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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P180029 / PAS001 |
| Date Original Protocol Accepted |
07/22/2019
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| Date Current Protocol Accepted |
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| Study Name |
Cont F/u of REPRISE III Trial Premarket Cohorts
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| Device Name |
LOTUS Edge Valve System
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
Sponsor Registry
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| Comparison Group |
Concurrent 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 under the REPRISE III study protocol under IDE G140090. 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 enrolled under the IDE (G140090) as part of the REPRISE III study
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| Sample Size |
All living subjects enrolled under the IDE (G140090) as part of the REPRISE III study
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| Key Study Endpoints |
The key safety and effectiveness endpoints include all-cause mortality, all-cause and disabling stroke, life-threatening and major bleeding events, stage 2 or 3 acute kidney injury, major vascular complications, paravalvular aortic regurgitation, valve performance and durability, myocardial infarction, re-operation for valve-related dysfunction, rehospitalization for valve-related symptoms or worsening congestive heart failure, new permanent pacemaker implantation, new-onset atrial fibrillation, functional status as evaluated by New York Heart Association (NYHA) Class 5-meter gait speed test at 1 year, and health status as evaluated by Kansas City Cardiomyopathy Questionnaire (KCCQ) and SF-12 Quality of Life questionnaire at 1, 3, and 5 years.
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| Follow-up Visits and Length of Follow-up |
Visits will be conducted annually through 5 years post-procedure
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
RCT
912 total; 607 in the Lotus ITT cohort and 305 in the CoreValve ITT cohort
Roll-in
102
CAS
295
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| Actual Number of Sites Enrolled |
Randomized controlled trial (RCT)
55 centers
Lotus only Roll-In
50 centers
Lotus US Continued Access Study (CAS)
34 centers
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| Patient Follow-up Rate |
RCT
The overall follow-up rate through 5 years was 84% for Lotus and 80.7% for CoreValve
Roll-in
The overall follow-up rate through 5 years was 87.3%
CAS
The overall follow-up rate through 4 years was 80.7%
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| Final Safety Findings |
RCT
The CEC-adjudicated safety outcomes at 5 years are summarized as follows:
All-cause mortality: 50.9% (Lotus); 52.8% (CoreValve)
Cardiovascular mortality: 35.7% (Lotus); 40.7% (CoreValve)
All-cause stroke: 14.1% (Lotus); 15.3% (CoreValve)
Disabling stroke: 8.3% (Lotus); 12.2% (CoreValve)
Major vascular complications: 7.5% (Lotus); 6.4% (CoreValve)
Life-threatening/disabling bleeding: 21.2% (Lotus); 21% (CoreValve)
Hospitalization for valve-related symptoms or worsening congestive heart failure: 34.7% (Lotus); 31.6% (CoreValve)
New permanent pacemaker: 38.9% (Lotus); 27.3% (CoreValve)
Valve thrombosis: 5.8% (Lotus); 1.8% (CoreValve)
Endocarditis: 1.7% (Lotus); 0.5% (CoreValve)
Roll-in
The CEC-adjudicated safety outcomes at 5 years are summarized as follows:
All-cause mortality: 52.3%
Cardiovascular mortality: 37.2%
All-cause stroke: 19.8%
Disabling stroke: 15.9%
Major vascular complications: 8.8%
Life-threatening/disabling bleeding: 34.9%
Hospitalization for valve-related symptoms or worsened CHF: 41.9%
New permanent pacemaker: 42.9%
Valve thrombosis: 9.5%
Endocarditis: 4.0%
CAS
The CEC-adjudicated safety outcomes at 4 years are summarized as follows:
All-cause mortality: 36.6%
Cardiovascular mortality: 18.5%
All-cause stroke: 14.4%
Disabling stroke rate: 8.7%
Major vascular complications: 8.6%
Life-threatening/disabling bleeding: 18.5%
Hospitalization for valve-related symptoms or worsened CHF: 24.7%
New permanent pacemaker: 35.7%
Valve thrombosis: 6.6%
Endocarditis: 4.0%
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| Final Effect Findings |
RCT
Key effectiveness outcomes are summarized as follows, in subjects who were evaluated for each outcome measure at the 5-year visit:
NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 80% of assessed Lotus subjects and 78% of assessed CoreValve subjects; this improvement was sustained for both groups at 5 years (82% for Lotus and 74% for CoreValve) for evaluable subjects.
KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects in the Lotus cohort, the overall summary score improved from 51.9 +/-5 at baseline to 73.0+/-3 at 30 days and remained high at 5 years (73.5+/-6). Similar results were seen in the CoreValve cohort.
Valve Performance Outcomes:
Mean aortic gradient improved in both cohorts from baseline values of 43.85+/-31 mmHg (CoreValve) and 44.64+/-35 mmHg (Lotus) to discharge values of 8.19+/-9 mmHg (CoreValve) and 12.20+/-1 mmHg (Lotus). Values remained low out to 5 years at 7.79+/-0 mmHg (CoreValve) and 12.64+/-8 mmHg (Lotus).
Mean EOA improved from 0.70+/-9 cm2 (CoreValve) and 0.69+/-9 cm2 (Lotus) at baseline to 1.96+/-2 cm2 (CoreValve) and 1.65+/-7 cm2 (Lotus) at discharge and remained high out to 5 years at 1.57+/-6 cm2 (CoreValve) and 1.42+/-2 cm2 (Lotus).
At 30 days, fewer subjects in the Lotus group compared to the CoreValve group had moderate or greater Paravalvular Regurgitation (0.6% vs. 7.2%). This result was maintained at 1 year (0.9% vs. 6.8%) through 5 years (0% vs. 1.9%).
Roll-in
NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 82.4% of assessed subjects; this improvement was sustained at 1 year (87.2%) and to 5 years for 73.3% of subjects.
KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects, the KCCQ overall summary score improved from 52.7+/-6 at baseline to 69.9+/-0 at 30 days and remained high at 1 year (75.6+/-3), 3 years (71.5+/-5), and 5 years (68.6+/-1).
Valve Performance Outcomes:
Mean aortic gradient improved from 47.9+/-3 mmHg at baseline to 12.1+/- mmHg at discharge and remained low out to 1 year (12.3+/- mmHg) and 5 years (11.8+/- mmHg).
Mean effective orifice area improved from 0.67+/-0 cm2 at baseline to 1.70+/-9 cm2 at discharge and was 1.53+/-9 cm2 at 1 year and 1.830+/-562 at 5 years.
At 30 days, 1% had moderate or greater Paravalvular Regurgitation, 0% at 1 year and 5.9% at 5 years.
CAS
NYHA Classification: There was improvement in NYHA classification from baseline to 5-years. At 30 days, improvement by at least 1 class was seen in 79% of assessed subjects; this improvement was sustained at 1 year (86%), 2 years (82%), 3 years (75%), and 4 years (77.3%).
KCCQ: Improvement was observed in both overall and clinical summary scores through five years. Among assessed subjects, the KCCQ overall summary score improved from 53.5+/-8 at baseline to 71.8+/-6 at 30 days and remained high at 1 year (74.7+/-6) and 3 years (74.4+/-5).
Valve Performance Outcomes:
Mean aortic gradient improved from 44.3+/-8 mmHg at baseline to 12.5+/- mmHg at discharge and remained low out to 30 days (12.2+/- mmHg), 1 year (12.7+/- mmHg) and beyond.
Mean effective orifice area improved from 0.68+/-9 cm2 at baseline to 1.61+/-2 cm2 at discharge and was sustained at 30 days (1.55+/-1 cm2), 1 year (1.51+/-6 cm2), and beyond.
At 30 days, 1.5% had moderate or greater Paravalvular Regurgitation. This result was maintained at 1 year (1.2%) through 4 years (1.1%).
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| Study Strengths & Weaknesses |
These continued follow-up studies provide longer-term data on the safety and effectiveness of the Boston Scientific Corporation Lotus Valve System in patients with symptomatic severe aortic stenosis who are at extreme or high risk for standard surgical valve replacement.
These studies were intended to evaluate the longer-term safety and effectiveness of the Lotus and LOTUS Edge Valve Systems (through 5 years). Due to voluntary recall and discontinuation of the LOTUS Edge system, the study timeline was truncated for the CAS and LOTUS Edge Nested Registry studies and safety and effectiveness data is collected through 4-year and 30-day follow-up, respectively.
For the Randomized controlled trial, generally, outcomes suggest that safety and effectiveness is maintained through 5 years post procedure, with meaningful improvements shown for key effectiveness endpoints from baseline to 5 years.
Across all studies, it should be noted that some subjects did not complete all visit assessments (e.g., echocardiographic imaging, NYHA, KCCQ). Incomplete data may introduce bias to study outcomes.
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| Recommendations for Labeling Changes |
No labeling changes recommended. The device has been recalled and discontinued, and is no longer commercially available.
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