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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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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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PROMUS Element Plus US PAS


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General
Study Status Progress Adequate
Application Number P110010 / PAS001
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) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description Prospective, open-label, multi-center registry study
Study Population Description 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.

Data Collection 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.


PROMUS Element Plus US PAS Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
three month report 02/22/2012 02/22/2012 On Time
six month report 05/22/2012 05/22/2012 On Time
9 month report 08/21/2012 08/22/2012 Overdue/Received
one year report 11/21/2012 11/16/2012 On Time
18 month report 06/01/2013 06/03/2013 Overdue/Received
two year report 11/21/2013 11/20/2013 On Time
three year report 11/21/2014 11/21/2014 On Time
four year report 11/21/2015 11/25/2015 Overdue/Received
five year report 11/21/2016 11/22/2016 Overdue/Received
six year report 11/21/2017 11/15/2017 On Time
Final Report 10/08/2018 10/05/2018 On Time


Contact Us

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

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