60-months. Data must be summarized descriptively, without statistical testing. Patient and physician labeling must be updated annually via a PMA supplement to include the effectiveness and safety outcomes listed above after the patients enrolled in this study complete each annual year of follow up.
Study Population	Male subject greater than or equal to 45 years old who has symptomatic BPH
Sample Size	A total of 40 subjects were enrolled in the ProVIDE II Bridging Study.
Key Study Endpoints	Effectiveness • Symptom improvement 1 (timeframe: procedure through 60 months) Percent of subjects who experienced at least a 30% improvement in IPSS from baseline from their baseline pre-treatment score annually through 60 months post treatment. • Symptom improvement 2 (timeframe: procedure through 60-months) Percent change in IPSS compared to baseline at all timepoints post treatment. • QoL Questionnaire (timeframe: procedure through 60-months) Mean improvement from baseline in QoL questionnaire annually through 60-months. • Uroflow Metrics 1 (timeframe: 1-month through 60-months) Mean improvement from baseline uroflowmetry measures of peak flow rate (Qmax) as measured at all timepoints. • Uroflow Metrics 2 (timeframe: 1-month through 60-months) Mean improvement from baseline in PVR as measured at all timepoints post treatment. • Re-intervention – device (timeframe: procedure annually through 60-months) post-procedure incidence of secondary reintervention using an alternative surgical LUTS therapy annually through 60 months. • Re-intervention – drug (timeframe: procedure annually through 60-months). Post-procedure incidence of secondary reintervention using standard pharmacological agents for LUTS therapy through 60 months. • Post procedure device removal rate (timeframe: 12-months through 60-months) Rate of post procedure incidence of device removal and summary of the reasons for removal. Safety • Adverse Events (Procedure through 5 years) Rate of device or procedure related adverse events at all time points. • Sexual Health Questionnaire (timeframe 3 months through 60-months) Change in sexual health characterized by change in International Index of Erectile Function, specifically the Erectile Function domain (IIEF-5) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD) at 3 months through 60 months. • Adverse Event Classification (timeframe: procedure through 60-months) Proportion of subjects with adverse events classified as Clavien-Dindo Grade IIIb or higher or any event resulting in persistent disability evidenced through 60-month follow-up visit. • Device removal related adverse events (timeframe: procedure through 60-months) Assessment of retrieval procedure related adverse events related to implant removal.
Follow-up Visits and Length of Follow-up	Follow-up annually through 5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S182/ PAS002
Date Original Protocol Accepted	04/30/2025
Date Current Protocol Accepted
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	Registry-Based Real-World Use Surveillance. The objective of the surveillance is to assess the real-world performance of the Edwards SAPIEN 3, SAPIEN 3 Ultra, and SAPIEN 3 Ultra RESILIA THV System and the clinical outcomes of the device in patient populations under-enrolled in the pivotal trial.
Study Population	Patients with asymptomatic severe native calcific aortic stenosis who are judged by a heart team to be appropriate for transcatheter heart valve replacement therapy.
Sample Size	All consecutive patients treated within the first 2 years following device approval or a total of 2,000 consecutively treated patients, whichever is greater, who are entered into the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry. Data collection will continue for under-enrolled racial and ethnic groups until each group has enrolled a minimum number of patients as specified: Black/African American, 100; Asian, 100, American Indian/Alaskan Native, 50, Native Hawaiian/Pacific Islander, 50; and Hispanic or Latino ethnicity, 100. Data collection will also continue for under-enrolled patients deemed to be at intermediate or greater risk for open surgical therapy until a minimum of 300 patients have been enrolled.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry. The follow-up data (including all-cause mortality, all stroke, and aortic valve reintervention) from year 2 through year 5 post-procedure will be obtained through linking the TVT Registry data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Ongoing
Application Number / Requirement Number	P240037 / PAS001
Date Original Protocol Accepted	07/11/2025
Date Current Protocol Accepted
Study Name	PAS Clinical Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this study is to confirm in a post market setting the clinical effectiveness of VENTANA MET (SP44) RxDx Assay as a companion diagnostic (CDx) device for the identification of NSCLC patients with MET protein who may benefit from treatment with telisotuzumab vedotin. The primary objectives of this study are to determine the prevalence of subjects whose MET-positivity at the greater than or equal to 50% strong TC cutoff is driven by different cellular compartments (predominant staining pattern: membrane-only, membrane and cytoplasm, and cytoplasm-only) and to determine efficacy of telisotuzumab vedotin for MET-positive subjects at the greater than or equal to 50% strong TC cutoff. The study design includes two cohorts of patients with NSCLC treated with telisotuzumab vedotin that come from either study M25-274, “A Phase 2, Open-Label, Randomized, Global Study of Three Telisotuzumab Vedotin Regimens In Subjects with Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advance/Metastatic Non-Squamous Non-Small Cell Lung Cancer.”, or study M18-868, “A Phase 3 Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Versus Docetaxel in Subjects with Previously Treated c-Met+, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer.”: - 13 – 15 patients from AbbVie study protocol M25-274 will be included in the primary efficacy analysis with a positive MET status at the =50% strong TC cutoff. - 45 patients from the M25-274 Phase 2 study, inclusive of the 15 patients discussed above, and all available patients pre-screened for the M18-868 Phase 3 study between January 2025 and April 2027 will be included in the primary prevalence analysis with a positive MET status at the greater than or equal to 50% strong TC cutoff.
Study Population	The study consists of 45 participants from study M25-274 and all available patients pre-screened for the M18-868 Phase 3 study between January 2025 and April 2027. Patients in these studies have previously treated MET overexpressing, EGFR wildtype, locally advanced/metastatic non-squamous non-small cell lung cancer.
Sample Size	The study consists of 45 participants from study M25-274 and all available patients pre-screened for the M18-868 Phase 3 study between January 2025 and April 2027. The total number of subjects included in this study will be dependent on the subject enrollment rates.
Key Study Endpoints	All patients enrolled into Arm 1 of the M25-274 Phase 2 study (1.9 mg/kg Q2W) (with a positive MET status at the greater than or equal to 50% strong TC cutoff) by May 2027 who have efficacy data (ORR) available will be included in the primary efficacy analysis. All patients enrolled (approximately 45) in the M25-274 Phase 2 study (with a positive MET status at the =50% strong TC cutoff) by May 2027 and all available enrolled patients who were pre-screened between January 2025 and April 2027 in the M18-868 Phase 3 study (with a positive MET status at the greater than or equal to 50% strong TC cutoff) will be included in the primary prevalence analysis.
Follow-up Visits and Length of Follow-up	Patients from M25-278 included in the efficacy assessment will have been followed for at least 12 weeks (two scheduled tumor assessments) from the first dose.
General
Study Status	Ongoing
Application Number / Requirement Number	P240004 / PAS001
Date Original Protocol Accepted	07/18/2025
Date Current Protocol Accepted	07/18/2025
Study Name	EndoForce Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Study Design and Objective(s) The purpose of this study is to collect post-approval, longer-term, real-world safety and effectiveness data for the use of the Phraxis EndoForce Connector for Endovascular Venous Anastomosis (EndoForce System) through 2 years post-implantation. The study is a prospective, multicenter, open-label study.
Study Population	Patients with End Stage Renal Disease who have a planned arteriovenous graft implant procedure for hemodialysis access and who meet the study enrollment criteria.
Sample Size	Number of subjects: 150 Number of sites: 20 Sites location: USA
Key Study Endpoints	Study Endpoints Assessments will be made at 2-weeks, 1, 3, 6, 12, 18 and 24 months following the index procedure. For the purposes of study outcome evaluation, the index procedure is defined as arteriovenous graft (AVG) implantation using the EndoForce System. With a 50% 2-year survival rate for ESRD patients, it is anticipated that 2-year data will be available on approximately 75 subjects. 1. Safety will be assessed by reporting all device and/or procedure-related events and all major adverse events that reasonably suggest the involvement of the EndoForce and that require or result in any of the following: death, emergent surgery, events requiring hospitalization, events requiring percutaneous interventions, vascular access infection requiring treatment, significant bleeding, pseudoaneurysm and serious adverse events through the 2-year visit. EndoForce migration, inadequate seal and leakage will also be collected acutely and at each in-person follow-up visit and reported through the 2-year visit. 2. AVG Cumulative Patency: Defined as the percentage of subjects free from loss of access of the study graft for hemodialysis. 3. AVG Primary Patency: Defined as the percentage of subjects free from the first occurrence of either access thrombosis or an access procedure performed to maintain access patency. 4. Number of AVG interventions until access abandonment or through study completion. 5. Acute Device Success: Defined as AV graft flow at the end of the procedure as determined by palpable graft thrill and/or audible bruit, without significant bleeding or emergent surgery. NOTE: Outcome measures will be evaluated acutely (at the time of implant), at time of any AVG intervention, and at all planned study visits. The study AVG patency evaluation starts immediately after the index procedure is completed (e.g., subject leaves the surgery suite). This means that once the AVG is created, patency evaluation begins. The occurrence of acute thrombus and treatment thereof during the index procedure while the vascular access is being created does not trigger the loss of primary patency. Secondary outcome measures will be further evaluated by relatedness to the EndoForce device.
Follow-up Visits and Length of Follow-up	Assessments will be made at 2-weeks, 1, 3, 6, 12, 18 and 24 months following the index procedure. The 1-month and 3-month follow-up will be phone visits, all other visits will be in-person.
General
Study Status	Ongoing
Application Number / Requirement Number	P240042 / PAS001
Date Original Protocol Accepted	05/23/2025
Date Current Protocol Accepted
Study Name	Continued Follow-up of SUMMIT MAC Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living Severe MAC cohort subjects who were enrolled under the IDE, including those enrolled in the continued access protocol (CAP) investigation. The objective of this study is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living Severe MAC cohort subjects who were enrolled under the IDE.
Sample Size	All living subjects.
Key Study Endpoints	All-cause mortality, all stroke, cardiovascular hospitalization, number of days alive and out of hospital, annualized rate of HFH, mitral valve reintervention or reoperation, 6MWT distance, KCCQ score, EQ-5D-5L score, SF-12 score, NYHA functional class, and echocardiographic endpoints.
Follow-up Visits and Length of Follow-up	5 years.
Interim or Final Data Summary
Interim Results	Safety Results: Severe MAC at 2Y (KM Rate): All-cause mortality: 31.8% Cardiovascular: 23.5% Non-Cardiovascular: 10.8% Cardiovascular Hospitalization: 49.4% Heart Failure Hospitalization: 34.7% Other Cardiovascular Hospitalization: 26.8% All stroke: 10.6% Mitral Valve Reintervention: 6.8% MAC CAP at 1Y (KM Rate): All-cause mortality: 33.8% Cardiovascular: 29% Non-Cardiovascular: 6.7% Cardiovascular Hospitalization: 38% Heart Failure Hospitalization: 20.3% Other Cardiovascular Hospitalization: 24.6% All stroke: 2.9% Mitral Valve Reintervention: 2.9% Effectiveness Results: Severe MAC at 2Y: NYHA: At baseline, 73.8% of the subjects were in NYHA Class III or IV and at the 2-Year Follow-up, 83.1% of subjects in NYHA Class I or II. Six-Minute Walk: The mean 6MWT distance at baseline was 203.6 -/+ 111.8. At follow-up, the mean 6MWT distance was 213.6 -/+ 117.0 (at 2-Year). KCCQ: At baseline, subjects had a mean KCCQ overall score of 49.2 -/+ 23.1. At follow up, the mean KCCQ overall score increased to 67.9 -/+ 25.1 (2-Year). EQ-5D: The mean utility index score was 0.73 -/+ 0.16 at baseline, compared to 0.75 -/+ 0.18 at 2-Years. At baseline, the mean EQ-VAS scores were 61.1 -/+ 20.5. The average score was higher at follow-up (68.5 -/+ 20.0 at 2-Years). SF-12: At baseline, the mean SF-12 physical component score was 32.0 -/+ 9.7, indicating populations with somewhat poor physical condition. This increased to 33.7 -/+ 10.6 at 2-Years. The mean mental component score was 48.3 -/+ 12.8 at baseline, which increased to 52.3 -/+ 11.2 at 2-Years. Mitral Regurgitation: At baseline, 87.1% of the subjects had MR Grade 3+ or 4+ in severity. In follow-up visits, all subjects had MR less than or equal to 2+. Mean mitral gradient: The mean mitral valve gradient decreased from 6.0 mmHg at baseline to 3.9 mmHg at 2-Year follow-up. PVL: The observed major PVL (Grade greater than or equal to 2+) rate was 3.7% at the 2-Year Follow-up (events did not lead to reintervention). MAC CAP at 1Y: NYHA: At baseline, 72.5% of the subjects were in NYHA Class III or IV and at the 1-Year follow-up 94.7% of subjects were NYHA Class I or II. Six-Minute Walk: The mean 6MWT distance at baseline was 203.7 -/+ 114.4 meters. At follow-up, the mean 6MWT distance was 232.6 -/+ 142.7 (at 1-Year) meters. KCCQ: At baseline, subjects had a mean KCCQ overall score of 53.6 -/+ 21.3 points. At follow up, the mean KCCQ overall score increased to 66.0 -/+ 37.6 (1-Year). EQ-5D: The mean utility index score was 0.75 -/+ 0.15 at baseline, compared to 0.73 -/+ 0.20 at 1-Year. At baseline, the mean EQ-VAS score was 61.5 -/+ 20.8. The average score was higher at follow-up (69.5 -/+ 19.4 at 1-Year). SF-12: At baseline, the mean SF-12 physical component score was 30.8 -/+ 10.6, indicating populations with somewhat poor physical condition. This increased to 31.7 -/+ 13.5 at 1-Year. The mean mental component score was 50.5 -/+ 11.1 (MAC CAP) at baseline, which increased to 53.5 -/+ 10.6 at 1-Year. Mitral Regurgitation: At baseline, 37.5% of the subjects had MR Grade 3+ or 4+ and 45.0% had MR Grade 2+ in severity. In follow-up visits, most subjects had MR less than or equal to 1+ (96.8% at pre-discharge, 100% at 30-Days, and 100% at 1-Year Follow-up). Mean mitral gradient: The mean mitral valve gradient decreased from 9.3 mmHg at baseline to 5.3 mmHg at 1-Year follow-up. PVL: There was no observed major PVL (Grade greater than or equal to 2+) at the 1-Year Follow-up. No device embolism or migration were observed.
Actual Number of Patients Enrolled	103 subjects (Severe MAC cohort), 40 subjects (MAC CAP cohort)
Actual Number of Sites Enrolled	45 sites
Patient Follow-up Rate	Severe MAC: 90.3% at 2Y MAC CAP: 87% at 1Y
General
Study Status	Ongoing
Application Number / Requirement Number	P240039 / PAS001
Date Original Protocol Accepted	09/26/2025
Date Current Protocol Accepted	01/16/2026
Study Name	Safety and Performance PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: Prospective, multicenter, observational post-market registry study with no investigational interventions. Objectives: (1) Assess adherence to surgical training requirements; (2) Monitor device performance including complaints and deficiencies/malfunctions; (3) Evaluate clinical outcomes as observed in routine practice; (4) Monitor safety outcomes including device-related adverse events as required by FDA Conditions of Approval.
Study Population	Adult patients with moderately to severely active rheumatoid arthritis who are indicated for the SetPoint System and have attempted implant procedures. Inclusion: (1) Indicated for SetPoint System; (2) Implant procedure attempted; (3) Willing to sign informed consent. Exclusion: (1) Contraindicated for SetPoint System; (2) Enrolled in concurrent drug/device studies; (3) Life expectancy <3 years.
Sample Size	Number of subjects: Approximately 150 participants Assumptions for sample size estimation: 90% power to detect adverse events occurring at =1.5% population rate; 98% power to demonstrate device failure rate <14% (assuming true rate of 5%); based on RESET-RA experience of 34/242 subjects with Charger deficiencies. Number of sites: Multiple rheumatology sites (unspecified) Sites location: United States
Key Study Endpoints	Safety Endpoints - Primary: Related adverse events attributed to implantation/explantation procedures, SetPoint System components, or stimulation therapy Safety Endpoints - Secondary: Device complaints and deficiencies; serious adverse events; device replacements due to cauterization or deficiencies. Effectiveness Endpoints - Primary: None specified (observational study) Effectiveness Endpoints - Secondary: Clinical Disease Activity Index (CDAI) assessments; device performance metrics (battery status, impedance, dose compliance).
Follow-up Visits and Length of Follow-up	Schedule: Screening, implant procedure, post-operative clearance, activation (14-21 days post-surgery), then every 6 months for 3 years (visits at 6, 12, 18, 24, 30, and 36 months post-activation). Length: Maximum 3 years post-implant. Additional visits: Explant and post-explant clearance visits as needed; unscheduled visits for adverse events or device deficiencies.
General
Study Status	Ongoing
Application Number / Requirement Number	P230022 / PAS001
Date Original Protocol Accepted	08/20/2025
Date Current Protocol Accepted	11/19/2025
Study Name	Jewel P-WCD Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This will be a prospective cohort study to demonstrate the continued safety and clinical effectiveness of the Jewel P-WCD. The study will also demonstrate the generalizability of the arrhythmia detection algorithm which was developed using techniques of artificial intelligence and machine learning (AI/ML). The study is also described by the sponsor as being an observational registry study. All Jewel P-WCDs will be collected by the Sponsor following the end of the prescription period or device use, per commercial process. Devices which cannot be retrieved per commercial process will be considered lost to follow up.
Study Population	All patients who are prescribed and receive a Jewel P-WCD device.
Sample Size	Number of subjects: 6,330 to capture 100 shockable VT/VF events. Assumptions for sample size estimation: It is assumed that the event rate will be similar to the KESTRA ACE PAS (Kestra Medical Technologies) which was 1.58%. Number of sites: N/A Sites location: N/A
Key Study Endpoints	Safety Endpoints Primary: The primary safety endpoint is to observe an inappropriate shock rate of no more than 2.0 inappropriate shocks per 100 patient-months using a one sided upper 90% confidence interval. Only first inappropriate shocks during analyzable wear time will contribute to the analysis of this endpoint. The appropriateness of shocks will be determined by the patient’s medical team. Secondary: The secondary endpoints (report only) for this study are to observe: the proportion of subjects experiencing skin related Adverse Device Effects classified as MDR reportable; and, the number of subjects who deferred a shock and percentage of events successfully deferred. Effectiveness Endpoints Primary: The primary effectiveness endpoint is to demonstrate an overall detection rate greater than 87%, using a 90% one-sided lower confidence limit. Secondary: N/A
Follow-up Visits and Length of Follow-up	this is a registry and has no investigational device or intervention. Data will be analyzed after the completion of the prescribed wear period.
Interim or Final Data Summary
Interim Results	N/A
Actual Number of Patients Enrolled	5
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
General
Study Status	Study Pending
Application Number / Requirement Number	P240042 / PAS002
Date Original Protocol Accepted	05/23/2025
Date Current Protocol Accepted	10/04/2025
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry-Based Real-World Use Surveillance. The objective of the surveillance is to assess the real-world performance of the Transcatheter Mitral Valve System.
Study Population	Patients with asymptomatic severe native calcific aortic stenosis who are judged by a heart team to be appropriate for transcatheter heart valve replacement therapy.
Sample Size	All consecutive severe MAC patients treated within the first 2 years following device approval or a total of 200 consecutively treated patients, whichever is greater, who are entered into the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry (enrollment period)
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry. The follow-up data (including all-cause mortality, stroke, mitral valve reintervention, and heart failure hospitalizations) from year 2 through year 5 post-procedure will be obtained through linking the TVT Registry data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years.
General
Study Status	Ongoing
Application Number / Requirement Number	P240015 / PAS001
Date Original Protocol Accepted	09/09/2025
Date Current Protocol Accepted	09/09/2025
Study Name	Post-Approval Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective is to evaluate the long-term safety of the Womed Leaf device. This is a continued follow-up of the patients enrolled under the PREG2 pivotal trial.
Study Population	The PAS population is the PREG2 trial cohort which included women with symptomatic (e.g., amenorrhea, infertility, recurrent pregnancy loss) moderate or severe intrauterine adhesions (AFS score >/= 5) confirmed by hysteroscopy, scheduled for hysteroscopic adhesiolysis.
Sample Size	160 participants
Key Study Endpoints	Primary endpoint: The primary endpoint is the live birth rate. Live birth rate must be reported at one, two, and three years follow-up. Live birth is defined as the delivery of a live born infant who breathes or shows any other evidence of life, such as heartbeat or movement, and refers to an individual newborn. Secondary endpoints: 1. Clinical pregnancy rates, whether spontaneous or assisted (ovulation induction, intrauterine insemination; in vitro fertilization (IVF) and embryo transfer (ET)), at one, two, and three years, where clinical pregnancy is defined as the presence of fetal sac or heartbeat confirmed by ultrasound. 2. Average time to first pregnancy (i.e., time between the second look hysteroscopy and estimated date of conception) at one, two, and three years. 3. Pregnancy rate leading to a live birth at one, two, and three years, where pregnancy rate is defined as the presence of fetal sac or heartbeat by ultrasound or a positive urinary test or blood test leading to a live birth. 4. Pregnancy related events at one, two, and three years: a. Miscarriage (intrauterine pregnancy loss before 20 weeks gestation) b. Ectopic pregnancy (defined as pregnancy outside of the endometrial cavity, diagnosed by ultrasound, surgical visualization, or histopathology) c. Retained products of conception d. Termination of pregnancy e. Intrauterine growth restriction f. Premature rupture of the membranes g. Placenta previa h. Premature delivery (defined as a delivery before the 37th week of pregnancy) i. Uterine rupture j. Postpartum hemorrhage k. Placenta accreta spectrum (accreta, increta, percreta) l. Intrauterine fetal demise defined as the death of a fetus of at least 20 weeks gestational age m. Other 5. Reintervention rate (repeat adhesiolysis) after second look hysteroscopy up to one year following the index procedure. 6. Average number of adhesiolysis procedures per patient after second look hysteroscopy up to one year following the index procedure. 7. Improvement in menstrual pattern at one, two, and three years compared to baseline. Menstrual pattern is considered improved if menses is resumed for amenorrheic patients or if hypomenorrhea (scant spotting or light period) patients experience an increased duration or increased volume of periods compared to that previously reported.
Follow-up Visits and Length of Follow-up	3 years
General
Study Status	Ongoing
Application Number / Requirement Number	P230003 S006/ PAS001
Date Original Protocol Accepted	09/10/2025
Date Current Protocol Accepted	09/10/2025
Study Name	Abbott Alinity m HR HPV US Supplemental Study
General Study Protocol Parameters
Study Design	Cross-Sectional Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will include 500 or more individuals with a cervix, 25 years or older, with referrals to colposcopy based on previous positive HPV test or abnormal cytology results. The study will provide additional data regarding clinical performance of the Alinity m HR HPV assay with vaginal specimens in a U.S. population. The clinical sensitivity, clinical specificity and false positive rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens will be evaluated. Additionally, the concordance of the Alinity m HR HPV assay results between the two sepecimen types will be evaluated.
Study Population	Individuals with a cervix, 25 years or older, who come to colposcopy with a referral based on previous positive HPV test or abnormal cytology results
Sample Size	500 or more
Key Study Endpoints	The clinical sensitivity, clinical specificity and false positive rate in detecting precancer/cancer as well as the corresponding ratio between vaginal and cervical specimens. The concordance of the Alinity m HR HPV Assay results between the two specimen types.
Follow-up Visits and Length of Follow-up	No follow-up, unless required for standard of care (SOC) clinical care purposes
General
Study Status	Study Pending
Application Number / Requirement Number	P240044 / PAS001
Date Original Protocol Accepted	06/23/2026
Date Current Protocol Accepted	06/23/2026
Study Name	PULSAR Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PULSAR PAS study is a prospective, multicenter, non-randomized, single-arm clinical study to evaluate the long-term safety and effectiveness of the Globe PF System for treating patients with symptomatic paroxysmal atrial fibrillation. Subjects who sign the informed consent are considered enrolled in the study. Enrolled subjects who satisfy all the eligibility criteria will then undergo the ablation procedure using the Globe PF System. After the study ablation procedure, subjects will enter a blanking period. The blanking period lasts for 90 days after the index ablation procedure, during which AF/AFL/AT recurrence, DC cardioversion, repeat ablation, and an increase in Antiarrhythmic Drug (AAD) dosage are not considered treatment failures. This is a standard window of time for a blanking period for AF ablation therapy studies. The Primary Effectiveness Evaluation Period extends from the end of the blanking period to the 12-month visit. The primary objectives of the PAS will be the following: - Estimating the primary safety adverse event rate for ablation using the Globe Pulsed Field System. - Estimating the rate of 12-month treatment success following ablation procedure using the Globe Pulsed Field System. Secondary/Additional objectives will include but are not limited to: - Estimating the rate of treatment success, evaluated at 24 months and 36 months following ablation procedure using the Globe Pulsed Field System. - Estimating the rate of device- or procedure-related serious adverse events through 12 months post-ablation using the Globe Pulsed Field System. - Estimating freedom from AF/AFL/AT recurrence and off Class I and III antiarrhythmic drugs at 12-, 24-, and 36-months following ablation procedure using the Globe Pulsed Field System. - Characterizing procedural data.
Study Population	This study will enroll up to 250 subjects diagnosed with PAF at up to 40 investigational sites in the US, Canada, and Europe. A minimum of approximately 50% of subjects will be enrolled at sites in the US. There will be a 20% subject enrollment limit per site. The study is expected to include the Medicare population (patients older than 65) who meet the study inclusion/exclusion criteria. Therefore, the results of the study are expected to be generalizable to the Medicare population based on age and cardiovascular risk factors. As this trial will enroll Medicare beneficiaries in the US, all standards of Medicare coverage requirements will be followed.
Sample Size	up to 250 subjects diagnosed with PAF
Key Study Endpoints	Primary Effectiveness Endpoints: The primary effectiveness endpoint is the rate of 12-month treatment success. Treatment success is defined as freedom from treatment failure. Treatment failure will include: - Documented recurrence of atrial fibrillation, atrial flutter,7 atrial tachycardia (AF/AFL/AT) as evidenced by episodes greater than or equal to 30 seconds on Holter monitoring or equivalent8 during the effectiveness evaluation period (i.e., after the 90-day blanking period through 12 months), or by an episode documented on the entire recording of the 12-lead ECG (greater than or equal to 10 seconds) at the 12-month evaluation/visit. - Acute procedural failure, defined as: 1. Inability to isolate all accessible targeted pulmonary veins (PV) (minimally assessed for entrance block and/or exit block) during the index procedure 2. Ablation using a non-study device in the left atrium (LA) - Direct Current (DC) cardioversion for AF/AFL/AT during the effectiveness evaluation period - Redo ablation failure, defined as: 1. Any LA repeat ablation procedure for recurrent AF/AFL/AT at any time during the effectiveness evaluation period - Antiarrhythmic Drugs (AADs) failure, defined as: 1. Administering during the effectiveness evaluation period a previously failed Class I or III AAD at a dose greater than the highest ineffective historical dose (for Amiodarone, the historical maximum ineffective dose is the maintenance dose administered prior to the index ablation procedure) 2. Starting a new Class I or III AAD for AF during the effectiveness evaluation period - Surgical treatment for AF/AFL/AT after the index procedure Secondary Effectiveness Endpoints The secondary effectiveness endpoints of this study are: - Rate of treatment success evaluated at 24 months and 36 months following ablation - Rate of subjects presenting with one or more device- or procedure-related serious adverse events through 12 months following ablation - Rate of subjects who are free from AF/AFL/AT recurrence and off Class I and Class III antiarrhythmic drugs at 12-, 24-, and 36-months following ablation using the Globe PF System - Proportion of subjects that experienced symptomatic AF/AFL/AT (episodes = 30 secs) during the effectiveness evaluation period Primary Safety Endpoints: Rate of subjects presenting with one or more primary safety events up to and including 7 days (or otherwise indicated) after the index ablation procedure. Primary safety events comprise the following device- or procedure-related serious adverse events: - Death - Cardiac tamponade/perforation - Heart Block - Major vascular access complication - Major bleeding - Myocardial infarction (MI) - Pericarditis requiring intervention - Pulmonary edema - Stroke/cerebrovascular accident (CVA) - Thromboembolism - Transient ischemic attack (TIA) - Vagal nerve injury resulting in gastroparesis - Atrio-esophageal fistula (within 2 months of ablation procedure) - Diaphragmatic paralysis/phrenic nerve injury (unresolved at 12 months) - Severe PV stenosis (=70%, within 12 months of ablation procedure)
Follow-up Visits and Length of Follow-up	The overall study duration for each subject is 36 months including follow-up visits at: - Discharge - 3-Month via a remote visit - 6-, 12-, 24- and 36-Month via a remote visit or in-person
General
Study Status	Ongoing
Application Number / Requirement Number	P250007 / PAS001
Date Original Protocol Accepted	12/11/2025
Date Current Protocol Accepted	12/11/2025
Study Name	The BREEZE Study - PMCF
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The BREEZE Study - PAS [Post-Approval Study of the Zenflow Spring System - A Minimally Invasive Treatment for LUTS associated with BPH (BREEZE Study CLIN-0130 – Long-term Follow-up)] is a continuation of annual follow-up through 60 months for any subjects who received a Spring Implant in the premarket BREEZE Study. The objective is to evaluate the continued long-term safety and effectiveness of the Zenflow Spring System in relieving lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
Study Population	Subjects enrolled and treated in the premarket BREEEZE Clinical Study (CLIN-0130), i.e., male volunteers greater than or equal to 45 years of age requesting treatment for the symptomatic relief of LUTS secondary to BPH.
Sample Size	A total of 223 subjects underwent a Spring Implant procedure, of which 221 were successfully implanted in the following cohorts: • Treatment Arm Cohort: N=136 • Crossover Cohort: N=59 • Roll-in Cohort: N=26 These 221 implanted subjects will be followed under this protocol through completion of 60-month follow-up, or through 6 months post implant removal for any subjects who have the implant removed. If no alternative treatments for BPH were performed by 6 months post removal the assessment will be repeated as 12 months.
Key Study Endpoints	Effectiveness assessments: • Mean change from baseline in International Prostate Symptom Score (IPSS) at 24/36/48/60 months post treatment. • Mean change from baseline in peak flow rate (Qmax) at 24/36/48/60 months post treatment. Safety assessments: • Rate of device or procedure related adverse events (AE) at 24/36/48/60 months post treatment. • Assessment of AEs outcomes related to a Spring Implant removal procedure. • Change in sexual health characterized by change in Sexual Health Inventory for Men (SHIM) and Male Sexual Health Questionnaire – Ejaculatory Domain (MSHQ-EjD) at 24/36/48/60 months post treatment. • Post-procedure incidence of secondary reintervention using an alternate surgical LUTS therapy. • Post-procedure incidence of secondary reintervention using standard pharmacological agents for LUTS therapy. Exploratory: • Mean change in ICIQ-SF Questionnaire at 24/36/48/60 months post treatment. • Mean change in BII Questionnaire at 24/36/48/60 months post treatment. • Incidence of reinitiation of BPH medication. • PSA (if collected). • Patient Satisfaction.
Follow-up Visits and Length of Follow-up	60 months
General
Study Status	Study Pending
Application Number / Requirement Number	P250017 / PAS001
Date Original Protocol Accepted	12/19/2025
Date Current Protocol Accepted	12/19/2025
Study Name	VNS 21-05 Continued follow-up study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will evaluate the long-term safety and effectiveness of the Gore Viabahn FORTEGRA Venous Stent. The VNS 21-05 study is a prospective, multicenter, single arm trial. This PAS is continued follow-up of the premarket cohort.
Study Population	Adult patients (at least 18 years of age) with symptomatic unilateral iliofemoral venous obstruction. The population is expected to be 55% thrombotic and 45% non-thrombotic. Patients with malignant obstruction are excluded.
Sample Size	All 85 patients remaining in the study after premarket approval
Key Study Endpoints	Secondary Endpoints Primary patency, secondary patency, clinically driven target lesion revascularization (CD-TLR), stent occlusion and device fracture through 60-month follow-up. Improvement in rVCSS, rVCSS Pain, VEINES, Villalta, and EQ-5D-5L measurements through 60-month follow-up compared to pre-treatment baseline
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P250017 / PAS002
Date Original Protocol Accepted	04/07/2026
Date Current Protocol Accepted	04/07/2026
Study Name	The GORE VIABAHN FORTEGRA Venous Stent New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, multicenter, single-arm, post-market clinical study. To evaluate the Gore Viabahn Fortegra Venous Stent in real world use.
Study Population	Adult patients (at least 18 years of age) intended to receive the Gore Viabahn Fortegra Venous Stent in endovascular treatment. Only patients who meet all the inclusion criteria and none of the exclusion criteria will be implanted. Significant Inclusion Criteria Preoperative - Presence of lesion expected to necessitate treatment with the Gore Viabahn Fortegra Venous Stent. Intraoperative - Patient has adequate inflow/outflow to/from the target lesion(s), per investigator/sub-investigator discretion. Significant Exclusion Criteria Intraoperative Patient is contraindicated for treatment with the Gore Viabahn Fortegra Venous Stent according to the IFU. Intent to Treat population: All subjects who had a study device introduced into the vasculature. Per Protocol population: All subjects who had a study device introduced into the vasculature and were not determined to be ineligible for the study.
Sample Size	Number of subjects: 150 subjects with the Gore Viabahn Fortegra device introduced into the vasculature, with a limit of 30 treated subjects per site Assumptions for sample size estimation: A sample size of 150 subjects with a study device introduced into the vasculature will be used to ensure broad representation of device usage. Number of sites: 20 sites up to a maximum of 35 sites will be enrolled Sites location: United States
Key Study Endpoints	Primary Effectiveness - Primary patency through 12 months Primary Safety - Device Freedom from device- or index procedure-related SAEs through 30 days Secondary Endpoints - Primary patency through 36 months - Secondary patency through 36 months - Clinically Freedom from clinically driven target lesion revascularization through 36 months - Stent embolization through 12-month follow-up - Device- or index procedure-related death through 30 days - Clinically significant pulmonary embolism through 30 days - Device- or index procedure-related vascular injury through 30 days requiring surgical or endovascular intervention - Device- or index procedure-related major bleeding events through 30 days - Change in EQ-5D-5L Measurement through 36-month follow-up compared to baseline prior to treatment - Technical success - Lesion success Additional assessment at 1, 6, 12, 24 and 36 months: - Adverse events - Concomitant medications - rVCSS and Villalta (applicable only to subjects intended to be treated in the IVC or iliofemoral veins) - Imaging of lesions /stents
Follow-up Visits and Length of Follow-up	Dischage,1, 6-, 12-, 24-, and 36 months post treatment Subjects Lost to follow-up A subject is considered lost to follow-up after 2 consecutive follow-up visits, and 3 documented attempts have been made by the investigator or designee to contact the subject or next of kin. One of the three documented attempts must include a certified letter.
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250022 / PAS001
Study Name	VOLT Post-Approval Study
General Study Protocol Parameters
General
Study Status	Study Pending
Application Number / Requirement Number	P250019 / PAS001
Date Original Protocol Accepted	02/19/2026
Date Current Protocol Accepted	02/19/2026
Study Name	Continued Follow-up of ENCIRCLE Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living patients who were enrolled under the IDE, including those enrolled in the continued access protocol (CAP) investigation. The objective of this study is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled under the IDE.
Sample Size	All living subjects.
Key Study Endpoints	All-cause death, all stroke, heart failure rehospitalization, mitral valve reintervention, 6-minute walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire score, New York Heart Association (NYHA) functional class, and echocardiographic endpoints.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P240035 / PAS001
Date Original Protocol Accepted	01/28/2026
Date Current Protocol Accepted	01/28/2026
Study Name	The Continuation of the Open Liver Clinical Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Other Data Source
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Post-approval observational study; continuation of a pre-market, prospective, randomized (2:1), multicenter pivotal clinical investigation. The objective of this post-approval study is to evaluate long-term cancer-related outcomes for patients undergoing liver resection for liver malignancy or metastases.
Study Population	Subjects undergoing liver resection for liver malignancy or metastases
Sample Size	Number of subjects: 105 (68 subject device, 37 TachoSil control) Assumptions for sample size estimation: N/A Number of sites: 9 Sites location: United States, Germany, The Netherlands
Key Study Endpoints	Observational study with no formal primary endpoints. Exploratory endpoints include: - Cancer free survival - Liver cancer free survival - Local cancer free survival - Overall survival These endpoints will undergo subgroup analysis by cancer type (hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma metastases, non-colorectal carcinoma metastases, and other cancer)
Follow-up Visits and Length of Follow-up	Every 3 months +/- 1 month for the first 12 months. Every 6 months +/- 3 months until the end of 5 years
General
Study Status	Protocol Pending
Application Number / Requirement Number	P990040 S034/ PAS001
Study Name	TRUFILL PAS
General Study Protocol Parameters
General
Study Status	Study Pending
Application Number / Requirement Number	P230030 S012/ PAS001
Date Original Protocol Accepted	08/06/2026
Date Current Protocol Accepted	08/06/2026
Study Name	FAR-AHEAD Study
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To obtain real world clinical data on the safety and effectiveness of the FARAPOINT catheter for CTI ablation as an adjunctive treatment of drug-refractory, symptomatic PsAF (episode duration <1 year) in support of the following objectives: 4. Estimating the primary safety adverse event rate at 30 days following PsAF ablation procedure using the FARAWAVE™ Pulsed Field Ablation Catheter and the FARAPOINT™ Pulsed Field Ablation Catheter. 5. Estimating the rate of chronic RCA stenosis (>= 50% obstruction) related to CTI ablation with the FARAPOINT™ Pulsed Field Ablation Catheter. 6. Estimating the rate of durable CTI conduction block following concomitant CTI ablation with the FARAPOINT™ Pulsed Field Ablation Catheter.
Sample Size	Number of subjects: 265 Assumptions for sample size estimation: Ensure a very high probability (99%-99.5%) to detect at least one primary safety event (primary study objective #1), assuming an event rate of 2% based on results from ADVANTAGE AF Phase 2 FARAPOINT treatment subjects Number of sites: 10 Sites location: TBA
Key Study Endpoints	Data collection will include the following: - Medical history and demographics - Acute procedural details - 30-day evaluation of primary safety - 6- and 12-month rhythm monitoring for recurrence - At least 60 PsAF subjects will undergo a baseline and 12-month post-procedure CTA to assess RCA stenosis - Re-mapping data for patients undergoing redo during the 12-month follow-up to evaluate the durability of the CTI lesion - 3-year post-discharge composite rate for acute coronary syndrome, new ischemic electrocardiogram (ECG) changes consistent with inferior ischemia requiring treatment, hemodynamically significant coronary artery spasm requiring intracoronary nitroglycerin and/or causing ST-segment elevation, urgent coronary angiography with an RCA culprit finding, and cardiac death - 36 – month freedom from AF/AFL/AT recurrence from medical chart review
Follow-up Visits and Length of Follow-up	Patients in FAR-AHEAD will be enrolled and followed for 36 months post-ablation.
General
Study Status	Ongoing
Application Number / Requirement Number	P250023 / PAS001
Date Original Protocol Accepted	02/20/2026
Date Current Protocol Accepted	02/20/2026
Study Name	Allurion Gastric Balloon PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective Cohort Study: The primary objective of this study is to assess the continued safety and performance of the AGBS in the commercial setting.
Study Population	Patients aged 22-65 who have a BMI of greater than or equal to 30 kg/m² and less than or equal to 40 kg/m²; and have failed to lose weight through diet and exercise. Patients willing to commercially purchase the AGBS.
Sample Size	250 patients
Key Study Endpoints	The primary endpoint of the study is to confirm the safety profile results for the Allurion Gastric Balloon System (AGBS) as obtained in the US pivotal clinical study, TRL-1000-0007. The secondary endpoint is to evaluate device effectiveness after the sequential balloon therapy. The effectiveness endpoints are evaluated as: 1) the percentage of patients with at least 5% Total Body Weight Loss (%TBWL) (responder rate) and 2) the mean %TBWL at 48 weeks. The primary safety endpoint is the percentage of patients who experience a Serious Adverse Event (SAE; Clavien-Dindo Class III or greater) that is device-or procedure-related. The secondary safety endpoint is the percentage of patients, frequency, and severity of individual Adverse Events (AEs) that are device- or procedure-related (e.g., abdominal pain, nausea, vomitting, bloating) during the balloon therapy period.
Follow-up Visits and Length of Follow-up	48 weeks
General
Study Status	Study Pending
Application Number / Requirement Number	P250009 / PAS001
Study Name	COSMIC Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Ongoing
Application Number / Requirement Number	P250028 / PAS001
Date Original Protocol Accepted	04/09/2026
Date Current Protocol Accepted	04/09/2026
Study Name	Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of a multi-center, prospective, non-randomized, historically controlled to evaluate the 5-year long-term safety and effectiveness of the Synergy Disc.
Study Population	Subjects implanted with the Synergy Disc during the IDE Study
Sample Size	Number of subjects: Up to 160 patients Assumptions for sample size estimation: Continued study participation from subjects available from the As Treated Analysis Set who were enrolled in the pivotal study Number of sites: Up to 20 study sites Sites location: United States
Key Study Endpoints	Primary: The primary safety endpoints for the post approval study are serious adverse events (SAEs), and device- or procedure-related adverse events (AEs). Secondary: Additional safety analyses will include the rate of AEs, including by relatedness to device or procedure and severity (mild, moderate, or severe), time-to-event, including mean and ranges if applicable, and Subsequent Surgical Intervention (SSI) by rate and type. Effectiveness Endpoints Primary: The primary endpoint of the investigation is individual patient success, which requires the patient to meet all of the following criteria at 60 months: Greater than or equal to 15-point improvement in NDI Score (out of 100) in subjects at 60 months compared with baseline; Maintenance or improvement in neurological status (motor and sensory only) at 60 months compared to baseline; No study failure due to secondary surgical interventions (revision, removal, re-operation, supplemental fixation) at the index level; Absence of radiographic failure, defined as any implant or component breakage or migration at the index level Absence of device-related Serious Adverse Event as adjudicated by the CEC Secondary: The following secondary evaluations will be collected: Health Survey (SF-36) at baseline and at each follow-up time-point Visual analogue scale (VAS) will be used to evaluate pain where a change of at least 20mm will be considered clinically significant Neck pain as measured on a 100mm VAS at baseline and at each follow-up time-point Left and Right arm/shoulder pain as measured on a 100mm VAS at baseline and at each follow-up timepoint. Please note, this assessment will include a “Worst” to pool together the left or right arm/shoulder scores with the higher baseline score. Patient Satisfaction
Follow-up Visits and Length of Follow-up	Annually through 60 months after surgery.
Interim or Final Data Summary
Interim Results	Safety Results: There was a total of 56 SAEs in 39 subjects in the PAS Analysis Set in the available data. The SAE rate was 24.4%, (39/160 subjects) with the majority of SAEs related to musculoskeletal and connective tissue disorders (20/56 events). 26 out of 56 SAEs of SAEs occurred beyond day 729. There was 1 device related and 3 procedure related SAEs. There is no current evidence that these event rates increase over time. Effectiveness Results: Preliminary data appears to show steady 15 point NDI improvement rates across given timepoints (91.6% at Month 24; 94.0% at Month 36; 95.2% at Month 48; 90.0% at Month 60) Neurological function (sensory and motor) appears to maintain across all timepoints One SSI has been reported for the PAS cohort (implant removal and fusion due to implant subsidence) Radiographic evaluations do not show problematic failure trends One device related SAE has been reported for the PAS cohort (adjacent segment disease)
Actual Number of Patients Enrolled	160
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	Month 24: 91% Month 36: 75% Month 48: 67% Month 60: 67%
General
Study Status	Study Pending
Application Number / Requirement Number	P200010 S027/ PAS001
Date Original Protocol Accepted	08/07/2026
Date Current Protocol Accepted	08/07/2026
Study Name	Guardant360 PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Other Data Source
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Study Pending
Application Number / Requirement Number	P170030 S058/ PAS001
Date Original Protocol Accepted	08/07/2026
Date Current Protocol Accepted	08/07/2026
Study Name	EVO Extended Diameter PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of this post-approval study is to confirm the clinical performance of the OrsiroTM MissionTM 4.5 mm and 5.0 mm diameter Sirolimus-Eluting Coronary Stent System for the treatment of subjects with atherosclerotic lesion(s) in the native coronary arteries with a reference vessel diameter of 4.5 mm to 5.0 mm (by visual estimate) and a lesion length of less than 26 mm (by visual estimate). This clinical trial will be prospective, multicenter, single-arm, observational study.
Study Population	Subjects with coronary artery disease (CAD), including those with diabetes mellitus, with symptomatic heart disease, stable angina, unstable angina, ST elevation myocardial infarction, non- ST elevation myocardial infarction or documented silent ischemia due to atherosclerotic lesions in the native coronary arteries with a reference vessel diameter of 4.5 mm to 5.0 mm and a lesion length of less than 26 mm.
Sample Size	Number of subjects: 100 Assumptions for sample size estimation: Number of sites: 20 Sites location: US and OUS
Key Study Endpoints	Primary: Target lesion failure (TLF) at 1 year post-index procedure. TLF is defined as a composite of cardiac death, target vessel Q-wave or non-Q-wave myocardial infarction (TV-MI), or clinically-driven target lesion revascularization (CD-TLR). Secondary: 1. Device success, defined as attainment of < 30% residual stenosis of the target lesion (based on operator visual estimate) using the study device only. Note: Post-dilatation is allowed to achieve device success. 2. Procedure success, defined as attainment of < 30% residual stenosis of the target lesion (based on operator visual estimate) using the study device only without occurrence of in-hospital major adverse cardiovascular events (MACE; composite of all cause death, Q-wave or non-Q-wave MI and any clinically-driven TLR). The following secondary endpoints will be evaluated at 6 months and 1, 2, 3, and 5 years post-index procedure: 3. All-cause death 4. Any MI 5. Cardiac death or MI 6. MACE and individual MACE components (MACE: composite of all-cause death, Q-wave or non–Q-wave MI, and any clinically driven TLR) 7. TLF (evaluated at 6 months, 2, 3 and 5 years) and individual TLF components (cardiac death, target vessel Q-wave or non–Qwave MI, and clinically-driven TLR) 8. Target vessel failure (TVF) and individual TVF components [TVF: composite of cardiac death, target vessel Q-wave or non-Q-wave MI, and clinically driven target vessel revascularization (CD-TVR)]. 9. Target lesion revascularization (TLR) 10. Target vessel revascularization (TVR) 11. Stent thrombosis according to Academic Research Consortium – 2 (ARC-2) definition.
Follow-up Visits and Length of Follow-up	Subjects will be followed for 5 years post-index procedure. Post-procedure follow-up intervals: 6 months and 1, 2, 3, and 5 years post-index procedure.
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250025 / PAS001
Study Name	TorEx Continuation Long-Term Post-Approval Study
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250025 / PAS002
Study Name	TorEx Lung Perfusion System Post-Approval Study
General Study Protocol Parameters
General
Study Status	Study Pending
Application Number / Requirement Number	P240014 / PAS001
Date Original Protocol Accepted	07/31/2026
Date Current Protocol Accepted	07/31/2026
Study Name	MAGiC-CHD Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The MAGiC-CHD Post-Approval Study is a prospective, nonrandomized, multi-center, single-arm study to confirm the effectiveness and safety of the MAGiC Ablation Catheter for the treatment of supraventricular tachycardia (SVT) in adult patients with congenital heart disease (CHD) and limited vascular access or difficult access to the target cardiac chamber. The objective of MAGiC-CHD is to collect device-related Major Adverse Events, and acute and chronic success rates with MAGiC in subjects with CHD being treated for a cardiac arrhythmia.
Study Population	Adult patients with congenital heart disease (CHD) and limited vascular access or difficult access to the target cardiac chamber.
Sample Size	Number of subjects: 40 Assumptions for sample size estimation: Number of sites: 10 Sites location: TBA
Key Study Endpoints	Safety Endpoints Safety will be assessed by the rate of device- or procedure-related serious adverse events through 7 days post procedure. Effectiveness Endpoints The primary endpoint is: 1. to estimate the rate of acute procedural success, defined as the percentage of patients with successful resolution of the treated index arrhythmia at the end of the procedure; and 2. to estimate the rate of chronic success through 6 months post-procedure, defined as the percentage of patients free from documented sustained recurrence of the treated index arrhythmia. Additional endpoints will be collected and reported: ¿ Rate of serious adverse events related to the MAGiC Ablation Catheter ¿ Acute procedural success and chronic success by type of target arrhythmia and by specific congenital defect and surgical repair. ¿ Arrhythmia or procedure related hospitalization and major adverse events through 6 months follow-up. ¿ All serious adverse events for severity, relatedness and outcome. ¿ Procedure Details o Procedure time (groin puncture to removal of all sheaths) o Total fluoroscopy time and dose ¿ Estimating the change in patient quality of life and arrhythmia burden.
Follow-up Visits and Length of Follow-up	Follow-up clinical data will be collected at discharge, 7 days, 1 month, and 6 months post-procedure.
General
Study Status	Ongoing
Application Number / Requirement Number	P960009 S219/ PAS002
Date Original Protocol Accepted	12/17/2025
Date Current Protocol Accepted	12/17/2025
Study Name	EPAS using RWD from the MORE Registry
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	Other Data Source
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Subjects will be selected from the MORE registry using the previously approved Epilepsy Post-Approval Study (EPAS) study inclusion and exclusion criteria, creating an ‘EPAS-like’ subgroup (EPAS-Like Cohort Criteria). Primary Effectiveness Objective - To evaluate the changes in total seizure frequency at 3 years Secondary Effectiveness Objectives - To evaluate the reduction in total seizure frequency assessed during the baseline phase to 12 months of DBS - To evaluate the reduction in disabling seizure frequency assessed during the baseline phase to 12 months of DBS - To evaluate the reduction in frequency of seizures originating in the temporal lobe assessed during the baseline phase to 12 months of DBS Secondary Safety Objective - To characterize the SUDEP rate
Study Population	The intended study population is subjects 18 years and older diagnosed with epilepsy characterized by focal-onset seizures that are refractory to at least 3 AEDs
Sample Size	There are 90 subjects that met the criteria.
Key Study Endpoints	Safety Endpoints Primary Effectiveness: To demonstrate that the total seizure frequency during is reduced by 40% after 3 years. Secondary: Secondary Effectiveness Objectives: 1. To demonstrate that the total seizure frequency assessed during the phase is reduced after 12 months 2. To demonstrate that the disabling seizure frequency assessed during the is reduced after 12 months 3. To demonstrate that the frequency of seizures originating in the temporal lobe assessed during the phase is reduced after 12 months Secondary Safety Objective: 4. To characterize the Sudden Unexpected Death in Epilepsy (SUDEP) rate
Follow-up Visits and Length of Follow-up	3 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	From the MORE registry Full Analysis Set of 170 subjects across 24 sites, a subset of 90 subjects from 20 sites were evaluated based on EPAS study-like eligibility criteria.
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	54 (60%) of the subset of 90 subjects completed 3-years follow-up
Final Safety Findings	The safety of Medtronic DBS Therapy for Epilepsy was studied in 90 EPAS-like implanted subjects who accumulated 320 years of device experience. In total, 251 AEs in 74 subjects (82.2%) and 88 SAEs in 41 subjects (45.6%) were reported over 3 years of FU. The most frequently reported event (>5% of EPASlike subjects) was seizure (AE: n=19, 21.1%; SAE: n=12, 13.3%). There were 8 AEs of depression (n=6), 1 AE suicidality (n=1), and 10 AEs of memory impairment (n=9) and all were assessed by the site as being related to the therapy. For seizure AEs, 52 were attributed to epilepsy (n=33), 17 AEs were related to therapy (n=13), 1 AE was related to procedure (n=1), and 0 seizure AEs were related to the device. There were no USADEs reported in the EPAS-like cohort. Two deaths occurred within the EPAS-like cohort. One of the deaths was assessed by the investigators as Possible SUDEP and the other death was due to endocarditis (Not SUDEP). Both deaths occurred more than 2 years after device implant and neither were related to the device or the therapy.
Final Effect Findings	There was a median 51.3% [95% CI: 35.8% - 65.0%] reduction in total seizures from Baseline at Year 3. Similarly, the responder rate was 53.7% at the Year 3 follow-up. The impact of missing data and dropouts were evaluated with sensitivity analyses, including Completer 2 Months (-50.8%), 70 Day Diary Completers (-51.1%) and repeated MI analyses (range: -48.3% to -55.1%). These analyses showed similar rates of seizure reduction, suggesting the missing data had minimal impact on improvement in outcomes.
Study Strengths & Weaknesses	Strengths: All patients had many years of drug-resistant partial onset seizures and were implanted with the Medtronic DBS system and Patients were followed for a minimum of 2 years, with many reaching 3 years of follow-up. Weakness: incomplete follow-up data, single arm study (no comparison), low number of subjects, greater variation in patient baseline characteristics, including differences in medical history, concomitant implants/devices, and other factors; greater variation in DBS targeting permitted in MORE due to real-world use settings; and analyses derived from registry data are frequently post-hoc, and therefore Type I error rates may be inflate
Recommendations for Labeling Changes	Yes
General
Study Status	Study Pending
Application Number / Requirement Number	P230013 S013/ PAS001
Date Original Protocol Accepted	10/31/2025
Date Current Protocol Accepted	10/31/2025
Study Name	Continued F/U of TRISCEND II Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living patients who were enrolled under the IDE, including those enrolled in the continued access protocol (CAP) investigation. The objective of this study is to characterize the clinical outcomes annually through 5 years (post-randomization for the control arm and post-procedure for the device arm of the randomized cohort, the single-arm registry, and CAP cohort).
Study Population	All living subjects enrolled under the IDE.
Sample Size	All living subjects.
Key Study Endpoints	Device deficiency, adverse events, all-cause mortality, heart failure hospitalization, non-elective tricuspid valve re-intervention (percutaneous or surgical), durable right ventricular assist device (RVAD) implantation or heart transplant, need for paracentesis, device success, echocardiographic parameters, 6-minute walk distance, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 36-Item Short Form Health Survey (SF-36) score, and EuroQoL 5-Dimensional Questionnaire (EQ-5D-5L) score.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P250019 / PAS002
Date Original Protocol Accepted	02/19/2026
Date Current Protocol Accepted	02/19/2026
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Registry-Based Real-World Use Surveillance. The objective of the surveillance is to assess the real-world performance of the SAPIEN M3 system.
Study Population	Patients treated for symptomatic moderate-to-severe or severe mitral regurgitation (MR) (Cohort A) and patients treated for symptomatic mitral valve dysfunction associated with mitral annular calcification (MAC) (Cohort B) that are entered into the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry.
Sample Size	Cohort A will involve all consecutive patients treated in the first 2 years following device approval or a total of 500 consecutively treated patients, whichever is greater (Cohort A enrollment period). Cohort B will involve all consecutive patients treated in the first 2 years following device approval or a total of 200 consecutively treated patients, whichever is greater (Cohort B enrollment period). Data collection in Cohort A will continue for under-enrolled racial and ethnic groups until each group has enrolled a minimum number of patients as specified: Black/African American, 50; Asian, 50, American Indian/Alaskan Native, 25, Native Hawaiian/Pacific Islander, 25; and Hispanic or Latino ethnicity, 50.
Key Study Endpoints	The clinical data through one (1) year will be collected through the TVT Registry. The follow-up data (including all-cause death, stroke, mitral valve reintervention, and heart failure rehospitalizations) from year 2 through year 5 post-procedure will be obtained through linking the TVT Registry data with the Centers for Medicare and Medicaid Services (CMS) claims database.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Study Pending
Application Number / Requirement Number	P220031 / PAS001
Date Original Protocol Accepted	04/08/2026
Date Current Protocol Accepted	04/08/2026
Study Name	LimiFlex Dynamic Sagittal Tether Cont F/U Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A descriptive prospective, single-center, single-arm study design. To evaluate the 5-year long-term safety and effectiveness of the LimiFlex Dynamic Sagittal Tether™.
Study Population	Enrollment of the patients included in the original PMA cohort (LimiFlex Dynamic Sagittal Tether™ study), who are evaluable for the long term 5 year follow up, which includes at least 124 LimiFlex Dynamic Sagittal Tether™ subjects in the Intent-to-Treat, Propensity Score Selected (ITT PS-Selected) population who were enrolled in the Pivotal study.
Sample Size	Number of subjects: 124
Key Study Endpoints	The primary effectiveness endpoint is a composite clinical success (CCS) responder endpoint based on clinical status at Month 60. An individual subject will be regarded as achieving Month 60 CCS only if they meet all of the following criteria at Month 60 compared to baseline: 5. Improvement of at least 15 points (100-point scale) on the Oswestry Disability Index (ODI) from baseline compared to 60 months. 6. Absence of a decrease in neurologic status (motor or sensory) at Month 60 compared to baseline unless attributable to a concurrent medical condition or other cause unrelated to the device and/ or study procedure. 7. Absence of additional surgical intervention, defined as revision, removal, reoperation or supplemental fixation/fusion, in a separate surgery subsequent to the index procedure, at the instrumented level or levels adjacent to the instrumented level, over the 60 months. 8. Absence of device integrity failures, defined as device breakage, device separation or disassembly, or device dislocation, over the 60 months. Secondary Endpoints: In addition, at Month 60, individual subjects will be assessed for the following endpoints: 3. No occurrence of any spinous process fractures at the implanted level (entire functional spine unit (FSU) instrumented with the subject device) up to 60-months follow-up and the time of occurrence relative to original index LimiFlex implant surgery. No occurrence of a major device-related adverse event. This includes no occurrence of device integrity failure, including but not limited to subsidence, migration and dislodgement at the LimiFlex implant level (entire FSU instrumented with the subject device).
Follow-up Visits and Length of Follow-up	Clinical follow-up evaluations will be conducted at 6 weeks, and 3, 6, 12, 24, 36, 48 and 60 months.
General
Study Status	Ongoing
Application Number / Requirement Number	P250013 / PAS001
Date Original Protocol Accepted	06/18/2026
Date Current Protocol Accepted	06/18/2026
Study Name	Cont F/u (OPSPREY Study)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A multi-center prospective, observational, open label, long-term follow-up of the Aura6000® System in patients who have completed the OSPREY clinical trial. OSPREY subjects will be evaluated for adverse events and will also undergo HSTs annually and/or PSG as well as an impedance check to assess IPG function twice a year. The purpose of this study is to quantify long-term efficacy and safety outcomes in subjects who have participated in the OSPREY clinical trial and have completed the M13 visit.
Study Population	All subjects participating in the OSPREY clinical trial who have completed M13 of the OSPREY study will be offered participation to this study.
Sample Size	Number of subjects: 150 Assumptions for sample size estimation: As a descriptive study there is no formal hypothesis, and a formal sample size calculation is not necessary. Number of sites: 30 Sites location: US
Key Study Endpoints	Primary: Descriptive evaluation of all reported Adverse events. Secondary: N/A Effectiveness Endpoints Primary: The primary endpoint is to evaluate change in AHI (Apnea Hypopnea Index) relative to the pre-therapeutic baseline in subjects implanted with Aura6000® System annually based on HST and/or PSG data. Secondary: The change in ODI, ESS and FOSQ between pre-therapeutic timepoint and annual visit. Clinical Global Impression S (CGI S) at pre-therapeutic timepoint and Clinical Global Impression I (CGI I) annually thereafter.
Follow-up Visits and Length of Follow-up	Enrollment is expected to be 24 months with follow up to additional 48 months. The M48 will equate to approximately 60 months (5 years) on therapy for subjects randomized to the active group and approximately 54 months (4.5 years) for subjects randomized to the control group.
General
Study Status	Hold
Application Number / Requirement Number	P250013 / PAS002
Date Original Protocol Accepted	04/30/2026
Date Current Protocol Accepted	04/30/2026
Study Name	New Enrollment Study PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
General
Study Status	Study Pending
Application Number / Requirement Number	P250024 / PAS001
Date Original Protocol Accepted	05/18/2026
Date Current Protocol Accepted	05/18/2026
Study Name	Continued Follow-up of the Premarket Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this trial was to evaluate the safety and effectiveness of the Trilogy device in symptomatic patients with severe aortic regurgitation who are at a high or greater risk for surgical aortic valve replacement (SAVR). The study includes continued follow-up of patients enrolled under the IDE, including the ALIGN-AR pivotal trial and the Continued Access Protocol (CAP) investigation. Patients will be followed from years 1-5 under the IDE protocol and from years 6-10 using CMS linkage.
Study Population	Patients with symptomatic, severe aortic regurgitation (not due to acute endocarditis, rheumatic heart disease, or acute aortic dissection) who are at a high or greater risk for surgical aortic valve replacement (SAVR)
Sample Size	Years 1-5: All living patients who were enrolled under the IDE Years 6-10: The subset of patients in the ALIGN-AR and ALIGN-AR CAP studies who are = 65 years old and able to be linked to Medicare fee-for-service and Medicare Advantage claims.
Key Study Endpoints	Years 1-5 data will be collected per the study protocol and summarized descriptively, including, but not limited to: • All-cause mortality • Adverse events • Aortic valve reintervention, • Heart failure hospitalizations • Echocardiographic parameters, • Kansas City Cardiomyopathy Questionnaire (KCCQ) score • New York Heart Association (NYHA) functional classification • 6-Minute Walk Test (6MWT) distance Bioprosthetic valve failure, assessed using established echocardiographic criteria, will be reported with a minimum of 80% completeness rate each year through 5 years. Years 6-10 data will be collected from CMS Linkage: • All-cause mortality • Stroke • Aortic valve reintervention • Hospitalization (all-cause) • Heart failure hospitalizations
Follow-up Visits and Length of Follow-up	Years 1-5 under IDE protocol. Years 6-10 through CMS linkage.
General
Study Status	Study Pending
Application Number / Requirement Number	P250024 / PAS002
Date Original Protocol Accepted	05/18/2026
Date Current Protocol Accepted	05/18/2026
Study Name	Registry-Based Real-World Use Surveillance
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Trilogy Post-Approval Surveillance Analysis is designed to assess the short-term and long-term safety and effectiveness outcomes associated with the use of the Trilogy Transcatheter Heart Valve System (Trilogy THV) in a routine clinical setting.
Study Population	Patients in the STS/ACC TVT Registry who are treated with the Trilogy THV during the 2-year enrollment period will be included. If data on greater than or equal to 2,000 patients are not available by the end of the study period, the enrollment period will be extended until at least 2,000 patients are included. Data collection will continue for under-enrolled racial and ethnic groups until each group has enrolled a minimum number of patients as specified: Black/African American, 100; Asian, 100; American Indian/Alaskan Native, 25; Native Hawaiian/Pacific Islander, 25; and Hispanic or Latino ethnicity, 100.
Sample Size	Number of subjects: greater than or equal to 2000, Data collection will continue for under-enrolled racial and ethnic groups until each group has enrolled a minimum number of patients as specified: Black/African American, 100; Asian, 100; American Indian/Alaskan Native, 25; Native Hawaiian/Pacific Islander, 25; and Hispanic or Latino ethnicity, 100. Assumptions for sample size estimation: N/A Number of sites: N/A Sites location: N/A
Key Study Endpoints	• All-cause mortality • Stroke • Aortic valve reintervention • Heart failure hospitalizations
Follow-up Visits and Length of Follow-up	30-days and 1-year through TVT-Registry. Years 2-10 through CMS link
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250021 / PAS001
Study Name	VOLIDO-PAS (PAS/FST)
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
General
Study Status	Protocol Pending
Application Number / Requirement Number	P250021 / PAS002
Study Name	PAS/Scale Validation
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P240033 / PAS001
Study Name	Long-Term Follow-up of EVP-DEV-LTX-301
General Study Protocol Parameters
General
Study Status	Protocol Pending
Application Number / Requirement Number	P240033 / PAS002
Study Name	LungFX PAS
General Study Protocol Parameters
General
Study Status	Study Pending
Application Number / Requirement Number	P250016 / PAS001
Date Original Protocol Accepted	08/31/2026
Date Current Protocol Accepted	08/31/2026
Study Name	Belotero Intense PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A Prospective, Post-Market, Open-Label, Multicenter, Single-Arm Study Evaluating the Safety and Effectiveness of Belotero® Intense (+) Lidocaine for Lip Augmentation in Participants with Fitzpatrick Skin Types V or VI Primary objective -Demonstrate safety of BIL for use in lip augmentation in participants with Fitzpatrick Skin Type (FST) V or VI Secondary objective -Demonstrate the effectiveness of BIL for lip augmentation in participants with FST V or VI
Study Population	Approximately 20 healthy male, female, or transgender participants will be screened to achieve approximately 16 participants for BIL treatment. Enrollment is planned across approximately three US investigational sites. Participants are expected to be healthy FST V or VI male, female, or transgender over 21 years and less than or equal to 65 years of age at the time of signing the informed consent and desiring lip augmentation to correct volume deficit with upper and/or lower lip deficit rating of 0 (very thin), 1 (thin), or 2 (medium) on the Merz Lip Fullness Assessment Scale (MLFAS), as determined by the treating investigator.
Sample Size	Number of subjects: 20 Assumptions for sample size estimation: n/a Number of sites: 3 Sites location: United States
Key Study Endpoints	Safety Endpoints Primary: Occurrence of related TEAEs, as documented by the investigator throughout the study Secondary: -Occurrence of TEAEs -Occurrence of serious TEAEs -Occurrence of TEAEs leading to discontinuation from the study -Occurrence of device deficiencies -Occurrence of prespecified CTRs as documented by the participant for 28 days after each treatment -Normal and abnormal results of active lip function and sensation assessments (Section 11.2.7). Abnormality is defined as a difference between pre- and post-treatment assessments. -Normal and abnormal results in the post-treatment lip function and sensation questionnaire (Section 11.2.7.3). Abnormality is defined as a score of greater than or equal to 4 for any item in the participant-assessed function and sensation questionnaires. -Normal and abnormal results of lip symmetry and lip movement assessments (Section 11.2.8). -Normal and abnormal results of the visual acuity test using the Snellen chart -Normal and abnormal results of the confrontation visual field test -Normal and abnormal results of the ocular motility examination -Normal and abnormal results of Facial drooping, Arm weakness, Speech difficulties, Time to call emergency services (FAST) test Effectiveness Endpoints Secondary: Responder rate at Visit V3, according to the MLFAS, as assessed live by the treating investigator, where response is defined as greater than or equal to 1-point improvement on participant’s treated lip(s) compared to baseline Tertiary: - Global Aesthetic Improvement Scale (GAIS) scores for treated participants at all post-baseline visits, as completed by the treating investigator (iGAIS) - GAIS scores for treated participants at all post-baseline visits, as completed by the participant (pGAIS)
Follow-up Visits and Length of Follow-up	The expected study duration per participant, excluding visit windows, is up to 30 weeks (up to 10 days screening period + baseline treatment + optional touch-up at Week 4 + 24-week follow-up). Participants without a touch-up will have seven onsite visits (including screening), and participants with a touch-up will have nine onsite visits (including screening). After the baseline visit, follow-up visits will occur at Weeks 2, 4, 8, 16, and 24 for participants without touch-up and Weeks 2, 4, 6, 8, 16, 20, and 28, for participants with touch-up.
General
Study Status	Study Pending
Application Number / Requirement Number	P250033 / PAS002
Date Original Protocol Accepted	07/24/2026
Date Current Protocol Accepted	07/24/2026
Study Name	Nexus New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, non-randomized, multi-center, single-arm, PAS evaluating subjects treated with NEXUS® device. The objective of the study is to evaluate long-term real-world safety and effectiveness outcome data on the NEXUS® device and to assess the adequacy of the training program.
Study Population	Subjects who are intended to be treated with NEXUS® device.
Sample Size	Number of subjects: Up to 150 (minimum of 135) Number of sites: Up to 60 sites globally Sites location: US and OUS
Key Study Endpoints	Co-Primary Endpoints: Device Technical Failure (through 30-Days): • Failure to accurately deliver, track and deploy all required endovascular device components at the intended implantation site and failure to retrieve the device delivery systems without the need for unplanned additional procedures • Device occlusion • Failed exclusion of primary entry tear • Additional unanticipated surgical or interventional procedure related to the device or procedure, to prevent life-threatening or permanent disabling event. Specifically, the below will be counted against the endpoint: ¿ Surgical conversion ¿ Re-intervention to treat migration ¿ Re-intervention to treat stenosis or occlusion ¿ Re-intervention to treat type Ia, Ib, III, IV endoleaks. ¿ Re-intervention for loss of device integrity Clinical Failure (through 30-Days): Subjects experiencing at least one of the following MAEs through 30-Day of Phase 1 procedure and 30-Day of Index procedure: • Lesion Related Mortality • Defined as: Death occurring after the procedure (Phae 1 or Index) or a secondary procedure and attributable to pathology involving the treated aortic segment, including deaths related to device malfunction; aortic rupture of the treated segment, retrograde dissection involving the treated segment, or fistula formation involving the treated segment. • Disabling Stroke • Defined as: a stroke with a mRS score of two or more at 30 days and an increase in at least one mRS category from an individual’s pre-stroke baseline • Permanent Paralysis/Paraplegia • Defined as: Spinal Cord Ischemia Scale > 3 (Non-ambulatory and/or wheelchair bound), persisting at least 30 days). • Renal failure • Defined as: new onset requiring permanent dialysis • Aortic rupture • Defined as: catastrophic rupture or tear of the aorta as confirmed by new hematoma or pericardial effusion based upon CT, MRI or Echocardiographic imaging. • Development of new dissections in the thoracic aorta or brachiocephalic artery • Defined as: any great vessel or brachiocephalic artery that clinically requires intervention Secondary Endpoints: • The individual elements of the primary endpoints • Device and procedure-related SAEs • Access-related complications (Index Procedure only) • Life Threatening Bleed (Index Procedure only) • All-cause mortality • Lesion related mortality • Neurological Events including Disabling Stroke • All neurological events will be measured for the overall rate along with the rate of disabling stroke reported separately. • Permanent Paralysis/paraplegia (Starting within 30 days only) • Myocardial Infarction (within 30 days only) • Laryngeal or Phrenic Nerve Injury (within 30 days only) • Development of new dissections proximal or distal to the treatment zone requiring clinical intervention • Development of new dissections proximal or distal to the treatment zone without clinical intervention • False lumen status: partially thrombosed, patent, thrombosed, complete thrombosis (chronic dissection cohort only) • False lumen perfusion source (chronic dissection cohort only) • Lesion enlargement of treated area • Endoleaks (Type I, III, IV, V) • Migration • Extension of Dissection • Patency Status • Loss of stent graft integrity • Lesion-Related Events • Conversion to open repair • All Secondary procedures in the treatment area • Device-related SAEs
Follow-up Visits and Length of Follow-up	30 days, 6 months, 1 year, annually thereafter through 10 years
General
Study Status	Hold
Application Number / Requirement Number	P150009 / PAS001
Date Original Protocol Accepted	08/14/2018
Date Current Protocol Accepted	06/18/2024
Study Name	AngelMed Guardian PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Positive predictive value (PPV) and false positive rate (FPR) will be examined. Prospective, non-randomized, single arm, event-based, multi-center trail to assess device diagnostic accuracy, physician compliance, implantation expertise, emergency department physician experience, patient compliance for alerts, and training for prescribing, implanting, and emergency physicians, as well as patients. New subjects will be enrolled and a past study will be used as a control.
Study Population	Patients with prior ACS events and high risk for recurrent ACS events.
Sample Size	A minimum of 500 patients for the purpose of accruing 314 adjudicated true positive or false positive events.
Key Study Endpoints	Co-primary endpoints include determination of PPV and FPR. Secondary endpoints include additional information: frequency of alarm-only ACS events (no signs of symptoms/discomfort), and the amount of time between patient symptom reports and medical presentation.
Follow-up Visits and Length of Follow-up	Completion of follow-up study is anticipated by March 2023.
Interim or Final Data Summary
Interim Results	study is ongoing
Actual Number of Patients Enrolled	53
Actual Number of Sites Enrolled	19
Patient Follow-up Rate	N/A. study is ongoing
General
Study Status	Study Pending
Application Number / Requirement Number	P160052 / PAS001
Date Original Protocol Accepted	10/11/2019
Date Current Protocol Accepted	10/11/2019
Study Name	PartoSure PAS
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is an observational study that collects data from medical records of pregnant women presenting with signs and symptoms of preterm labor with clinically intact membranes, a cervical dilatation <3 cm, a singleton gestation between 240/7 and 346/7 weeks of gestation and tested with the PartoSure Test in routine clinical care. Results of the PartoSure Test (positive or negative) and delivery status (defined as whether a spontaneous preterm delivery (SPTD) occurred within 7 days of testing with the PartoSure Test) will be observed and assessed.
Study Population	The study population consists of all women who present to the clinic or labor and delivery suite who are tested with the PartoSure test and meet the following inclusion/exclusion criteria.: Inclusion Criteria: 1. Singleton pregnancy 2. Between 240/7 and 346/7 weeks of gestation 3. PartoSure test performed and test result available 4. Presentation suspicion, signs, or symptoms suggestive of pre-term labor with one or more of the following criteria: • Uterine contractions, with or without pain • Intermittent lower abdominal pain • Dull backache • Pelvic pressure • Bleeding during the second or third trimester • Menstrual-like or intestinal cramping, with or without diarrhea • Patient not feeling “right”, which may include such symptoms as general malaise, aches, and/or discomfort that are suggestive of possible preterm labor Exclusion Criteria: 1. Cervical dilatation = 3 centimeters 2. Known or suspected placenta previa 3. Cervical cerclage in place 4. Presence of moderate to gross vaginal bleeding 5. Subjects who had rupture of the fetal membranes 6. The subject has used a lubricant or antiseptic (e.g. K-Y® or Surgilube® lubricating jelly, Betadine® Cleanser) within 24 hours 7. The subject has applied a topical disinfectant (e.g. Monistat®, micanozole nitrate cream) to the vaginal area within 24 hours 8. Subjects who are less than 18 years old in jurisdictions where individuals less than 18 years old are not considered as emancipated minors
Sample Size	The study will enroll 4800 subjects in order to observe 168 spontaneous preterm deliveries within 7 days of PartoSure testing, assuming a prevalence of 3.5%.
Key Study Endpoints	PartoSure Test (positive or negative) and the patient’s delivery status, defined as whether a spontaneous preterm delivery occurred within 7 days of testing with the PartoSure Test, will be observed for each subject.
Follow-up Visits and Length of Follow-up	The sponsor will attempt to collect missing delivery data via follow-up telephone calls up to the point the subject reaches 39 weeks of gestation.
General
Study Status	Completed
Application Number / Requirement Number	P810002 S101/ PAS001
Date Original Protocol Accepted	03/06/2018
Date Current Protocol Accepted
Study Name	Cont f/u of the premarket HALO Cohort
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this study is to evaluate long term safety and effectiveness of the SJM™ Masters Series Hemodynamic Plus (HP) 15mm mitral mechanical heart valve as a replacement device for pediatric patients with a diseased, damaged, or malfunctioning mitral valve. The study includes continued follow-up of patients enrolled in the HALO study, which was a single arm, prospective, non-randomized, multi-center clinical trial of the SJM™ Masters Series Hemodynamic HP 15mm mitral heart valve.
Study Population	The study population consists of pediatric subjects that are 5 years or less in age with a diseased, damaged, or malfunctioning mitral heart valve.
Sample Size	This study will continue to follow subjects that are alive and in which the valve is still implanted from the following groups: Subjects enrolled in the HALO study, Subjects enrolled under Continued Access, and Emergency/compassionate use subjects who have consented for prospective follow-up.
Key Study Endpoints	The following adverse events (if determined to be valve related and serious) will be summarized annually with descriptive statistics: Death; Endocarditis; Hemorrhage (whether or not due to anticoagulant/antiplatelet medication); Nonstructural dysfunction (including perivalvular leak, hemolysis, and hemolytic anemia); Reoperation (including valve explant, not due to anatomical growth of the subject); Structural valve deterioration; Thromboembolism; and Valvular thrombosis. The following effectiveness endpoints will be reported at any/all time point(s) available: Mean gradient as assessed by echocardiography; Peak gradient as assessed by echocardiography; and Valvular regurgitation grade as assessed by echocardiography.
Follow-up Visits and Length of Follow-up	Study subjects will be followed annually either for five years from the date of implant, until subject withdrawal, or until end of device use, whichever occurs earliest.
Interim or Final Data Summary
Actual Number of Patients Enrolled	23 (20 IDE & 3 CAP)
Actual Number of Sites Enrolled	15
Patient Follow-up Rate	The final study follow-up rate at 5 years is 95.6% (22/23)
Final Safety Findings	At 12 months, the K-M freedom from valve-related adverse events was 64.3% for all study subjects. Within 12 months of implant, the following CEC-Adjudicated Valve-related Adverse Events occurred: 6 all-cause deaths, 1 endocarditis, 5 all hemorrhage, 1 nonstructural dysfunction, 5 reoperations, 1 thromboembolism, and 5 thrombus on device. Between 12 months and 5-years, the following additional events occurred: 2 all hemorrhage, 1 nonstructural dysfunction, and 2 reoperations.
Final Effect Findings	Patients showed improvement from baseline in peak and mean valve gradient and valve regurgitation until valve was removed/replaced due to anatomical growth.
Study Strengths & Weaknesses	One strength of the study was that it had a high follow-up rate (95.6%) with only 1 patient lost to follow-up. A weakness of the study is that it is a single arm study with a smaller sample size.
Recommendations for Labeling Changes	Updates to the labeling are recommended
General
Study Status	Ongoing
Application Number / Requirement Number	P810002 S101/ PAS002
Date Original Protocol Accepted	12/07/2018
Date Current Protocol Accepted
Study Name	HALO PAS
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Neonate: Birth < 29 days, Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs
Detailed Study Protocol Parameters
Study Objectives	This PAS is an observational single arm, non-randomized, multi-center clinical trial. Data from patients prospectively and retrospectively enrolled may contribute to the study dataset as follows: Enrollment of new, prospective patients receiving a 15 AHPJ-505 MHV in the aortic position; Enrollment of patients previously implanted with a 15AHPJ-505 MHV in the aortic position consenting for retrospective inclusion
Study Population	Patients requiring aortic valve replacement with anatomy that requires a 15mm valve (< 18 years old)
Sample Size	No. of subjects: A minimum of 20 subjects implanted with the 15mm HP aortic valve (echocardiography data reported whenever it is available); or A minimum of 12 subjects with echocardiography data at a time point(s) greater than 90 days No. of sites: 40 sites across US and 10 sites outside of the US
Key Study Endpoints	Safety Endpoints Primary: The actuarial (Kaplan-Meier) rate of total serious valve-related adverse events experienced through 5 years post implant or until the valve is removed/replaced (whether or not the replacement or removal is due to anatomical growth of the subject), whichever occurs first. Valve-related adverse events to be evaluated are: - Death; - Endocarditis; - Hemorrhage (whether or not due to anticoagulant/antiplatelet medication); - Nonstructural dysfunction (including perivalvular leak, hemolysis, and hemolytic anemia); - Reoperation (including valve explant, not due to anatomical growth of the subject); - Structural valve deterioration; - Thromboembolism; and - Valvular thrombosis. Secondary: -All-cause mortality -Valve-related mortality -Reoperation or explant excluding replacement due to somatic growth Effectiveness Endpoints: Primary: - Peak gradient as assessed by echocardiography; - Mean gradient as assessed by echocardiography; - Valvular regurgitation type (central or perivalvular) and grade as assessed by echocardiography.
Follow-up Visits and Length of Follow-up	Frequency: Baseline, procedure, post procedure, 30D, 6mo, 1 year and annually thereafter Length: 5 years or explant
General
Study Status	Terminated
Application Number / Requirement Number	P830060 S062/ PAS001
Date Original Protocol Accepted	01/14/2011
Date Current Protocol Accepted	01/14/2011
Study Name	Longitudinal Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The LSS of 4-SITE is a prospective, nonrandomized, multi-center registry of patients implanted with the 4-SITE Lead/Header system.
Study Population	Patients implanted with the 4-SITE Lead/Header system
Sample Size	1,780 patients.(assuming an annual attrition rate of 10%, a minimum of 1,780 patients implanted with the 4-SITE lead is necessary to obtain 5-year follow-up data on approximately 1050 patients)
Key Study Endpoints	For the 4-SITE Lead/Header system, the primary endpoint for this registry will evaluate the proportion of patients without a chronic 4-SITE Lead/Header-related complication within five years post-implant.
Follow-up Visits and Length of Follow-up	Five-years post implant Every six months
General
Study Status	Completed
Application Number / Requirement Number	P960040 S198/ PAS001
Date Original Protocol Accepted	11/10/2010
Date Current Protocol Accepted	12/21/2012
Study Name	Longitudinal Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The LSS of 4-SITE is a prospective, nonrandomized, multi-center registry of patients implanted with the 4-SITE Lead/Header system.
Study Population	Patients implanted with the 4-SITE Lead/Header system
Sample Size	1,780 patients.(assuming an annual attrition rate of 10%, a minimum of 1,780 patients implanted with the 4-SITE lead is necessary to obtain 5-year follow-up data on approximately 1050 patients
Key Study Endpoints	For the 4-SITE Lead/Header system, the primary endpoint for this registry will evaluate the proportion of patients without a chronic 4-SITE Lead/Header-related complication within five years post-implant.
Follow-up Visits and Length of Follow-up	Five-years post implant Every six months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1820 subjects
Actual Number of Sites Enrolled	111 sites
Patient Follow-up Rate	5 years post-implant
Final Safety Findings	The sponsor reported a complication-free rate through 60 months for the 4-SITE Lead/Header system of 98.9% with a one-sided 95% lower confidence limit of 98.5%. The lower confidence limit is higher than the performance goal of 92.5%. The sponsor also reported 17 adverse events that contributed to the primary endpoint. All lower confidence limits for all events types are within 1% of the complication free rate.
Final Effect Findings	Please see above
Study Strengths & Weaknesses	The sponsor has collected sufficient data to address the primary objective of the study which was to estimate the five year Endotak Reliance 4-Site defibrillation lead related chronic complication-free rate. The Agency recommends that the sponsor update the labeling to incorporate the study findings.
Recommendations for Labeling Changes	FDA recommends that the sponsor update the labeling for these devices to reflect the long-term data from the Post Approval Study.
General
Study Status	Completed
Application Number / Requirement Number	P830061 S129/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P050016 / PAS001
Date Original Protocol Accepted	07/03/2007
Date Current Protocol Accepted	11/04/2008
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a multi-center, non-randomized, cohort study, which includes the extended follow-up of the premarket cohort.
Study Population	Study population is as per device indication.
Sample Size	The sample size is up to 448 patients.
Key Study Endpoints	Data collection includes patient demographic data and medical history. A functional evaluation will be performed including a Harris Hip Score. Radiographic examination will encompass anteroposterior (AP) and lateral plain film studies.
Follow-up Visits and Length of Follow-up	Patients will receive clinical and radiographic examination at 3, 4, 5, 8 and 10 postoperative years. In addition, patients will receive brief questionnaires at 6, 7, and 9 postoperative years. For both primary efficacy endpoints (freedom from revision and composite clinical success) , the primary objective will be met by way of estimation using 95% exact binomial confidence intervals. Device survival will be illustrated by life tables and the plotting of a Kaplan-Meier curve.
Interim or Final Data Summary
Interim Results	At 60 post-operative months, 94.5% of study participants attained a good-excellent Harris Hip Score.. Reported serious adverse events in the study population included 1 case of femoral fracture, 1 case of acetabular component loosening, and 1 case of dislocation.
Actual Number of Patients Enrolled	A total of 258 hips in 231 subjects were enrolled in the study.
Actual Number of Sites Enrolled	A total of 5 study sites were enrolled.
Patient Follow-up Rate	The follow-up rate was 81.7% at 10 post-operative years
Final Safety Findings	Female gender and relatively smaller component size were risk factors for device revision. Metal ion results at 5+ post-operative years were as follows: mean whole blood cobalt: 2.509 microg/L and mean whole blood chromium: 2.408 microg/L.
Final Effect Findings	Calculated composite clinical success at 10 post-operative years was 88.2% without imputation and 73.2% with imputation.
Study Strengths & Weaknesses	Study strengths included the use of the Harris Hip Score, a recognized and validated measure of device performance and the use of radiographic examination that allowed the detection of adverse events that are not detectable on history and physical examination. An important weakness of the post-approval study was the limited number of patients who received the device because of an underlying diagnosis other than osteoarthritis (e.g. avascular necrosis).
Recommendations for Labeling Changes	The label of the device should be revised to include the results of this post-approval study
General
Study Status	Completed
Application Number / Requirement Number	P830063 S002/ PAS001
Date Original Protocol Accepted	08/28/2002
Date Current Protocol Accepted
Study Name	Gambro PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was an un-controlled, open study design in which patients deemed treatable by their physician with the Gambro Prisma TPE System and the Gambro Plasmafilter PF 2000N were included in the PAS.
Study Population	Study population is as per device indication. The Gambro Fiber Plasmafilter PP is indicated for use in performing therapeutic plasma separation from whole blood in a clinical setting to remove circulating plasma components or protein-bound toxins.
Sample Size	The conditions of approval required a study of at least 400 patients from a minimum of three sites and the first 10 patients who received at least 4 treatments were to be followed for a month following these treatments.
Key Study Endpoints	The data collected for each individual treatment during this post-market surveillance study should include: the patient identification number, the ordinal number of treatment, the duration of treatment, all patient complications, all device difficulties, and a brief description of the extracorporeal blood and plasma circulation system used for the therapy including manufacturer's name, model number, and operating parameters (TMP, blood flow rate, plasma flow rate, device inlet pressure, venous outlet pressure). The data should be divided into two general categories: 1) patient complications (including symptoms) and 2) difficulties experienced with the operation of the device together with a record of all alarms. Patient complications should be further divided into two sections:1. I) device-refated complications and 1.2) other complications. The section of the data concerning patient complications should include all operator interventions or responses either to the device or the patient's condition.
Follow-up Visits and Length of Follow-up	1 month
Interim or Final Data Summary
Actual Number of Patients Enrolled	total of 414 treatments were performed on 31 subjects at 7 centers.
Actual Number of Sites Enrolled	7
Patient Follow-up Rate	100%
Final Safety Findings	A number of symptoms were seen at varying prevalences. Chills were most common (25% of treatments), followed by access problems (10%). Other symptoms were seen at lower frequency. All the relatively common symptoms seen were those associated with extracorporeal blood treatment generally rather than specifically with plasma filtration. A decision was made to discontinue plasmafiltration in 24 (5.8%) of the treatments. This however, was far more common when there were access problems that when there were not (88% of severe access problems, versus 4% of no access problem treatments). Clotting of the plasmafilter occurred in 6% of treatments; repeated clotting was also associated with discontinuation of the plasmafiltration. Discontinued treatments averaged 0.38 filter changes each, versus 0.04 for the treatments that were completed. Blood leaks from the plasmafilter occurred in 3 of the 414 treatments. This low rate of complications did not interfere with the ability to deliver the prescribed treatment - more than half the treatments delivered an exchange volume within 1% of that prescribed. The 414 treatments included 56 with blood access flow problems. However, only one of these was related to the Prisma TPE. There was a total of 6 unanticipated serious adverse events. None of these was fatal Three were judged 'definitely not' and the other three 'probably not' related to the study. These figures indicate that the Prisma TPE provides the required therapy effectively, and that it has a very low rate of complications.
Study Strengths & Weaknesses	Strength: Sample size was larger than required. Weakness, descriptive nature. No comparison group
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P860004 S056/ PAS001
Date Original Protocol Accepted	09/12/2003
Date Current Protocol Accepted	09/12/2003
Study Name	Synchromed II
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a 12-month, multi-center, single arm prospective cohort study. All subjects in the study receive the device.
Study Population	Study population: Patients at least 18 years old receiving the infusion system for the treatment of chronic, intractable pain or severe spasticity of spinal or cerebral origin and those receiving an initial pump or replacement pump. Indication for use: The SynchroMed II infusion system is an implantable, programmable drug delivery system used to treat pain, spasticity, and cancer. It is indicated for: 1) Chronic intraspinal (intrathecal or epidural) infusion of sterile, preservative-free morphine sulfate for chronic, intractable pain of malignant and/or benign origin; 2) Chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain; 3) Chronic intrathecal infusion of Lioresa Intrathecal (baclofen injection) for severe spasticity of spinal or cerebral origin; and 4) Chronic intravascular infusion of methotrexate and floxuridine for the treatment of cancer (not included in this study).
Sample Size	100 subjects, 13 sites
Key Study Endpoints	Primary endpoint: comparison of observed refill measurements to calculated volume dispensed for patients with at least 2 refills during the first six months. Secondary endpoint: descriptive evaluation of all adverse events and technical observations through 12 months post-implant.
Follow-up Visits and Length of Follow-up	Data were to be collected at the following visits: baseline evaluation, system implant, 1, 6, and 12 months post-implant, interim refill visits, and visits for adverse events.
Interim or Final Data Summary
Actual Number of Patients Enrolled	82 patients enrolled, 80 implanted
Actual Number of Sites Enrolled	9
Patient Follow-up Rate	85%
Final Safety Findings	All the subjects included in the primary analysis had accuracy ratios within the prespecified interval. Thirty-eight subjects experienced 58 device-related events, the most frequent were: implant site effusion (n=16 events), lumbar puncture headache (n=8), catheter dislodgement (n=5), and implant site inflammation (n=4). Three events were treated with device explant. The probability of pump survival at 12 months was 95.8%.
Study Strengths & Weaknesses	Strengths: The study assessed known potential serious adverse event through capturing dispensing. Weaknesses: The study did not capture over- and under-infusions resulting in toxicity/overdose or decreased therapeutic responses as potentially device-related events. The study did not account for differences in pump function with approved, non-approved, or compounded drugs. The pre-specified interval was wide and included both very high and very low values.
Recommendations for Labeling Changes	There were no recomendations were made for labeling changes.
General
Study Status	Completed
Application Number / Requirement Number	P030025 S028/ PAS002
Date Original Protocol Accepted	09/24/2008
Date Current Protocol Accepted	09/24/2008
Study Name	Fatigue/Matter Testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a simulated use particulates testing, 10-year equivalent pulsatile particulates on a curve testing, 10-year equivalent pulsatile fatigue on a curve testing.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	This is a simulated use particulates testing, 10-year equivalent pulsatile particulates on a curve testing, 10-year equivalent pulsatile fatigue on a curve testing.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Interim Results	N/A, This is a bench testing study.
Actual Number of Patients Enrolled	NA
Actual Number of Sites Enrolled	NA
Patient Follow-up Rate	NA
Final Safety Findings	NA
Final Effect Findings	NA
Study Strengths & Weaknesses	NA
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P860057 S029/ PAS001
Date Original Protocol Accepted	12/05/2008
Date Current Protocol Accepted	01/24/2014
Study Name	Long Term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A prospective, single-arm, multi-center study that will enroll a minimum of 250 patients implanted with the Carpentier-Edwards PERIMOUNT 7000 TFX, 72000 TFX and 73000 TFX, Magna Ease, Model 3300TFX, in order to achieve 101/Aortic valve replacement subjects each followed for a minimum of 8 years. A new enrollment study.
Study Population	Study Population: Patients must be at least 18 years of age eligible for mitral valve replacement. Indication: It is intended for patients who require replacement of their diseased, damaged or malfunctioning native or prosthetic aortic valve and whose prognosis without aortic valve replacement is unacceptably poor. No comparator group.
Sample Size	A minimum of 250/Subjects at up to 25/Sites in order to obtain a minimum of 8 years data on 101 subjects.
Key Study Endpoints	Endpoints include thrombo-embolism, perivascular leak, hemorrhage, endocarditis, and heart failure. Early AE (within 30 days of implant) are summarized as the percent (events /subjects) of subjects experiencing an early event. Late post- operative AE (>30 days post-implant) are summarized in terms of linearized rates (events /patient years).
Follow-up Visits and Length of Follow-up	8 years - Patients will be followed at discharge, 6-months, one year, and annually thereafter for a minimum of 8 years.
Interim or Final Data Summary
Actual Number of Patients Enrolled	329
Actual Number of Sites Enrolled	19
Patient Follow-up Rate	The study met its minimum required follow-up target of 101 patients for 8 years of follow-up. Of the 329 implanted patients, 109 patients completed follow-up through 8 years.
Final Safety Findings	The study device was found to meet all Objective Performance Criteria with the exception of Bleeding in which the upper 95% confidence limit was above 2xOPC (6.9 vs 2.8 for All Bleeding). These results are acceptable when considering the cause of bleed for affected patients. The Kaplan-Meier rate for Freedom from Structural Valve Deterioration (SVD) was 83.7% at 8 years.
Final Effect Findings	At all follow-up timepoints out to 8 years 87.7% of patients were NYHA Class I or Class II. At 8 years, 77.9% of patients had trivial or none central regurgitation and 22.1% of patients had mild regurgitation. No patients had moderate or severe central regurgitation or PVL at 8 years.
Study Strengths & Weaknesses	Strengths of the study included the overall follow-up of patients through 8 years (109 patients completed 8-year follow-up). Weaknesses of the study include that the study was a single-arm trial which is true for most recent surgical valve studies. Additionally, the final dataset was limited by missing NYHA data at 8-years.
Recommendations for Labeling Changes	Labeling update is recommended
General
Study Status	Completed
Application Number / Requirement Number	P060008 / PAS001
Date Original Protocol Accepted	10/10/2008
Date Current Protocol Accepted	10/10/2008
Study Name	Outcomes TAXUS ATLAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	The MACE (cardiac death, MI, and TVR) rate at 4 years post stent implantation was comparable between the TAXUS ATLAS Group and the Control Group (22.5% versus 23.8%, P=0.5015). There was no statistically significant difference in MI, cardiac death, TVR, TLR, stent thrombosis and death rates between the two groups. The principal safety and efficacy outcomes just noted in the interval from 3 to 4 years post stent implantation were comparable as well. Despite greater lesion complexity in the TAXUS ATLAS Group, the 4 year post implantation data presented by the sponsor demonstrate that the TAXUS Liberté stent is comparable to the TAXUS Express stent with respect to MACE (including individual MACE components cardiac death, MI, and TVR), TLR, and TVF. There are no new safety or effectiveness concerns raised by this data.
Actual Number of Patients Enrolled	867
Actual Number of Sites Enrolled	60
Patient Follow-up Rate	91.7%
Final Safety Findings	The MACE (cardiac death, MI, and TVR) rate at 5 years post stent implantation was comparable between the TAXUS ATLAS Group and the Control Group (26.2% versus 27.1%, P=0.7026). There was no statistically significant difference in MI, cardiac death, TVR, TLR, overall stent thrombosis and death rates between the two groups. The 1461-1855 day stent thrombosis rate was 2.4% in the TAXUS ATLAS group and 0% in the control group. This, with a 5-year stent thrombosis rate of 2.3% in the TAXUS ATLAS group and 2% in the control group.
Final Effect Findings	See above
Study Strengths & Weaknesses	Despite greater lesion complexity in the TAXUS ATLAS Group, the 5 year post implantation data presented by the sponsor demonstrate that the TAXUS Liberté stent is comparable to the TAXUS Express stent with respect to MACE (including individual MACE components cardiac death, MI, and TVR), TLR, and TVF.
Recommendations for Labeling Changes	The 1461-1855 day stent thrombosis rate was 2.4% in the TAXUS ATLAS group and 0% in the control group. This, with a 5-year stent thrombosis rate of 2.3% in the TAXUS ATLAS group and 2% in the control group is higher than would be expected and was updated in a labeling change.
General
Study Status	Completed
Application Number / Requirement Number	P030032 / PAS001
Date Original Protocol Accepted	04/22/2004
Date Current Protocol Accepted	04/22/2004
Study Name	Fitzpatrick skin types
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a 24- week, open-labeled, randomized, multi-center study to evaluate the safety of the Hylaform family dermal fillers in the augmentation of dermal tissue to temporarily correct the wrinkle and nasolabial folds in patients of Fitzpatrick Skin Types IV, V and VI. Eligible patients will be randomized (1:1:1 ratio) to receive a single treatment of one of the three dermal fillers (Hylaform, Hylaform Plus, and Captique Injectable Gel), which will be injected intradermally to both nasolabial folds.
Study Population	Study population: Patients with Fitzpatrick Skin Phototypes IV, V, or VI. Indication: Correction of the nasolabial folds with Hylaform, Hylaform Plus, or Captique.
Sample Size	100 patients, 3 sites
Key Study Endpoints	Safety endpoints include keloid formation, hypertrophic scarring, hypopigmentation, hyperpigmentation, and symptoms of potential hypersensitivity. In addition, serum IgG antibody titers will be assessed at each visit. Effectiveness will not be evaluated in this study.
Follow-up Visits and Length of Follow-up	The patients will return for safety assessments at weeks 2, 4, 12, and 24 months. Baseline and follow-up blood samples (at weeks 4 and 12) will be collected to measure the serum IgG antibody to determine immunological response to the devices. The length of follow-up is 24 weeks (up to additional 24 weeks if needed).
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	119 subjects were randomized and treated (39 Hylaform, 41 Hylaform Plus, and 39 Captique)
Actual Number of Sites Enrolled	3 sites
Patient Follow-up Rate	98%
Final Safety Findings	There were no reports of keloid formation, hypertrophic scarring, hypopigmentation, or symptoms of potential hypersensitivity. Three patients experienced mild, device-related hyperpigmentation [two (4.9%) in the Hylaform Plus group and one (2.6%) in the Captique group) > The hyperpigmentation resolved within 3 months using a mild bleaching agent]. Approximately 28.6% (34/119) of the subjects in the treatment group experienced a total of 78 Treatment Emergent Adverse Events, most of which had short duration (7 days or less), and mild severity. The most common Treatment Emergent Adverse Events was injection site bruising (13.4%), followed by injection site nodule (5.0%), pain (4.2%), and swelling (3.4%). The duration of the most common TEAEs that lasted longer than 7 days (injection site nodules) ranged from 70 to 85 days. There were no deaths or no immunological positive responses. One angioedema occurred in the Captique group and the patient recovered the same day without intervention.The results from this study with persons with skin color are similar to that observed in the Hylaform/Hylaform Plus pivotal studies with mostly Caucasians.
Study Strengths & Weaknesses	The strength was that is was a randomized study with concurrent controls to evaluate device safety. The weakness of the study was that patients received only one single treatment of one of the three dermal fillers and that no additional touch-up was allowed. It is not clear if the results can be extrapolated to postmarket when under the general conditions of use where the repeated treatments are likely.
Recommendations for Labeling Changes	Based on the results of the post-approval study, the sponsor changed the label of Captique to include an update of the precaution section and an addition of the PAS study data. The sponsor updated only the Captique labeling as Hylaform and Hylaform Plus are no longer manufactured
General
Study Status	Completed
Application Number / Requirement Number	P870072 S027/ PAS001
Date Original Protocol Accepted	08/03/2004
Date Current Protocol Accepted	08/03/2004
Study Name	Thoratec IVAD
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a one armed, observational prospective cohort study of consectutive patients implanted with the Thoratec VAD.
Study Population	Consecutive patients who meet the requirements for device use. This is for use in bridge to transplant patients who meet all of the following criteria: candidate for cardiac transplantation, imminent risk of dying before donor heart procurement, dependence on, or incomplete response to, continued vasopressor support. It is also indicated for postcardiotomy recovery
Sample Size	50 patients
Key Study Endpoints	Number of patients weaned, transplanted, explanted, or died.
Follow-up Visits and Length of Follow-up	Patients are followed until outcome is reached or for 180 days.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	50 patients
Actual Number of Sites Enrolled	23 sites
Patient Follow-up Rate	100%
Final Safety Findings	Of patients enrolled in the study, 52% died before weaned or transplanted
Study Strengths & Weaknesses	The strength of the study was the 100% follow-up
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P030054 S067/ PAS001
Date Original Protocol Accepted	01/13/2009
Date Current Protocol Accepted	05/07/2009
Study Name	SJ4 Post Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Actual Number of Patients Enrolled	1701
Actual Number of Sites Enrolled	58
Patient Follow-up Rate	78.01%
Final Safety Findings	The 95% Lower Confidence Bound (LCB) for the freedom from complications using the Kaplan-Meier method at 5 years was 95.5%.
Final Effect Findings	The mean RV lead capture threshold is less than 1 V for all follow-up visits.
Study Strengths & Weaknesses	1) Large sample size of 1701 subjects 2) Long-term follow-up for 5 years) Weakness: 2) Study deviation rate of 14.39% per visit
Recommendations for Labeling Changes	no
General
Study Status	Completed
Application Number / Requirement Number	P890003 S119/ PAS001
Date Original Protocol Accepted	05/13/2008
Date Current Protocol Accepted	05/13/2008
Study Name	Longterm PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a 5-year, prospective, non-randomized, multi-center parallel study of implanted nEw3 (Adapta /Sensia/Versa) devices using a historical comparison group. Subjects will be compared against the U.S. market released Adapta /Sensia/Versa IPGs historical control group consisting of Medtronic registered devices as reported in the Medtronic Cardiac Rhythm Disease Management Product Performance Report.
Study Population	Study Population: All enrolled subjects have been implanted with a nEw3 device. Indication: The indications include: 1) rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity, 2) accepted patient conditions warranting chronic cardiac pacing, 3) symptomatic paroxysmal or transient sinus node dysfunctions with or without associated AV conduction disorders, 4) the Medtronic AT500 system is also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of AV synchrony.
Sample Size	At least 222 patients to ensure that at least 200 subjects are followed for 5 years, it is estimated that approximately 336 subjects will need to be enrolled, 72 sites
Key Study Endpoints	Medtronic CRDM considers a device as having malfunctioned whenever the analysis shows that any parameter was outside the performance limits established by Medtronic while implanted and in service. To be considered a malfunction, the device must have been returned to Medtronic and analyzed as a confirmed device malfunction. All subjects in the SLS study with a nEw3 device will be included until the cohort for analysis is met. Any nEw3 devices returned to Medtronic through returned product and found to have malfunctioned within 6 months after implant will also be included in the analysis. Devices damaged after explant, damaged due to failure to heed warnings or contraindications in the labeling, or damaged due to interaction with other implanted devices (including leads) are not considered device malfunctions.
Follow-up Visits and Length of Follow-up	All subjects who are included in the analysis of the primary objective will continue to be followed for a total of 5 years post-implant. The follow-up schedule for this study is based on utilizing routine, scheduled office/clinic visits and unscheduled office/clinic visits prompted by symptoms or complaints. Follow-up office/clinic visits post-implant are suggested to be at least annually for subjects with an IPG, and a minimum of one follow-up visit every 24 months.
Interim or Final Data Summary
Interim Results	There were 18 deaths reported which represents 2.4% of the subjects enrolled. No deaths were deemed as system related. Two deaths were reported with unknown causes. To be considered a malfunction, the device must have been returned to Medtronic for analysis. Currently, 7 of 11 failure devices were returned. Six of the returned devices found "no anomolies" and one device revealed misshapen multi beam connectors after microscopic visual analysis of the atrial connector block.
Actual Number of Patients Enrolled	2927
Actual Number of Sites Enrolled	132
Patient Follow-up Rate	75.23%
Final Safety Findings	The 5-year device survival probability was 100.0%, with 95% CI (99.7%, 100.0%).
Final Effect Findings	N/A
Study Strengths & Weaknesses	1) large sample size of 2927 subjects 2) long-term follow-up for 5 years Weakness: 1) study deviation rate of 12.16% per visit
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P980035 S073/ PAS001
Date Original Protocol Accepted	05/13/2008
Date Current Protocol Accepted	05/13/2008
Study Name	Longterm Study PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a 5-year, prospective, non-randomized, multi-center parallel study of implanted nEw3 (Adapta /Sensia/Versa) devices using a historical comparison group. Subjects will be compared against the U.S. market released Adapta /Sensia/Versa IPGs historical control group consisting of Medtronic registered devices as reported in the Medtronic Cardiac Rhythm Disease Management Product Performance Report
Study Population	Study Population: All enrolled subjects have been implanted with a nEw3 device. Indication: The indications include: 1) rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity, 2) accepted patient conditions warranting chronic cardiac pacing, 3) symptomatic paroxysmal or transient sinus node dysfunctions with or without associated AV conduction disorders, 4) the Medtronic AT500 system is also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of AV synchrony.
Sample Size	At least 222 patients to ensure that at least 200 subjects are followed for 5 years, it is estimated that approximately 336 subjects will need to be enrolled, 72 sites
Key Study Endpoints	Medtronic CRDM considers a device as having malfunctioned whenever the analysis shows that any parameter was outside the performance limits established by Medtronic while implanted and in service. To be considered a malfunction, the device must have been returned to Medtronic and analyzed as a confirmed device malfunction. All subjects in the SLS study with a nEw3 device will be included until the cohort for analysis is met. Any nEw3 devices returned to Medtronic through returned product and found to have malfunctioned within 6 months after implant will also be included in the analysis. Devices damaged after explant, damaged due to failure to heed warnings or contraindications in the labeling, or damaged due to interaction with other implanted devices (including leads) are not considered device malfunctions.
Follow-up Visits and Length of Follow-up	All subjects who are included in the analysis of the primary objective will continue to be followed for a total of 5 years post-implant. The follow-up schedule for this study is based on utilizing routine, scheduled office/clinic visits and unscheduled office/clinic visits prompted by symptoms or complaints. Follow-up office/clinic visits post-implant are suggested to be at least annually for subjects with an IPG, and a minimum of one follow-up visit every 24 months.
Interim or Final Data Summary
Interim Results	There were 18 deaths reported which represents 2.4% of the subjects enrolled. No deaths were deemed as system related. Two deaths were reported with unknown causes. To be considered a malfunction, the device must have been returned to Medtronic for analysis. Currently, 7 of 11 failure devices were returned. Six of the returned devices found "no anomolies" and one device revealed misshapen multi beam connectors after microscopic visual analysis of the atrial connector block.
Actual Number of Patients Enrolled	2927
Actual Number of Sites Enrolled	132
Patient Follow-up Rate	75.23%
Final Safety Findings	The 5-year device survival probability was 100.0%, with 95% CI (99.7%, 100.0%).
Final Effect Findings	N/A
Study Strengths & Weaknesses	1) large sample size of 2927 subjects 2) long-term follow-up for 5 years Weakness: 1) study deviation rate of 12.16% per visit
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P890003 S338/ PAS001
Study Name	MR conditional Tachy Therapy Systems Stud
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P890003 S354/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P890003 S372/ PAS001
Date Original Protocol Accepted	09/01/2017
Date Current Protocol Accepted	04/26/2024
Study Name	Heart Failure Risk Status (HFRS) PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To characterize clinical actions taken for each risk status as reported by HFRS report. The HFRS PAS is a US, prospective, observational, multi-center study
Study Population	The study population includes all patients meeting the indication for a Medtronic ICD or CRT device approved for commercial release with the OptiVol fluid monitoring feature who participate in Medtronic’s CareLink Network and consent to the study.
Sample Size	A sample size of 430 unique high risk transmissions will produce a two-sided 95% confidence interval with a width of less than 10% when the sample proportion is 65%, which was derived from the TRIAGE-HF study that worsening HF signs/symptoms were present in 65% of the High Risk Evaluations. The HFRS PAS is designed to obtain a reliable estimate of the positive predictive value (PPV) of the HFRS High Status associated with worsening heart failure and to gain a better understanding of HF patient management practices. The HFRS PAS is based on several assumptions to estimate the timeframe needed to obtain a meaningful effective sample size for the parameter of interest including: Number of eligible ICD/CRT system implants during the desired study duration % of ICD/CRT patients who participate in Medtronic Carelink Network and transmit data through the network Estimated number of transmissions/year/enrollment % of transmissions with a HFRS High Risk Status An estimated 2,000 patients implanted with an eligible device with a 60% CareLink participation rate and two transmissions per year will achieve the effective sample size for the parameter of interest within an estimated two-year period.
Key Study Endpoints	Primary endpoint: The positive predictive value (PPV) of HFRS High Risk Status associated with worsening heart failure. A true positive will be defined as a high-risk status and reported patient signs/symptoms Positive Predictive Value will be calculated by dividing the number of True Positive by all transmissions reviewed with a high-risk status Secondary endpoints The number of HF hospitalization or HF related deaths that were not preceded by a High Risk Status The purpose of this objective is to report on false negatives. The study will collect data on all incidences of HF related hospitalization and/or death, and identify if transmission data for 30-day period prior to the incidence is available. A patient with a reported HF hospitalization and/or death with available transmission data for 30-day period prior to the date of the reported event with no High-Risk Triggers will be reported regardless of whether the transmission was reviewed by the site. Reported HF related hospitalization or death with no transmission data availability within 30 days of the event will not be included for this objective. This is a post market observational study by design, there is no formal interim analysis defined. However, the study will continuously monitor the status of clinician behavior: the proportion of transmissions when HFRS is reviewed will be summarized periodically. In addition, HF related events and hospitalization rates will be monitored in reports.
Follow-up Visits and Length of Follow-up	Patients will be followed for a minimum of 12 months. The primary objective will be analyzed when the effective size of 430 patients with “High” risk trigger transmissions are collected or 3 years post-approval.
Interim or Final Data Summary
Actual Number of Patients Enrolled	1875
Actual Number of Sites Enrolled	76
Patient Follow-up Rate	Follow-up Rate The follow-up schedule for patients enrolled prospectively through the PSR is based on utilizing routine, scheduled office/clinic visits and unscheduled office/clinic visits prompted by symptoms or complaints, and CareLink transmissions (scheduled or unscheduled). For ICD and CRT patients, an in-person follow-up is anticipated to occur approximately every 3 to 9 months. Additionally, visits may be prompted by patient signs/symptoms and/or a patient’s high-risk status reported by HFRS. Transmission review of HFRS high-risk status include assessment of the HFRS report review status, clinician assessment of patient status (i.e. signs/symptoms, compliance, device parameters, and comorbidities), and clinical actions taken. There were 27 missing CareLink follow-ups out of 29,528 CareLink follow-up months.
Final Safety Findings	TriageHF algorithm is safe to use in combination with site assessment and follow up to help manage treatment/actions taken for heart failure patients.
Final Effect Findings	The PPV was 48% (95% CI = 44-53%) for the overall cohort, with 232 out of 480 new high-risk alerts showing evidence of worsening heart failure reported within 45 days of the alert. 104 reported HF-related hospitalizations or deaths qualified to be included in the TriageHF sensitivity analysis (proportion of events preceded by a high-risk alert). To qualify, events must have occurred after 64 days of algorithm training and had a CareLink transmission within 30 days before the event. Of 104 fully qualified HF-related hospitalizations or deaths, 59 (57%; 95% CI = 47-66%) did not trigger a high-risk alert. Therefore, TriageHF has estimated 43% sensitivity to trigger high-risk alerts before qualifying HF-related hospitalizations of deaths.
Study Strengths & Weaknesses	Strengths: • Provides real-word evidence of HF management, integrating TriageHF alerts with clinical assessments and standard care pathways. Weaknesses: • TriageHF alert data is dependent on transmissions received by the site. TriageHF alert transmissions are not automatically triggered; they rely on another alert to automatically trigger a transmission, a scheduled transmission, or manual initiation by the patient. • Confirmation of HF signs and symptoms, diagnosis, treatments and events depend on standard of care pathways per individual site assessments and documentation. • Variability in standardized adjudication of events versus standard of care per site for assessments, including the timeframe the assessment took place.
Recommendations for Labeling Changes	Recommend the study results are added to the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P890055 S026/ PAS003
Date Original Protocol Accepted	12/17/2010
Date Current Protocol Accepted	03/15/2011
Study Name	Drug Stability Study
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	Other Data Source
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	This is a non-clinical study. There are no stated hypotheses.
Study Population	Not applicable. This is a bench/lab study.
Sample Size	Not applicable. This is a bench/lab study.
Key Study Endpoints	Drug samples will be collected from the distal end of the pump catheter.
Follow-up Visits and Length of Follow-up	Not applicable. This is a bench/lab study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	N/A Bench Study
Actual Number of Sites Enrolled	N/A Bench Study
Patient Follow-up Rate	N/A Bench Study
Final Safety Findings	1. Stability of Lioresal® baclofen solutions in MedStream infusion pumps for a period of 120 days 2. Stability of Lioresal® baclofen after multiple refills over the lifetime of pump (8 years) in pump reservoir 3. Pump function by assessing the pump flow rate yearly through 8 years.
Final Effect Findings	1. Stability of Lioresal® baclofen solutions in MedStream infusion pumps for a period of 120 days 2. Stability of Lioresal® baclofen after multiple refills over the lifetime of pump (8 years) in pump reservoir 3. Pump function by assessing the pump flow rate yearly through 8 years.
Study Strengths & Weaknesses	N/A Bench Study
Recommendations for Labeling Changes	No Labeling change recommended
General
Study Status	Completed
Application Number / Requirement Number	P900030 / PAS001
Date Original Protocol Accepted	09/30/1993
Date Current Protocol Accepted
Study Name	Long term Cohort C
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is open-label and multi-center. Cohort C included patients aged 30 and younger who are to be followed for 10 years post implant. Although there are no study hypotheses, the primary objectives of the study are: 1. To determine the duration of improvement 2. To measure various serologic values over time following exposure to bovine collagen 3. To evaluate rheumatologic history 4. To monitor adverse events
Study Population	The study population is male and female patients who were 30 years or younger at enrollment and had urinary incontinence due to intrinsic sphincter deficiency and have been incontinent for at least 12 months. The device is indicated to treat urinary incontinence.
Sample Size	100 male, 100 female
Key Study Endpoints	Data collection included: Effectiveness was measured by incontinence grading, described as follows: Grade 0 Continent dry, Grade 1 Patient loses urine with sudden increases in abdominal pressure but never in bed at night, Grade 2 Patient s incontinence worsens with lesser degrees of stress such as walking standing erect from a sitting position or sitting up in bed Grade 3 Patient has total incontinence without any relation Safety: 1. Serological hypersensitivity reaction through measurement of enzyme-linked immunosorbent assay (ELISA). 2. Local hypersensitivity 3. Urinary retention
Follow-up Visits and Length of Follow-up	visits every 6 months up to 10 years
Interim or Final Data Summary
Interim Results	Study is completed. See Final Results
Actual Number of Patients Enrolled	62
Actual Number of Sites Enrolled	Not mentioned
Patient Follow-up Rate	21%
Final Safety Findings	During the study, 66.1% (N=41) of the 62 patients experienced a total of 161 adverse events.71.4% of the females and 61.8% of the malesexperienced adverse events. There was no significant difference in the AE rate of both genders. 66.7% of the dry patients and 82.4% of the improved incontinence patients and 70.6% of the not improved incontincence patients experienced adverse events. THe differences are not statistically significant.
Study Strengths & Weaknesses	Low follow-up rate
Recommendations for Labeling Changes	labeling should be updated to include the long-term findings, specifically that there may be a higher incidence of autoimmune responses in females.
General
Study Status	Completed
Application Number / Requirement Number	P940008 / PAS001
Date Original Protocol Accepted	11/28/1995
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a registry-based study that includes all patients who have received the Res-Q Automatic Implantable Cardioverter Defibrillator System (ACD) Model 101-01 and 101-01R Epicardial Patch and Non-thoracotomy Lead System.The purpose of the registry is to monitor the performance of the epicardial lead system post-PMA approval.
Study Population	The study proposed to follow the patient population enrolled in the RES Q ACD PATCH protocol to monitor the performance of the epicardial patch leads. This proposal is for the patient population enrolled in the Res Q ACD PATCH protocol IDE 900143 implanted with Res-Q/ Res-Q Micron ICD Models . These are patients who are at high risk of sudden death due to ventricular arrhythmias and have experienced one of the following situations: (1) survival of at least one episode of cardiac arrest (manifested by a loss of consciousness) due to a ventricular tachyarrhythmia, or (2) recurrent, poorly tolerated sustained ventricular tachycardia. There were 16 patients eligible for postmarket follow-up.
Sample Size	16 patients eligible for postmarket follow-up
Key Study Endpoints	The data endpoints were actuarial lead survival (lead failures) and fatal events.
Follow-up Visits and Length of Follow-up	Patients are assessed periodically (approximately every 4 months) and data is reported annually .
Interim or Final Data Summary
Actual Number of Patients Enrolled	16 patients eligible for postmarket follow-up.
Actual Number of Sites Enrolled	unknown
Patient Follow-up Rate	15/16 had their devices removed from service or are deceased, the remaining patient has been lost to follow-up. No patients were followed-up.
Final Safety Findings	The final report did not include statistical analysis for this study since there is only one patient remaining in the study.
Study Strengths & Weaknesses	Weakness: The report does not include statistical analysis for this study since there is only one patient remaining in the study.
Recommendations for Labeling Changes	None
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P100034 / PAS001
Date Original Protocol Accepted	04/08/2011
Date Current Protocol Accepted	02/09/2016
Study Name	New Enrollment Study for NovoTTF-100A
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is a prospective, non-randomized open-label concurrent control study of NovoTTF-100A in recurrent GBM patients. A prospective, international, multi-center study, will include 30 centers in the US, EU and Israel, at least 15 centers in the US. The study will include 2 groups: an Investigational Group composed of patients treated with the NovoTTF-100A and a Control Group of concurrent best standard of care chemotherapy. Patients in the NovoTTF-100A group will be treated continuously until disease progression and then followed by telephone interview until death. Minimal recommended treatment duration is 4 weeks and minimal recommended treatment compliance is 18h/day (monthly average).
Study Population	The NovoTTF-100A System is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM), following histologically- or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy. NovoTTF-100A Group ¿ Patients treated with the NovoTTF-100A ¿ Patients will be treated continuously until disease progression ¿ Minimal recommended treatment duration ¿ 4 weeks ¿ Minimal recommended treatment compliance ¿ 18h a day (monthly average) Control Group ¿ Concurrent best standard of care chemotherapy (control) group
Sample Size	30 centers in the US, EU and Israel. At least 15 centers in the US. Test arm: N1=243 NovoTTF-100A patients Comparator arm: N2=243 Concurrent best standard of care control patients Definitions: λ1 = hazard of death in the test arm λ2 = hazard of death in the comparator arm Primary Statistical Hypothesis: H0: λ1 / λ2 > 1.375 H1: λ1 / λ2 ≤ 1.375 Assumptions: Type I error: 0.05 Power: 0.80 Test statistics: Log-rank test Lost to follow-up: 10%
Key Study Endpoints	Primary ¿ Overall survival (months) Secondary ¿ Change in neuro-cognitive function from baseline based on the MMSE ¿ Genetic profiling of tumors and correlation with response to NovoTTF-100A treatment, specifically: o MGMT promoter methylation status o EGFR amplification, over expression or rearrangement o Chromosomes 1p/19q deletion status o IDH1 mutation ¿ Adverse event incidence by body system and term, including: o Incidence of seizures and headaches o Anticonvulsant use
Follow-up Visits and Length of Follow-up	¿ Recruitment: 48 months ¿ Follow-up: 12 months from recruitment of last patient ¿ NovoTTF-100A treatment until clinical disease progression. ¿ Patients will continue to be followed until death Baseline: ¿ Eligibility assessment ¿ MMSE ¿ Genetic profiling of tumor tissue ¿ Adverse event symptoms ¿ Concomitant medication Monthly until clinical disease progression: ¿ Vital status ¿ MMSE ¿ Adverse event record ¿ Concomitant medication (including steroid and anticonvulsant dosing) ¿ Evaluation of progression Monthly after disease progression: ¿ Vital status
General
Study Status	Delayed
Application Number / Requirement Number	P170039 / PAS001
Date Original Protocol Accepted	09/23/2019
Date Current Protocol Accepted
Study Name	PAS, Adult and Pediatric
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, nonrandomized, multi-center, safety study. This is an extended follow-up post-approval study (PAS). The study population is limited to adult and pediatric subjects who participated in the previous 12-month AI-001 IDE clinical trial and are implanted with the CUSTOMFLEX®ARTIFICIALIRIS for less than 36 months (adults) or 60 months (pediatrics).
Study Population	The study includes the implanted subjects. There is no control arm. The postoperative outcomes are compared to their preoperative baseline.
Sample Size	Up to 527 adult and pediatric eyes implanted with the CUSTOMFLEX®ARTIFICIALIRIS in the AI-001 IDE clinical trial. The sample size is based on demonstrating the cumulative device related adverse event rate was less than 5% for all adverse events in the study and, no individual adverse event should exceed a rate of 1%. The proposed sample size (527 adult and pediatric eyes) is sufficient to achieve >90% power of detecting an individual device related adverse rate with an incidence of at least 2.0%.
Key Study Endpoints	The primary study outcome is to evaluate device related adverse events (AEs) postoperatively at the Month 36 (adults) or Month 60 (pediatrics). The secondary study outcome is to evaluate the cumulative rate of intraocular lens (IOL)-related AEs at the Month 36 (adults) or Month 60 (pediatrics). Other outcomes: Secondary surgical interventions, implant position, device or surgery related complications, and device malfunctions or defects. Outcomes that will be evaluated include, but are not limited to: Cumulative AEs Endothelial cell density (ECD) changes Device malfunction or defects Device related complications
Follow-up Visits and Length of Follow-up	36 months postoperatively for adults and 60 months post-operatively for pediatric subjects.
General
Study Status	Completed
Application Number / Requirement Number	P920015 S151/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. ¿ Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P160001 S003/ PAS001
Date Original Protocol Accepted	07/19/2017
Date Current Protocol Accepted	08/08/2019
Study Name	Obalon Balloon System PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	*Please Note: P160001 and P160001/S003 are bundled* Design: New enrollment, prospective, single arm, observational, sequentially enrolling, open label multi-center study. Objective: The primary objective of the study is to assess the continued safety and performance of the Obalon Balloon System in the commercial setting.
Study Population	In addition to the patients’ ability to commercially purchase the device, patients shall meet all inclusion criteria and no exclusion criteria to be considered eligible for study enrollment. Inclusion Criteria 1. Minimum 22 years of age 2. BMI of 30.0-40.0 kg/m2 3. Previously attempted to lose weight unsuccessfully using a medically supervised or non-medically supervised diet 4. Study enrollment before or within 7 days of the initial balloon administration. Exclusion Criteria 1. Contraindicated for use of the Obalon Balloon System per Obalon Balloon System, Instructions for Use (LIT-7500-0011, page 3) 2. Use of medications or medical devices known to induce weight gain or weight loss within the preceding 6 months. 3. Known history of endocrine disorders affecting weight. 4. Participation in any clinical study which could affect weight loss within the past year. 5. Known history or present condition of structural or functional disorders of the esophagus that may impede passage of the device through the gastrointestinal tract, including, Barrett’s esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, diverticula, or any other disorder of the esophagus. 6. Life expectancy less than 1 year or severe renal, hepatic, pulmonary or other medical condition, in the opinion of the investigator.
Sample Size	The study will include 15 sites in the United States. A total of 200 subjects will be enrolled, 180 are needed with data through 6 months. No single site is allowed to treat more than 15% of the maximum total or 30 patients.
Key Study Endpoints	Primary and Secondary Endpoints Safety Endpoints The study primary endpoint is a safety endpoint that evaluates the percentage of subjects who experience a Serious Adverse Event that is device or procedure related. Device or Procedure Related Serious Adverse Event Rate The percentage of subjects who experience a Serious Adverse Event that is device or procedure related will be evaluated. Effectiveness Endpoints This trial is designed to evaluate co-secondary effectiveness endpoints comprised of (1) the mean % TWL and (2) the proportion of subjects achieving at least 5% TWL. Co-Secondary Endpoint: Mean Percent Total Weight Loss The mean percent Total Weight Loss (%TWL) will be evaluated as the first portion of the co-primary endpoint. %TWL is calculated as the ratio of a subject’s weight loss to their starting weight as measured on the date of their first course, first administration procedure. Co-Secondary Endpoint: 5% TWL Responder Rate The responder rate will be evaluated as the second portion of the co-secondary endpoint. For the purpose of this co-secondary endpoint, a responder is defined as a subject that achieves at least 5% TWL based on their starting weight as measured on the date of receiving their first balloon.
Follow-up Visits and Length of Follow-up	52 weeks. Patient participation time includes up to 4 weeks for screening, 24 weeks of balloon therapy period and 24 weeks post-balloon removal. Patients will be followed after post-balloon removal regardless of weight loss results during balloon therapy period.
Interim or Final Data Summary
Actual Number of Patients Enrolled	201 Subjects
Actual Number of Sites Enrolled	18 sites
Patient Follow-up Rate	201 (100% completed phase I of the study (end of balloon therapy). 180 (89.6%) completed phase II (1-Year Follow-up).
Final Safety Findings	All Adverse Events: 879 in 167 subjects. Serious Adverse Events: 0 device/procedure related; 1 Not Device/procedure related. Most of the adverse events (94.2%) are classified as mild. The most common reported adverse events are nausea (76.6%), retching (48.8%), vomiting (41.8%), and abdominal pain (16.9%). The other reported adverse events are observed in less than 10% of subjects.
Final Effect Findings	Weight loss data from 197 (98%) of the subjects that completed balloon therapy subjects is included in the results. Four (4) subjects were lost to follow-up. The mean weight loss results were 20.3 lbs. and 9.4% TBL. The mean weight loss results were higher compared to the pivotal SMART Study (14.4 lbs. and 6.6% TBL).
Study Strengths & Weaknesses	Strengths: Large enough sample size of sites (18) and patients (201) Weaknesses: No concomitant comparator group
Recommendations for Labeling Changes	Yes, the results of the post-approval study must be included in the labeling.
General
Study Status	Completed
Application Number / Requirement Number	P950037 S156/ PAS001
Date Original Protocol Accepted	06/08/2016
Date Current Protocol Accepted	04/15/2019
Study Name	Siello Pacing Lead Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is designed to gather safety data on BIOTRONIK’s lead using active monitoring of Medicare fee-for-service (FFS) claims data. The design is a prospective, single-arm, non-randomized, observational cohort study utilizing real world data.
Study Population	Patients who are implanted with the lead and are in the beneficiary match population for the claims data are included in the patient population.
Sample Size	750 minimum evaluable sample required to demonstrate superiority to a complication-free rate of 92.5%.
Key Study Endpoints	The purpose of primary endpoint 1 is to evaluate the overall incidence of complications attributable to the lead through 5 years post-implant.
Follow-up Visits and Length of Follow-up	5 years post-implant
Interim or Final Data Summary
Actual Number of Patients Enrolled	1,015 patients implanted with a Siello lead on or between March 13, 2013 and July 20, 2015.
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	There were a total of 33 complications identified in 33 out of 1,841 Siello leads as attributable or possible attributable to the device. Of the 1174 evaluable patients for this endpoint, there were 33 Siello leads with a qualifying event, resulting in an CFR of 97.19%.
Final Effect Findings	N/A
Study Strengths & Weaknesses	This study’s use of real-world data captures a large representative assessment of device performance. While data granularity is limited, the study confirms there are no significant safety concerns with the device’s long term performance.
Recommendations for Labeling Changes	Yes
General
Study Status	Completed
Application Number / Requirement Number	P920015 S163/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P920015 S166/ PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted
Study Name	PCT Change Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will be conducted within Medtronic’s Product Surveillance Registry (PSR). The PSR platform is designed to conduct non-randomized, active, prospective post-market surveillance. Patients implanted with a MR Conditional CIED system and enrolled in the PSR will be followed per the expected standard of care practice of their care provider. Pacing capture thresholds (PCT) measurements of MR conditional CIED systems enrolled in the PSR will be used to prospectively monitor changes in PCT following 3T MR exposure. Patient status is collected approximately every 6 to 12 months including MRI scan information, if applicable. Sites will report patient baseline information (e.g. height, weight, etc.) the occurrence of a medically indicated MRI scan, reason for scan, anatomical region scanned, magnet strength, and MRI related events. Analysis of the primary objective will be performed 4-years following approval
Study Population	All patients implanted with a MR Conditional CIED system and enrolled in the PSR who subsequently receive an MRI scan using a 3T system within the 4-years post approval that meets approved labelling requirements.
Sample Size	The following assumptions were used to estimate the PAS duration and number of 3T scans projected to be obtained during the 4-years study period: MR Conditional CIED enrollment of approximately 2,400 patients Annual MRI scan rate of 9% Participating sites with 3T scanning capability: 25% - 40% % of patients with a 3T MRI scan: 30% - 45% Table 3: 3T Scan Rate Assumptions Over 4-Year Study Duration Assumptions Year 1 Year 2 Year 3 Year 4 Cumulative MR Conditional Enrollments (*) 1260 1674 2047 2382 Cumulative # of completed MRI Scans 113 264 450 571 Assumption for % centers with 3T capability 25% 25% to 40% % MR scans through 3T in these centers 30% 30% - 45% Cumulative # of completed 3T scans 9 43 to 103 (*) Assumes a 10% annual attrition Contribution from enrollments outside the US to the primary objective will be limited to no more than 50% of the total sample size.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of patients implanted with an MR conditional CEID system with a pre to post MRI scan PCT measure change of more than 0.5 V following 3T scan exposure. Definitions for pre and post PCT measurements Pre-MRI PCT measure: max PCT value preceding the SureScan mode enabled and prior to the 3T MRI scan Post-MRI PCT measure: 1st max PCT measurement at a time point >30 days (chronic PCT) following 3T MRI exposure. Further investigation will be carried out to identify root cause if the observed proportion of PCT changes following 3T scan exposure is greater than 8% (i.e. 2X the observed proportion in the PSR SureScan data) and more than 50% of those observed >0.5V PCT changes reflect an increase.
Follow-up Visits and Length of Follow-up	4 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	8388
Actual Number of Sites Enrolled	191
Final Safety Findings	One patient showed a ¿PCT greater than 0.5V within the analysis window. As this does not meet the 8% threshold proportion of patients and/or scans with a greater than 0.5V change pre- to post-3T MRI, no additional comparative analyses were performed. No adverse events, deaths, or device deficiencies related to 3T scan.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The primary endpoint was acceptable. The results are favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P920015 S178/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P910073 S077/ PAS001
Date Original Protocol Accepted	11/10/2010
Date Current Protocol Accepted	01/14/2011
Study Name	Longitudinal Surveillance Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The LSS of 4-SITE is a prospective, nonrandomized, multi-center registry of patients implanted with the 4-SITE Lead/Header system.
Study Population	Patients implanted with the 4-SITE Lead/Header system
Sample Size	1,780 patients.(assuming an annual attrition rate of 10%, a minimum of 1,780 patients implanted with the 4-SITE lead is necessary to obtain 5-year follow-up data on approximately 1050 patients)
Key Study Endpoints	For the 4-SITE Lead/Header system, the primary endpoint for this registry will evaluate the proportion of patients without a chronic 4-SITE Lead/Header-related complication within five years post-implant.
Follow-up Visits and Length of Follow-up	Five-years post implant Every six months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1820 subjects
Actual Number of Sites Enrolled	111 sites
Patient Follow-up Rate	5 years post-implant
Final Safety Findings	The sponsor reported a complication-free rate through 60 months for the 4-SITE Lead/Header system of 98.9% with a one-sided 95% lower confidence limit of 98.5%. The lower confidence limit is higher than the performance goal of 92.5%. The sponsor also reported 17 adverse events that contributed to the primary endpoint. All lower confidence limits for all events types are within 1% of the complication free rate.
Final Effect Findings	Please see above.
Study Strengths & Weaknesses	The sponsor has collected sufficient data to address the primary objective of the study which was to estimate the five year Endotak Reliance 4-Site defibrillation lead related chronic complication-free rate. The Agency recommends that the sponsor update the labeling to incorporate the study findings.
Recommendations for Labeling Changes	FDA recommends that the sponsor update the labeling for these devices to reflect the long-term data from the Post Approval Study.
General
Study Status	Completed
Application Number / Requirement Number	P930014 S045/ PAS001
Date Original Protocol Accepted	05/03/2011
Date Current Protocol Accepted	09/18/2015
Study Name	New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective of this study is to demonstrate superiority of the AcrySof® IQ Toric High Cylinder Power study group (IOL Models SN6AT6-SN6AT9) to the AcrySof® IQ Aspheric NATURAL IOL Model SN60WF concurrent control group with spectacle correction, for the rate of severe visual distortions at 6 months post bilateral implantation in subjects with pre-operative corneal astigmatism greater than or equal to 2.57 D. This is a prospective, non-randomized, unmasked study, with data collection through electronic case report forms (eCRF).
Study Population	Adult subjects in need of bilateral cataract surgery with pre- operative corneal astigmatism in the targeted range
Sample Size	Total Sample size: 400 -AcrySof® IQ Toric IOL Model SN6AT6-SN6AT9: 230 -AcrySof® IQ Aspheric NATURAL IOL Model SN60WF:170
Key Study Endpoints	The primary safety endpoint for this study is the rates of severe visual distortions as measured by the Assessment of Photic Phenomenon & Lens EffectS (APPLES) - Visual Distortion Questionnaire. Subjects in both groups will be categorized as experiencing a severe visual distortion if they indicate ¿severe¿ as a response to any one of the three visual distortion related questions on the APPLES - Visual Distortion Questionnaire. In this study the following supportive safety variables will be evaluated: - Adverse events o Lens dislocation o Pupillary block o Cumulative rate of any ocular SSIs at 6 months - Cumulative rate of IOL repositioning at 6 months - Cumulative rate of IOL explantation at 6 months - Cumulative rate of ocular SSIs related to visual distortions at 6 months - Any other vision-threatening adverse event related to the IOL - Uncorrected Distance Visual Acuity (UCDVA) - Best Corrected Distance Visual Acuity (BCDVA) - Lens axis misalignment For serious adverse events, the following change of definition is made in protocol version 3.0 Serious Adverse Event (SAE) - adverse event that led to any of the following: - Death. - A serious deterioration in health that either resulted in: a) A life-threatening illness or injury. NOTE: Life-threatening means that the individual was at immediate risk of death from the event as it occurred, i.e., it does not include an event which hypothetically might have caused death had it occurred in a more severe form. b) Any potentially sight-threatening event or permanent impairment to a body structure or a body function c) In-patient hospitalization or prolonged hospitalization. NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the clinical investigation plan, without serious deterioration in health, is not considered a serious adverse event. In general, hospitalization signifies that the individual remained at the hospital or emergency ward for observation and/or treatment (usually involving an overnight stay) that would not have been appropriate in the physician's office or an out-patient setting. Complications that occur during hospitalization are adverse events. If a complication prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to whether hospitalization occurred, the event should be considered serious. d) A medical intervention to prevent a) or b), or any surgical intervention (excluding posterior capsulotomy) e) Any indirect harm as a consequence of incorrect diagnostic test results when used within manufacturer's instructions for use. -Fetal distress, fetal death, or a congenital abnormality or birth defect.
Follow-up Visits and Length of Follow-up	Six months, except those with Secondary Surgical Intervention (360-420 days).
Interim or Final Data Summary
Actual Number of Patients Enrolled	409
Actual Number of Sites Enrolled	85
Patient Follow-up Rate	95.6% (391/409)
Final Safety Findings	The “severe” visual distortion is reported low, 0% in Toric and 0.6% (1 subject) in non-Toric study arms at 6 months follow-ups. The superiority of AcrySof IQ Toric IOL to AcrySof IQ IOL was not established in this study because the low incidence rate of severe visual distortions reported in both groups. The incidence of “moderate” distortions also does not appear to be clinically significantly different between study arms. For subjects with > 10 degrees of lens axis misalignment, there were not severe visual distortions or documented reports of visual impairment, and no interventions were performed to reposition the IOL for those subjects at any time during the study. Non-Serious Ocular Adverse Events There were no important differences between the Toric (‘Overall’ column) and the non-Toric groups regarding in terms of the rate of ocular AEs that occurr ed at the rate of 1% or greater. In the first eye implanted there were 11 cases of dry eye (4.8%), 11 (4.8%) posterior capsule opacification, nine (3.9%) intraocular pressure increased, four (1.7%) allergic conjunctivitis, four (1.7%) visual impairment, three (1.3%) vision blurred, three (1.3%) vitreous detachment, three (1.3%) corneal abrasion, two (0.9%) eye allergy, one (0.4%) eye irritation, one (0.4%) blepharitis, and one (0.4%) iritis. In the second eye implanted, there were 12 cases of dry eye (5.3%), 10 (4.4%) posterior capsule opacification, six (2.7%) intraocular pressure increased, six (2.7%) vitreous detachment, five (2.2%) vision blurred, four (1.8%) allergic conjunctivitis, three (1.3%) eye irritation, three (1.3%) eye irritation, three (1.3%) eye pruritus, three (1.3%) punctate keratitis, three (1.3%) visual impairment, three3 (1.3%) intraocular lens reposition, one (0.4%) blepharitis, one (0.4%) iritis, and one (0.4%) lacrimation increased. Monocular UCDVA and BCDVA A greater proportion of subjects in the Toric group had a 20/40 or better Uncorrected Distance Visual Acuity (UCDVA) in both eyes compared to the non-Toric group. The majority of subjects in both groups had 20/40 or better Best Corrected Distance Visual Acuity (BCDVA). However, the proportion of eyes with BCDVA of 20/20 or better was considerably lower in the non-Toric group. A higher proportion of subjects in the Toric group had BCDVA of 20/25 or better compared to the proportion of subjects in the non-Toric group. A comprehensive review of the subject level demographics, manifest refraction, SLE findings, DFE findings, and AEs did not reveal any systemic differences between the groups which may explain the observed difference. One eye (C11020.1838.4403) in the Toric group had a BCDVA worse than 20/63 at Visit 2. Overall analysis of the PAS supportive safety endpoints, do not raise concerns regarding the safety of the Toric IOL models when compared to the Non-Toric.
Final Effect Findings	No effectiveness endpoints were included in the study.
Study Strengths & Weaknesses	Strengths: A concomitant comparator group treated with a non-Toric device is included A high follow-up rate was achieved Weaknesses: ¿ Sample size was not large enough to be able to evaluate t he primary endpoint because an unexpected low incidence rate of severe visual distortions was found. ¿ No randomization of treatments was conducted (Toric vs. non-Toric) ¿ No masking procedures were included
Recommendations for Labeling Changes	The results of the post-approval study, MDR analyses and literature review during post-market did not show any data that may be different than that obtained in pre-market and already included in the labeling.
General
Study Status	Other
Application Number / Requirement Number	P930016 S025/ PAS001
Date Original Protocol Accepted	07/11/2007
Date Current Protocol Accepted	04/02/2008
Study Name	Star 4 Monovision Lasik
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	This study will be a multi-center, single-arm prospective Post-Approval Study in which a subject's pre-operative status will serve as the control for 6-month post-surgical outcomes. The objectives are (1) To estimate the proportion of patients who undergo CustomVue LASIK for monovision who experience visual disturbances that are severe enough to limit activities or adversely affect a patient's quality of life, especially those associated with monovision, in a broad patient population of presbyopic patients with myopia who undergo LASIK performed by a diverse group of surgeons. An additional focus to the study includes the incidence of visual disturbances related to symptoms of ghosting and diplopia and will be documented in a non-validated subjective patient questionnaire. (2) To determine baseline patient characteristics associated with visual disturbances that are severe enough to limit activities or adversely affect a patient's quality of life. This study was never started because there was a device recall prior to patient enrollment begun.
Study Population	Study population is as per approved indications: This device uses a 6.0 mm optical zone, an 8.0 mm treatment zone, and is indicated for wavefront-guided (WFG) laser assisted in situ keratomileusis (LASIK) to achieve monovision by the targeted retention of myopia (-1.25 to -2.00 D) in the non-dominant eye of presbyopic myopes:* 40 years or older who may benefit from increased spectacle independence across a range,of distances with useful near vision;* with myopic astigmatism up to -6.00 D MRSE, with cylinder up to -3.00 D, and minimum pre-operative myopia in their non-dominant eye at least as great as their targeted myopia;* with documented evidence of a change in manifest refraction of no more than 0.50 D (in both cylinder and sphere components) for at least one year prior to the date of preoperative examination; and* with a successfuil preoperative trial of mionovision or history of monovision experience.
Sample Size	525 subjects
Key Study Endpoints	The DataFax system will be utilized to transmit CRF and questionnaire data to AMO. Requests for data clarification will be handled through this same system. Detailed instructions are provided in Attachment C. To minimize data omissions, AMO may review forms and provide investigators with clarification lists with a request to resolve the discrepancies noted. Such discrepancies shall be reviewed by the investigator and refaxed to AMO in a timely manner, as necessary. Demographic information, preoperative monovision screening, uncorrected and best corrected vision (monocular and binocular) at distance and near, manifest refraction, and NEI-RQL and NEI-driving scores.
Follow-up Visits and Length of Follow-up	baseline & 6 month
General
Study Status	Ongoing
Application Number / Requirement Number	P930016 S053/ PAS001
Date Original Protocol Accepted	01/29/2019
Date Current Protocol Accepted	08/09/2024
Study Name	STAR-122-MVPM Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Wavefront-Guided Lasik for Monovision Treatment of Myopic Subjects with Presbyopia. A multi-center, single-arm, prospective new-enrollment post-approval study in which each subject’s preoperative status is serving as the control for post-surgical outcomes. The study is observational in nature. Several of the study endpoints rely on Patient Reported Outcomes (PRO) which will be measured by the Patient Reported Outcomes with LASIK for Monovision (PROWL-M) questionnaire. A questionnaire was developed to show that patients tolerate the contact lens monovision experience and do not have significant reductions in their functioning. Cognitive debriefing will be conducted to determine that patients understand the intent of the contact lens questionnaire and that the questions are relevant to the population. The specific study objectives include: 1) to assess the effect of monovision LASIK treatment on difficulty with driving as measured by the driving scale within Patient Reported Outcomes with LASIK (PROWLM), 2) to determine the proportion of subjects who required secondary surgery to reverse monovision, 3) to determine the proportion of subjects who experience visual symptoms that are severe enough to limit usual activities after undergoing monovision LASIK treatment in a population of myopic subjects with presbyopia, 4) to identify baseline subject characteristics [including age, gender, race, pupil diameter, refraction, add requirement, and binocular stereopsis and visual acuities (near, intermediate, distance) with monovision contact lens in place] associated with adverse safety outcomes of difficulty driving and/or visual symptoms, and to assess simultaneous binocular distance and near vision acuity.
Study Population	This study will include only subjects who have stable myopic refractive error with presbyopia and are undergoing monovision Lasik treatment and who meet all of the study inclusion and exclusion criteria in both eyes. All subjects who meet the inclusion/exclusion criteria will be offered treatment in the study. The dominant eye of each subject will be targeted for emmetropia and the non-dominant eye will be targeted for myopic outcome (-1.25 to -2.00 D) based on the amount of myopic retention that was determined to be acceptable by the patient during the contact lens trial. A minimum of 8 and maximum of 14 sites across US. Sites/investigators across different US geographies will be recruited. Each site will be able to enroll no more than 25% of the number of subjects included in the analysis to ensure a diverse investigator/subject population which is representative of the entire target population.
Sample Size	The study will enroll 219 subjects who have stable myopic refractive error with presbyopia from 8 to 14 sites/investigators across different US geographies. Assuming no more than 30% screen failures and 10% of attrition rate, 159 subjects are to be treated and will undergo 12 months of follow up.
Key Study Endpoints	Co-primary study endpoints: 1) the change in driving scale score from preoperative to postoperative as measured by the driving scale within PROWL-M, 2) and the proportion of subjects who required secondary surgery to reverse monovision. Secondary study endpoints: 1) the proportion of subjects who experienced bothersome visual symptoms (e.g., halo, glare, starburst, double images), 2) the proportion of subjects who experienced ‘Moderate to Severe Difficulty with Activities’, 3) the proportion of subjects with ‘Satisfaction with Vision’ as measured by PROWL-M, 4) the proportion of subjects with ‘Satisfaction with Surgery’ as measured by PROWL-M 5) the proportion of subjects who achieve 20/40 or better uncorrected distance and near vision. Exploratory study endpoints: 1) the proportion of subjects whose driving scale within PROWL-M score increases or decreases by more than 8 points from preoperative visit; 2) the proportion of subjects who experience visual symptoms that are severe enough to limit usual activities after undergoing monovision LASIK treatment; 3) baseline subject characteristics associated with difficulties with driving (based on driving scale score) and/or visual symptoms. Other study endpoints: Uncorrected distance visual acuity (UCDVA), monocular (all treated dominant eyes), uncorrected near visual acuity (UCNVA), monocular (all treated eyes), uncorrected intermediate visual acuity (UCIVA), binocular (subjects), best corrected spectacle visual acuity (BSCVA), monocular (all treated eyes), depth perception, binocular (subjects), manifest refraction (all treated eyes), non-directed visual symptoms, mean change from baseline in visual symptoms via the PROWL questionnaire, and adverse event type and rates.
Follow-up Visits and Length of Follow-up	~20 subjects/month enrollment to complete enrollment by December 2023 and complete follow-up by December 2024. Subjects will be followed for 12 months after undergoing monovision LASIK treatment. The frequency of follow-up assessments is: preoperative, operative day, and postoperative 1 day, 1 week, and 1, 3, 6, 12 months.
Interim or Final Data Summary
Actual Number of Patients Enrolled	216 enrolled, 153 treated
Actual Number of Sites Enrolled	14 approved, 8 enrolled
General
Study Status	Completed
Application Number / Requirement Number	P930039 S140/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P930039 S142/ PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted
Study Name	PCT Change Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will be conducted within Medtronic’s Product Surveillance Registry (PSR). The PSR platform is designed to conduct non-randomized, active, prospective post-market surveillance. Patients implanted with a MR Conditional CIED system and enrolled in the PSR will be followed per the expected standard of care practice of their care provider. Pacing capture thresholds (PCT) measurements of MR conditional CIED systems enrolled in the PSR will be used to prospectively monitor changes in PCT following 3T MR exposure. Patient status is collected approximately every 6 to 12 months including MRI scan information, if applicable. Sites will report patient baseline information (e.g. height, weight, etc.) the occurrence of a medically indicated MRI scan, reason for scan, anatomical region scanned, magnet strength, and MRI related events. Analysis of the primary objective will be performed 4-years following approval
Study Population	All patients implanted with a MR Conditional CIED system and enrolled in the PSR who subsequently receive an MRI scan using a 3T system within the 4-years post approval that meets approved labelling requirements.
Sample Size	The following assumptions were used to estimate the PAS duration and number of 3T scans projected to be obtained during the 4-years study period: MR Conditional CIED enrollment of approximately 2,400 patients Annual MRI scan rate of 9% Participating sites with 3T scanning capability: 25% - 40% % of patients with a 3T MRI scan: 30% - 45% Table 3: 3T Scan Rate Assumptions Over 4-Year Study Duration Assumptions Year 1 Year 2 Year 3 Year 4 Cumulative MR Conditional Enrollments (*) 1260 1674 2047 2382 Cumulative # of completed MRI Scans 113 264 450 571 Assumption for % centers with 3T capability 25% 25% to 40% % MR scans through 3T in these centers 30% 30% - 45% Cumulative # of completed 3T scans 9 43 to 103 (*) Assumes a 10% annual attrition Contribution from enrollments outside the US to the primary objective will be limited to no more than 50% of the total sample size.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of patients implanted with an MR conditional CEID system with a pre to post MRI scan PCT measure change of more than 0.5 V following 3T scan exposure. Definitions for pre and post PCT measurements Pre-MRI PCT measure: max PCT value preceding the SureScan mode enabled and prior to the 3T MRI scan Post-MRI PCT measure: 1st max PCT measurement at a time point >30 days (chronic PCT) following 3T MRI exposure. Further investigation will be carried out to identify root cause if the observed proportion of PCT changes following 3T scan exposure is greater than 8% (i.e. 2X the observed proportion in the PSR SureScan data) and more than 50% of those observed >0.5V PCT changes reflect an increase.
Follow-up Visits and Length of Follow-up	4 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	8388
Actual Number of Sites Enrolled	191
Final Safety Findings	One patient showed a ¿PCT greater than 0.5V within the analysis window. As this does not meet the 8% threshold proportion of patients and/or scans with a greater than 0.5V change pre- to post-3T MRI, no additional comparative analyses were performed. No adverse events, deaths, or device deficiencies related to 3T scan.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The primary endpoint was acceptable. The results are favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Ongoing
Application Number / Requirement Number	P950037 S255/ PAS001
Date Original Protocol Accepted	10/11/2024
Date Current Protocol Accepted	10/11/2024
Study Name	Solia S LBBA EP PASSION
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Real World Evidence (RWE) methodology study with the purpose of evaluating long-term performance of BIOTRONIK’s Solia S lead when implanted in the left bundle branch area (LBBA) using active monitoring of Medicare fee-for-service claims data. The study is a retrospective and prospective, single-arm, non-randomized, observational cohort study using RWE methodologies from the Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION) project. This is a hybrid cohort study in which data are collected both retrospectively and prospectively.
Study Population	The study will include all patients registered in BIOTRONIK’s device tracking database who meet all inclusion criteria and no exclusion criteria with implant date between December 12, 2022, and July 30, 2025, who 1) had a successful Solia S lead implanted in the left bundle branch area, as identified in BIOTRONIK’s device tracking database; 2) are matched with beneficiary file using identifiers obtained from BIOTRONIK’s device tracking database (Social Security Number (including partial), last name, date of birth, gender, and zip code) to a unique beneficiary in the Medicare database; 3) have fee-for-service Medicare coverage during month of successful Solia S LBBA lead implant; and, had at least 1 Medicare claim in the inpatient, outpatient, or carrier files
Sample Size	Number of subjects: At least 750 patients. Assumptions for sample size estimation: n/a, For primary endpoint 1, a total of 750 evaluable Solia S LBBA leads would be required to demonstrate superiority to a complication-free rate of 92.5%. Number of sites: n/a Site’s location: n/a
Key Study Endpoints	Primary endpoint: Overall incidence of complications attributable to the Solia S LBBA lead through 5 years post-implant. Secondary endpoints: 1) Incidence of complications attributable to a Solia S LBBA lead or possibly attributable to a Solia S LBBA lead through 5 years post-implant, and 2) Incidence of complications potentially related to a Solia S LBBA lead (e.g. cardiac perforation) not included in another primary or secondary endpoint
Follow-up Visits and Length of Follow-up	Visits: N/A Length of F/U: Patients will be followed through at least 5 years following the end of enrollment.
Interim or Final Data Summary
Interim Results	Safety Results • Primary Endpoint 1 - Overall incidence of complications attributable to the Solia S LBBA lead through 5 years post-implant (excluding first 30 days). 14 events were reported resulting in an Incidence Rate of 0.014 events/system year. The current lower confidence interval estimated freedom from complications rate for this endpoint is 95.08%. • Secondary Endpoint 1 - Incidence of complications attributable to a Solia S LBBA lead or possibly attributable to a Solia S LBBA lead through 5 years post-implant (excluding first 30 days). 23 events were reported resulting in an Incidence Rate of 0.022 events/system year. The current lower confidence interval estimated freedom from complications rate for this endpoint is 93.44%. • Secondary Endpoint 2 - Incidence of complications potentially related to a Solia S LBBA lead (e.g. cardiac perforation, events occurring within 30 days of implant) not included in another primary or secondary endpoint. Due to CMS cell size suppression policy no information could be provided because the number of qualifying events was <11. The current lower confidence interval estimated freedom from complications rate for this endpoint is 98.42%.
Actual Number of Patients Enrolled	1529
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
General
Study Status	Study Pending
Application Number / Requirement Number	P250042 / PAS001
Date Original Protocol Accepted	09/22/2026
Date Current Protocol Accepted	09/22/2026
Study Name	Continued Follow-up Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of the BAGUERA® C subjects to evaluate the 5-year long-term safety and effectiveness for single- and two contiguous-level total disc replacement
Study Population	Subjects implanted with the BAGUERA® C during the IDE Studies (G200182 and G200239)
Sample Size	Number of subjects: 178 for single level study and 193 for two contiguous-level Assumptions for sample size estimation: Continued study participation from subjects available from the modified intent to treat (mITT) Set who were enrolled in the pivotal study and were not a CCS failure at Month 24. Number of sites: 23 Sites location: United States
Key Study Endpoints	Safety Endpoints Primary: - No secondary surgical intervention defined as revision, removal, reoperation, or supplemental fixation at the index level(s) - No serious adverse event(s) confirmed as definitely related to the device or index procedure (as determined by the CEC) Secondary: -Evaluation of the incidence and severity of complications and adverse reactions associated with the treatment Effectiveness Endpoints Primary: -Improvement from baseline in pain and function, as measured through the Neck Disability Index (NDI), of at least 15 percentage points -Maintenance or improvement in neurological status at 60 months compared to baseline (as determined by the CEC) Secondary: - Left and right arm pain 100 mm Visual Analogue Scale (VAS) (an improvement in pain of at least 20 mm on the VAS is considered clinically significant) - Neck pain 100 mm Visual Analogue Scale (VAS) (an improvement in pain of at least 20 mm on the VAS is considered clinically significant) - Health Related Quality of Life (SF-12 v 2) Physical Component Summary (PCS) and Mental Component Summary (MCS) - Patient Satisfaction - Dysphagia Handicap Index - Odom Criteria to measure surgical success (determined by the implanting surgeon)
Follow-up Visits and Length of Follow-up	Annually through 60 months after surgery
General
Study Status	Ongoing
Application Number / Requirement Number	P200039 S019/ PAS001
Date Original Protocol Accepted	02/20/2026
Date Current Protocol Accepted	02/20/2026
Study Name	DISRUPT CAD PRESTO
General Study Protocol Parameters
Data Source	External Registry
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Ongoing
Application Number / Requirement Number	P110042 S203/ PAS001
Date Original Protocol Accepted	07/07/2026
Date Current Protocol Accepted	07/07/2026
Study Name	EMBLEM S-ICD Modified 3501 Electrode PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this analysis is to verify the continued the safety and effectiveness of the EMBLEM™ Subcutaneous Implantable Defibrillator (S-ICD) Model 3501 Electrode.
Study Population	Analyses using CMS real-world data will include patients from the entire US fee-for-service Medicare patients, typically >65 years old. All patients that have been successfully implanted with an EMBLEM 3501 electrode, aligned with existing CMS coverage criteria, will be included in analyses of CMS data. Analyses using LATITUDE data will include patients from the entire US population of implanted EMBLEM S-ICD 3501 Electrode patients who are being followed on LATITUDE.
Sample Size	Number of subjects: 1013 electrodes Assumptions for sample size estimation: ¿ Expected performance = 95% ¿ Performance goal = 92.5% ¿ One-sided significance level = 2.5% ¿ Power = 90% Number of sites: N/A Sites location: N/A – CMS -US
Key Study Endpoints	Safety Endpoints Primary: % of electrodes free from electrode-related complication from 1 month through 5- years Secondary: Effectiveness Endpoints Primary: Secondary: % of system impedances within range (obtained from US LATITUDE)
Follow-up Visits and Length of Follow-up	5 year follow-up
General
Study Status	Ongoing
Application Number / Requirement Number	P950037 S280/ PAS001
Date Original Protocol Accepted	04/02/2026
Date Current Protocol Accepted	04/02/2026
Study Name	Solia CSP S EP PASSION
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Real World Evidence (RWE) methodology study with the purpose of evaluating long-term performance of BIOTRONIK’s Solia CSP S lead when implanted when implanted in the left bundle branch area (LBBA) using active monitoring of Medicare fee-for-service claims data. The study is a retrospective and prospective, single-arm, non-randomized, observational cohort study using RWE methodologies from the Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION) project. This is a hybrid cohort study in which data are collected both retrospectively and prospectively.
Study Population	The study will include all U.S. patients registered in BIOTRONIK’s device tracking database who meet all inclusion criteria and no exclusion criteria, who: 1) had a successful Solia CSP S lead implanted, as identified in BIOTRONIK’s device tracking database; 2. are matched with Medicare beneficiary using identifiers obtained from BIOTRONIK’s device tracking database (Social Security Number (including partial), last name, date of birth, gender, and zip code) to a unique beneficiary in the Medicare database; 3) have fee-for-service Medicare coverage during month of successful Solia CSP S lead implant; and, 4) at least 1 Medicare claim in the inpatient, outpatient, or carrier files.
Sample Size	Number of subjects: At least 750 patients. Assumptions for sample size estimation: N/A. For primary endpoint 1, a total of 750 evaluable Solia CSP S leads would be required to demonstrate superiority to a complication-free rate of 92.5%. Number of sites: N/A. Sites’ locations: N/A.
Key Study Endpoints	Primary Endpoint #1: Overall incidence of complications attributable to the Solia CSP S lead through 5 years post-implant. Secondary Endpoint #1: Incidence of complications attributable to a Solia CSP S lead or possibly attributable to a Solia CSP S lead through 5 years post-implant. Secondary Endpoint #2: Incidence of complications potentially related to a Solia CSP S lead (e.g., cardiac perforation) not included in another primary or secondary endpoint.
Follow-up Visits and Length of Follow-up	5 years follow-up
General
Study Status	Study Pending
Application Number / Requirement Number	P960058 S167/ PAS001
Date Original Protocol Accepted	09/18/2026
Date Current Protocol Accepted	09/18/2026
Study Name	AHL/SSD New Enrollment PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P020018 S010/ PAS001
Date Original Protocol Accepted	09/07/2006
Date Current Protocol Accepted	09/07/2006
Study Name	AAA Flex 36mm
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Australian study is a multi-center, non-randomized prospective clinical study, with six Australian sites participating. The U.S. physician sponsored pre market study is a single center, non-randomized retrospective study. The plan is to assess patients from both studies for a total duration of five years.
Study Population	Patients who were implanted with the device in the original study, with an abdominal aortic aneurysm or aortic-ileac aneurysm of at least 5 cm or expanding at a rate of at least 0.5 cm per year, who does not meet the study's exclusion criteria.
Sample Size	15 Austrailian and 26 US patients
Key Study Endpoints	Endpoints include: 1) adverse events, 2) endoleaks, 3) secondary interventions, 4) aneurysm enlargement, 5) rupture, 6) conversion, and 7) aneurysm-related death.
Follow-up Visits and Length of Follow-up	Length of follow-up is five years. Patients will be followed on an annual basis.
Interim or Final Data Summary
Interim Results	The size of the postapproval study making the power of the study to detect a high rate of aneurysm-related deaths low. However, the consensus of the FDA review team is that the confidence in the safety and effectiveness of this device is high because the only modification from the previous approved device is an enlargement of the size. Furthermore, the study was approved with full knowledge that the sample size would be small, no aneurysm-related deaths have been reported to this date, and because the device is rarely used it would be very difficult to recruit substantial new cases at this time.
Actual Number of Patients Enrolled	41
Actual Number of Sites Enrolled	8
Patient Follow-up Rate	18% through five years
Final Safety Findings	There were no aneurysm-related deaths or conversions to open surgery. There was one ruptured aneurysm which occurred within the first year post implant..
Final Effect Findings	There were no cases of device migration, and aneurysms were far more likely to shrink than grow in size during the course of the study.
Study Strengths & Weaknesses	Follow-up rate was very poor. That plus the fact that the study was very small to begin with means that the data were too sparse to make any definitive conclusions.
Recommendations for Labeling Changes	None. The data from this study do not change current knowledge of device performance
General
Study Status	Completed
Application Number / Requirement Number	P070012 / PAS001
Date Original Protocol Accepted	10/23/2007
Date Current Protocol Accepted	10/23/2007
Study Name	MAVErIC II Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the MAVErIC Phase I and II studies was to demonstrate the safety and efficacy of the Exponent Self-Expanding Carotid Stent System with the GuardWire Plus Temporary Occlusion and Aspiration System for the treatment of carotid stenosis. A Supplement (S059) to the IDE reducing the patient follow-up from the existing 5-year to 3-year follow up for both the MAVErIC Phase I and Phase II Clinical Trials was submitted on June 6, 2006, and approved on June 16, 2006.
Study Population	This device is indicated for use, in conjunction with a Medtronic Vascular embolic protection system, for improving carotid luminal diameter in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: 1) Patients with neurological symptoms and > 50% stenosis of the common or internal carotid artery by either ultrasound or angiogram, or patients without neurological symptoms and > 80% stenosis of the common or internal carotid artery by either ultrasound or angiogram, and 2) Patients having a vessel with reference diameters between 4.5 mm and 9.5 mm at the target lesion.
Sample Size	399 patients
Key Study Endpoints	The protocol defined primary endpoint for each phase of the trial was the cumulative incidence of major adverse events at 1-year, defined as a composite of all-cause death, myocardial infarction (Q wave and non-Q wave), and ipsilateral stroke. The primary endpoint in the statistical analysis plan is defined as the cumulative incidence of major adverse events at 1-year post-procedure, defined as all-cause death, stroke, or MI at 30 days plus all-cause death, MI or ipsilateral stroke within 31 days to 365 days post-procedure.
Follow-up Visits and Length of Follow-up	Patient follow up occurring at 30 days for all 1500 patients enrolled in the study and 365 days for the first 500 patients enrolled.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	MAVErIC I study: 99 patients; MAVErIC II study: 399 patients
Actual Number of Sites Enrolled	NA
Patient Follow-up Rate	69%
Final Safety Findings	Adjudicated all-cause death rate at 3-years postprocedure was 21.8% (87/399). The total rate of myocardial infarction was 3.8% (15/399). The total rate of stroke was 6.5% (26/399). The rate of target lesion revascularization was 3.5% (14/399).
Study Strengths & Weaknesses	Strengths: The sponsor did enroll and follow-up additional subjects then was originally asked for by FDA. Weaknesses: Sponsor did not calculate lost to follow-up based on an intention to treat method. If one was to substitute the study sample size of 399 as the denominator the 3-year follow-up would be 69%.
Recommendations for Labeling Changes	Labeling was not updated since the device is no longer marketed.
General
Study Status	Ongoing
Application Number / Requirement Number	P910073 S145/ PAS001
Date Original Protocol Accepted	05/04/2018
Date Current Protocol Accepted	07/07/2020
Study Name	MOUNTAIN PAS
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	Admin Database
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The purpose of the MOUNTAIN PAS program is to provide a sustainable mechanism for the collection of data to assess the short and long term performance of Boston Scientific BSC pacing and defibrillation leads. The data sources used to evaluate the ACUITY X4 lead include four existing Real-World Data (RWD) databases and one clinical trial database.
Study Population	All patients added to each database (CMS, Device Tracking, LATITUDE, Complaints database) during the evaluation period will be included in the analyses as specified.
Sample Size	Data from all US centers that contribute data to any of the databases will be used in the analysis.
Key Study Endpoints	The sponsor states that the short-term safety and short- and long-term effectiveness objectives have already been fulfilled through evaluation of clinical trial data. The long-term safety objective has yet to be fulfilled and will be assessed by the Primary Safety Endpoint, Sensitivity Analysis and other analysis specified.
Follow-up Visits and Length of Follow-up	Data will be collected during routine device follow-up and patient care. No additional follow-ups or procedures are required.
Interim or Final Data Summary
Interim Results	Safety Results The observed primary event-free rate at 5 years equaled 99.5% with a lower confidence limit of 99.2%. In addition, the shape of curve indicates no signal of accelerating risk of failure (Weibull shape [95% CI] = 0.57 [0.41, 0.80]). No secondary or tertiary analyses were triggered due to the results of this analysis. There were 5097 RELIANCE 4-FRONT leads in single-chamber systems that contributed to the sensitivity analysis. The observed primary event-free rate at 5 years equaled 97.7% with a lower confidence limit of 97.0% (Figure 7-6). There was no signal of accelerating risk failure. No secondary or tertiary analyses were triggered due to the results of this analysis. Effectiveness Results N/A
Actual Number of Patients Enrolled	CMS Fee-for-Service patients with RELIANCE 4-FRONT leads: N = 10,678 There is no concern for the sample size since this sample size exceeds the minimum 1000 leads required.
Actual Number of Sites Enrolled	N/A; This study uses RWD
Patient Follow-up Rate	The 10,678 RELIANCE 4-FRONT leads with fee-for-service coverage at time of implant have been followed for a median of 39.2 months. Chronic follow-up: 10,298 No concern for the follow-up sample size. Since this study uses RWE, there is no calculated follow-up rate.
General
Study Status	Ongoing
Application Number / Requirement Number	P220024 / PAS001
Date Original Protocol Accepted	07/28/2023
Date Current Protocol Accepted	01/14/2026
Study Name	LiquiFix Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	A Post Approval Observational study using real-world data (RWD). The objective of the study is to evaluate the long-term safety of the LIQUIFIX implanted adhesive using real-world evidence methods through the ACHQC. Also see figure below (4.6)
Study Population	Patients for this study will include all USA patients undergoing open or laparoscopic groin (inguinal/femoral) hernia repair, recruited from ACHQC participating institutions whose mesh fixation and peritoneal closure (in TAPP repair) is undertaken with the LIQUIFIX cyanoacrylate adhesive. As the data will be collected using real world evidence, sex, age, race will be most frequently observed in male, white, aged population and not further dictated by AMS. Inguinal hernias are the most common form of groin hernia and have a 9:1 male predominance, with a higher incidence among men over the age of 40 [1][2]. Additionally, white men have 2-times higher rate of incidence of inguinal hernia than black men [1]. Femoral hernias account for only 2% to 4% of all groin hernias and are more likely to occur in women than in men [3]. Any concomitant procedures will also be captured as part of the data collection. A source comparator group will be used. This group will be concurrent propensity match scored and generated via ACHQC and will consist of patients where an alternative mesh fixation and peritoneal closure (for TAPP repair) was used. There will be a separate comparator group for each device specification (open and laparoscopic). Each comparator group has been selected based on current state of the art devices for each technique application: For LIQUIFIX Fix8™ - Two groups of controls, Absorbable and Permanent Tackers will be used as the comparator For LIQUIFIX Precision™ - Sutures, Staples and Tackers (absorbable and permanent) will be used as the comparator
Sample Size	Number of subjects: n = 206 for LiquiFix Precision™ and n = 103 for LiquiFix Fix8™ or the number of patients at who are registered into the ACHQC at one year, whichever is the largest.
Key Study Endpoints	Primary: The incidence of hernia recurrence in patients following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for a minimum of 2 years post-surgery. Secondary 1: The incidence of reoperation in patients following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for a minimum of 2 years post-surgery. Secondary 2: The incidence of surgical site infection in patients following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for a minimum of 2 years post-surgery. Secondary 3: Levels of reported pain in patients following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for a minimum of 2 years post-surgery, Secondary 4: Reported Quality of life in patients following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for a minimum of 2 years post-surgery Secondary 5: The incidence of post operative complication rates following groin hernia repair using LIQUIFIX will be measured using a concurrent propensity match control (via ACHQC) at 30 days and annually for minimum 2 years post-surgery.
Follow-up Visits and Length of Follow-up	Passive long-term follow up rates including email-based PRO engagement and routine clinical long-term follow up result in an estimated 20% completion at 2 years. Subjects follow up data collection intervals will occur at 30 days and annually for a minimum of 2 years post-surgery
Interim or Final Data Summary
Interim Results	Safety Results: LIQUIFIX FIX8™ 30 day follow up: • 81% (n=157) of patients were evaluated • N=2 (1.3%) Gastrointestinal complications o n=1 underwent a reoperation for bowel obstruction o n=1 a readmission for a for a gastrointestinal bleed which was related to nonsteroidal pain management use. • N=1 (0.7%) Bleeding complication • N=1 (0.6%) Hernia recurrence/ n=1 (0.6%) Re-operation for hernia recurrence • N=2 (1.3%) (n=2) Surgical site infection. • N=19 (12%) (n=19) Surgical site occurrences (1 wound cellulitis and 18 seroma) 1 year follow up: • N=2 (1.3%) Re-operation for recurrence the patient is an 81 year old male, ASA 3, who had bilateral hernia repair for mesh fixation and peritoneal closure. Patient returned at 1 year with symptomatic hernia on left (L3L) that was confirmed by CT scan. This was treated with reoperation for recurrence. • No Surgical site infections No Surgical site occurrence 2 year follow up • N=1 (1.1%) Surgical site infection • N=1 (1.1%) Surgical site occurrence • No reoperation for recurrence. LIQUIFIX Precision™ 30 day follow up: • 70% (n=55) of patients were evaluated • N=1 (1.8%) Readmission for wound complication • No Recurrence recorded. • N=1 (1.8%) Surgical site infection • N=12 (22%) Surgical site occurrence (1 wound purulent drainage, 9 seroma, 1 infected seroma, 1 wound cellulitis and 2 haematoma). Patients may have multiple surgical site occurrences (patients could have more than one surgical site occurrence). 1 year follow up: • N=1 (3.4%) Surgical site infections • N= 1 (3.4%) Surgical site occurrence (mesh excision) • N= 1 (2.2%) re-operation for port site hernia recurrence which was unrelated to LIQUIFIX Precision™ 2 year follow up • No reoperation for recurrence • No surgical site infections • No surgical site occurrences Effectiveness Results: LIQUIFIX FIX8™ • 30 day: 1.3% (n=2) gastrointestinal complications, one underwent a reoperation for bowel obstruction, one for a GI bleed which was related to nonsteroidal \ pain management, 0.7% (n=1) for post-operative bleeding and 0.6% (n=1) underwent a reoperation for recurrence • 1 year: 1.3% (n=2) reoperation for recurrence. One patient, an 81 year old male, ASA 3, who had bilateral hernia repair for mesh fixation and peritoneal closure. Patient returned at 1 year with symptomatic hernia on left (L3L) that was confirmed by CT scan. This was treated with reoperation for recurrence. • had a very complex course-multiple recurrent inguinal hernia repair, came back with an infection that required IR drainage and suppressive antibiotics. • 2 year: no reoperation for recurrence LIQUIFIX Precision™ • 30 day: n=1 (4%) readmission for a wound complication • 1 year: 2.2% (n=1) reoperation for port site hernia recurrence, which was unrelated to LIQUIFIX Precision™, 3.4% (n=1) Surgical Site Occurrence, this was a case in which the mesh was excised. • 2 year: No reoperation for recurrence
Actual Number of Patients Enrolled	273 patients are enrolled (194 for FIX8 and 79 for Precision)
Actual Number of Sites Enrolled	This study is based on data already collected in the ACHQC.
Patient Follow-up Rate	For FIX8, the 30 day, 1 year, and 2 year follow up rates are at 81%, 72.7%, and 54.6%, respectively. For Precision, the 30 day, 1 year, and 2 year follow up rates are at 69.6%, 40.5%, and 7.6%, respectively. (NOTE that the percentages for 1 and 2 year follow up pertain to recurrence follow up). Due to the nature of this observational post-approval study and use of registry data, the Sponsor is unable to get patient lost-to-follow-up information at this interim timepoint as aggregate information is provided. In accordance with the Protocol, missing data will be minimized in the following manner: Data collection for each time point will continue until the desired number of patients required to fulfill this study are entered into the ACHQC, i.e., numbers enrolled at 1 year post approval or n=206 for LIQUIFIX Precision™ and n= 103 LIQUIFIX FIX8™ whichever is the largest, as well as continued follow-up of the available IDE patients (approximately 103). Also, any patients who do not provide follow-up data at any time points defined in this protocol may be entered into the ACHQC patient outreach program. This program is a proactive method of follow-up provided by ACHQC and consists of qualified clinicians who will contact patients and/or undertake a historical and retrospective chart review.
General
Study Status	Completed
Application Number / Requirement Number	P960040 S385/ PAS001
Date Original Protocol Accepted	08/07/2017
Date Current Protocol Accepted	11/17/2017
Study Name	SMART-MSP PAS
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Evaluate the effectiveness of Boston Scientific (BSC)’s LV MSP (Left Ventricular MultiSite Pacing) feature in the Resonate family of CRT-D devices1 and confirm safety in a post approval study when used in accordance with its approved labeling. Prospective, multi-center, single arm, post approval study to be conducted in the United States.
Study Population	Subjects who are non-responders to conventional Biventricular (BiV) CRT-D therapy
Sample Size	Primary Safety Endpoint: The overall study sample size of 586 subjects is driven by the primary effectiveness endpoint. The sample size of 61 subjects is required to evaluate the Primary Safety Endpoint. Since a power calculation cannot be directly calculated for a one group Kaplan-Meier analysis, an exact test was used. A power calculation using a sample size of 61 subjects as the non-responders with the LV MSP on was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions: Performance goal = 90% Expected LV MSP feature-related CFR rate between 6 and 12 Month Visit = 98% Significance level = 5% Power = 80% Primary Effectiveness Endpoint: The sample size of 110 subjects with paired CCS calculation from the 6 Month Visit through 12 Month Visit is required to evaluate the Primary Effectiveness Endpoint. For further details on overall sample size and attrition see Figure 12.3-1. The overall study sample size is driven by the primary effectiveness endpoint. This sample size was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions: Performance goal = 5% Expected performance = 15% One-sided significance level = 5% Power = 95%
Key Study Endpoints	The primary safety endpoint for SMART-MSP is LV MSP feature-related complication-free rate between the 6 Month Visit and the 12 Month Visit in non-responders with the LV MSP turned on for any duration and the primary effectiveness endpoint is Proportion of the LV MSP Group subjects with Improved Clinical Composite Score (CCS) from the 6 Month Visit through the 12 Month Visit.
Follow-up Visits and Length of Follow-up	The length of follow-up is maximum of 12 months. Subjects determined to be a responder at their 6 month visit will complete the study. Subjects in the non-responder group, including those subjects who have no LV MSP turned on, will complete the study at their 12 month visit.
Interim or Final Data Summary
Actual Number of Patients Enrolled	594 patients
Actual Number of Sites Enrolled	52 sites
Patient Follow-up Rate	The mean months +/- SD of all enrolled subjects was 7.0 +/- 3.1.
Final Safety Findings	The LV MSP feature related complication-free rate was 99.0% with a lower 95% confidence limit of 94.9%, which was higher than the performance goal of 90%.
Final Effect Findings	The proportion of Non-Responder subjects with an improved CCS from 6-12 months was 51.3% with a lower 95% confidence limit of 41.4%, which was higher than the performance goal of 5%.
Study Strengths & Weaknesses	The firm has fulfilled the conditions of approval by completing the study as planned. There are no safety concerns raised by this large study. Detailed review of the adverse events shows no specific adverse event types are increased over what we might see in this population. Overall, the MSP approach shows a substantial minority of subjects benefitted.
Recommendations for Labeling Changes	Yes, a labeling change is recommended. The study results are favorable, free of new safety signals and show a promising effectiveness signal. These results should be included in an update to the label.
General
Study Status	Ongoing
Application Number / Requirement Number	P140031 S028/ PAS001
Date Original Protocol Accepted	11/20/2017
Date Current Protocol Accepted
Study Name	SAPIEN 3 Aortic Valve-in-Valve Comp Surv
General Study Protocol Parameters
Study Design	Comprehensive/Linked/RegistryBased Surveillance
Data Source	External Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Comprehensive- Linked/Registry Based Surveillance. The purpose of this Surveillance Plan is to utilize the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry to monitor long term durability, safety and effectiveness of the SAPIEN 3 Transcatheter Heart Valve in patients with a failed surgical bioprosthetic aortic valve for 2 years following device approval. Follow-up of these patients will be linked to the Centers for Medicare and Medicaid Services (CMS) database for long-term surveillance through 5 years post implantation. This is a new enrollment study.
Study Population	Patients with symptomatic heart disease due to a failed surgical bioprosthetic aortic valve (stenosed, insufficient or combined) who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e. predicted risk of surgical mortality greater than or equal to 8% at 30 days, based on the STS risk score and other clinical co-morbidities unmeasured by the STS risk calculator).
Sample Size	Enrollment will consist of all patients with SAPIEN 3 transcatheter heart valve in the STS/ACC TVT Registry for the 2 years following device approval (i.e. from June 5, 2017 to June 4, 2019). All aortic transcatheter SAPIEN 3 Valve in Surgical Valve patients who have the procedure date in the period of June 5, 2017 to June 4, 2019 will be included in the analysis.
Key Study Endpoints	TVT-Captured Safety Endpoints at intra-procedure: Device Implanted Successfully TVT-Captured Safety Endpoints at discharge, 30 days and 12 months: All-cause mortality All stroke Life threatening/major bleeding complications* New requirement of dialysis Peri-procedural myocardial Infarction Repeated procedure for valve-related dysfunction (surgical or interventional therapy) TIA Vascular complications *endpoints not available at discharge TVT-Captured Effectiveness Endpoints (30 days and 12 months): KCCQ CMS-Captured Safety Endpoints (year 2 to 5): All-cause mortality All Stroke Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
Follow-up Visits and Length of Follow-up	5 years post-implantation
Interim or Final Data Summary
Interim Results	TVT-R at 12 Months: All-cause mortality: 12.1% All stroke: 2.8% Life-threatening bleeding: 3.4% Myocardial infarction: 1.5% New Requirement for dialysis: 1.6% Transient ischemic attack (TIA): 0.4% Vascular Complications: 4.1% Aortic valve reintervention: 1.5% KCCQ (Mean Change from Baseline): 39.3 Transvalvular mean gradient: 19.2 mmHg Greater than or equal to Moderate Total Aortic Regurgitation: 1% Greater than or equal to Moderate Total Aortic Paravalvular Regurgitation: 0.4% CMS Linked at 48 Months: All-cause mortality: 42.5% All-stroke: 9.7% Aortic Valve Reintervention: 4.0%
Actual Number of Patients Enrolled	TVT Registry: 1,874 (attempted); 1,854 (implanted)
Actual Number of Sites Enrolled	TVT Registry: 408 sites
Patient Follow-up Rate	TVT-R (patient status known at 1 year): 77% CMS Linked: 81.7% (1282) of eligible patients matched with the CMS database. CMS data was available for 100% of the matched patients at 1, 2, and 3 years and 87.4% of patients at 4 years.
General
Study Status	Completed
Application Number / Requirement Number	P960040 S385/ PAS002
Date Original Protocol Accepted	07/25/2017
Date Current Protocol Accepted	08/26/2022
Study Name	MANAGE-HF
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Device Subjects Serve as Own Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	1. To evaluate and optimize HeartLogic Heart Failure Diagnostics clinical integration and the alert management process (Phase I). 2. To evaluate Heart Logic in regards to patient outcomes of death and heart failure hospitalizations (Phase II).
Study Population	Test Device: Phases I and II: ICD and CRT-D devices with HeartLogic turned ON Control Device: Phase II: ICD and CRT-D devices with HeartLogic alerts turned OFF
Sample Size	Between 1700 and 2700 subjects will be enrolled in the study: Phase I: Up to 200 subjects Up to 200 subjects are required in Phase I to build critical knowledge regarding the clinical integration of HeartLogic and the alert management process. Phase II: 1500-2500 subjects The sample size required for Phase II of MANAGE-HF is event-driven. Between 1500 and 2500 subjects will be enrolled in the trial to accrue the necessary number of endpoint events to sufficiently power the primary endpoint. A total of 864 endpoints events from randomized subjects in Phase II are required to sufficiently power the primary endpoint, based on the following assumptions: Expected control group incidence of annual heart failure hospitalization and death = 20% One-sided Alpha = 5% Power = 90% Hazard Ratio = 0.8 Estimated enrollment period = 24 months Expected Follow-up period = minimum of 24 months for last patient enrolled Final sample size will be determined during the study using a sample size re-estimation interim analysis.
Key Study Endpoints	LATITUDE NXT 5.0 System
Follow-up Visits and Length of Follow-up	Follow-Up Schedule: Enrollment Visit Baseline Visit Scheduled follow-up Visits Annual Phone Calls (6, 18,30, 42 months… from baseline) Annual In-Clinic (12,24,36,48 months…from baseline visit) Additional Follow-up Visits HeartLogic Alert Action Visit Additional Subject Interactions (i.e., Not in Response to HeartLogic Alerts) End of Study Visit
Interim or Final Data Summary
Actual Number of Patients Enrolled	Phase 1: 200 subjects Phase 2: 3886 subjects
Actual Number of Sites Enrolled	Phase 1: 29 sites Phase 2: N/A
Patient Follow-up Rate	Phase 1 Rate = 72% 191 completed the baseline visit 144 followed until the last patient enrolled completed their 12- month visit 37 withdrawals 19 subjects died Phase 2: N=1458 patients were included in the analysis, of which 19 died or their device was no longer in service. These were followed for an average of 1.08 years
Final Safety Findings	Phase 1 does not have s safety endpoint Phase 2 does not have a safety endpoint
Final Effect Findings	Phase 1 does not have effectiveness endpoints Phase 2: The observed Sensitivity was 74.5% and an adjusted Sensitivity (95% confidence interval) was 71.3% (65.4%, 76.6%). The False Positive rate (95% confidence interval) was 1.48 (1.42, 1.59).
Study Strengths & Weaknesses	Phase 1 Patients that were included in Phase I of MANAGE-HF were required to meet specific study inclusion and exclusion criteria. This included evidence of worsened heart failure prior to enrollment. In addition, patients with severe kidney impairment or short life expectancy were excluded. Thus, the results are limited to the population that was studied. Furthermore, the small sample size and lack of a control group limits the interpretation of the results. Finally, the study was primarily conducted in the US, and results may vary in other geographies. Phase 2: • The pre-specified endpoints were met. • Analysis was retrospective - The data source for HFE was CMS claims, so there was no event or site monitoring. - Events were not independently adjudicated. - Some results were coarsened due to low numbers as required by CMS reporting policies. - Only US patients are included, and results may be different in other geographies. - Only CMS patients were included, and on average were older with more comorbidities than the patients included in the pre-market (MultiSENSE) study.
Recommendations for Labeling Changes	Phase 1 - No labeling changes are recommended Phase 2 - Labeling changes are recommended
General
Study Status	Completed
Application Number / Requirement Number	P050052 / PAS002
Date Original Protocol Accepted	12/22/2006
Date Current Protocol Accepted	12/22/2006
Study Name	Short Term (Fitzpatrick)
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective open-label study with no control group. The study was designed to assess the development of keloid formation, hypertrophic scarring, and pigmentation changes.
Study Population	This device is indicated for subdermal implantation for the correction of moderate to severe facial wrinkles and folds such as nasolabial folds. The study population includes patients 18 years or older with Fitzpatrick skin types IV-VI who receive Radiesse for treatment of nasolabial folds.
Sample Size	100 patients, 5 sites
Key Study Endpoints	There were no primary effectiveness endpoints defined. Adverse events were assessed at 3 month and 6 month office visits.
Follow-up Visits and Length of Follow-up	The study required 6 month follow-up. Evaluation was done at baseline, 3 months, and 6 months.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	100 patients
Actual Number of Sites Enrolled	5 sites
Patient Follow-up Rate	98%
Final Safety Findings	There was one case of hyperpigmentation on the lip noted.
Study Strengths & Weaknesses	The weakness of the study was that there was no control group.
Recommendations for Labeling Changes	Update labeling to reflect the results of the PAS taking into account study limitations
General
Study Status	Completed
Application Number / Requirement Number	P970003 S050/ PAS002
Date Original Protocol Accepted	07/15/2005
Date Current Protocol Accepted	07/15/2005
Study Name	Dosing Study D-21
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a multicenter, randomized, double-blind comparison of VNS Therapy using output currents of 0.25 mA, 0.5-1.0 mA, or 1.25-1.5 mA.
Study Population	The device is indicated for the adjunctive long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments. The study Inclusion Criteria: 1. Patient has a diagnosis of chronic (¿ 2 years) or recurrent (two or more prior episodes) depression and is currently experiencing a major depressive episode as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria (DSM-N-TR); the diagnosis will by determined based on the Mini-International Neuropsychiatric Interview (MINI). 2. Patient has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories. 3. Patient must have minimum prestudy and baseline scores of 24 on the MontgomeryAsberg
Sample Size	A minimum of 330 patients will be implanted with the VNS Therapy System at up to 30 study sites. The maximum number of patients enrolled (implanted) at any site will be 40.
Key Study Endpoints	The following effectiveness evaluations will be obtained at the intervals specified on the study procedures flow chart. - Inventory of Depressive Symptomatology Clinician Administered Version (IDS-C)-- a clinician-rated 30-item multidimensional depression rating - Montgomery-Asberg Depression Rating Scale (MADRS)--a clinician-rated 10item multidimensional depression rating
Follow-up Visits and Length of Follow-up	During the treatment period, the investigator obtains the evaluations specified on the study procedures flow chart at the specified intervals (2, 3, 4, 5, 6, 10, 18, 18, 22, 26, 32, 38, 44, and 50 weeks post-implant; some latitude is permitted in scheduling these visits as indicated on the study procedures flow chart). The investigator may schedule additional non-study visits to manage the patient's depression as necessary and according to the investigator's usual practice.
Interim or Final Data Summary
Actual Number of Patients Enrolled	331
Actual Number of Sites Enrolled	29
Patient Follow-up Rate	95.8% at the end of the acute 22-week phase (primary endpoint)
Final Safety Findings	AEs were relatively well tolerated, as suggested by the low rate of subjects discontinuing due to AEs (1 subject in the Medium Dose group during the Acute Phase, and 1 subject in the Low Dose group during the Long-term Phase). Dose-effect relationships were generally absent: 97% of subjects experienced at least 1 AE, and the distribution across treatment groups was similar (95.5%, 97.2%, and 98.2% for the Low Dose, Medium Dose, and High Dose groups, respectively). However, some AEs showed a dose-response trend: asthenia (7.1% high vs. 2.8% medium vs. 4.5% low), pain (41.6% high vs. 28% medium vs. 25.2% low), dysphagia (15.9% high vs. 15.9% medium vs. 9.0% low), metabolic system adverse events (12.4% high vs. 8.4% medium vs. 6.3% low), nervous system AEs overall (75.2% high vs. 64.5% medium vs. 69.4% low) and paresthesia in particular (34.5% high vs. 32.7% medium vs. 27.9% low), and voice alteration (76.1% high vs. 76.6% medium vs. 64.0% low).
Final Effect Findings	The study did not meet the primary effectiveness outcome. The mean IDS-C 30-item change from baseline over weeks 10, 14, 18, and 22 (the Acute Phase) was not statistically different between the high dose and the low dose groups (Low vs. High stimulation group: P=0.8027) as well as between the medium dose and the low dose groups (Low vs. Medium stimulation group: P=0.8131).. Although on average the score for all 3 groups showed an improved score over time, this was not set as the primary study outcome and could be due to response to other treatments as well as natural course of the disorders or statistical regression to the mean, and perhaps to a placebo effect since the study was blinded to dosage but not to VNS Therapy implant. No statistically significant differences were noted between treatment groups for any of the effectiveness outcomes, in either of the study periods (Acure Phase or Long-term Phase).
Study Strengths & Weaknesses	The main study strength is the randomized nature of the design. A weakness is that masking was not perfect since most patients in the low dose group could correctly guess that they were assigned to the low dose.
Recommendations for Labeling Changes	Labeling changes are recommended to incorporate in the labeling the results of the randomized dosing study which showed no dose-response for VNS in TRD patients.
General
Study Status	Completed
Application Number / Requirement Number	P970051 S028/ PAS002
Date Original Protocol Accepted	03/01/2005
Date Current Protocol Accepted	03/01/2005
Study Name	Adult Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was conducted as a within-subject repeated-measures experiment (each subject served as his or her own control) to accommodate the heterogeneity of hearing-impaired populations. The study was an ABAB design in which subjects were randomly divided into Group A and Group B. Group A subjects were fit with ACE rates (a coding strategy using stimulation rates of 500 Hz, 900 Hz and 1200 Hz) at initial stimulation and Group B with the ACE RE rates (a coding strategy using stimulation rates of 1800 Hz, 2400 Hz and 3500 Hz).
Study Population	Study subjects were to be 18 years of age and older, with post-lingual onset of bilateral severe to profound sensor-neural hearing loss. Subjects' preoperative CNC word recognition scores were to be <= 30% in the best-aided condition at 60 dB SPL
Sample Size	50 patients
Key Study Endpoints	Tests of auditory speech perception were the primary outcome: Hearing in Noise Test (HINT) sentences, City University of New York (CUNY) sentences and Consonant Nucleus Consonant (CNC) monosyllabic words/phonemes. Additional measures include routine psychophysical measurements, measurements of electrical impedance and a patient questionnaire.
Follow-up Visits and Length of Follow-up	at week 0, 3, 5, 8, 10, 12, 14, 16, 24, 12-month
Interim or Final Data Summary
Interim Results	Study is completed. See Final Results
Actual Number of Patients Enrolled	76 patients
Actual Number of Sites Enrolled	14
Patient Follow-up Rate	71%
Final Safety Findings	There were progressive improvements in mean percent correct scores across the test intervals for CNC Words (60 dB SPL), HINT (in quiet) at 60 dB SPL, HINT (in noise) at 60 dB SPL and +10 dB signal-to-noise ratio (SNR), and CNC Words at 70 dB SPL.
Study Strengths & Weaknesses	Prospective Randomized Controlled Study
Recommendations for Labeling Changes	Label needs to be updated to refelct the findings of the Adult PAS study
General
Study Status	Completed
Application Number / Requirement Number	P060040 S005/ PAS001
Date Original Protocol Accepted	05/07/2010
Date Current Protocol Accepted	05/07/2010
Study Name	Destination Therapy-INTERMACS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective registry of patients receiving the HeartMate II LVAS for the Destination Therapy indication. The purpose of a post-approval study for the HeartMate II as Destination Therapy is to assess whether the commercial use of the device produces results that are comparable to results observed in the HM II Destination Therapy clinical trial.
Study Population	Study Populaton: The post-approval study is a prospective registry of patients receiving the HeartMate II LVAS for the Destination Therapy indication. The HeartMate II LVAS is intended for use as a bridge to transplantation in cardiac transplant candidates at risk of imminent death from non-reversible left ventricular failure. The HeartMate II LVAS is also indicated for use in patients with New York Heart Association (NYHA) Class 3B or 4 with endstage left ventricular failure who have received therapy for at least 45 of the last 60 days, and who are not candidates for cardiac transplantation.
Sample Size	247 patients, over 105 sites, utilizing the INTERMACS Registry
Key Study Endpoints	The primary objective of the HeartMate II Destination Therapy Post-Approval Study is to assess two-year patient survival free of stroke or reoperation to replace the device following HeartMate II implantation for Destination Therapyin a commercial setting. The following secondary objectives will be evaluated: 1) Incidence of adverse events 2) Clinical reliability; percutaneous lead (malfunctions/failures), and 3) Quality of Life as measured by EuroQOL instrument.
Follow-up Visits and Length of Follow-up	Post implant, patients will be assessed at 1 week, 1, 3, 6, 12, and 24 months.
Interim or Final Data Summary
Interim Results	No safety data is available for this study.
Actual Number of Patients Enrolled	247
Actual Number of Sites Enrolled	61
Patient Follow-up Rate	99.6%
Final Safety Findings	Most frequent overall: Bleeding (54%, 0.84 per patient year [ppy]) Infection (57%, 0.88 ppy) Respiratory failure (27%, 0.23 ppy) Most frequent <30 Days: Bleeding (38%, 7.19 ppy) Infection (24%, 4.23 ppy) Respiratory failure (19%, 3.01 ppy) Most frequent >30 Days Bleeding (36%, 0.50 ppy) Infection (52%, 0.70 ppy) Cardiac Arrhythmia (24%, 0.23 ppy) Device Malfunction (17%, 0.13 ppy) There were 9 reports of thrombus as reported by INTERMACS. - Death n=1 - Exchange/explant n=9 - Support durations 0.2 - 16.9 months QoL improved for both patient groups from pre-implant to 24 months.
Final Effect Findings	Success rate including transplant/recovery pts HMI II ¿ 139 (56%) vs. IDE ¿ 58 (44%); p=0.0236 Success rate excluding transplant/recover pts HMI II ¿ 54% vs. IDE 44%; p=0.0819 24-month survival for HM II ¿ 61.3%
Study Strengths & Weaknesses	High follow-up rate, but concerns about possible unreported adverse events. Without a requirement for device explant studies, no further investigation into the location of the 9 thrombus events can be conducted.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P970004 S022/ PAS003
Date Original Protocol Accepted	09/24/2002
Date Current Protocol Accepted	04/02/2010
Study Name	Single Tined Lead (protocol 1634)
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multicenter Phase I -randomized trial Phase II- non-randomized
Study Population	Phase I: Subjects enrolled and randomized either to InterStim Therapy (without OAB medications) or to Standard Medical Therapy and followed for # months. At month #, subjects in the Standard Medical Therapy group may undergo test stimulation and if successful receive the InterStim device. Phase II: A sufficient number of additional subjects will be enrolled and not randomized. They will undergo test stimulation and if successful will receive the InterStim device in order to meet long-term follow-up sample size requirement.
Sample Size	Phase I: # (#) will be randomized. Phase II: # subjects receiving full implant for # year endpoint
Key Study Endpoints	Efficacy: At least # improvement in average voids/day from baseline or a return to normal voiding frequency (#) for subjects with urinary frequency at baseline. At lease # improvement in average leaks/day from baseline for subjects with urinary incontinence at baseline. Subjects with both frequency and incontinence at baseline must meet at least one of the above criteria to be considered a success. Safety: Demonstrate that the upper bound of the #CI for the cumulative five-year rate of adverse events related to tined lead that require surgery after a full system implant is less than #.
Follow-up Visits and Length of Follow-up	5 years After full-system implant, follow-up visits will be completed for subjects at months 3, 6, 12, 24, 36, 48, and 60 months. For subjects randomized to InterStim who fail test stimulation will be followed for # months. Subjects in Phase II who fail test stimulation will be exited from the study.
Interim or Final Data Summary
Actual Number of Patients Enrolled	571 subjects were enrolled in the study, 272 subjects were implanted with the full system, and 169 had 5year data.
Actual Number of Sites Enrolled	38 sites
Patient Follow-up Rate	62% (169/272)
Final Safety Findings	The primary safety objective was to demonstrate that the upper bound of the 95% confidence interval for the cumulative 5-year rate of adverse events related to the tined lead requiring surgery was less than 33%. In the InSite study, the 5-year cumulative event rate was 22.4% (95% CI: 16.6%-27.7%). With an upper 95% CI limit of 27.7%, the study primary safety endpoint was met.
Final Effect Findings	The primary effectiveness analysis demonstrated that, at 5 years post-implant, 67% of subjects were OAB responders (meaning reduced symptoms of urinary urge incontinence). In addition, 64%, and 57% of subjects were urge incontinence (UI) responders and urgency-frequency (UF) responders, respectively, at 5 years. Sensitivity analyses demonstrated similar results, indicating that the main study findings regarding the treatment effect of InterStim is impacted substantially by missing data.
Study Strengths & Weaknesses	Strengths of this study include a multi-center, prospective design of adequate sample size for long-term (5-year) evaluation of the safety and effectiveness endpoints. The main weakness of the study is the limited generalizability of the long-term results. Given the attrition rate of 26.9% at 5 years, the main study findings may be an over-estimate of true device performance by potentially excluding patients who were poor responders to InterStim treatment.
Recommendations for Labeling Changes	Labeling changes are recommended based on the long-term (5-years) safety and effectiveness results of the PAS.
General
Study Status	Completed
Application Number / Requirement Number	P060040 S005/ PAS002
Date Original Protocol Accepted	05/07/2010
Date Current Protocol Accepted	05/07/2010
Study Name	Heartmate II Bleeding Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	External Registry
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is a prospective non-randomized observational study,with a primary objective of comparing high molecular weight von Willebrand factor multimer levels in nonpulsatile versus pulsatile left ventricular assist device recipients.
Study Population	Study Population: Patients who are identified pre-implant in the INTERMACS database as "Bridge to Transplant (patient currently listed for transplant)" or "Possible Bridge to Transplant - Likely to be eligible" will be enrolled in the post market study. Patients implanted with the Heartmate II will comprise the study group and patients implanted with any other LVAD will comprise a concurrent comparator group.
Sample Size	10 nonpulsatile and 5 pulsatile (HeartMate XVE, Thoratec PVAD) for a total sample size of 15 patients
Key Study Endpoints	Primary endpoint is to examine the change high molecular weight mutlimer von Willebrand factor from pre-operative levels in nonpulsatile and pulsatile device recipients to 7 days post procedure. Secondary endpoint examine HMW multimer vWF levels in patients who experience a bleeding event.
Follow-up Visits and Length of Follow-up	All subjects will be assessed pre-procedure and 7days, 30 days and 6 months after device implantation (and/or preheart transplant and 7 days after heart transplant)
Interim or Final Data Summary
Interim Results	No safety data is available for this study.
Actual Number of Patients Enrolled	53 enrolled (36 included in analyses)
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	18/52
Final Safety Findings	All non-pulsatile VAD patients demonstrated significant reductions in vWF HMW multimer levels following VAD placement. By 30 days postimplantation 100% of non-pulsatile patients tested had reduction in their HMWM levels and AvWS. Therefore, there are additional factors related to AVWF beyond decreased HMVM. 1. Higher vWF Ag levels pre-implant were measured in the pulsatile recipients versus non-pulsatile and decreased slightly by 30 days post-implant in both. 2. VWF Ag levels were higher in the bleeders at all time points in non-pulsatile patients; and both bleeders and non-bleeders had lower 30 day and 6 month vWF Ag levels compared to pre-implant levels. 3. P-selectin levels did not change significantly from baseline following non-pulsatile pump implantation. P-selectin levels were significantly lower in non-bleeders prior to implant and at 30 days post-implantation. 4. D-dimer levels declined following surgery but remained elevated through the 12 months follow up measurements.
Study Strengths & Weaknesses	Weaknesses: First, there were too few patients in the pulsatile group to power the study. Protocol deviations resulted in only 4 of the 10 pulsatile pumps being included. Of the 4 pulsatile pumps in the study, 3 patients recevied the HeartMate XVE and 1 received the Thoratec PVAD. Second, it was unclear if the loss of large mutlimers was inside or outside of the normal range of values for multimers seen in populations not included in the study. Strengths: This study is hypothesis generating for future research to see if certain preoperative characteristics, such as high P-Selectin and high vWF levels, could help to identify patients who could be at an increased risk of bleeding postoperatively.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P970018 S033/ PAS001
Date Original Protocol Accepted	12/02/2016
Date Current Protocol Accepted
Study Name	BD SurePath Collection Vial-Post-Approval Study
General Study Protocol Parameters
Study Design	Prospective & Retrospective Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The primary objective is to evaluate the performance of the BD SurePath Collection Vial in detection of LSIL+ results in a clinical use setting. The PAS consists of two study arms to compare the performance of the BD SurePath Liquid-based Pap Test when using 1) the modified BD SurePath Collection Vial (modified vial), and 2) historical data with the previously approved SurePath vial (previous vial). In both study arms, collected cells will be enriched using the BD PrepMate, slides will be prepared using the BD PrepStain and then slides will be evaluated using the FocalPoint GS Imaging System (FPGS). The study population is the entire routine screening population; approximately 15,000 results will be collected per arm. Historical and prospective calculated Bethesda result rates will be stratified into following categories: a) NILM, b) ASCUS, c) ASC-H, d) LSIL and e) HSIL+; and reported for the entire cohort, as well as by laboratory (site). False negative fraction will be calculated by site utilizing each site's quality control (QC) results from NILMs and overall. False negatives are defined as QC results of ASCUS+, LSIL+ and HSIL+, with overall and by site, including 95% confidence interval. The similarity and difference in Bethesda category (abnormality) rates will be calculated (within the context of the unmatched Historical and Prospective populations). If the PAS results indicate clinically and statistically significant inferior performance attributable to use of the Modified Vial, then a limitation will be included in the device labeling and a field action will be conducted to inform users that all potentially impacted slides should undergo re-evaluation using full manual slide review.
Study Population	The study population is the entire routine screening population of the selected sites.
Sample Size	There will be at least two (2) clinical laboratories participating in this study. Approximately 15,000 data points will be collected per study arm.
Key Study Endpoints	Based on the false negative rate for each cut-off (ASCUS+, LSIL+ and HSIL+), the ratios of 1 minus sensitivity and ratio of specificities for the modified vial vs. previous vial at each cut-off will be calculated.
Follow-up Visits and Length of Follow-up	N/A
Interim or Final Data Summary
Actual Number of Patients Enrolled	Prospective arm Historical arm Total Site 1 14,768 15,119 29,887 Site 2 4,930 5,100 10,030 Site 1+2 19,698 20,219 39,917
Actual Number of Sites Enrolled	2
Patient Follow-up Rate	All data were obtained from the two laboratories’ normal cervical cancer screening procedures and patient populations. There was no study related patient follow up.
Final Safety Findings	The study assessed False Negative Fraction (FNF) and Ratio of Specificity from the Quality Control (QC) cohorts in both historical and prospective arms and their 95% Confidence Intervals (CI). All of the CIs for FNF and Ratio of Specificity contain ‘1’ in both ASCUS+ and LSIL+ categories indicating that there is no significant change in rates of either false negative or false positive. Therefore, the study demonstrated that use of the Totalys BD SurePath Collection vial with the legacy BD PrepMate and BD PrepStain instruments, along with imaging-assisted screening using BD FocalPoint GS Imaging System has no impact on the safety of the BD SurePath Liquid-based Pap Test.
Final Effect Findings	The study results indicated that the 95% CI of the cumulative Bethesda percentages of ASCUS+, LSIL+ and HSIL+ from the prospective and historical routine population all contain ‘0’. Furthermore, the study results indicated that the 95% CI of the comparison of cumulative Bethesda percentages of ASCUS+, LSIL+ and HSIL+ from the prospective and historical QC cohorts all contain ‘0’. Therefore, the study demonstrated that the use of the Totalys BD SurePath Collection vial with the legacy BD PrepMate and BD PrepStain instruments, along with imaging-assisted screening using BD FocalPoint GS Imaging System has no impact on the effectiveness of the BD SurePath Liquid-based Pap Test.
Study Strengths & Weaknesses	Study strength: A large number of cases were enrolled: the initial study targets of 15,000 routine prospective, 15,000 routine historical, 1,500 ASC-US+ and 50 HSIL were all exceeded. Furthermore, there was no HSIL+ cases observed in either QC cohorts. Study weakness: Only two sites were enrolled (originally required three sites
Recommendations for Labeling Changes	No labeling changes are required.
General
Study Status	Terminated
Application Number / Requirement Number	P050024 / PAS001
Date Original Protocol Accepted	03/13/2008
Date Current Protocol Accepted	03/13/2008
Study Name	Cryocor Ablation PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a two armed observational study. The sponsor states sequential subjects who do not meet the exclusion criteria are enrolled into the study from a registry of patients treated for right atrial flutter with the CryoCor Cardiac Cryoablation System (study subjects) or approved radiofrequency catheter (controls). Enrollment will be sequential for eligible subjects, except that when the ratio of patients in the control arm to patients in the study arm exceeds 4:1, enrollment in the control arm will temporarily cease until an equal number of subjects have been enrolled in the study arm.
Study Population	Sequential subjects who do not meet the exclusion criteria are enrolled into the study from a registry  of patients treated for right atrial flutter with the CryoCor Cardiac Cryoablation System (study subjects) or approved radiofrequency catheter (controls). Enrollment will be sequential for eligible subjects, except that when the ratio of patients in the control arm to patients in the study arm exceeds 4:1, enrollment in the control arm will temporarily cease until an equal number of subjects have been enrolled in the study arm.
Sample Size	325 pattients from 30 sites.
Key Study Endpoints	Procedure-related adverse events within 7 days of procedure; 12 month atrial flutter recurrence free rate.
Follow-up Visits and Length of Follow-up	A clinical assessment for adverse events is scheduled at 7 days post-procedure. After that, patients are contacted by phone at 3, 6, and 12 months post-procedure to assess the patient for adverse events and recurrence of atrial flutter.
General
Study Status	Terminated
Application Number / Requirement Number	P990018 S002/ PAS001
Date Original Protocol Accepted	07/12/2002
Date Current Protocol Accepted	07/12/2002
Study Name	Menicon RGP
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The PAS was designed as a prospective, multi-center (up to 200 investigational sites) epidemiological evaluation based upon 12 months data from a minimum of 5,000 subjects followed for up to 24 months. The protocol did not specify a hypothesis, however the main purpose of the study is to estimate the incidence of microbial keratitis.
Study Population	Menicon Z tisilfocon A spherical aspheric non prism ballast toric and non prism ballast multifocal lenses are indicated for extended wear from 1 to 30 days between removals for cleaning and disinfection of the lenses as recommended by the eyecare professional for the correction of refractive error myopia hyperopia presbyopia and or astigmatism in non aphakic persons with non diseased eyes. The lens may be prescribed in spherical and aspheric powers ranging from 25.00 D to 25.00 D for daily wear and 25.00 D to 8.00 D for up to 30 days extended wear Toric lenses are designed to correct up to 5.00 D of astigmatism and multifocal lenses to provide up to 3.00 D of reading add power for up to 30 days extended wear. The study population is as per device indication
Sample Size	5000 subjects (both eyes), over 200 sites
Key Study Endpoints	Any ulcerative and microbial keratitis on the cornea in the study population
Follow-up Visits and Length of Follow-up	baseline, 6 m, 12 m, 18 m & 24 m
Interim or Final Data Summary
Interim Results	Study was terminated. See final results
Actual Number of Patients Enrolled	507
Actual Number of Sites Enrolled	65
Patient Follow-up Rate	50%
Final Safety Findings	No MK identified.
Study Strengths & Weaknesses	Enrollment not met expectation, follow-up rate too low.
Recommendations for Labeling Changes	Labeling was updated to reflect the results of the post-approval study.
General
Study Status	Other
Application Number / Requirement Number	P970029 S014/ PAS001
Date Original Protocol Accepted	02/22/2012
Date Current Protocol Accepted	01/28/2014
Study Name	PEARL 8.0 New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a new enrollment, a prospective single arm study of the Cardiogenesis PEARL 8.0 Handpiece Delivery System.
Study Population	Patients treated with PEARL 8.0 Handpiece, Cardiogenesis TMR must meet the following inclusion criteria: ¿ Class IV angina ¿ Ejection Fraction > 30% ¿ Patients with regions of myocardium in the distal two- thirds of the left ventricle with reversible ischemia and who are not eligible for direct coronary revascularization ¿ amenable to thoracoscopic TMR AND not meet the exclusino criteria listed below: ¿ Age less than18-years ¿ Pregnant or nursing mothers ¿ Unable to undergo a surgical procedure or general anesthesia ¿ Hepatic disease, renal failure, cancer or major infection ¿ Severely unstable angina (un-weanable from intravenous anti-anginals for 48-hours) ¿ Patients with mechanical/prosthetic heart valves ¿ Myocardial ischemia limited to the right ventricular wall ¿ Q-Wave myocardial infarction within three (3) weeks prior to the procedure ¿ Non Q-Wave myocardial infarction within two (2) weeks prior to the procedure ¿ Requires anticoagulation medications or has other hemorrhagic propensity ¿ Severe arrhythmia within one week prior to the procedure The comparison group is the historic control with a non-inferiority margin.
Sample Size	Stage 1: 10 patients with no mortalities Stage 2: 22 patients if 1 mortality in stage 1 Futility: 2 or more mortalities Site: 5 Sample size calculation assumptions: Patients will be enrolled at a rate of 1 patient per month, therefore, 30-day mortality will be known for all currently enrolled patients at the time each new patient is enrolled. The probability of 30-day mortality for the PEARL 8 device, p, has an assumed Beta prior distribution [p] ~ Beta(0.1, 0.9) This prior distribution is based on the previous study of the PEARL 8 device and is equivalent to observing one patient¿s worth of information with a mean 30-day mortality rate of 10%. A minimum of 10 patients will be enrolled. There will be one interim analysis and one final analysis. At each analysis, the number of observed deaths, X, among the currently enrolled patients, N, follows a binomial distribution [X] ~ Binomial(N, p) The resulting posterior distribution with the currently observed data (X, N) is [p | X,N] ~ Beta (0.1X,0.9 +N-X) The non-inferiority margin for this study is 6.6% (4.4% + 2.2%) and the success criterion at 90%. The success stopping boundaries for this study are 0 10, and 1 22. Thus, if no deaths are observed among the first 10 patients, the study will stop for success. If 1 death is observed among the first 10 patients, the study will continue to enroll. If among the first 22 patients, only 1 death is observed (there are no additional deaths), the study will stop for success. At any time, if 2 or more deaths are observed, the study will stop for futility.
Key Study Endpoints	Primary: 30 day mortality Secondary: Major adverse coronary and cerebrovascular events (MACCE)
Follow-up Visits and Length of Follow-up	30 days 30 days post procedure
General
Study Status	Completed
Application Number / Requirement Number	P920014 S016/ PAS001
Date Original Protocol Accepted	11/06/2002
Date Current Protocol Accepted	11/06/2002
Study Name	Continued Access/Registry/IDE
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was a one-armed, observational, multi-site, prospective cohort study of patients implated with the Heartmate VE VAD.
Study Population	The inclusion criteria were patients who were implanted with HeartMate VE left ventricular assist system for destination therapy, who were New York Heart Association Class IV heart patients, had been on optimal medical therapy for 60 out of the past 90 days, had a life expectancy of at least two years, and who were ineligible for cardiac transplanatation.
Sample Size	232 patients, 47 sites.
Key Study Endpoints	Vital status, whether explanted or transplanted with an artificial heart, adverse events, neurocognitive function, quality of life, 6-minute walk test.
Follow-up Visits and Length of Follow-up	Length of follow-up was one year. Follow-up visits were conducted at baseline, 1 month, 3 months, 6 months and 12 months
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	109 patients
Actual Number of Sites Enrolled	47 sites
Patient Follow-up Rate	99%
Final Safety Findings	The success criteria for this study were met
Study Strengths & Weaknesses	Weakness: There were some secondary endpoints for which data were missing on a large percent of subjects.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P970029 / PAS001
Date Original Protocol Accepted	10/20/2009
Date Current Protocol Accepted	10/20/2009
Study Name	TMR
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Historical Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study was initially designed as a randomized study comparing 300 eligible patients receiving TMR immediately to 300 patients receiving TMR following a 30-day delay period. Enrollment in this study as originally designed was not successful. The postmarket study was redesigned as a nonrandomized registry with a sample size of 500. Eligible patients can be enrolled prospectively and retrospectively.
Study Population	Study Population: Patients who may benefit from maintenance of AV synchrony. Indication: Transmyocardial revascularization with the Eclipse TMR System is indicated for treatment of adult patients with ejection fractions of 25% or more and with stable angina (Canadian Cardiovascular Society Class 4). These patients also have a region of the myocardium with reversible ischemia, however are not candidates for bypass surgery or angioplasty.
Sample Size	500 patients, 25 sites
Key Study Endpoints	The primary endpoint of this study is all-cause 30-day mortality. An additional analysis to be reported in this study is the 30-day risk of major adverse cardiovascular events, defined as the incidence of cardiac-related death, myocardial infarction Q-wave and non Q-wave), congestive heart failure/ cerebrovascular accident, and serious arrhythmia.
Follow-up Visits and Length of Follow-up	The patients will be followed in the hospital and 30 calendar days following the TMR procedure or to discharge, whichever is later.
Interim or Final Data Summary
Interim Results	The 30-day all-cause mortality risk in the PAS is 2.8% (8/358) [2.8% (2/72) prospectively enrolled and 2.1% (6/286) retrospectively enrolled). Six deaths were cardiac related and 4 deaths were not. Of the 26 patients removed from the study, 2 died within 30 days one death was cardiac related. Baseline demographic variables and clinical risk factors were included in an analysis to determine predictors of 30-day all-cause mortality. A multivariable logistic analysis showed there were no variables significant at the p = 0.05 level. There were 43 major adverse cardiac events that occurred in 33 patients for an overall major adverse cardiac event rate of 9.2% (33/358). Of the 33 patients with at least one major adverse cardiac event, 7 (9.7%) patients were enrolled prospectively and 26 (9.1%) patients were enrolled retrospectively. Serious arrhythmia accounted for the majority of major advers cardiac events (6.7%). Among the 25 episodes of arrhythmia in 24 patients. 14 events occurred within 48-hours of the TMR procedure; 4 events occurred within 72-hours; and the remaining 7 events occurred between day 4 and day 29 days post TMR procedure. Of the 26 patients who were removed from the study as of this report, two experienced a major adverse cardiac event (arrhythmia). The results of the analyses shown in Table 8 indicate that only the number of TMR channels is a statistically significant independent predictor of 30- day major adverse cardiac event. The number of channel counts was also further analyzed, grouped by increments of 10, to determine if a trend existed toward increased major adverse cardiac event with increased numbers of TMR Channels.
Actual Number of Patients Enrolled	358
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	100%
Final Safety Findings	In the Post-Approval Study of 358 patients treated with the Sologrip or Pearl 5.0 Handpieces, patients with ejection fractions ¡Â30% were at higher risk of death at 30-days (11.1%) compared to patients with ejection fractions >30% (1.5%). The number of TMR channels is a statistically significant independent predictor of 30- day MACE. The 30-day mortality proportion in the PAS (2.8%) is lower than the pre-approval study (5.3%).
Final Effect Findings	The post-approval study was not designed to examine effectiveness.
Study Strengths & Weaknesses	Strength: The study included 358 patients providing a fair characterization of the 30-day mortality and MACE proportions. Weakness: The post-approval study included a large proportion of retrospectively (n=286) (i.e., since the time of the original FDA approval [March 1999]) enrolled participants compared to the prospectively (n=72) enrolled.
Recommendations for Labeling Changes	In the Post-Approval Study of 358 patients treated with the Sologrip or Pearl 5.0 Handpieces, patients with ejection fractions ¡Â30% were at higher risk of death (11.1%) compared to patients with ejection fractions >30% (1.5%). A typical application of the device creates the lowest number of TMR channels yielding a density of 1 TMR channel/cm©÷ in ischemic myocardium. The benefits of creating larger numbers of channels (> 40), either to treat broader areas of ischemia or to achieve a higher channel density, should be weighed against the potential risks of adverse events for each patient.
General
Study Status	Completed
Application Number / Requirement Number	P970030 / PAS001
Date Original Protocol Accepted	11/04/1997
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study was a multi-center, observational, prospective trial, without concurrent or matched controls, conducted under a common protocol. A subset of subjects from the IDE study were followed until 100 subjects reached the endpoint of a minimum of 10 years. The focus of the study was to: 1) evaluate hemodynamic performance of the Toronto SPV valve and 2) monitor occurrence of adverse effects that may occur.
Study Population	The device is a tissue heart valve and is indicated for the replacement of malfunctioning native or prosthetic aortic valves. This `surveillance study' is a patient device tracking database.
Sample Size	Minimum of 100 patients, 6 sites
Key Study Endpoints	Study endpoint include death, re-operation and explant rates.
Follow-up Visits and Length of Follow-up	Patients were to be followed-up at 3-6 months and annually thereafter up to 10 years.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	417 patients
Actual Number of Sites Enrolled	6 sites
Patient Follow-up Rate	85%
Final Safety Findings	The early rate for all cause death of 0.9% for the post-approval study is significantly lower (better) than the early rate for all cause death of 2.8% for the pre-market study.The linearized late rate for major anticoagulant-related hemorrhage of 0.06%/patient-year for the post-approval study is significantly lower (better) than the linearized late rate for major anticoagulant-related hemorrhage of 0.3%/patient-year for the pre-market study. The linearized late rate for re-operation (including explants) of 1.7%/patient-year for the post-approval study is significantly higher (worse) than the linearized late rate for re-operation (including explants) of 0.3%/patient-year for the pre-market study, but the 1.7%/patientyear post-approval study rate is still acceptable according to the clinical reviewer. This rate is also similar to what is in the published literature. The linearized late rate for all cause death of 4.0%/patient-year for the post-approval study is significantly higher (worse) than the linearized late rate for all cause death of 2.3%/patient-year for the original premarket study, but the 4.0%/patient-year post-approval study rate is still acceptable, according to the clinical reviewer, and more importantly is much less relevant to the Toronto SPV valve evaluation than the acceptable linearized late rate for valve-related death of 0.7%/patient-year for the post-approval study. These rates are also similar to what is in the published literature.
Study Strengths & Weaknesses	Strengths: The study aimed to use the denominator for this post-market surveillance study as all Toronto SPV valve patients in the SJMD Patient Device Tracking database. This would minimize selection bias. Weaknesses: There were not postmarket study questions outlined for this study.
Recommendations for Labeling Changes	There were no recommendations for changes to the labeling based on the results of the post-approval study.
General
Study Status	Completed
Application Number / Requirement Number	P990046 / PAS001
Date Original Protocol Accepted	04/24/2009
Date Current Protocol Accepted	04/24/2009
Study Name	Wear testing
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	Bench study
Study Population	Test valves: ATS Medical Open Pivot Bileaflet Mechanical Heart Valves, Model No.: 500DM21 and 500DM25. Control valves: St. Jude Medical standard mechanical heart valves (Model No.: 21MJ-501 and 25MJ-501) of the same size as the test article.
Sample Size	N/A
Key Study Endpoints	n/a
Interim or Final Data Summary
Interim Results	N/A, This is a bench testing study.
Actual Number of Patients Enrolled	10 mechanical prosthesis aortic valves tested including two control valves
Actual Number of Sites Enrolled	Test sites; 2
Patient Follow-up Rate	100% at 0, 40, 80, 160, 400, 600 million cycles
Final Safety Findings	Each of the tested valves shall have a minimum expected life due to mechanical wear of 100 in vivo years as extrapolated from the test results.
Final Effect Findings	N/A
Study Strengths & Weaknesses	The test is carried out based on ISO and FDA guidelines for mechanical prosthesis valves and fulfils the condition of approval. The results are supportive to the study purpose and meet the acceptation criteria per protocol.
Recommendations for Labeling Changes	None
General
Study Status	Completed
Application Number / Requirement Number	P970051 S028/ PAS001
Date Original Protocol Accepted	03/01/2005
Date Current Protocol Accepted	03/01/2005
Study Name	Pediatric Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Infant: 29 days < 2 yrs, Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a multi-center, prospective, single-arm study. It is a was a within-subject self-control experiment design.
Study Population	The study includes patients as per device indication. The device is Intended to restore a level of auditory sensation via the electrical stimulation of the auditory nerve.
Sample Size	At least 50 patients; up to 5 centers
Key Study Endpoints	Children under 3 years of age: * Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) Children 3 to 5 years of age: * Meaningful Auditory Integration Scale (MAIS) * Multisyllabic Lexical Neighborhood Test (MLNT), if child is developmentally capable. Children 5 years and up * Lexical Neighborhood Test (LNT) * Hearing In Noise Test for Children (HINT-C) 3 Sentences in Quiet. Complication questionnaires.
Follow-up Visits and Length of Follow-up	A follow-up evaluation was to take place 1 month post-activation and threshold and comfort levels were to be assessed. The auditory performance was to be assessed at 3, 6 and 12 months post-activation, using the same tests given at pre-operative evaluation. In addition, to monitor safety, complication questionnaires were to be completed by investigators at initial activation and at 1-month, 3-months, 6-months, and 12-months post-activation. All complications and adverse events were to be obtained from the investigational sites and entered into a computer database by complaint type.
Interim or Final Data Summary
Interim Results	Study completed. See Final Study Results
Actual Number of Patients Enrolled	69 enrolled and implanted patients above 12 months of age
Actual Number of Sites Enrolled	7 centers
Patient Follow-up Rate	72.50%
Final Safety Findings	No unanticipated AEs and 9 complications overall. Type of Complication - Number of occurrences - Rate of occurrence per 100 implant years Dizziness - 2 - 2.60 Dermatological Issues - 2 - 2.60 Facial Nerve Stimulation - 1 - 1.3 Revision Surgery following accident - 1 - 1.3 Short/Open Electrodes - 3 - 3.91
Study Strengths & Weaknesses	Low follow up rate. No controls.
Recommendations for Labeling Changes	None
General
Study Status	Hold
Application Number / Requirement Number	P050025 / PAS002
Date Original Protocol Accepted	10/12/2006
Date Current Protocol Accepted	10/12/2006
Study Name	SONOMA
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Historical Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This was a nonrandomized, open-label study intended to confirm the safety of the NexStent Carotid Stent System and the FilterWire EZ Embolic Protection System in routine clinical practice and to identify rare or unanticipated device-related events that may occur with the use of this system.
Study Population	Study Population: Patients with neurological systems associated with >50% stenosis of the common or internal carotid artery OR patients without neurological symptoms and >80% stenosis of the common or internal carotid artery by ultrasound or angiogram and patients must have a reference vessel diameter within the range of 4 mm and 9 mm at the target lesion and a stenosis less than 30 mm in length. Indication: The NexStent Carotid Stent System used in conjunction with the FilterWire EZ System, is indicated for treatment of patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization.
Sample Size	1650 patients, number of sites not specified
Key Study Endpoints	The primary endpoints included 30-day rate of major adverse events defined as all deaths, strokes, and myocardial infarctions that occur within 0-30 days, 12-month composite rate of major adverse events, and ipsilateral stroke events that occur within 31-365 days for all subjects.
Follow-up Visits and Length of Follow-up	Though 1,650 subjects were planned for the SONOMA study, only 298 had been enrolled at the point of study termination. Subjects were to be evaluated at 30 day and 12 month follow-up. As of July 24, 2009, the follow-up of all enrolled subjects (87.5%) was completed.
Interim or Final Data Summary
Interim Results	See final results
Actual Number of Patients Enrolled	298 patients
Actual Number of Sites Enrolled	62 sites
Patient Follow-up Rate	88%
Final Safety Findings	The sponsor voluntarily recalled this device in June of 2008 due to complaints involving detachment of the tip from the stent delivery System.
Study Strengths & Weaknesses	Strengths: Post approval study aided in uncovering problem with stent delivery. Weaknesses: There was no control group enrolled in this study.
Recommendations for Labeling Changes	Not applicable, stent no longer marketed.
General
Study Status	Redesigned/Replaced Study
Application Number / Requirement Number	P160015 S001/ PAS001
Date Original Protocol Accepted	06/05/2020
Date Current Protocol Accepted	07/16/2026
Study Name	AED 3 and Pad Placement PAS
General Study Protocol Parameters
Study Design	Other Study Design
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, observational study. Enrollment in this study is expected to take approximately 36 months. The full study timeline is below. Subjects are enrolled once EMS personnel are on-scene and able to make an assessment of outcome measures listed below. No data will be collected about CPR quality or patient outcomes. Subjects will not be followed after the assessment of study objectives. The objectives of the study are: • Demonstrate appropriate CPR sensor placement on pediatric and adult patients • Demonstrate delivery of appropriate energy level shocks to pediatric and adult patients Additionally, a limited human factors study will be conducted using manikins. Participants will be randomly assigned to either the ‘adult scenario’ or the ‘pediatric scenario’.
Study Population	Candidates for this study must meet all of the following Inclusion criteria: 1. Suspected out-of-hospital cardiac arrest 2. Use of ZOLL AED 3 PAD (running software v. 1.03.602 or newer (US) or v. 6.03.006 or newer (International)) with Uni-padz III 3. Unconsciousness 4. Absence of breathing 5. Absence of pulse and other signs of circulation The limited human factors study will be conducted using adult and pediatric manikins.
Sample Size	Approximately 73 adult subjects and 15 pediatric subjects were planned to be enrolled in this study. Only 38 adult subjects have been enrolled so far. There are currently two sites: 1. The University at Buffalo (UB), initiated on March 30, 2021. 2. Colonie EMS (New York) initiated on December 19th, 2022. The human factors study will be conducted in 32 lay rescuers and 32 professional users.
Key Study Endpoints	Study endpoints include appropriate placement of the electrodes which will be assessed by EMS personnel based on observations made when they arrive on scene, the appropriate selection of adult or pediatric mode which will be assessed by identifying that the child button was pressed when the estimated age is less than 8 years old, and the delivery of defibrillation energy which will be determined by documented whether the energy was age-appropriate if a shock was delivered. Endpoints assessed for the human factors study are: - The appropriate placement of the CPR sensor - The appropriate selection of adult or pediatric mode
Follow-up Visits and Length of Follow-up	Subjects will not be followed after the assessment of study objectives
Interim or Final Data Summary
Interim Results	Safety Results: N/A Effectiveness Results: N/A
Actual Number of Patients Enrolled	No subjects enrolled. Will be a total of 64 user participants.
Actual Number of Sites Enrolled	One study site: Fieldwork Boston; simulation laboratory.
Patient Follow-up Rate	N/A
General
Study Status	Completed
Application Number / Requirement Number	P890003 S179/ PAS001
Date Original Protocol Accepted	01/09/2012
Date Current Protocol Accepted	11/22/2013
Study Name	Chronic Lead Performance
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The Medtronic Post-Approval Network (PAN) is designed to conduct non-randomized, active prospective post-market Surveillance. The Registry is sponsored by Medtronic and is comprised of a global network of hospitals, clinics and clinicians from which reliable ¿real world¿ product safety and patient clinical outcome information is generated. Primary objective: To demonstrate that the complication- free probability is greater than 92.5% at five years post- implant for the high voltage DF4 connector.
Study Population	This study will consist of 1,778 patients implanted with a DF- 4 connector system, enrolled at one of approximately 150 centers globally. Subjects that meet the following inclusion criteria and do not meet any of the following exclusion criteria are eligible for enrollment. Inclusion Criteria ¿ Subject or legally authorized representative provides written authorization and/or consent per institution and geographical requirements ¿ Subject is implanted with a DF-4 connector system. ¿ Subject within 30 days of implant Exclusion Criteria ¿ Subject who is, or will be inaccessible for follow-up at a site ¿ Subject with exclusion criteria required by local law (Europe, Central Asia [ECA] only) ¿ Complete implant and follow-up data, including any product-related events at implant through the time of enrollment are unavailable
Sample Size	Accounting for attrition, a minimum enrollment of 1778 DF4 connectors are estimated to be required in order to achieve the desired sample size for the primary objective analysis at five years.
Key Study Endpoints	A list of lead-related events eligible to be included in the primary objective: Failure to capture, Failure to sense/ Undersensing, Oversensing, Threshold rise, Abnormal pacing impedance, Abnormal defibrillation impedance (RV and/or SVC coil), Lead insulation breach, Lead conductor fracture, Extra cardiac stimulation, Lead dislodgement, Cardiac perforation, Structural Lead Failure.
Follow-up Visits and Length of Follow-up	Subjects will be followed for a minimum of 5 years from their implant date. Therefore, the expected duration of the DF4 PAS is approximately 7 years. Frequency of Follow-up Assessments Every 6 months
Interim or Final Data Summary
Actual Number of Patients Enrolled	1778
Actual Number of Sites Enrolled	104
Patient Follow-up Rate	38.5%
Final Safety Findings	The complication-free survival probability in this group was 98.6%.
Final Effect Findings	The sponsor presented Pacing Thresholds, Pacing and Defibrillation Impedance, and Sensing data for the subjects who remained in the study at 6 month intervals by lead type associated with the DF4 connector. The results confirm that the electrical performance of the DF4 connector leads is stable over time and within expected ranges.
Study Strengths & Weaknesses	A strength of this study is that the results reflect what is expected to be observed in routine clinical practice. A weakness includes the premature exit of some study sites and patients due to the longer-term nature of the study, thus limiting patient follow-up. Despite this barrier, the primary objective of the study was met, demonstrating the safety and efficacy of the DF4 connector.
Recommendations for Labeling Changes	Yes, completed.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S394/ PAS001
Date Original Protocol Accepted	09/25/2013
Date Current Protocol Accepted	09/25/2013
Study Name	LIA in Non-MDT Leads Surveillance Update Analysis
General Study Protocol Parameters
Study Design	Retrospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This analysis plan is created to leverage data that is already available as part of the Medtronic CareLink remote management system. An RV LIA trigger requires 2 of 3 components to be satisfied within 60 days: abrupt pace sense impedance change, frequent extremely short R-R intervals, and rapid non-sustained VT episodes. The save-to-disk file associated with each of these alert (RV LIA or impedance nominal threshold) triggers, and any associated data from DRS and/or GCHS, will be reviewed by the lead failure adjudication committee to determine the cause of the RV LIA alert or impedance nominal threshold crossing.
Study Population	This is a retrospective analysis of existing data from CareLink. Among the large number of patients and clinics that use CareLink to manage their devices, there are some that have already been implanted with a combination of an RV LIA enabled device and an RV defibrillation lead not manufactured by Medtronic. There are three Medtronic sources of information that will be used to support this analysis: ¿X Data Warehousing and Analytics Services (DWAS) ¿X Device Registration System (DRS) ¿X Global Complaint Handling System (GCHS) The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013
Sample Size	As there are no hypotheses being tested for this analysis, there are no powered sample size estimates. However, two requirements were identified to determine the sample size and timing of the analysis. First was to ensure the amount of lead follow-up is at least the size of the PMA analysis (11,052 RV LIA years of follow up across both St. Jude and Boston Scientific leads) and secondly the analysis will occur after PMA approval. Current estimates are that the RV LIA years of follow-up since the PMA cut off of October 4, 2011 has already been exceeded with approximately 14,500 years of RV LIA enabled follow-up. Therefore, assuming event rates remain the same as in the PMA cohort, it is expected at 77 additional lead events will be included in this study which is 28% more than the 60 true lead events observed across both manufacturers in the PMA analysis. The data cut off for analysis will be the first day after PMA approval in which the RV LIA enabled years of follow-up is greater than 11,050 years of follow-up.
Key Study Endpoints	There are three Medtronic sources of information that will be used to support this analysis: ? Data Warehousing and Analytics Services (DWAS) ? Device Registration System (DRS) ? Global Complaint Handling System (GCHS) The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013. Primary Objective: To summarize the number of lead failure events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads). Secondary Objective: To summarize the number of other detected events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads).
Follow-up Visits and Length of Follow-up	No follow-up visits and length of follow-up
Interim or Final Data Summary
Actual Number of Patients Enrolled	5753 devices
Actual Number of Sites Enrolled	N/A
Patient Follow-up Rate	N/A
Final Safety Findings	N/A
Final Effect Findings	The incidence of right ventricular (RV) Lead Integrity Alert (LIA) trigger or impedance nominal threshold during the post-approval period was low in St. Jude Medical (STJ) Riata/Durata leads and Boston Scientific (BSX) Endotak leads (0.725% per device year in STJ leads and 1.23% per device year in BSX leads). The majority of identified triggers classified as lead failure events (LFEs) or other detected events (ODE) were detected by only the RVLIA criterion in both STJ and BSX leads. These findings were consistent with events identified during the original analysis supporting the PMA labeling language for RV LIA use with Non- Medtronic leads.
Study Strengths & Weaknesses	Strength: Large sample size; Weakness: Retrospective data analysis. Lack of data presented to support advance warning of RV LIA relative to lead failure events. No data available on the positive predictive value or negative predictive value.
Recommendations for Labeling Changes	No
General
Study Status	Completed
Application Number / Requirement Number	P980016 S536/ PAS001
Study Name	MR conditional Tachy Therapy Systems
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. ¿ Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S555/ PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted
Study Name	PCT Change Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	The study will be conducted within Medtronic’s Product Surveillance Registry (PSR). The PSR platform is designed to conduct non-randomized, active, prospective post-market surveillance. Patients implanted with a MR Conditional CIED system and enrolled in the PSR will be followed per the expected standard of care practice of their care provider. Pacing capture thresholds (PCT) measurements of MR conditional CIED systems enrolled in the PSR will be used to prospectively monitor changes in PCT following 3T MR exposure. Patient status is collected approximately every 6 to 12 months including MRI scan information, if applicable. Sites will report patient baseline information (e.g. height, weight, etc.) the occurrence of a medically indicated MRI scan, reason for scan, anatomical region scanned, magnet strength, and MRI related events. Analysis of the primary objective will be performed 4-years following approval
Study Population	All patients implanted with a MR Conditional CIED system and enrolled in the PSR who subsequently receive an MRI scan using a 3T system within the 4-years post approval that meets approved labelling requirements.
Sample Size	The following assumptions were used to estimate the PAS duration and number of 3T scans projected to be obtained during the 4-years study period: MR Conditional CIED enrollment of approximately 2,400 patients Annual MRI scan rate of 9% Participating sites with 3T scanning capability: 25% - 40% % of patients with a 3T MRI scan: 30% - 45% Table 3: 3T Scan Rate Assumptions Over 4-Year Study Duration Assumptions Year 1 Year 2 Year 3 Year 4 Cumulative MR Conditional Enrollments (*) 1260 1674 2047 2382 Cumulative # of completed MRI Scans 113 264 450 571 Assumption for % centers with 3T capability 25% 25% to 40% % MR scans through 3T in these centers 30% 30% - 45% Cumulative # of completed 3T scans 9 43 to 103 (*) Assumes a 10% annual attrition Contribution from enrollments outside the US to the primary objective will be limited to no more than 50% of the total sample size.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of patients implanted with an MR conditional CEID system with a pre to post MRI scan PCT measure change of more than 0.5 V following 3T scan exposure. Definitions for pre and post PCT measurements Pre-MRI PCT measure: max PCT value preceding the SureScan mode enabled and prior to the 3T MRI scan Post-MRI PCT measure: 1st max PCT measurement at a time point >30 days (chronic PCT) following 3T MRI exposure. Further investigation will be carried out to identify root cause if the observed proportion of PCT changes following 3T scan exposure is greater than 8% (i.e. 2X the observed proportion in the PSR SureScan data) and more than 50% of those observed >0.5V PCT changes reflect an increase.
Follow-up Visits and Length of Follow-up	4 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	8388
Actual Number of Sites Enrolled	191
Final Safety Findings	One patient showed a ¿PCT greater than 0.5V within the analysis window. As this does not meet the 8% threshold proportion of patients and/or scans with a greater than 0.5V change pre- to post-3T MRI, no additional comparative analyses were performed. No adverse events, deaths, or device deficiencies related to 3T scan.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The primary endpoint was acceptable. The results are favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S586/ PAS001
Study Name	MR conditional Tachy Therapy Systems Stud
General Study Protocol Parameters
Study Design	Active Surveillance
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Detailed Study Protocol Parameters
Study Objectives	MR conditional tachyarrhythmia therapy systems enrolled in the Medtronic CareLink® (CL) Network will be used to prospectively assess spontaneous VF episode detection following MRI exposure.
Study Population	All patients who will be implanted with an MR conditional tachyarrhythmia therapy system and followed in the Medtronic CL network with de-identified data accessibility.
Sample Size	A sample size of 50 patients with a true VF episode will produce a 2-sided 95% confidence interval upper bound for the estimate of approximately 11% (i.e. no more than one VF that will have = 5 second detection delay). The following assumptions were used to define the surveillance scope and duration: ¿ CL participation estimates: o An estimated 65% of US ICD implants currently enroll in CL and approximately 60% of those patients regularly transmit device data. o An estimated 69% of US CRT-D implants currently enroll in CL and approximately 55% of those patients regularly transmit device data. ¿ Applying CL use/transmission rate to the current estimated US sales projections: o An estimated 10,979 MR ICD System Evera MRI patients will be actively monitored in CL within three years of product approval. o An estimated 14421 MR CRT-D system patients will be actively monitoring within three years of product approval ¿ Annual MRI scan rate of 9%, an estimated 4143 patients will have at least one MRI scan within approximately 4 years post product approval. Annual true VF/PMVT episode rate of approximately 2%, based on episode adjudication data collected in Medtronic PainFree SST and Shockless studies. Year 1 Year 2 Year 3 Projected US MR ICD Sales per year 6450 10000 11700 Estimated # of Patients with CareLink Transmissions (0.65|0.6) 2516 3900 4563 Projected US MR CRT-D Sales per year 12000 14000 12000 Estimated # of Patients with CareLink Transmissions (0.69|0.55) 455 5313 455 Total Estimated (MR ICD + MR CRT-D) with CareLink Transmissions 7070 9213 9117 MRI after 1 year (0.09 ) 635 829 819 MRI after 2 years (0.172) 1214 1583 MRI after 3 years (0.246) 1741 Total Estimated # of Patients with an MRI 4143 Per the above assumptions, a statistical simulation indicates that approximately 40 to 97 patients will have 40 to 194 true VF/PMVT detected episodes, following an MRI, within approximately 5 years of product approval.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of episodes with = 5 seconds VF detection delay in the MR conditional tachyarrhythmia therapy system following MRI exposure. No VF/PMVT detection delays of = 5 seconds were observed in the Evera MRI IDE study. A previous Medtronic study estimated a 0.08% detection delay rate in non-MRI patients based on a cohort of 1177 induced VF episodes. Therefore, the probability of observing at least one VF/PMVT episode with = 5 seconds detection delay in the study cohort of 50 patients with VF episodes is 2%. Other endpoints: 1) Multiple MRI Scans Data regarding the number of patients presumed to have had 2 or more scans will be provided. The time stamp of a when a device was last programmed to the MRI compatible mode (i.e. SureScan mode) will be tracked from CL transmission to transmission. Any change in the time stamp of an MR mode safe switch of greater than 20 minutes will indicate the occurrence of an MRI. The estimate of patients receiving multiple MRI scans will include all patients regardless if the patient has experienced a VF episode. 2) LV Pacing Capture Threshold Left ventricular lead Pacing Capture Threshold (PCT) values are automatically stored by the device through the Left Ventricular Capture Management feature and obtained through CareLink transmissions. Pre-MRI and post-MRI4 LV lead PCT measurements obtained through CareLink will be summarized for MR CRT-D patients. Summary statistics will be presented separately for pre-MRI and post-MRI PCT measurements. It is anticipated that PCT measurements from approximately 2,444 patients with a MRI will be presented.
Follow-up Visits and Length of Follow-up	50 patients with a VF episode following MR exposure have been identified or 5-years post-approval, whichever comes first.
Interim or Final Data Summary
Actual Number of Patients Enrolled	90,709 MR Tachy patients were captured by the Carelink Transmissions. 5,104 MR tachy patients with at least one MR scan were captured in the CL system.
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	The primary safety endpoint is the proportion of episodes with >5 seconds VF detection delay in an MR conditional tacharrhythmia therapy system following MRI exposure. There were no episodes observed.
Final Effect Findings	The LV PCT data was captured. The mean post MRI PCT is lower than the mean pre-MRI; therefore, there are no additional concerns.
Study Strengths & Weaknesses	Given the expected low incidence rate of spontaneous VF episodes, device data obtained through Medtronic CL transmissions is the most suitable data source available for assessing potential VF detection delay following MR exposure in a timely manner. The de-identified CL dataset is limited to US, Canada, Australia & New Zealand geographies. Additionally, the analysis is limited to only CL enrolled patients who also routinely transmit device data.
Recommendations for Labeling Changes	yes
General
Study Status	Completed
Application Number / Requirement Number	P010031 S674/ PAS001
Date Original Protocol Accepted	04/23/2020
Date Current Protocol Accepted	04/26/2024
Study Name	iATP PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs
Detailed Study Protocol Parameters
Study Objectives	To further characterize iATP effectiveness in real world clinical practice to pace-terminate VT. The study is a global, non-randomized, prospective post-market surveillance study.
Study Population	Subjects with an implanted Cobalt ICD or CRT-D with iATP enabled and enrolled in the Medtronic CareLink Network.
Sample Size	Approximately 2200 patients will be enrolled to review 241 eligible episodes.
Key Study Endpoints	To demonstrate the effectiveness performance of iATP in the fast VT (FVT) zone is acceptable, i.e. iATP success rate is greater than 60%. Secondary objectives: To demonstrate the effectiveness performance of iATP in the FVT zone exceeds expectations, i.e., iATP success rate is greater than 70% To characterize arrhythmia-related syncope events To characterize unnecessary and inappropriate shocks
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1875
Actual Number of Sites Enrolled	76
Patient Follow-up Rate	Overall follow-up rate (within window patient contact rate) was 87.97%.
Final Safety Findings	iATP therapy is safe with low rates of arrythmia-related syncope and MVT acceleration resulting in shock. The percentage of patients having arrhythmia-related syncope events where iATP therapy was used was 0.48% (9/1875). The GEE-estimated rate for iATP associated MVT acceleration resulting in shock was 2.3% (95% CI: 1.5% - 3.5%).
Final Effect Findings	iATP is a highly effective therapy to treat MVT. The GEE-estimated iATP success rate in the FVT zone was 89.7% (95% CI: 83.6% - 93.7%). The GEE-estimated iATP success rate in the VT zone was 92.1% (95% CI: 89.0% - 94.4%). The GEE-estimated iATP success rate in the VF zone was 72.8% (95% CI: 63.6% - 80.4%)
Study Strengths & Weaknesses	Strengths: Reflects real world data as patients were managed per physician discretion and standard of care. Collects patient characteristics and clinical outcomes through CRFs and device data through CareLink transmissions. Weaknesses: There was missing patient characteristics data likely due to standard of care and evolution of CRF development over years.
Recommendations for Labeling Changes	Recommend the labeling is updated to include the study results.
General
Study Status	Completed
Application Number / Requirement Number	P980016 S713/ PAS001
Date Original Protocol Accepted	04/23/2020
Date Current Protocol Accepted
Study Name	iATP PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Analytical
Detailed Study Protocol Parameters
Study Objectives	To further characterize iATP effectiveness in real world clinical practice to pace-terminate VT. The study is a global, non-randomized, prospective post-market surveillance study.
Study Population	Subjects with an implanted Cobalt ICD or CRT-D with iATP enabled and enrolled in the Medtronic CareLink Network.
Sample Size	Approximately 2200 patients will be enrolled to review 241 eligible episodes.
Key Study Endpoints	To demonstrate the effectiveness performance of iATP in the fast VT (FVT) zone is acceptable, i.e. iATP success rate is greater than 60%. Secondary objectives: To demonstrate the effectiveness performance of iATP in the FVT zone exceeds expectations, i.e., iATP success rate is greater than 70% To characterize arrhythmia-related syncope events To characterize unnecessary and inappropriate shocks
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	1875
Actual Number of Sites Enrolled	76
Patient Follow-up Rate	Overall follow-up rate (within window patient contact rate) was 87.97%.
Final Safety Findings	iATP therapy is safe with low rates of arrythmia-related syncope and MVT acceleration resulting in shock. The percentage of patients having arrhythmia-related syncope events where iATP therapy was used was 0.48% (9/1875). The GEE-estimated rate for iATP associated MVT acceleration resulting in shock was 2.3% (95% CI: 1.5% - 3.5%).
Final Effect Findings	iATP is a highly effective therapy to treat MVT. The GEE-estimated iATP success rate in the FVT zone was 89.7% (95% CI: 83.6% - 93.7%). The GEE-estimated iATP success rate in the VT zone was 92.1% (95% CI: 89.0% - 94.4%). The GEE-estimated iATP success rate in the VF zone was 72.8% (95% CI: 63.6% - 80.4%)
Study Strengths & Weaknesses	Strengths: Reflects real world data as patients were managed per physician discretion and standard of care. Collects patient characteristics and clinical outcomes through CRFs and device data through CareLink transmissions. Weaknesses: There was missing patient characteristics data likely due to standard of care and evolution of CRF development over years.
Recommendations for Labeling Changes	Recommend the labeling is updated to include the study results.
General
Study Status	Completed
Application Number / Requirement Number	P190019 / PAS001
Date Original Protocol Accepted	12/16/2020
Date Current Protocol Accepted
Study Name	RANGER II SFA Cont F/u Study
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of premarket cohort: RCT
Study Population	Test: Ranger DCB Control: PTA
Sample Size	376
Key Study Endpoints	The primary effectiveness endpoint is primary patency of the target lesion at 24 months. The primary safety endpoint is a composite of freedom from device- and procedure-related death at 30 days and freedom from target limb major amputation and clinically-driven target lesion revascularization (CD-TLR) at 24 months. The endpoints to be assessed through 5 years post-procedure are rate of: (1) major adverse events (MAE), (2) clinically-driven target lesion revascularization (CD-TLR), (3) all TLR, (4) clinically-driven target vessel revascularization (CD-TVR), (5) target limb major amputation, (6) arterial thrombosis and (7) mortality status. The endpoints to be assessed at 2 and 3 years post-procedure are: (1) patency, (2) change in ankle-brachial index (ABI), (3) change in walking impairment questionnaire (WIQ), (4) change in walking distance, (5) change in Rutherford classification, and (6) change in quality of life assessment by EQ-5D questionnaire.
Follow-up Visits and Length of Follow-up	5 years
Interim or Final Data Summary
Actual Number of Patients Enrolled	376 enrolled (Ranger DCB – 278 / Standard PTA – 98)
Actual Number of Sites Enrolled	67 sites enrolled
Patient Follow-up Rate	Overall follow-up was 84.4% (Ranger DCB – 85.3% / Standard PTA – 81.7%)
Final Safety Findings	60 months MAE was 73.2% (156/213) for the Ranger DCB, and 68.5% (50/73) for Standard PTA. Mortality at 60 month follow up was 16.1% (40/248) for the Ranger DCB, and 18.8% (16/85) for Standard PTA.
Final Effect Findings	Primary Patency rate for the Ranger DCB was 66.8% (125/187) at 36 months. Primary Patency rate for the Standard PTA was 62.5% (45/72) at 36 months.
Study Strengths & Weaknesses	This was a global, prospective, multi-center, single-blind, superiority, 3:1 (Ranger DCB vs. Standard PTA) controlled randomized clinical trial. Follow-up was 85.3% for the Ranger DCB and 81.7% for Standard PTA. There was no hypothesis testing on the follow-up results.
Recommendations for Labeling Changes	A labeling update will be requested to include the longer-term data in the IFU.
General
Study Status	Completed
Application Number / Requirement Number	P030016 / PAS001
Date Original Protocol Accepted	12/22/2005
Date Current Protocol Accepted	06/08/2012
Study Name	Adverse Event Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective Registry with patients reporting outcomes
Study Population	The device is indicated for adults 21-45 years of age:to correct myopia ranging from -3.0 diopters to < - 15.0 diopters with less, than or equal to 2.5 diopters of astigmatism at the spectacle, plane; * to reduce myopia ranging from greater than -15.0 diopters to - 20.0, diopters with less than or equal to 2.5 diopters of astigmatism at tile spectacle plane; and, with an anterior chamber depth (ACD) 3.00 mm or greater, and a stable refractive history within 0.5 diopter for 1 year prior to implantation. The Study includes subjects who are 21-45 years of age with myopia of -3.0 diopters to -20 diopters.
Sample Size	3,000 eyes will be enrolled 2,000 treated eyes needed with 5-year data
Key Study Endpoints	Corneal edema, cataract, chronic uveitis, glaucoma, retinal detachment, second surgery, and other complications assessed by patient questionnaire
Follow-up Visits and Length of Follow-up	6, 12, 18, 24, 36,48, and 60 months after implantation
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 2,999 eyes of 1,547 patients were enrolled in the US between April 2006 through October 2013.
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	100% at 6 months, 100% 12 months, 99.9% 18 months, 98.7% 24 months, 97.4% 36 months, 96.5% 48 months, 96.2% at 60 months (2,125 eyes were followed for 5 years).
Final Safety Findings	Cumulative Adverse Event rates at 60 months (upper 90%CI) Corneal problems: 0.0% (0.18%) Cataract: 2.0% (2.65%) Treated intraocular inflammation: 0.2% (0.51%) Treated IOP or glaucoma: 0.2% (0.52%) Retinal detachment surgery: 0.2% (0.41%) Remove, replace, or reposition ICL: 1.8% (2.42%) Other ocular conditions/complications Glare: 0.8% Halo: 1.5% Dryness: 1.3% Secondary surgery (SSI) to address residual astigmatism: 0.7% Patients and eyes with multiple adverse events Adverse Events Patients Eyes 2 78 114 3 6 8 4 4 4 Total 88 126 Most common adverse event combination: Cataract/Lens removal in 69 patients (104 eyes). Cumulative adverse events and comparison with premarket study: Adverse Event Post-Market Pre-market Study Corneal problems 0.3%, (5/2999) 0%, (0/526) Cataract development 5.1%, (154/2999) 8.6%, (45/526) Treated intraocular inflammation 0.5%, (14/2999) 0.0%, (0/526) Treated IOP or glaucoma 1.6%, (47/2999) 1.3%, (7/526) Retinal Detachment Surgery 0.4%, (13/2999) 0.6%, (3/526) Remove, replace or reposition ICL 4.2%, (126/2999) 4.3%, (23/526) Glare 2.6%, (66/2527) 9.6%, (34/351) Halos 5.6%, (142/2527) 11.5%, (40/350) SSI for residual astigmatism 76/2527 (3.0%) 21/526 (4.0%) Note: Data at 60 months after surgery for Post-Market, and at =60 months after surgery for Premarket)
Final Effect Findings	This study was required for safety endpoints.
Study Strengths & Weaknesses	Strengths: Sponsor have enrolled the required sample size and completed the follow-up ahead of schedule. Follow-up rate was higher than 96.2% at 60 months. Therefore, sample size at the end of the follow-up exceeded the minimum number required for analysis. Data quality control showed 91.4% “no adverse event” agreement in a random sample of study data. A comparison with the premarket data showed comparable event rates in Corneal problems, treated intraocular inflammation, treated IOP or glaucoma, retinal detachment surgery, remove, replace or reposition ICL and secondary surgery to address residual astigmatism. However, slightly lower adverse event rates for cataract development, glare and halos were found in the post-approval study. Weaknesses: No concomitant comparator group was included. The study was designed to provide descriptive estimates of the rates for the safety endpoints of interest.
Recommendations for Labeling Changes	No label update recommended because although some results of the PAS show lower incidence rates than in premarket, the differences can be explained by differences in data collection methods. For example, in the premarket study the investigators reported changes in lens opacity based on slit lamp observation at each visit, while survey questionnaires were used in the post-approval study, which may capture the practice of physicians who are less likely to report clinically insignificant changes.
General
Study Status	Terminated
Application Number / Requirement Number	P050009 / PAS001
Date Original Protocol Accepted	12/16/2005
Date Current Protocol Accepted	12/16/2005
Study Name	Long Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study design is single-arm, prospective cohort. There are no formal study hypotheses. 10 year post-marketing prospective hip study enrolling a minimum of 257 primary total hip replacements of whom a minimum of 160 will be followed out to 5 years and a minimum of 100 patients will be followed for 10 years. The first phase of the investigation will gather clinical, radiographic, and survivorship data for 5 years following implantation. The second phase, years 6 through 10, will utilize mailings to gather survivorship information. However, because of the lack of progress on the original PAS, FDA asked the sponsor to redesign the PAS. The PAS was revised per a FDA letter dated 7/14/09. The new protocol is not approved yet [Aug 13, 2010]. The description presented here is for the old study
Study Population	Patients who underwent total hip arthroplasty using a C2 a-Taper Acetabular System ceramic on ceramic hip articulating system.
Sample Size	The sample size is 257 patients.
Key Study Endpoints	Study endpoints include device revision and Harris Hip Score during the first five years of follow-up.
Follow-up Visits and Length of Follow-up	Patients will undergo clinical and radiographic examination for their first five years of follow-up. During their last 5 years of follow-up patients will receive annual questionnaires regarding the status of their total hip replacements.
General
Study Status	Completed
Application Number / Requirement Number	P110004 S001/ PAS001
Date Original Protocol Accepted	05/14/2015
Date Current Protocol Accepted	11/01/2017
Study Name	NIRTRAKS PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This is a prospective, post-marketing, non-randomized, multi-center, single-arm clinical study that will be conducted at up to 15 sites in the United States (US). All subjects will be treated with the NIRxcell Stent System and followed at 30 days, 9 months and 1, 2 and 3 years post-index stenting procedure. An unscheduled follow up may be conducted as clinically warranted.
Study Population	Subjects with symptomatic ischemic heart disease due to a single de novoI stenotic lesion contained within a native coronary artery with a reference vessel diameter between 2.5 mm and 4.0 mm and lesion length less than or equal to 30 mm that is amenable to percutaneous revascularization with stent deployment.
Sample Size	Per agreement with the FDA (P110004/S021), only 65 of the originally 131 planned subjects will be enrolled. Assuming loss of approximately 7.0% per year, there is anticipated to be approximately 52 evaluable subjects after 3 years.
Key Study Endpoints	Primary Endpoint Target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) [Q wave or non-Q wave], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 3 years post-procedure. Secondary endpoints -TVF at 9 months -All Death at 30 days, 1, 2 and 3 years -Cardiac Death at 30 days, 1, 2 and 3 years -All cause MI at 30 days, 1, 2 and 3 years -Target vessel MI at 30 days, 1, 2 and 3 years -Clinically driven TVR at 30 days, 1, 2 and 3 years -Clinically driven target lesion revascularization (TLR) at 30 days, 1, 2 and 3 years -Acute Success Rates Device Success: Attainment of < 50% final residual stenosis of the target lesion using only Presillion plus Stent Systems. Lesion Success: Attainment of < 50% final residual stenosis of the target lesion using any percutaneous method. Procedure Success: Attainment of < 50% residual stenosis of the target lesion and no in-hospital death, MI, or TLR. Stent Thrombosis at hospital discharge, at 30 days, 1, 2 and 3 years.
Follow-up Visits and Length of Follow-up	Patients will be followed up for 3 years. Follow-up will be performed at 30 days, 1, 2 and 3 years post-procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	February 14, 2017, 65 of the planned 131 subjects were enrolled in the study.
Actual Number of Sites Enrolled	8 Total clinical sites. 5 sites enrolled subjects. 3 of the initially 8 enrolled sites were closed due to no enrollment
Patient Follow-up Rate	Of the 65 subjects enrolled, all (100%) completed the 30-day visit. Between 30 days and 9 months, one subject died for a total of 64 subjects eligible for the 9-month visit; 62 (96.9%) completed the visit. Between 9 months and 1 year, one subject died, and one was lost to follow-up for a total of 62 subjects eligible for the 1-year visit; 61 (98.4%) completed the visit. Between 1 and 2 years, 5 subjects died, one subject withdrew consent to participate, and one subject was lost to follow-up for a total of 55 subjects eligible for the 2-year visit; 54 (98.2%) completed the visit. Between 2 and 3 years, 3 subjects died, and 4 subjects discontinued due to an adverse event. An additional 11 subjects have not yet reached the point of eligibility for the 3-year visit (1125 days [1095 days+ 30 days]). 37 subjects are eligible at the 3-year visit; 36 (97.3%) completed the visit.
Final Safety Findings	There have been no device malfunctions, failures or misuse issues reported since the writing of the previous Interim PAS Status Report in December 2018. The number of devices that had malfunctions, failures or misuse, and the number of subjects who experienced those incidents since the start of the study are summarized in Table 4. Overall, 89.23% of subjects experience at least one AE. The most frequent AEs were cardiac disorders experienced by 37 of 65 (56.92%) enrolled subjects. Compared to the 2019 report that had 230 AEs with 65 cardiac disorders, the 2020 report is reporting 239 AEs with 69 cardiac disorders. See Table 5 in the submission for details. Overall, 40 of 65 (61.54%) enrolled subjects experience at least one SAE. The most frequent SAEs were cardiac disorders experienced by 29 of 65 (44.62%) enrolled subjects. Compared to the 101 SAEs and 41 cardiac disorders, the 2020 report had 108 SAEs with 43 cardiac disorders. There have been no unanticipated serious adverse device effects (SADEs) reported as of the data export data (July 7th, 2019).
Final Effect Findings	The data for the primary endpoint of TVF at 3 consisted of a total of 61 subjects that experienced an event or had sufficient follow-up to be included in the analysis. Of these, 15/61 (24.6%) experienced a TVF event with a breakdown of 11.5% (7/61) suffering cardiac death, 8.2 % (5/61) experiencing Target Vessel MI, and 13.1% (8/61) experiencing clinically-driven target vessel restenosis.
Study Strengths & Weaknesses	This study is a new enrollment prospective trial evaluated the long term performance of the NIRxcell device. The study is limited by the low overall enrollment.
Recommendations for Labeling Changes	No changes recommended as the device has been official withdrawn from the market.
General
Study Status	Ongoing
Application Number / Requirement Number	P980023 S113/ PAS001
Date Original Protocol Accepted	01/20/2023
Date Current Protocol Accepted
Study Name	Pamira EP PASSION PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Real World Evidence (RWE) methodology study with the purpose of evaluating safety data of BIOTRONIK’s Pamira lead using active monitoring of Medicare fee-for-service claims data. The study is a prospective, single-arm, non-randomized, observational cohort study using RWE methodologies from the Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION) project.
Study Population	All U.S. patients registered in BIOTRONIK’s device tracking database and successfully implanted with a Pamira lead after U.S. market approval, who match a unique beneficiary ID in the Medicare claims dataset, have fee-for-service Medicare coverage during month of Pamira lead implant, and have at least 1 Medicare claim in the inpatient, outpatient, or carrier files.
Sample Size	At least 750 patients.
Key Study Endpoints	Primary endpoint: overall incidence of complications attributable to the Pamira lead through 5 years post-implant. Secondary endpoints: 1) incidence of complications attributable to the Pamira or possibly attributable to the Pamira lead through 5 years post-implant, and 2) incidence of complications potentially related to the Pamira lead (e.g. cardiac perforation) not included in another primary or secondary endpoint.
Follow-up Visits and Length of Follow-up	5 years
General
Study Status	Completed
Application Number / Requirement Number	P950022 S042/ PAS001
Date Original Protocol Accepted	01/13/2009
Date Current Protocol Accepted	05/07/2009
Study Name	SJ4 PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Interim or Final Data Summary
Interim Results	There were 34 device-related complications in 22 patients in the post-approval study. Of the 34 complications, 13 have been classified as right ventricular lead or SJ4 connector related complications.
Actual Number of Patients Enrolled	1701
Actual Number of Sites Enrolled	58
Patient Follow-up Rate	78.01%
Final Safety Findings	The 95% Lower Confidence Bound (LCB) for the freedom from complications using the Kaplan-Meier method at 5 years was 95.5%.
Final Effect Findings	The mean RV lead capture threshold is less than 1 V for all follow-up visits.
Study Strengths & Weaknesses	1) Large sample size of 1701 subjects 2) Long-term follow-up for 5 years) Weakness: 2) Study deviation rate of 14.39% per visit
Recommendations for Labeling Changes	no
General
Study Status	Completed
Application Number / Requirement Number	P980035 S013/ PAS001
Date Original Protocol Accepted	10/03/2003
Date Current Protocol Accepted	10/03/2003
Study Name	RESPECT
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a multi-center, randomized, single-blind, crossover prospective clinical study. All subjects in the study receive the device. Patients meeting criteria are enrolled and implanted with a Medtronic AT500 or EnRhythm system and a high septal (Bachmann's Bundle region) atrial lead placement. Three months of observation are followed by randomization to first having pacing on or off. Six months of the randomized intervention pacing are followed by the opposite pacing condition.
Study Population	Study population: Patients who meet the Class I or Class II implantation criteria for dual chamber pacing according to the guidelines described by American College of Cardiology/American Heart Association and patients who have had documented paroxysmal atrial tachycardia. Indication: The Medtronic AT500 DDDRP and model P1501DR EnRhythm pacing systems are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity. Both systems are also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of atrioventricular synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of both rate and atrioventricular synchrony.
Sample Size	400 subjects, 90 sites
Key Study Endpoints	Endpoints include adverse events (patient death, serious injury or device malfunction).
Follow-up Visits and Length of Follow-up	Baseline data are collected prior to implant. Clinical data are collected at the time of enrollment, implant/pre-hospital discharge, at 3 months (with randomization), 9 months (after 6 months ON or OFF), and 15 months post-implant (after crossover and additional 6 months OFF or ON). Adverse event data are also captured via phone every two weeks through the randomization period.
Interim or Final Data Summary
Interim Results	There were 11 deaths to date and 18 total adverse events have occurred to date. Description rather than categories of adverse events are provided by the sponsor. Adverse events included: 6 dislodgements, 3 change in sensing threshold/loss of capsure, 2 dizziness, and 1 each of pleural effusion, pneumothorax, infection/errosion, atrial fibrillation during lead placement, no atrial sensing during lead placement, arm swelling, and shortness of breath/nausea/vomitting.
Actual Number of Patients Enrolled	402 patients (both randomized and non randomized)
Actual Number of Sites Enrolled	37 centers in the United States and Canada.
Patient Follow-up Rate	Cumulative follow-up for ON Programming was 1389 months; for OFF programming was1296 months. Average follow-up for ON Programming was 5.6 months; for OFF programming was 5.3 months.
Final Safety Findings	The study did not provide any data to suggest there are patient safety concerns associated with the use of intervention pacing therapies in the patient population. A total of 19 adverse events (AEs) were reported. Of the AEs reported, 5% (7/132) occurred in the ON-OFF subjects, 6% (8/124) in the OFF-ON subjects and 3% (4/144) in the non-randomized subjects. Procedure related AEs were reported in 5% (6/132) and 2% (3/124) of ON-OFF and OFF-ON subjects, respectively. System related AEs were reported in 4% (5/132) and 5% (6/124) of ON-OFF and OFF-ON subjects respectively. A total of 11 deaths were reported among the 400 subjects with available data. Ten of the deaths occurred while the intervention pacing therapies were programmed OFF and 1 death occurred while the intervention pacing therapies were programmed ON. None of the deaths were related to the device, the system, or procedure. The relatedness of 1 death to device or system was unknown.
Final Effect Findings	Primary Objective To demonstrate a reduction in the frequency of symptomatic AT/AF episodes as measured by the Patient Assistant. Among the 222 subjects with available device data for both randomized study periods, the average ON minus OFF difference in symptomatic AT/AF episode rate was 0.1 episodes per month (upper 1-sided 95% CI 0.5%). The upper 1-sided 95% confidence interval for the difference was > 0. Therefore the primary objective was not met (P = 0.629). Secondary Objectives 1. Evaluated subject symptoms with the AF symptom checklist. A total of 211 out of 256 randomized subjects completed the AF symptom checklist (subject perception of frequency and 16 arrhythmia related symptoms) at 9 and 15 months visits. No difference in the frequency (P = 0.165), severity (P = 0.421) or number of AF symptoms (P = 0.172) was observed during periods of ON versus OFF programming. 2. Evaluated the time to first cardioversion for AF. Among the 256 subjects, 15 cardioversion attempts in 11 subjects during 1473 months of follow-up with ON programming, and 17 cardioversion attempts in 13 subjects during 1383 months of follow-up with OFF programming were reported. There was no difference in the risk of cardioversion for AF between ON and OFF programming (P=0.603). 3. Evaluated the intervention pacing feature effect on AT/AF burden. A total of 225 of 256 randomized subjects had AT/AF burden data available for both randomized periods. An average of 3.6 h/day of AT/AF burden during ON programming compared to 3.5 h/day of AT/AF burden during OFF programming was observed (P=0.499). The results were similar across all subject subgroups. 4. Evaluated the intervention pacing feature effect on AT/AF symptomatic days. This evaluation included only randomized subjects implanted with the AT500 device since only the AT500 device recorded Patient Assistant activations. Fifty-eight (58) of 69 randomized subjects implanted with the AT500 device had device data available in both randomized periods. During ON programming symptomatic AT/AF was recorded on 5.3% of randomized days versus 4.8% of randomized days during OFF programming (P=0.966).
Study Strengths & Weaknesses	A well designed randomized single-blind multicenter study. The ON-OFF and OFF-ON programming arms were well balanced with regard to baseline characteristics indicating that the randomization was satisfactory. Exceptions included gender (higher percentage of females randomized to ON-OFF) and age (ON-OFF group was older). However, since the study design was a crossover, each subject served as his/her own control and the potential effect of differences in subject characteristics at baseline were minimized for the pre-specified analyses.
Recommendations for Labeling Changes	Yes, there were recommendations to the labeling to update with data from the post-approval study results.
General
Study Status	Completed
Application Number / Requirement Number	P980035 S442/ PAS001
Date Original Protocol Accepted	04/01/2016
Date Current Protocol Accepted
Study Name	PCT Change Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study will be conducted within Medtronic’s Product Surveillance Registry (PSR). The PSR platform is designed to conduct non-randomized, active, prospective post-market surveillance. Patients implanted with a MR Conditional CIED system and enrolled in the PSR will be followed per the expected standard of care practice of their care provider. Pacing capture thresholds (PCT) measurements of MR conditional CIED systems enrolled in the PSR will be used to prospectively monitor changes in PCT following 3T MR exposure. Patient status is collected approximately every 6 to 12 months including MRI scan information, if applicable. Sites will report patient baseline information (e.g. height, weight, etc.) the occurrence of a medically indicated MRI scan, reason for scan, anatomical region scanned, magnet strength, and MRI related events. Analysis of the primary objective will be performed 4-years following approval
Study Population	All patients implanted with a MR Conditional CIED system and enrolled in the PSR who subsequently receive an MRI scan using a 3T system within the 4-years post approval that meets approved labelling requirements.
Sample Size	The following assumptions were used to estimate the PAS duration and number of 3T scans projected to be obtained during the 4-years study period: MR Conditional CIED enrollment of approximately 2,400 patients Annual MRI scan rate of 9% Participating sites with 3T scanning capability: 25% - 40% % of patients with a 3T MRI scan: 30% - 45% Table 3: 3T Scan Rate Assumptions Over 4-Year Study Duration Assumptions Year 1 Year 2 Year 3 Year 4 Cumulative MR Conditional Enrollments (*) 1260 1674 2047 2382 Cumulative # of completed MRI Scans 113 264 450 571 Assumption for % centers with 3T capability 25% 25% to 40% % MR scans through 3T in these centers 30% 30% - 45% Cumulative # of completed 3T scans 9 43 to 103 (*) Assumes a 10% annual attrition Contribution from enrollments outside the US to the primary objective will be limited to no more than 50% of the total sample size.
Key Study Endpoints	Primary Endpoints: To characterize the proportion of patients implanted with an MR conditional CEID system with a pre to post MRI scan PCT measure change of more than 0.5 V following 3T scan exposure. Definitions for pre and post PCT measurements Pre-MRI PCT measure: max PCT value preceding the SureScan mode enabled and prior to the 3T MRI scan Post-MRI PCT measure: 1st max PCT measurement at a time point >30 days (chronic PCT) following 3T MRI exposure. Further investigation will be carried out to identify root cause if the observed proportion of PCT changes following 3T scan exposure is greater than 8% (i.e. 2X the observed proportion in the PSR SureScan data) and more than 50% of those observed >0.5V PCT changes reflect an increase.
Follow-up Visits and Length of Follow-up	4 years post-approval
Interim or Final Data Summary
Actual Number of Patients Enrolled	8388
Actual Number of Sites Enrolled	191
Final Safety Findings	One patient showed a ¿PCT greater than 0.5V within the analysis window. As this does not meet the 8% threshold proportion of patients and/or scans with a greater than 0.5V change pre- to post-3T MRI, no additional comparative analyses were performed. No adverse events, deaths, or device deficiencies related to 3T scan.
Final Effect Findings	n/a
Study Strengths & Weaknesses	The primary endpoint was acceptable. The results are favorable.
Recommendations for Labeling Changes	The results of the study are acceptable and should be added to the device labeling.
General
Study Status	Terminated
Application Number / Requirement Number	P080009 / PAS001
Date Original Protocol Accepted	03/29/2013
Date Current Protocol Accepted	03/23/2015
Study Name	Open Label PAS of SEDASYS Syst User Resp
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is designed to evaluate the SEDASYS® System can be used safely in routine clinical practice by measuring the trained users responses to System alarms. The intent of this study, as well as the companion study, is to remove the Restriction of Use limiting initial use of the SEDASYS System to settings where an anesthesia provider is immediately available.
Study Population	Up to 32 users in up to 15 sites.
Sample Size	Accounting for a 3% patient dropout, the resulting sample size will be 866.
Key Study Endpoints	The primary endpoint will be the percentage of documented responses to alarms. The secondary endpoint will be the sufficiency of response, which is measured by a score for success. Other Safety Endpoints: Adverse events (defined by MeDRA) and all hands-on airway rescue interventions by anesthesia providers will be reported. Stopping Rules: The study may be stopped by the Sponsor in the event of a single confirmed non-response to an alarm (desaturation, apnea, hypotension, bradycardia). Confirmation of a non- response will be determined by the EAC; assessment will include if the Data Acquisition System (DAQ) failed to record a response. The reason for failure to respond will be assessed by EES and continuance of the study will be based on this assessment. The expected rate of DAQ failure is approximately one percent. Confirmed non-responses will be sent to the Agency within 15 days of the EAC notifying the Sponsor.
Follow-up Visits and Length of Follow-up	Duration of each subject's participation is approximately 2 days (one day participation and one day follow up).
Interim or Final Data Summary
Actual Number of Patients Enrolled	51
Actual Number of Sites Enrolled	1
Patient Follow-up Rate	n/a
Final Safety Findings	n/a
Final Effect Findings	n/a
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	no
General
Study Status	Terminated
Application Number / Requirement Number	P080009 / PAS002
Date Original Protocol Accepted	03/29/2013
Date Current Protocol Accepted	03/25/2015
Study Name	Open Label Post Market Registry in Clinical Practi
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Objective Performance Criterion
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The study is an observational, single arm, non-randomized, non-blinded, multi-center, prospective, safety study of sedation with the SEDASYS System during colonoscopy and EGD, performed in routine clinical practice.
Study Population	Adult patients who satisfy the approved FDA labeling and are scheduled for non-emergent endoscopy procedures, including those from PAS I (CI-13-000X)
Sample Size	7430 patients; including subject population (approximately 866) from CI-13-000X (PAS I). This sample size will allow confidence of 99% that the rate is less than 1/1,000 (allowing for one anesthesia professional rescue intervention). No dropouts are anticipated. There will be 40 - 60 trained users at up to 30 sites Cases per Trained User 120-320 Cases per Institution 240-720 Anesthesia Professional Rescue Interventions per Trained User: <=1 Anesthesia Professional Rescue Interventions per Institution: <=1
Key Study Endpoints	Primary: Total number of anesthesia professional rescue interventions <=1 Secondary: Subjects sedated requiring BMV and/or AAI Safety: The incidence of adverse events (AEs) will be assessed at the preferred term (PT) level using the Medical Dictionary for Regulatory Activities (MedDRA) for event categorization. Incidence of AEs will also be assessed by 1) onset time with respect to alarm condition; 2) relationship to endoscopic procedure (Colonoscopy or EGD); 3) relationship to the device (alarm response); and 4) severity.
Follow-up Visits and Length of Follow-up	Adult male and female subjects who satisfy the approved FDA labeling and are scheduled for non-emergent endoscopy procedures during the study timeframe will be invited to participate in the study. Patients will be enrolled with informed consent including those from companion study (CI-13-000X). Visit 1: Screening. Visit 2: Pre-procedure <=15 days of the procedure(Visit 1 (screening) and Visit 2 (procedure) could occur on the same day). Length of Follow-up 1-day per patient.
Interim or Final Data Summary
Actual Number of Patients Enrolled	n/a
Actual Number of Sites Enrolled	n/a
Patient Follow-up Rate	n/a
Final Safety Findings	n/a
Final Effect Findings	n/a
Study Strengths & Weaknesses	n/a
Recommendations for Labeling Changes	no
General
Study Status	Completed
Application Number / Requirement Number	P130009 S037/ PAS001
Study Name	COMPASSION Cohort
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Child: 2 yrs < 12 yrs, Adolescent: 13-18 yrs, Transit.Adolescent A (distinctively):18 yrs<22 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Continued follow-up of all living subjects who were enrolled under the IDE (G060242). The objective of this PAS is to characterize the clinical outcomes annually through 5 years post-procedure.
Study Population	All living subjects who were enrolled in the IDE
Sample Size	All living subjects
Key Study Endpoints	The safety and effectiveness endpoints include freedom from device- or procedure-related death or reintervention, freedom from MACCE, functional improvement (decrease in pulmonary regurgitation, improvement in NYHA functional class, freedom from recurrent pulmonary stenosis), procedural- and device-related adverse events, stent fracture, reintervention on the THV or conduit, and death.
Follow-up Visits and Length of Follow-up	5 years All subjects are followed at 30 days, 6 months, 12 months, and annually thereafter through 5 years post procedure
Interim or Final Data Summary
Actual Number of Patients Enrolled	81 subjects were enrolled, of which 79 had an attempted implant, and 69 had a successful implant.
Actual Number of Sites Enrolled	Seven study sites were enrolled.
Patient Follow-up Rate	The follow-up rate through five years approximately 80%. Compliance with visit assessments (e.g. NYHA classification, chest x-ray, CT angiogram, exercise testing) ranged from 55% to 86% of subjects who attended the final 5-year visit.
Final Safety Findings	Approximately 50% of subjects experienced a serious adverse event during the study duration. The most frequently observed adverse event (occurring more than 30-days post-procedure) were: arrhythmia (observed in approximately 12% of subjects), infections other than endocarditis (observed in approximately 10% of subjects), valve stenosis (observed in approximately 10% of subjects, and the catchall “other serious adverse event” category (“other” serious adverse events including but not limited to: fractures, small bowel obstruction, chest pain, and dysfunctional dialysis grafts were observed in approximately 20% of subjects).
Final Effect Findings	Approximately 73% of subjects implanted with the device and followed through 5-years showed overall functional improvement through 5-years. Approximately 84% of subjects implanted and followed-through five years remained free of recurrent pulmonary stenosis. The survival rate through five years was approximately 97% for this same population. Freedom from valve dysfunction (defined as freedom from death, surgical pulmonary valve replacement, valve frame fracture, recurrent pulmonary stenosis, moderate/sever regurgitation, or reintervention) was approximately 73% through 5 years for the same population.
Study Strengths & Weaknesses	This continued follow-up study provides longer-term data (through five years) on the safety and effectiveness of a transcatheter valve used for RVOT repair in the pulmonic position. The lack of completion of some assessments of interest including NYHA Classification, and echocardiographic imaging at the five-year study visit presents some challenges to the interpretability of longer-term effectiveness outcomes. Additionally, it should be noted that some subjects withdrew or were lost to follow-up in this study. Incomplete follow-up may also lead to biased longer-term results.
Recommendations for Labeling Changes	No. The device is no longer going to be sold or marketed
General
Study Status	Completed
Application Number / Requirement Number	P980040 S058/ PAS001
Date Original Protocol Accepted	07/31/2015
Date Current Protocol Accepted	03/03/2017
Study Name	ECR IOL PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The objective of this post-approval study is to evaluate the rates of severe visual distortions for the TECNIS Toric IOLs with Extended Cylinder Range of approximately 3.00 D to 4.75 D of cylinder correction at the corneal plane (Models ZCT450, ZCT525 and ZCT600) in clinical practice and to ensure the continued safety of the approved devices. Study Design: Prospective, multicenter, bilateral, non-randomized, open-label clinical new enrollment study.
Study Population	Bilateral cataracts with corneal astigmatism of approximately 2.00 D to 4.75 D (with 3.00 D to 4.75 D in at least one eye) based on the combination of preoperative keratometirc cylinder and the expected effect of surgicallyinduced astigmatism (SIA).There is no control group.
Sample Size	Up to 120 subjects will be enrolled to achieve bilateral implantation in approximately 80 subjects; a minimum of 15 subjects will be implanted with a TECNIS Toric ZCT600 in at least one eye, and the remaining subjects will be implanted with either a TECNIS Toric ZCT450, ZCT525 or ZCT600 in at least one eye. With 80 subjects and a severe visual distortion rate of 0.025, this study has 86% probability of achieving a half-width of 0.05 for a 95% confidence interval for the rate of severe visual distortions. Subjects will be enrolled at up to 20 sites in the United States. Each site should implant a minimum of 6 subjects, and no site may enroll more than 20% of the enrollment total.
Key Study Endpoints	Study Endpoints Primary Endpoint The primary endpoint is the rate of severe visual distortions based on data collected from a self-administered Patient Reported Visual Distortion Questionnaire (PRVDQ). The rate of severe visual distortions is defined as the percentage of subjects who report a severe visual distortion under overall circumstances at 6 months postoperative for any of the following 5 visual distortion items of interest: lines that slant, tilt, split or separate flat surfaces appearing curved objects appearing further away or closer than they actually are objects appearing to have a different size or shape physical discomfort related to vision Distortions will be assessed using the overall circumstance reply at the 6-month visit. The frequency and proportion of subjects reporting one or more of these items as severe will be used to determine the rate of severe visual distortions. Secondary Endpoints Ratings of individual items included in the visual distortion questionnaire (PRVDQ) Mean percent reduction in absolute cylinder Mean refractive cylinder, mean refractive cylinder compared to intended, mean spherical equivalent and mean spherical equivalent compared to intended Percent of eyes with absolute cylinder within 0.50 D and within 1.00 D of intended Percent of eyes with spherical equivalent within 0.50 D and within 1.00 D of intended Uncorrected distance visual acuity (monocular and binocular) Best corrected distance visual acuity (monocular and binocular) Rates of medical and/or lens findings Rates of IOL repositioning procedures (secondary surgical intervention) due to IOL misalignment Mean difference between IOL axis marker location and postoperative steep keratometry meridian Rates of other adverse events
Follow-up Visits and Length of Follow-up	6 months total follow up
Interim or Final Data Summary
Actual Number of Patients Enrolled	118 (101 patients implanted)
Actual Number of Sites Enrolled	20
Patient Follow-up Rate	Overall follow-up rate among those enrolled: 86% (101/118) The follow-up rate among those implanted was 100% (101/101).
Final Safety Findings	Of the 100 subjects completing the PRVDQ questionnaire at 6 months, none reported severe visual distortions under overall circumstances for any of the five items of interest. A small number of subjects reported severe symptoms on questions in the PRVDQ questionnaire, pertaining to other visual symptoms. Lens findings of misalignment were the most common finding reported by the investigator, for a total of 18 eyes. A total of 15 subjects experienced 17 ocular serious/device-related adverse events (SAE/ADEs) in 17 eyes as determined by the investigators. Sixteen events were categorized as serious by medical monitor(s) based on the definition of SAE per the protocol. These included 12 reports (a rate of 11.9%) of IOL misalignment that required secondary surgical intervention to reposition the lens. One had an IOL exchange due to residual astigmatism and myopia from the initial IOL. One incidence of iridocyclitis was reported but was not considered serious nor device-related and resolved without sequelae. One report of cystoid macular edema was reported but has also resolved without sequelae.
Final Effect Findings	The refractive endpoint outcomes and visual acuity results do not raise any concerns because the refractive endpoint outcomes included satisfactory effectiveness results. However, I will defer Dr. Hilmantel, clinical reviewer, for his clinical assessment.
Study Strengths & Weaknesses	Strength: 100% follow-up rate, there is a comparator group. Weaknesses: Small sample size (100), no randomization, lack of representativeness (94% were White).
Recommendations for Labeling Changes	The PAS study design, methods and results must be included in the labeling. ¿ Additionally, it should be included the following: Demographic distribution results. o Protocol deviations reported during the study: 118 enrolled patients 76 deviations (64.4%). o Numbers and rates of secondary surgical interventions to correct misalignments for the lenses with the high corneal astigmatism under investigation. Rates should be reported both “per eye” and “per subjects”. o A full description of the distributions of residual refractive cylinder and “residual cylinder – target cylinder.” These should include the following percentiles: 0th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 100th percentiles. o Secondary surgical interventions occur at a substantially higher rate for subjects receiving implants for TECNIS® Toric IOL models with higher cylinder powers than for those receiving lower cylinder models; and o Patients requiring implants for TECNIS® Toric IOL models with higher cylinder powers are likely to have greater residual astigmatism and poorer uncorrected visual acuities than those requiring lower cylinder models. Those requiring high cylinder models are more likely to need spectacle correction at distance for some tasks. o A full description of the distribution of monocular uncorrected visual acuities, including the proportions of eyes with logMAR acuity worse than 0.3, 0.2, and 0.1. They should also provide the following percentiles for monocular uncorrected acuities: 0th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 100th percentiles.
General
Study Status	Completed
Application Number / Requirement Number	P980040 S065/ PAS001
Date Original Protocol Accepted	07/10/2018
Date Current Protocol Accepted	06/16/2021
Study Name	TECNIS Symfony Toric New Enrollment Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Design: Prospective, multicenter, non-randomized, open-label, bilateral comparative clinical study (Protocol TIOL-205-STPA). Objective: To evaluate the rates of bothersome visual symptoms in a larger population in clinical practice for the TECNIS Symfony Toric IOLs with approximately 2.0 D or more of cylinder correction at the corneal plane (Models ZXT300 and ZXT375, higher-cylinder group), compared to the Symfony Toric IOL with approximately 1.0 D of cylinder correction at the corneal plane (Model ZXT150, lower-cylinder group), and to ensure the continued safety of the approved devices.
Study Population	All study subjects (Minimum 22 years of age) will be enrolled from the normal surgical cataract population at up to 50 sites in the U.S.A. This study will include only subjects intended to undergo bilateral primary phacoemulsification cataract extraction and IOL implantation who have either approximately 2.00 D to 3.00 D (higher-cylinder group) or approximately 1.00 D to JOHNSON & JOHNSON SURGICAL VISION, INC. CONFIDENTIAL Version 4.0 12 PR/TIOL-205-STPA 1.50 D (lower- cylinder control group) of corneal astigmatism requiring correction in at least one eye.
Sample Size	Up to 634 subjects will be enrolled to achieve bilateral implantation in approximately 506 subjects, resulting in approximately 240 evaluable subjects in the higher-cylinder group and 240 evaluable subjects in the lower-cylinder group at 6 months (assumes a 20% screen-fail rate and a 5% lost-to-follow up rate).
Key Study Endpoints	Primary Endpoint: The primary co-endpoints are the rate of bothersome visual symptoms and the rate of difficulty with an activity due to the symptoms at 6 months postoperative. The rate of bothersome visual symptoms is defined as the percentage of subjects who reported a visual symptom that “very” or “extremely bothered” them. The rate of difficulty with an activity due to the symptoms is determined by the percentage of subjects who respond “Yes” to the question “Is there anything you have a lot of difficulty with, or do not do, because of (visual symptom) at 6 months postoperative. For these endpoints, the visual symptoms include: o halos o glare o starbursts The frequency and proportion of subjects reporting one or more of these items as very or extremely bothersome and impacting daily life via PRVSQ questionnaire will be used to determine the primary endpoint. This rate will be calculated for the higher-cylinder (ZXT300 and ZXT375) and lower-cylinder (ZXT150) groups. Other Endpoints: Other questionnaire responses, such as rates of degree of bother Rates of IOL repositioning procedures (secondary surgical intervention) due to IOL misalignment Rate of explants related to visual symptoms Rates of other adverse events Monocular uncorrected distance visual acuity Monocular best corrected distance visual acuity Mean percent reduction in absolute cylinder Mean refractive cylinder and mean refractive cylinder compared to preoperatively-predicted cylinder Mean spherical equivalent and mean spherical equivalent compared to preoperatively- predicted spherical equivalent Percent of eyes with absolute cylinder within 0.50 D and within 1.00 D of preoperatively- predicted cylinder Percent of eyes with spherical equivalent within 0.50 D and within 1.00 D of preoperatively- predicted spherical equivalent Rates of medical and/or lens findings
Follow-up Visits and Length of Follow-up	6 months or 1-year if required
Interim or Final Data Summary
Actual Number of Patients Enrolled	A total of 535 subjects were enrolled, resulting in two unilaterally and 256 bilaterally evaluable subjects in the higher-cylinder group and 209 bilaterally evaluable subjects in the lower-cylinder group at the 6-month visit.
Actual Number of Sites Enrolled	23 investigative sites (all in the U.S.) have been approved by IRB
Patient Follow-up Rate	For primary eyes in the test (higher-cylinder) group, 99.2% (258/260) were available at the primary 6-month visit. There were 26 seen out of interval but included in the analysis, and two that were not seen but accounted for. The additional 12-month visit, a requirement for a small number of subjects/eyes based on secondary surgical intervention and complaint reporting, was available for 90.9% (20/22) of evaluable eyes (Table 12.1-3). For fellow eyes in the test (higher-cylinder) group, 100.0% (98/98) of eyes were available at the primary 6-month visit. There were 11 eyes that were out of interval but included in the analysis, and no other missing eyes/subjects. At the 12-month visit, 80.0% (4/5) of evaluable eyes were available for analysis (Table 12.1-4).
Final Safety Findings	The most commonly reported medical findings/AEs at 1 month across both groups were blepharitis, dermatochalasis, dry eye, posterior capsular opacity (PCO), and posterior vitreous detachment (PVD). At the primary 6-month visit, PCO was the most commonly reported medical finding/AE for primary eyes in both groups. PCO occurred in 36.4% (94/258) of test eyes and 32.5% (68/209) of control eyes with the majority in both groups being classified as trace. The second most common medical finding at 6 months was PVD, which occurred in 20.2% (52/258) of test eyes and 17.7% (37/209) of control eyes. At the primary 6-month visit, PCO was the most commonly reported medical finding/AE for fellow eyes in both groups. PCO occurred in 32.7% (32/98) of test eyes and 35.8% (39/109) of control eyes with the majority in both groups being classified as trace. The second most common medical finding at 6 months was PVD, which occurred in 22.4% (22/98) of test eyes and 26.6% (29/109) of control eyes.
Final Effect Findings	The primary endpoints were the rate of bothersome visual symptoms and the rate of reported difficulty with an activity due to visual symptoms at 6 months postoperative. For these primary endpoints, the visual symptoms are: • halos • glare • starbursts The bothersome question states “Overall, how much were you bothered by [visual symptom]”. The possible answers are ‘not at all bothered’, ‘slightly bothered’, ‘moderately bothered’, ‘very bothered’ and ‘extremely bothered’. The first primary endpoint of bothersome visual symptom is a dichotomous outcome, derived from the original 5 level response. Bothersome is defined as having ‘very’ or ‘extremely’ bothered’ in any of the visual symptoms (halos, glare and starbursts). The second primary endpoint is the rate of reported difficulty with an activity due to one or more visual symptoms (halos, glare and starbursts), determined by a “Yes” response to the question “Is there anything you have a lot of difficulty with, or do not do, because of [visual symptom]”) at 6 months postoperative The frequency and proportion of subjects with bothersome visual symptoms for one or more visual symptoms, and the frequency and proportion of subjects reporting difficulty with an activity due to one or more visual symptoms at the 6-month visit were summarized along with the calculation of the two-sided, one sample 95% confidence interval based on a large sample normal approximation for each IOL group. There were ten higher-cylinder subjects and zero lower-cylinder subjects that had a repositioning procedure or IOL removal procedure, nine subjects had questionnaire data prior to the IOL repositioning or removal procedure and one subject did not have questionnaire data prior to the IOL repositioning or removal procedure. For those who had questionnaire data prior to the IOL repositioning or removal, data was carried forward from the visit with data taken prior to the IOL repositioning or removal for the primary endpoints at 6 months. For the one subject who did not have questionnaire data prior to lens reposition/removal, the subject was reported as missing at 6 months in the primary analysis and was imputed in the sensitivity analyses; though the subject reported no bothersome nor no difficulty at the 6 month visit.
General
Study Status	Completed
Application Number / Requirement Number	P980050 / PAS001
Date Original Protocol Accepted	03/26/2003
Date Current Protocol Accepted	03/26/2003
Study Name	RESPECT
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	The post-approval study is a multi-center, randomized, single-blind, crossover prospective clinical study. All subjects in the study receive the device. Patients meeting criteria are enrolled and implanted with a Medtronic AT500 or EnRhythm system and a high septal (Bachmann's Bundle region) atrial lead placement. Three months of observation are followed by randomization to first having pacing on or off. Six months of the randomized intervention pacing are followed by the opposite pacing condition.
Study Population	Study population: Patients who meet the Class I or Class II implantation criteria for dual chamber pacing according to the guidelines described by American College of Cardiology/American Heart Association and patients who have had documented paroxysmal atrial tachycardia. Indication: The Medtronic AT500 DDDRP and model P1501DR EnRhythm pacing systems are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity. Both systems are also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of atrioventricular synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of both rate and atrioventricular synchrony.
Sample Size	400 subjects, 90 sites
Key Study Endpoints	Endpoints include adverse events (patient death, serious injury or device malfunction).
Follow-up Visits and Length of Follow-up	Baseline data are collected prior to implant. Clinical data are collected at the time of enrollment, implant/pre-hospital discharge, at 3 months (with randomization), 9 months (after 6 months ON or OFF), and 15 months post-implant (after crossover and additional 6 months OFF or ON). Adverse event data are also captured via phone every two weeks through the randomization period.
Interim or Final Data Summary
Interim Results	There were 11 deaths to date and 18 total adverse events have occurred to date. Adverse events included: 6 dislodgements, 3 change in sensing threshold/loss of capsure, 2 dizziness, and 1 each of pleural effusion, pneumothorax, infection/errosion, atrial fibrillation during lead placement, no atrial sensing during lead placement, arm swelling, and shortness of breath/nausea/vomitting.
Actual Number of Patients Enrolled	402 patients (both randomized and non randomized)
Actual Number of Sites Enrolled	37 centers in the United States and Canada.
Patient Follow-up Rate	Cumulative follow-up for ON Programming was 1389 months; for OFF programming was1296 months. Average follow-up for ON Programming was 5.6 months; for OFF programming was 5.3 months.
Final Safety Findings	The study did not provide any data to suggest there are patient safety concerns associated with the use of intervention pacing therapies in the patient population. A total of 19 adverse events (AEs) were reported. Of the AEs reported, 5% (7/132) occurred in the ON-OFF subjects, 6% (8/124) in the OFF-ON subjects and 3% (4/144) in the non-randomized subjects. Procedure related AEs were reported in 5% (6/132) and 2% (3/124) of ON-OFF and OFF-ON subjects, respectively. System related AEs were reported in 4% (5/132) and 5% (6/124) of ON-OFF and OFF-ON subjects respectively. A total of 11 deaths were reported among the 400 subjects with available data. Ten of the deaths occurred while the intervention pacing therapies were programmed OFF and 1 death occurred while the intervention pacing therapies were programmed ON. None of the deaths were related to the device, the system, or procedure. The relatedness of 1 death to device or system was unknown.
Final Effect Findings	Primary Objective To demonstrate a reduction in the frequency of symptomatic AT/AF episodes as measured by the Patient Assistant. Among the 222 subjects with available device data for both randomized study periods, the average ON minus OFF difference in symptomatic AT/AF episode rate was 0.1 episodes per month (upper 1-sided 95% CI 0.5%). The upper 1-sided 95% confidence interval for the difference was > 0. Therefore the primary objective was not met (P = 0.629). Secondary Objectives 1. Evaluated subject symptoms with the AF symptom checklist. A total of 211 out of 256 randomized subjects completed the AF symptom checklist (subject perception of frequency and 16 arrhythmia related symptoms) at 9 and 15 months visits. No difference in the frequency (P = 0.165), severity (P = 0.421) or number of AF symptoms (P = 0.172) was observed during periods of ON versus OFF programming. 2. Evaluated the time to first cardioversion for AF. Among the 256 subjects, 15 cardioversion attempts in 11 subjects during 1473 months of follow-up with ON programming, and 17 cardioversion attempts in 13 subjects during 1383 months of follow-up with OFF programming were reported. There was no difference in the risk of cardioversion for AF between ON and OFF programming (P=0.603). 3. Evaluated the intervention pacing feature effect on AT/AF burden. A total of 225 of 256 randomized subjects had AT/AF burden data available for both randomized periods. An average of 3.6 h/day of AT/AF burden during ON programming compared to 3.5 h/day of AT/AF burden during OFF programming was observed (P=0.499). The results were similar across all subject subgroups. 4. Evaluated the intervention pacing feature effect on AT/AF symptomatic days. This evaluation included only randomized subjects implanted with the AT500 device since only the AT500 device recorded Patient Assistant activations. Fifty-eight (58) of 69 randomized subjects implanted with the AT500 device had device data available in both randomized periods. During ON programming symptomatic AT/AF was recorded on 5.3% of randomized days versus 4.8% of randomized days during OFF programming (P=0.966).
Study Strengths & Weaknesses	A well designed randomized single-blind multicenter study. The ON-OFF and OFF-ON programming arms were well balanced with regard to baseline characteristics indicating that the randomization was satisfactory. Exceptions included gender (higher percentage of females randomized to ON-OFF) and age (ON-OFF group was older). However, since the study design was a crossover, each subject served as his/her own control and the potential effect of differences in subject characteristics at baseline were minimized for the pre-specified analyses.
Recommendations for Labeling Changes	Yes, there were recommendations to the labeling to update with data from the post-approval study results.
General
Study Status	Completed
Application Number / Requirement Number	P060033 / PAS001
Date Original Protocol Accepted	02/01/2008
Date Current Protocol Accepted	02/01/2008
Study Name	5yr Clinical Outcomes
General Study Protocol Parameters
Study Design	Randomized Clinical Trial
Data Source	Sponsor Registry
Comparison Group	Concurrent Control
Analysis Type	Analytical
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study is design to obtain long term follow-up of the premarket study cohort patients.
Study Population	This device is indicated for improving coronary luminal diameter in patients with ischemic heart disease due to de novo lesions of length < 27mm in native coronary arteries with reference vessel diameters of > 2.5mm to < 3.5 mm.
Sample Size	Endeavor I: 100 patients, 8 sites; Endeavor II: 1197 patients, 72 sites; Endeavor II CA: 296 patients, 15 sites; Endeavor III: 436 patients, 29 sites; Endeavor IV: 1548 patients, 80 sites; Endeavor PK: 43 patients, 6 sites
Key Study Endpoints	Endeavor IV: The primary endpoint was target vessel failure at 9 months post-procedure.
Follow-up Visits and Length of Follow-up	Annually to five years
Interim or Final Data Summary
Interim Results	Endeavor IV: The overall rate of 36-month major adverse cardiac events was 11.4% (84/734) for the Endeavor subjects vs. 13.8% (101/724) for the Taxus subjects. Between 720 and 1080 days postprocedure in the Endeavor arm, 11 subjects experienced the following new major adverse cardiac events: 1 cardiac death, 5 non-cardiac deaths, 1 NQWMI, and 4 TLRs. For Taxus, 25 subjects experienced new major adverse cardiac events consisting of 7 cardiac deaths, 6 non-cardiac deaths, 1 QWMI, 5 NQWMI, and 10 target lesion revascularization. In the Endeavor arm the target vessel failure rate at 1080 days was 12.4% (91/734) compared with 16.1% (118/734) in the Taxus arm (p=0.052). The target lesion revascularization rate at 1080 days in the Endeavor arm was 6.5% (48/734) compared with 6.0% (44/734) in the Taxus arm (p=0.747). The target lesion revascularization rate at 1080 days in the Endeavor arm was 9.9% (73/734) compared with 10.9% (80/734) in the Taxus arm.
Actual Number of Patients Enrolled	Overall, there are a total of 3,621 patients enrolled for Endeavor trials.
Actual Number of Sites Enrolled	Overall, there are a total of 210 study sites enrolling patients for Endeavor trials (I, II, II-CA, III, IV, and PK).
Patient Follow-up Rate	60-month follow-up is complete on 97%, 96.8%, 96.9%, 88%, 93%, and 100% of patients enrolled in Endeavor I, II, II-CA, III, IV, and PK, respectively.
Final Safety Findings	The cumulative 5-year MACE rates were 7.2% (7/97), 15.4% (89/577), 17.8% (51/287), 14.0% (43/307), 17.9% (129/722) and 20.9% (9/43) in Endeavor I, II, II-CA, III, IV, and PK, respectively.
Final Effect Findings	The cumulative 5-year TVF rates were 5.2% (5/97), 15.4% (89/577), 21.6% (62/287), 17.9% (55/307), 17.3% (125/722), and 27.9% (12/43) in Endeavor I, II, II-CA, III, IV, and PK, respectively. The cumulative 5-year TLR rates were 3.1% (3/97), 7.5% (43/577), 7.3% (21/287), 8.1% (25/307), 7.8% (56/722), and 7.0% (3/43) in Endeavor I, II, II-CA, III, IV, and PK, respectively. The cumulative 5-year TVR rates were 5.2% (5/97), 10.7% (62/577), 16.4% (47/287), 16.9% (52/307), 12.7% (92/722), and 18.6% (8/43) in Endeavor I, II, II-CA, III, IV, and PK, respectively. The cumulative 5-year ARC definite+probable ST rates were 1% (1/97), 0.9% (5/577), 0% (0/287), 0.7% (2/307), 1.4% (10/722), and 2.3% (1/43) in Endeavor I, II, II-CA, III, IV, and PK, respectively.
Study Strengths & Weaknesses	Strength: The follow-up rates for all Endeavor trials meet the requirement of 80% specified in the condition of approval #1. Weakness: The sample size for the Endeavor PK is too small to make any definitive conclusions of safety and effectiveness.
Recommendations for Labeling Changes	Labeling changes are being requested.
General
Study Status	Completed
Application Number / Requirement Number	P980052 / PAS001
Date Original Protocol Accepted	07/02/1999
Date Current Protocol Accepted	07/02/1999
Study Name	Long term
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adolescent: 13-18 yrs, Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Completed
Application Number / Requirement Number	P000035 / PAS001
Date Original Protocol Accepted	02/27/2001
Date Current Protocol Accepted
Study Name	TMJ
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Transit.Adolescent B(as adults): 18 yrs < 22 yrs, Adult: At least 22 yrs
General
Study Status	Other
Application Number / Requirement Number	P870072 S037/ PAS001
Date Original Protocol Accepted	11/14/2007
Date Current Protocol Accepted	11/14/2007
Study Name	Thoratec TLC-ii portable
General Study Protocol Parameters
Study Design	Bench/Lab Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	This study requires the sponsor submit data on driver failure on a quaterly basis.
Study Population	N/A
Sample Size	N/A
Key Study Endpoints	Reporting includes: 1) the number of adverse events reported that are potentially related to driver malfunction or failure, along with a narrative description of each case and the percent brush remaining (if known); and 2) the percent brush remaining for all motors you replaced or serviced, along with duration of use prior to servicing.
Follow-up Visits and Length of Follow-up	N/A
General
Study Status	Completed
Application Number / Requirement Number	P970021 S014/ PAS001
Date Original Protocol Accepted	01/29/2008
Date Current Protocol Accepted	01/29/2008
Study Name	Long-Term Study
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	New Data Collection
Comparison Group	No Control
Analysis Type	Analytical
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	Prospective, multi-center, historically controlled study to confirm that the post-procedure incidence of amenorrhea observed with GYNECARE THERMACHOICE III (TC-III) Uterine Balloon Therapy System is comparable to that in the original THERMACHOICE I (TC-I) UBT System at 24 and 36 month post-procedure.
Study Population	381 subjects with the length of follow-up up to 36-month post-ablation procedure. Among the 381 subjects, 131 subjects were from TC-I study, and 250 subjects from TC-III study who will continue to be followed up to 36 months post-procedure.
Sample Size	The study statistical hypotheses, for the rate of amenorrhea, at 24 and 36-month post-procedure are: A power analysis estimated the sample size to be 121 subjects in each group to achieve 80% power to detect differences at 0.13 (this number was selected based on findings in the TC-I study).
Key Study Endpoints	In addition to clinical visit at week 2, month 6 and 12 post-procedure, patients were contacted by telephone and/or by mail at 24 and 36 months following their ablation procedures to document long term response. If a patient reported any problems during the telephone contact that warranted further evaluation, a visit was scheduled to evaluate and treat the problem. The following information was obtained: menstrual bleeding and pain patterns, incidence of pregnancy, contraception status, and incidence of any adverse events and/or complications. Information was also be obtained related to incidence of intervening gynecologic surgery such as hysterectomy or repeat ablations for continued or recurrent menorrhagia, and incidence of neoplasia or malignancy of the uterus. A quality-of-life questionnaire was completed at each clinical visit (week 2, month 6 and 12) and at 24 and 36 month post-procedure follow-up.
Follow-up Visits and Length of Follow-up	Clinical visits were scheduled at week 2, month 6 and 12 months post-procedure. Telephone and/or mail interviews were done at 24 and 36 months following ablation procedure.
Interim or Final Data Summary
Actual Number of Patients Enrolled	250
Actual Number of Sites Enrolled	13
Patient Follow-up Rate	72.4%
Final Safety Findings	The incidence of subjects with at least one adverse event was comparable in NPPC and PPC groups. A number of 56 subjects (45.2%) in NPPC experienced a total of 98 adverse events and a number of 57 subjects (45.2%) in PPC group experienced a total of 104 adverse events. The incidence of subjects with severe adverse events was 12.1% (15 subjects) in NPPC group and 10.3% (13 subjects) in PPC group. The incidence of subjects with adverse events related to study device was 3.2% (4 subjects) in NPPC group and 5.6% (7 subjects) in PPC group. The incidence of subjects with adverse events related to study procedure was 6.5% (8 subjects) in NPPC group and 8.7% (11 subjects) in PPC group. Furthermore, there was no unanticipated adverse event reported in this study. The incidence of subjects with adverse events that needed action was 44.4% (55 subjects) in NPPC group and 42.1% (53 subjects) in PPC group. The rate of adverse events was comparable between curettage and no curettage groups. The loss to follow-up was 11.6% overall, however long term-data is only available for 72.4%., making assessment of safety difficult
Final Effect Findings	Analysis #1 (Missing data imputed as failures) ¨C Primary Effectiveness Analysis The success rate at 36-months was greater in TCIII group (26.8%, 67 of 250 subjects) compared to TCI group (13.0%, 17 of 131 subjects). The difference in amenorrhea rates between TCIII group and TCI group was statistically significant, based on a one-sided Chi-Square test (p=0.001). The one-sided 95% confidence interval (CI) for the difference (TCIII minus TCI) in proportion of amenorrhea rates between two groups was (7.1%, 100%). Therefore, the sponsor concluded that the difference in true success rates between TCIII and TCI groups was at least 7.1% with 95% confidence. The one-sided 95% confidence interval for the success rate in TCIII group was (22.2% - 100%), while the one-sided 95% confidence interval for the success rate in TCI group was (8.4% - 100%). The observed amenorrhea rates in TCIII and TCI groups, the associated one-sided 95% confidence intervals for these success rates, as well as the p-value and confidence interval for the comparison of the amenorrhea rates recorded in TCIII and TCI groups, are presented in Text Table 7 below
Study Strengths & Weaknesses	Strengths include hypothesis driven sample size that was achieved for the duration of the study allowing greater than 80% power to detect differences, however the follow-up rate was 72.4%, decreasing the ability to accurately measure the rate and type of adverse events. Since treatment failures did not include those who had additional procedures, the ability to fully assess safety was minimized.
Recommendations for Labeling Changes	Ethicon is required to submit revised labeling to include these long-term results as per their approval order. For the primary effectiveness endpoint, they should report the results using an ITT analysis where all treatment failures (including repeat EA/ hysterectomy) and loss to follow-up are counted as failures. Secondary endpoints may be reported using an evaluable analysis. Data tables should be revised to reflect the 24 and 36 month results including the revisions that were made in response to this deficiency
General
Study Status	Completed
Application Number / Requirement Number	P990036 / PAS001
Date Original Protocol Accepted	11/03/2000
Date Current Protocol Accepted
Study Name	PAS
General Study Protocol Parameters
Study Design	Prospective Cohort Study
Data Source	Sponsor Registry
Comparison Group	No Control
Analysis Type	Descriptive
Study Population	Adult: At least 22 yrs
Detailed Study Protocol Parameters
Study Objectives	GAMMA V was a prospective, multicenter, non-randomized trial. Patients entering the trial may or may not have had new stents implanted at operator discretion. Patients either received new stent placement, intravascular radiation therapy and 12 months of antiplatelet therapy or no new stent placement and 6 months of dual antiplatelet therapy.
Study Population	Patients with de novo coronary artery lesions in vessels 2.75 - 4.0 mm in diameter and for lesions up to and including 45 mm in length.
Sample Size	600 patients
Key Study Endpoints	The primary enpoints included 1) Target Lesion Revascularization, 2) Target vessel revascularization, 3) Major Cardiac Adverse events, defined as death, myocardial infarction (Q-wave and non-Q-wave), emergent bypass surgery or TLR, 4) Canadian Cardiovascular Society Assessment Classification (class I (ordinary activity)-class IV (inability to carry out any physical activity)), 5) Late Thrombosis: myocardial infarction attributable to the target vessel with angiographic documentation of thrombus or total occlusion at the target site > 30 days after the index procedure in the absence of an intervening revascularization of the target vessel, 6) Repeat hospitalization), and 7) Outpatient diagnostic testing.
Follow-up Visits and Length of Follow-up	The study was originally planned for three years, but extended to five years to meet the conditions of approval. The protocol called for follow-up visits at 1, 3, 6, 9, 12, 15, 24, 36, 48 and 60 months. Follow-up included clinic visits, angiographic studies and telephone contact.
Interim or Final Data Summary
Interim Results	Study completed, see final results.
Actual Number of Patients Enrolled	579 patients
Actual Number of Sites Enrolled	38 sites
Patient Follow-up Rate	There were 76 patients who did not consent to the extended follow-up (years 4 and 5). Thirty seven (37) of the patients who refused to participate in the study follow-up provided follow-up safety information.
Final Safety Findings	The final effectiveness results were: 43.1% of patients with new stents were free of target lesion revascularization at 1800 days and 56.2% of patients without new stents were free of target lesions revascularization at 1800 days. The final safety results were: the late thrombosis rate for newly stented patients was 3.1% and 2.8% for non-stented patients and major adverse cardiac events, emergent bypass surgery or target lesion revascularization was 62.7% for stented patients and 55.1% for non-stented patients.
Study Strengths & Weaknesses	Strength: This study provided data on stented and non-stented patients with the Cordis Checkmate System, however the 5 year follow-up was only available for 465 out of 579 patients (80%).
Recommendations for Labeling Changes	None

Contact Us

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Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

Additional Resources

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• Guidance Document: "Procedures for Handling Post-Approval Studies Imposed by PMA Order"
• PAS Program Background