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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P100009 S028/ PAS001 |
| Date Original Protocol Accepted |
03/14/2019
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| Date Current Protocol Accepted |
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| Study Name |
Cont f/u of the COAPT Trival Pivotal Cohort
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| Device Name |
MitraClip NT Clip Delivery System and MitraClip NTR/XTR Clip Delivery System
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| Clinical Trial Number(s) |
NCT01626079
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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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 in the COAPT Trial pivotal cohort. 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 IDE pivotal cohort.
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| Sample Size |
All living subjects
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| Key Study Endpoints |
The key safety and effectiveness endpoints include all-cause mortality, stroke, single leaflet device attachment, device embolization, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, heart failure (HF) related hospitalization, New York Heart Association (NYHA) classification, 6-Minute Walk Distance (6MWD) through 2 years, Kansas City Cardiomyopathy Questionnaire (KCCQ) score through 2 years, 36-Item Short Form Survey (SF-36) score through 2 years, mitral valve surgery (including type of surgery), new use of Cardiac Resynchronization Therapy (CRT), new use of single or dual chamber pacemaker, permanent left ventricular assist device (LVAD) implant, heart transplant, additional MitraClip device intervention or de novo MitraClip device intervention, including reason for intervention, number of hospitalizations and reason for hospitalization (i.e., heart failure, cardiovascular, non-cardiovascular) through 2 years, number of days alive and out of hospital, number of days hospitalized, proportion of subjects living in the baseline location, new onset of permanent atrial fibrillation, mitral stenosis, clinically significant atrial septal defect (ASD) that requires intervention, and dosages of guideline directed medical therapy (GDMT).
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
665 subjects were enrolled or treated in the study, including subjects randomized for test group – MitraClip (302), subjects randomized for control – GDMT (312), and roll-in subjects (51).
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| Actual Number of Sites Enrolled |
Eighty-four (84) sites enrolled at least 1 Roll-In or Randomized subject
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| Patient Follow-up Rate |
Test group (MitraClip): 75% (104/139);
Control group (GDMT): 59% (75/128)
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| Final Safety Findings |
The Kaplan-Meier curve showed the freedom from the primary safety endpoint (Composite of Single Leaflet Device Attachment (SLDA), device embolization, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, and any device-related complications requiring non-elective cardiovascular surgery) in the safety analysis population as 89.2% (event rate was 10.8%).
No new SLDAs (0.7%), embolization (0.3%) and device related complications requiring non-elective cardiovascular surgery (0.3%) were reported between 12 months and 60 months.
93.5% of subjects treated with the study device were free from LVAD implantation and 93.5% of subjects treated with the study device were free from heart transplant at 5 years.
Kaplan-Meier estimate of all-cause mortality at 5 years was 57.3% for the Device group, compared to 67.2% for the Control group. The rate of cardiovascular mortality was 48.8% in the Device group and 57.2% in the Control group, and the rate of heart failure mortality was 30.9% in the Device group and 42.8% in the Control group, respectively, at 5 years.
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| Final Effect Findings |
26.4% of the Device group subjects and 8.5% of the Control group subjects were alive or free from a HF related hospitalization after 5 years.
A higher proportion of subjects in the Device group achieved =1+ secondary mitral regurgitation (SMR) compared to the Control group, and the reduction in MR was durable through 5-year follow-up in the Device group: 89.5% of the subjects in the Device group and 78.3% of the subjects in the Control group had MR < 2+.
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| Study Strengths & Weaknesses |
Strength: This study was able to follow the enrolled and treated subjects in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation trail (The COAPT Trial) per protocol through 5 years. The data reported demonstrate that the safety and effectiveness of the MitraClip System is maintained through 5 years, with favorable results compared to Guideline Directed Medical Therapy (GDMT) alone.
Weakness: Deaths occurring over the 5-year follow-up reduced the number of available subjects for long-term assessment, reducing randomized subjects with a visit completed at 5 years to 179 (67% follow-up rate adjusted for deaths). Sample sizes for other endpoints, such as echocardiographic endpoints, were further reduced due to missing endpoint data deviations. For example, only 5% (14/267) and 39% (103/267) of subjects (adjusted for death) contributed to Effective Regurgitant Orifice Area and Mitral Regurgitation analyses at 5 years.
Although the primary safety and effectiveness endpoints were demonstrated over the COAPT Trial 5-year follow-up, the lower samples sizes in echocardiographic endpoints due to deaths confounds interpretation of long-term clinical effectiveness
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| Recommendations for Labeling Changes |
Yes, labeling change recommended to update the device labeling with the final, long-term study results
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