Multicentre Study of MITRACLIP® Transcatheter Mitral Valve Repair in Patients With Severe Primary Mitral Regurgitation Eligible for High-risk Surgery

Study Overview
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Brief Summary
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The objective of the study is to demonstrate the non-inferiority for clinical efficacy of an endovascular treatment strategy with the MitraClip® in comparison with a surgical treatment strategy in patients with severe primary mitral regurgitation judged eligible for anatomical repair with the MitraClip® or mitral valve surgery with high surgical risk. This trial is a French and Monegasque, multicenter and randomized trial. Patients enrolled will be clinically followed for 2 years ( clinical visit at 1 month, at 6 months and 12 months, phone call at 18 months and clincial visit at 24 months).

Official Title
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Multicentre and Randomized Study of MITRACLIP® Transcatheter Mitral Valve Repair in Patients With Severe Primary Mitral Regurgitation Eligible for High-risk Surgery

Conditions
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Mitral Regurgitation

Intervention / Treatment
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* Device: percutaneous mitral valve repair with MITRACLIP NT, MITRACLIP NTR/XTR, MITRACLIP G4NT/XT, MITRACLIP G4NTW/XTW
* Procedure: cardiac surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary Mitral Regurgitation grade 3+ or 4+ Patients in class II to IV NYHA Mitral valve anatomy appropriate to MitraClip® therapy and mitral valve surgery Adult patients judged eligible for mitral valve surgery by the local heart team but at high surgical risk defined as: age ≥ 75 years and STS score ≥ 6 % or one frailty index or one major organ system compromise or one possible procedure-specific impediment (using MVARC definitions) ; or age < 75 years and STS score > 8 % or at least one other high-risk criterion following the MVARC definitions; or age > 80 years and judged at high risk for surgery by the local heart team Isolated Mitral valve pathology If revascularization procedures are required, they must be performed more than 30 days from intervention (D0) Patients affiliate to social security Non-inclusion Criteria: Life expectancy < 1 year due to non-cardiac conditions Secondary Mitral regurgitation Evolving endocarditis or active endocarditis or inflammatory disease in the last 3 months Patient who cannot tolerate procedural anticoagulation or post procedural antiplatelet regimen Rheumatic mitral valve disease Evidence of intracardiac, inferior vena cava or femoral venous thrombus Valve anatomy not compatible with MitraClip® implantation (cf. colum 3 table 3 page 57) Stroke or transient ischaemic event within 30 days before D0 Modified Rankin Scale ≥4 disability (appendix 9) TAVR within 30 days before D0-Untreated, clinically significant coronary artery disease requiring revascularization Any percutaneous cardiovascular intervention within 30 days before D0 including ATC Cardiovascular surgery, or carotid surgery within 30 days before D0 Any prior mitral valve surgery or transcatheter mitral valve procedure Need for any concomitant cardiac surgery including treatment of severe secondary tricuspid regurgitation in accordance with class I recommendation in 2017 ESC guidelines. Surgical treatment of mild or moderate secondary tricuspid regurgitation (Class IIa and IIb recommendations) can still be performed in the protocol according to the local heart team decison NYHA functional class I LVEF < 30% Primary MR grade 1 to 2 Subjects in whom transesophageal echocardiography or transseptal catheterization are contraindicated or high-risk Any condition preventing the patient from completing all protocol procedures (including compliance with guidelines directed medical therapy) and follow-up visits Patient unable or unwilling to provide written, informed consent before study enrolment Pregnant or nursing women Vulnerable people: persons deprived of liberty; under trusteeship or under curatorship Participation in another trial that would interfere with this trial Exclusion criteria Not eligible for a MitraClip® intervention after Core Lab evaluation Before randomization (D-21) the patient no longer fulfills eligibility criteria (inclusion criteria and non-inclusion criteria)

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MITRACLIP NT, MITRACLIP NTR/XTR, MITRACLIP G4NT/XT, MITRACLIP G4NTW/XTW Device<br>MitraClip NT System includes a MitraClip device, a steerable guide catheter and a MitraClip delivery system | Device: percutaneous mitral valve repair with MITRACLIP NT, MITRACLIP NTR/XTR, MITRACLIP G4NT/XT, MITRACLIP G4NTW/XTW<br>* percutaneous mitral valve repair Percutaneous MitraClip Device Implantation<br>* Other names: MITRACLIP;|
| Active Comparator: cardiac surgery<br>mitral valve repair in first intervention, valve replacement if repair not feasible | Procedure: cardiac surgery<br>* mitral valve repair or mitral valve remplacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality, unplanned hospitalizations for heart failure and mitral valve reintervention | comparison between arms of: number and reason of death number and reason unplanned rehospitalisation for cardiovascular reasons, number of mitral valve reintervention | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of a major adverse event | all-cause death, need for non-elective cardiovascular or thoracic surgery, device or procedure-related adverse events, major bleeding complications or serious bleeding, major access site vascular complications, major cardiac structural complications, pulmonary complications (device or procedure-related), stroke and other cerebrovascular events, myocardial infarction, acute kidney injury or progression of chronic kidney disease, arrhythmias and conduction system disturbances, unplanned mitral valve surgery due to device/procedure failure or malfunction, requirement for valve replacement after valve repair failure, unplanned cardiac surgery for any cause | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MITRACLIP, primary Mitral Regurgitation, high surgical risks