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|
| 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
|
| Device Name |
EDWARDS SAPIEN XT TRANSCATHETER HEART VALVE AND ACCESSORIES
|
| Clinical Trial Number(s) |
NCT01314313
|
| 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
|
| 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
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| 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 ali
|
| 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%
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| 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.
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| Recommendations for Labeling Changes |
No. SAPIEN XT has been discontinued.
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