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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100009 / PAS002 |
| Date Original Protocol Accepted |
10/24/2013
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| Date Current Protocol Accepted |
04/05/2016
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| Study Name |
New EnrollMitraClip Analysis Cohort (MAC)
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| Device Name |
MITRACLIP DELIVERY SYSTEM
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
External Registry
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
A prospective cohort study, a subset of patients entered into the MitraClip TVT-Registry who fulfill the enrollment criteria and from sites/centers of excellence and experienced with performing and collecting 6MWT data and KCCQ data (i.e. sites/centers with at least 75% completion rate in terms of collecting both 6MWT and KCCQ data) will be included in MAC.
This is a new-enrollment study.
NOTE: Annual follow up (e.g. death, stroke, surgical intervention, hospitalizations) from year 2 through year 5 post-implant through linkage to the CMS database will be reported as part of P100009/PAS001- OSB-lead Comprehensive/Linked-Registry Based Surveillance. PAS1
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| Study Population |
A subset of approximately 420 patients entered into the MitraClip TVT-Registry who fulfill the following criteria in MAC:
Significant symptomatic MR (greater than or equal to 3+) due to primary abnormality of the mitral apparatus, otherwise known as Degenerative Mitral Regurgitation (DMR).
Prohibitive risk for mitral valve surgery (MV) as determined by a heart team, which includes a cardiologist experienced in MV disease and a cardiac surgeon experienced in MV surgery, and existing comorbidities that would not preclude the expected benefit from reduction of the MR.
Perform the 6MWT at baseline or unable to perform the 6MWT due to cardiac reasons.
No comparator group.
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| Sample Size |
Assuming 10% withdrawal at 12 months, a sample size of 420
patients from the Prohibitive Risk DMR Patient Registry (PAS 1
Device Registry) is expected to provide 420 evaluable patients (not
lost-to-follow-up or discontinued) at 12 months post procedure.
Assumptions: The reported death rate at 30 days was 6.3% in the Prohibitive Risk DMR Cohort (Lim et al 2013); the all-cause mortality rate at 30 days was assumed to be 6.5%. The device- related complication rate was assumed to be ~6% at 12 months.
Because a majority of device-related complications are expected to occur within 30 days of the MitraClip procedure, the rate at 30
days was also assumed to be ~6%. Two thousand (2,000) simulations were performed to calculate sample size and power for the primary safety endpoint. A sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the
5% significance level.
Two thousand (2,000) simulations were performed to calculate sample size and power for the primary effectiveness endpoint. Assuming 37% attrition (25% death, 10% withdrawal, and 2% missing data) at 12 months, a sample size of 420 evaluable patients provides >95% power to reject the null hypothesis at the 5% significance level.
There will be a minimum of 15 sites and a maximum of 40 sites, with no more than 10% of patients (up to 46) from each site. Sites selected for participation in this study will be centers of excellence and experienced with performing and collecting 6MWT data and KCCQ data.
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| Key Study Endpoints |
Main safety endpoints:
A composite of death and device-related complications at 30 days
post-procedure. The device-related complications include single leaflet device attachment (SLDA), device embolization, device thrombosis, and other device-related events (e.g., endocarditis, MV stenosis), which result in MV re-intervention, unplanned other cardiac surgery, or unplanned vascular surgery or intervention through 30 days post-procedure.
Secondary safety endpoints:
All-cause mortality at 12 months, and device-related complications at 12 months.
Main effectiveness endpoints:
The change in 6MWT distance at 12 months over baseline.
Secondary effectiveness endpoints:
MR severity at 12 months
Change in LVEDV at 12 months over baseline
Change in LVIDd at 12 months over baseline
Change in KCCQ QoL at 12 months over baseline
NYHA Functional Class at 12 Months
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| Follow-up Visits and Length of Follow-up |
5 years
Active follow-up of patients will be performed through 12 months
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total 554 study subjects who entered into STS/ACC Transcatheter Valve Therapy (TVT) registry between November 04, 2013 and July 29, 2015 and met eligibility criteria for this study were enrolled in this post-approval study.
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| Actual Number of Sites Enrolled |
A total of 50 sites (sites with at least 75% data completeness of both baseline 6-minute walking test and KCCQ data) were included in this post-approval study.
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| Patient Follow-up Rate |
The overall follow-up rate at 1-year through the Mitral Module of the TVT registry is 78.2%.
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| Final Safety Findings |
The primary safety endpoint of rate of freedom from composite of death and device-related complications at 30 days was 95.5% (529/554), which was significantly higher than the pre-specified performance goal of 80% (P<0.0001). For secondary safety endpoints, freedom from all-cause mortality at 12 months was 80.2% (SE: 1.85%; performance goal=66%, P<0.0001), and freedom from the composite device-related complications at 12 months was 98.9% (SE: 0.45%; performance goal=90%, P<0.0001). All primary and secondary safety endpoints were successfully met.
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| Final Effect Findings |
The primary effectiveness endpoint of mean improvement in 6-minute walking test (6MWT) at 12 months from baseline was 31.56±115.24 meters. The results showed significantly improvement at 12 months (one-sided p-value=0.0001). Analysis of secondary effectiveness endpoints shows significant mitral regurgitation (MR) reduction (P<0.0001) and improvement in NYHA class (P<0.0001) at 12-months from baseline, reduction in left ventricular size at 12-months from baseline as per LVEDV (-10.9 ± 48.9 ml, P=0.0111) and LVIDd (-0.22±0.72 cm; P<0.0001) measurements as well as improvement of Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months over baseline (30.40±25.77, P<0.0001).
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| Study Strengths & Weaknesses |
Strength: This study was able to demonstrate the safety and effectiveness of Mitral Valve Repair and Clip Delivery Systems (MitraClip®) using real-world data collected through the national STS/ACC TVT Registry.
Weakness: Sample size for some of the subgroup analyses, such as recurrent mitral regurgitation
subgroup, was relatively small, resulting in large standard deviations for the estimates. Although primary effectiveness endpoint was successfully met, only about 62.1% patients among those who have completed 12-month visit had 6MWT information available (including patients who performed 6MWT or were unable to perform due to cardiac reasons). High proportion of missing values were also reported for LVEDV endpoint at 12 months (36.8% of patients who completed 12-month have information available). Patients included in this study were enrolled from sites with at least 75% completion rate in terms of collecting both baseline 6MWT and KCCQ data, and results may not be generalizable to patients enrolled from sites with less experience performing and collecting 6MWT and KCCQ data.
Finally, the data available are limited to 1-year follow-up currently; additional data on longer term (5- year) safety and effectiveness remain to be assessed.
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| Recommendations for Labeling Changes |
Yes, labeling change recommended to update the device labeling with the final study results.
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