Edwards Cardioband System ACTIVE Pivotal Clinical Trial (ACTIVE)

Study Overview
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Brief Summary
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To establish the safety and effectiveness of the Edwards Cardioband System in patients with functional mitral regurgitation (FMR).

Detailed Description
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The ACTIVE Trial is a prospective, randomized, multicenter trial. Patients with clinically significant functional mitral regurgitation will be randomized 2:1 to receive either transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT) or GDMT alone. Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 5 years.

Official Title
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Annular ReduCtion for Transcatheter Treatment of Insufficient Mitral ValvE (ACTIVE): A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Assess Transcatheter Mitral Valve Repair With Edwards Cardioband System and GDMT vs GDMT Alone in Patients With FMR and Heart Failure

Conditions
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Functional Mitral Regurgitation, Mitral Regurgitation, Mitral Insufficiency

Intervention / Treatment
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* Device: Edwards Cardioband System
* Drug: Guideline Directed Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years; Clinically Significant Functional Mitral Regurgitation (MR); Symptomatic heart failure; Patient hospitalized due to heart failure during 12 months prior to submission to Central Screening Committee OR elevated Brain Natriuretic Peptid (BNP); Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow-up visit compliance. Exclusion Criteria: Primarily degenerative MR; Mitral annular calcification that would impede implantation of device; Other severe valve disorders requiring intervention; Mitral valve anatomy which may preclude proper Edwards Cardioband deployment; Life expectancy of less than twelve months; Patient is participating in concomitant research studies of investigational products which have not reached their primary endpoint; Unwillingness or inability to undergo follow-up investigations/visits; Other medical, social, or psychological conditions that precludes appropriate consent and follow-up

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: Randomized - Edwards Cardioband System<br>Transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT) | Device: Edwards Cardioband System<br>* Transcatheter mitral valve repair with the Edwards Cardioband System<br>* Other names: Transcatheter mitral valve repair (TMVr);Drug: Guideline Directed Medical Therapy<br>* GDMT Only<br>|
| Active Comparator: Randomized - Control<br>Guideline directed medical therapy (GDMT) | Drug: Guideline Directed Medical Therapy<br>* GDMT Only<br>|
| Experimental: Roll-In - Edwards Cardioband System<br>Transcatheter mitral valve repair with the Edwards Cardioband System plus guideline directed medical therapy (GDMT) | Device: Edwards Cardioband System<br>* Transcatheter mitral valve repair with the Edwards Cardioband System<br>* Other names: Transcatheter mitral valve repair (TMVr);Drug: Guideline Directed Medical Therapy<br>* GDMT Only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of MR ≤ 2+ and Hierarchical Comparison of Randomized Device and Randomized Control Groups [Cardiovascular Death, Number of Heart Failure Hospitalizations, Improvement in 6 MWT Distance (in Meters) and KCCQ (Number of Points Improved)]. | Hierarchical comparison of device and control groups (for randomized groups): MR ≤ 2+ and cardiovascular death, number of heart failure hospitalizations, improvement in 6 MWT distance (in meters) and KCCQ (number of points improved). | 1 year | 
| Number of Participants With Major Adverse Events (MAE) [Device Group Only] | Overall rate of device and procedure related Major Adverse Events (MAEs) through 30 days post procedure (including death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention, and access site and vascular complications requiring intervention | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Safety Endpoints [Device Group Only] | Components will be calculated with 95% confidence intervals 1. Death 2. Stroke 3. Myocardial infarction 4. Pericardial effusion requiring drainage 5. Mitral valve reintervention 6. Access site and vascular complications requiring intervention 7. Left circumflex coronary artery injury requiring intervention 8. Need for a new permanent pacemaker | 30 days | 
| Secondary Endpoints Through 1 Year (Powered for Randomized Arms Only) | The following key secondary efficacy endpoints will be tested in comparison to control in a hierarchical order to preserve statistical power. 1. MR ≤ 1+ 2. NYHA Class 3. Kansas City Cardiomyopathy Questionnaire (KCCQ) 4. 6 Minute Walk Test (6MWT) 5. SF-36v2 Health Survey (SF-36) 6. Heart Failure Hospitalizations 7. Cardiovascular mortality | 1 year | 
| Device Success | Device is deployed as intended and the delivery system is successfully retrieved as intended at the time of the patient's exit from the cardiac catheterization laboratory (per device analysis). | 30 days | 
| Procedural Success | Device success with evidence of MR reduction to ≤ MR2+ at discharge and without the need for a surgical or percutaneous intervention prior to hospital discharge (per patient analysis). | 30 days | 
| Clinical Success | Procedural success with evidence of MR reduction ≤ MR2+ and without MAEs* at 30 days (per patient analysis). *Major adverse events (MAE) defined as death, stroke, myocardial infarction, pericardial effusion requiring drainage, left circumflex coronary artery injury requiring intervention, mitral valve reintervention and access site and vascular complications requiring intervention. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Edwards Cardioband, Mitral Valve, Transcatheter, Mitral repair, Functional mitral regurgitation, Secondary mitral regurgitation, Annuloplasty