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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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Study Status Completed
Application Number P140031 / PAS001
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: >21
Detailed Study Protocol Parameters
Study Design Description 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 Description All living subjects who were enrolled in the PIIS3HR cohort and Nested Registry #7 under the IDE
Sample Size All living subjects
Data Collection 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.

Continued f/u of premarket cohort Schedule

Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
one year report 06/16/2016 06/13/2016 On Time
two year report 06/16/2017 06/13/2017 On Time
three year report 06/16/2018 06/14/2018 On Time
four year report 06/16/2019 06/17/2019 Overdue/Received
five year report 06/15/2020 06/18/2020 Overdue/Received
final report 06/17/2021 04/05/2021 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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