A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation

Study Overview
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Brief Summary
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To study the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with New York Heart Association (NYHA) Functional Class II to Class IV chronic heart failure.

Detailed Description
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The trial is designed to provide additional evidence regarding appropriate recommendations for use of the MitraClip System for patients with chronic heart failure and clinically significant functional mitral regurgitation. Additionally, the trial will collect evidence regarding health economics of the MitraClip System for use in this patient population.

Official Title
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A RandomizEd Study of tHe MitrACliP DEvice in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation

Conditions
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Mitral Valve Insufficiency

Intervention / Treatment
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* Device: MitraClip
* Other: standard of care


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinically significant functional mitral regurgitation (moderate-to-severe or severe MR) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization. Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 days preceding randomization Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate Left ventricular ejection fraction (LVEF) of ≥ 15% to ≤ 35% (if in NYHA Functional Class II) or of ≥ 15% to ≤ 45% (if in NYHA Functional Class III or IV). Note: LVEF needs to be determined by one of the following methods: transthoracic echocardiography (TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance) within 90 days prior to randomization - Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness Key Exclusion Criteria: Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE). Status 1 heart transplant or prior orthotropic heart transplantation. Introduction of a new heart failure drug class within the last 2 weeks prior to randomization. Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization. Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD)) within 90 day prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization. Need for any cardiovascular surgery. Mitral valve surgery is considered the preferred therapeutic option for the subject Renal replacement therapy 6-Minute Walk Test (6MWT) distance > 475 meters Mitral Valve Area (MVA) by planimetry < 4.0 cm2; if MVA by planimetry is not measurable, pressure half-time measurement is acceptable; MVA must be confirmed by the Echocardiography Core Laboratory

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 |
| --- | --- |
| Active Comparator: Control Group<br>optimal standard of care therapy | Other: standard of care<br> <br> |
| Experimental: Device Group<br>MitraClip device plus optimal standard of care therapy | Device: MitraClip<br>* Implantation of the MitraClip System for patients with chronic heart failure.<br>Other: standard of care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death | Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitral Regurgitation (MR) severity reduction | Mitral Regurgitation (MR) severity reduction to mild or mild-to-moderate at 12 and 24 months; | at 12 and 24 months | 
| Change in 6 Minute Walk Test (6MWT) | Change in 6 Minute Walk Test (6MWT) distance at 6, 12 and 24 months over baseline; | at 6, 12 and 24 months | 
| CV hospitalizations and CV death | Rate of recurrent CV hospitalizations and CV death | 24 months | 
| Quality of Life (QoL) overall score | Change in Quality of Life (QoL) overall score, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) at 12 months over baseline | 12 months | 
| New York Heart Association (NYHA) Functional Class | Change in New York Heart Association (NYHA) Functional Class over baseline and proportions of patients in NYHA Functional Class I/II at 6, 12 and 24 months | at 6, 12 and 24 months | 
| Patient-reported Global Assessment (PGA) | Change in Patient-reported Global Assessment (PGA) of well-being at 6, 12 and 24 months | at 6, 12 and 24 months |