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U.S. Department of Health and Human Services

Post-Approval Studies (PAS) Database

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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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Continued f/u of premarket cohort


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General
Study Status Completed
Application 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
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description 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 Description 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.
Data Collection 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.


Continued f/u of premarket cohort Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
one year report 01/17/2017 01/18/2017 Overdue/Received
two year report 01/17/2018 01/18/2018 Overdue/Received
three year report 01/17/2019 01/17/2019 On Time
four year report 01/17/2020 01/16/2020 On Time
final report 04/30/2021 04/28/2021 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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