A Multicenter, Randomized, Controlled Study to Assess Mitral vAlve reconsTrucTion for advancEd Insufficiency of Functional or iscHemic ORigiN

Study Overview
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Brief Summary
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Study to assess mitral valve therapy for advanced insufficiency of functional or ischemic origin in patients with moderate-to-severe mitral regurgitation (MR) of primarily functional pathology and reduced left ventricular function considered to be at high surgical risk

Detailed Description
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Secondary or functional mitral regurgitation (MR) results from a geometrical distortion of a dysfunctional left ventricle leading to tethering of mitral valve leaflets by papillary muscle displacement, annular dilatation and/or reduced closing forces in a structurally normal mitral valve. It occurs in over 30% of patients with systolic heart failure. Despite optimal medical care it is associated with increased mortality and hospitalization rates leaving elimination of MR as the only therapeutic option. Nevertheless, traditionally, mitral valve surgery has been the therapy of choice in this setting. As mitral valve surgery has so far been only investigated in retrospective single center registries, which have shown conflicting results. it has a class IIb recommendation, level of evidence C, in these patients without indication for coronary revascularization in the current guidelines of the European Society of Cardiology. In recent years percutaneous mitral valve repair with the MitraClip (PMVR) has evolved as an important therapeutic option in this type of patient with widespread use particularly in Europe, where the device was CE-marked in 2008. PMVR has been compared to mitral valve surgery (repair and replacement) in the randomized, controlled EVEREST II trial in patients with primary MR, which were good candidates for surgery, and was shown to be less effective than surgery in this context. However, no randomized, controlled data are available comparing PMVR and mitral valve surgery in patients with depressed left ventricular function and secondary MR, who have a considerably higher perioperative risk than the EVEREST II population. Like mitral valve surgery it has a class IIb, level of evidence C, recommendation in current guidelines.

Official Title
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A Multicenter, Randomized, Controlled Study to Assess Mitral vAlve reconsTrucTion for advancEd Insufficiency of Functional or iscHemic ORigiN

Conditions
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Mitral Valve Insufficiency

Intervention / Treatment
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* Device: MitraClip system (Abbott Vascular, Menlo Park, USA)
* Procedure: Mitral valve surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically significant mitral regurgitation of primarily functional pathology Left Ventricular Ejection Fraction (LVEF) ≥20% determined by echocardiography High surgical risk as determined by Heart Team consensus Documented New York Heart Association Class II to Class IV heart failure, despite optimal standard of care therapy Written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Exclusion Criteria: Echocardiographic evaluation not available or not suitable for analysis at baseline Severe tricuspid regurgitation according to current guidelines5 Other severe valve disorders requiring intervention according to current Coronary revascularization or cardiac resynchronization (CRT) device implantation within 1 month before the procedure Patient not amenable for mitral valve surgery/ percutaneous mitral valve reconstruction as judged by Heart Team Key information from patients (e.g. NYHA, MR grade) not available

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: Percutaneous mitral valve repair (MitraClip system )<br>Percutaneous mitral valve repair (simultaneous left atrial and ventricular pressure assessment suggested) with MitraClip system (Abbott) | Device: MitraClip system (Abbott Vascular, Menlo Park, USA)<br>* Valve repair with the MitraClip system (Abbott Vascular, Menlo Park, USA) consists of a steerable guide through which a Clip Delivery System is advanced to the left atrium.<br>|
| Active Comparator: Mitral valve surgery<br>Mitral valve surgery or mitral valve replacement (technique and access at the discretion of the participating surgical center, MACE procedure and tricuspid annuloplasty possible) | Procedure: Mitral valve surgery<br>* Mitral valve surgery or mitral valve replacement (technique and access at the discretion of the participating surgical center, MACE procedure and tricuspid annuloplasty possible)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of death, rehospitalisation for heart failure, reintervention (repeat operation or repeat intervention), assist device implantation and stroke (whatever is first) 12 months post intervention; equivalently freedom from event | Composite of death, rehospitalisation for heart failure, reintervention (repeat operation or repeat intervention), assist device implantation and stroke (whatever is first) 12 months post intervention; equivalently freedom from event | 12 months post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of grade 3 or 4 mitral regurgitation within 12 months post intervention | Recurrence of grade 3 or 4 mitral regurgitation within 12 months post intervention | 12 months post intervention | 
| Change in 6 Minute Walk Test distance from baseline to 12 month post intervention (difference 12 months minus baseline | Change in 6 Minute Walk Test distance from baseline to 12 month post intervention (difference 12 months minus baseline | 12 months post intervention | 
| Change in NYHA functional class from baseline to 12 months post intervention | Change in NYHA functional class from baseline to 12 months post intervention | 12 months post intervention | 
| Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 12 months post intervention | Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 12 months post intervention | 12 months post intervention | 
| Echocardiographic assessment of left ventricular remodelling |  | 12 months post intervention | 
| Change in serum BNP from baseline to 12 months post intervention |  | 12 months post intervention | 
| Length of stay ICU / hospital |  | Participants will be followed for the duration of hospital stay, an expected average of 1 week. However, in some patients the hospital stay can be exceed this time frame, when complications occur. | 
| Number of patients in whom operative or interventional mitral valve repair can not be performed (need for mitral valve replacement) | The primary therapeutic strategy should be a repair of the study. For patients undergoing interventional therapy this endpoint is reached if the clip procedure is aborted and a mitral valve replacement is performed. In patients undergoing surgery the endpoint is reached if the surgeon decides to implant a mitral valve during the same procedure. | 12 months post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitral Valve Insufficiency