MitraClip REPAIR MR Study

Study Overview
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Brief Summary
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The objective of this randomized controlled trial (RCT) is to compare the clinical outcome of MitraClip™ device versus surgical repair in patients with severe primary MR who are at moderate surgical risk and whose mitral valve has been determined to be suitable for correction by MV repair surgery by the cardiac surgeon on the local site heart team.

Official Title
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Percutaneous MitraClip Device or Surgical Mitral Valve REpair in PAtients With PrImaRy MItral Regurgitation Who Are Candidates for Surgery (REPAIR MR)

Conditions
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Mitral Valve Regurgitation

Intervention / Treatment
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* Device: MitraClip™ device implantation
* Procedure: Mitral Valve Repair Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has severe (Grade III or greater per the ASE criteria, which includes severity grades of 3+ and 4+) primary MR (mixed etiology is acceptable provided the principal mechanism of action is a degenerative mitral valve) as assessed by the ECL. The cardiac surgeon of the Site Heart Team (consisting of at least one interventionalist, and one cardiac surgeon) has confirmed that the subject is a candidate for mitral valve surgery and the EC have confirmed that the subject's mitral valve anatomy is suitable for percutaneous repair with the MitraClip™ device with high certainty of achieving MR ≤ mild Subject is symptomatic (NYHA Class II/III/IV) or asymptomatic with LVEF ≤ 60%, pulmonary artery systolic pressure > 50 mmHg, or LVESD > 40 mm Subject is at moderate surgical risk defined as being at least 75 years of age at the time of EC review. If younger than 75 years, then the subject should have: Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) Repair Score ≥ 2%, OR Presence of other comorbidities which may introduce a potential surgery-specific impediment Subject provides written informed consent Subject is ≥ 18 years of age Exclusion Criteria: Subject is currently participating in another clinical investigation Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results. Subject has ischemic or non-ischemic secondary MR Concomitant severe tricuspid valve regurgitation Ejection fraction <30% Severe mitral annular calcification Acute myocardial infarction in the past 12 weeks Need for cardiac surgery to correct pulmonary valve disease, aortic valve disease, or tricuspid valve disease Subjects who have concurrent coronary artery disease that needs to be treated may be included provided the subjects are eligible for both percutaneous coronary intervention (PCI) and coronary artery bypass surgery. Subjects randomized to the device group, must undergo PCI before the MitraClip™ device procedure. Subjects randomized to the surgical (control) arm may undergo coronary artery revascularization during mitral valve repair surgery Surgical procedure performed in the past 30 days Femoral vein cannot accommodate a 24 F catheter or presence of IVC filter would interfere with the catheter or ipsilateral DVT Transesophageal echocardiography (TEE) is contraindicated. Hemodynamic instability: systolic pressure ≤ 90 mmHg without afterload reduction, cardiogenic shock, or the need for inotropic support or IABP Need for emergency surgery for any reason Prior mitral valve surgery, valvuloplasty, mechanical prosthetic valve or VAD Systolic anterior motion of the mitral valve Hypertrophic cardiomyopathy Renal insufficiency requiring dialysis Active infections requiring current antibiotic therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Arm<br>Mitral Valve Repair Surgery | Procedure: Mitral Valve Repair Surgery<br>* Surgical repair of the mitral valve<br>|
| Experimental: Device Arm<br>MitraClip™ device implantation | Device: MitraClip™ device implantation<br>* Transcatheter repair of the mitral valve using MitraClip™ device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality, stroke, cardiac hospitalization, or acute kidney injury requiring renal replacement therapy at 2 years (any cardiac hospitalizations in the first 30 days post treatment will be excluded) | The proportion of subjects who are alive, without stroke, CV hospitalization or acute kidney injury requiring renal replacement therapy at 2 years in the Device and Control groups, respectively | 2 Years | 
| Proportion of subjects with moderate or less MR (≤2+), without mitral valve replacement, and without recurrent mitral valve intervention (surgical or percutaneous) | Proportion of subjects with moderate or less MR (≤2+), without mitral valve replacement, and without recurrent mitral valve intervention (surgical or percutaneous) from the time of index procedure through 2 years in the Device and Control groups, respectively | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with MR ≤ mild at 30 days post index procedure among survivors | The proportion of subjects with MR ≤ mild at 30 days post index procedure among survivors will be compared between the Device and Control groups | 30 Days | 
| Number of days at hospital from index procedure to home discharge | Hospital length of stay from index procedure to home discharge (days) in Device group compared to the Control group | At Discharge (≤ 14 days following index procedure) | 
| Proportion of subjects discharged to home post index hospitalization | The proportion of subjects who are discharged to home post index hospitalization will be compared between the Device and Control groups | At Discharge (≤ 14 days following index procedure) | 
| Quality of life improvement assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) of at least 10 points at 2 years compared to baseline among survivors. | The proportion of subjects who have at least a 10 point improvement in KCCQ at 2 years post index procedure from baseline among survivors will be compared between the Device and Control groups for non-inferiority. The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered questionnaire used for quantifying patient's health status including the symptoms (frequency and burden), physical and social limitations, and quality of life impact due to the heart failure syndrome. Validity, reproducibility, responsiveness and interpretability of the scores have been independently established for each of these health status domains, and overall summary scores are reported in a range of 0-100, in which higher scores reflect better health status. | 2 Years | 
| Severe symptomatic mitral stenosis at 1 year | The proportion of subjects who have severe symptomatic mitral stenosis at 1 year post index procedure will be compared between the Device and Control groups | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MitraClip