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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P140031 / PAS001 |
| Date Original Protocol Accepted |
06/17/2015
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| Date Current Protocol Accepted |
07/23/2018
|
| Study Name |
Continued f/u of premarket cohort
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| Device Name |
SAPIEN 3 TRANSCATHETER HEART VALVE AND ACCESSORIES
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
Sponsor Registry
|
| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Study Population |
Adult: >21
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| 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.
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| Study Population |
All living subjects who were enrolled in the PIIS3HR cohort and Nested Registry #7 under the IDE
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| Sample Size |
All living subjects
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| 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.
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| 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).
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| Actual Number of Sites Enrolled |
40 (39 US and 1 Canada)
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| 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.
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| 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)
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| 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)
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| 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.
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| 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.
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