The EMPOWER Trial - The Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild FMR

Study Overview
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Brief Summary
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The objective of this prospective, randomized, blinded clinical trial is to assess the safety and efficacy of the Carillon Mitral Contour System in treating heart failure with functional regurgitation (FMR).

Detailed Description
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A total of 300 subjects will be randomized at up to 75 investigational sites in the United States, Canada, Europe and Australia. Subjects will be randomized into one of two study groups using a 1:1 (Intervention : Control) ratio. Study subjects who are eligible for this clinical study will undergo a transthoracic echocardiographic examination prior to randomization to evaluate the inclusion criteria associated with the severity of mitral regurgitation. A coronary angiogram will be performed to evaluate the coronary artery anatomy and a venogram to assess the suitability of the coronary sinus/great cardiac vein (CS/GCV) for placement of the Carillon implant. If the subject meets the anatomic requirements for device placement, the subject will be randomized. Subjects who meet all eligibility criteria will be randomized into one of two study groups (Intervention or Control). Subjects randomized to the Intervention group will undergo the Carillon implant procedure. Subjects randomized to the Control group will experience an index procedure similar to the Intervention group (without device placement) to ensure they will not be able to deduce the group assignment based on the type of intervention or time associated with the procedure. After the study subjects are discharged, the subjects' primary care specialists (cardiologist/heart failure physician) and clinical investigation site staff will coordinate follow-up evaluations. Subjects will be evaluated at one (1), six (6), twelve (12), eighteen (18) and twenty-four (24) months post-randomization, to assess long-term safety, and functional and clinical status. After the 24-month evaluation, all subjects will be unblinded. All Intervention and Control subjects will be followed with an abbreviated annual contact and echocardiogram for an additional three (3) years, for a total of five (5) years.

Official Title
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Assessment of the Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild Functional Mitral Regurgitation

Conditions
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Functional Mitral Regurgitation, Heart Failure, Mitral Valve Insufficiency, Heart Diseases, Cardiovascular Diseases, Heart Valve Diseases

Intervention / Treatment
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* Device: Carillon Mitral Contour System
* Other: Guideline Directed Heart Failure Medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ischemic or non-ischemic cardiomyopathy Symptomatic functional (secondary) mitral regurgitation of at least 1+ (Mild) severity Note: 4+ can only be included if multidisciplinary site assessment (including a surgeon) determines that surgery is not necessary within the 1-year follow-up period for this study. NYHA Class II, III, or IV Six Minute Walk distance ≥ 150 meters and ≤ 450 meters Left Ventricular Ejection Fraction ≤ 50% LVEDD ≥ 60 mm and LVESD ≤ 75 mm Corrected BNP of ≥ 300 pg/ml, or corrected NT-proBNP ≥ 1200 pg/ml, or one or more heart failure hospitalizations within six months prior to consent Guideline directed heart failure medication regimen. Exclusion Criteria: Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV) Class I indication for cardiac resynchronization therapy (CRT), or anticipated need for CRT within twelve (12) months Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty, or leaflet repair device Significant organic mitral valve pathology (e.g., moderate or severe myxomatous degeneration, with or without mitral leaflet prolapse, rheumatic disease, full or partial chordal rupture), as assessed by the Imaging Core Laboratory Severe tricuspid regurgitation associated with right ventricular dysfunction and enlargement, as assessed by the Imaging Core Laboratory Severe mitral annular calcification Severe aortic stenosis Expected to require any cardiac surgery, including surgery for coronary artery disease (CAD) or valve disease within one (1) year Presence of left atrial appendage (LAA) clot or presence of LAA occluder Chronic, severe, medical conditions or pathology, other than heart failure, that will prevent likely survival beyond twelve (12) months An entire list of eligibility is available in the clinical investigational plan

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Carillon Mitral Contour System and Guideline Directed Heart Failure Medication | Device: Carillon Mitral Contour System<br>* The Carillon implant is designed to be deployed, tensioned, and locked in the coronary vein in order to reshape the mitral annulus and thus reduce mitral annular dilation and mitral regurgitation.<br>* Other names: Percutaneous mitral valve repair;Other: Guideline Directed Heart Failure Medication<br>* Heart failure medication per ACC/AHA guidelines<br>|
| Active Comparator: Control Group<br>Guideline Directed Heart Failure Medication | Other: Guideline Directed Heart Failure Medication<br>* Heart failure medication per ACC/AHA guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Objective - Freedom from Major Adverse Events | Freedom from a composite of major adverse events (defined as Device Embolization, Vessel Erosion, Cardiac Perforation, and occurrence of cardiac surgery or percutaneous coronary intervention) in the Intervention group is greater than performance goal of 90%. | 12 months | 
| Primary Efficacy Objective 1 - Hierarchical Clinical Composite | To demonstrate that the Carillon Mitral Contour System (Intervention) group is superior to the Control group on the hierarchical composite endpoint of death, transplant or LVAD, percutaneous or surgical mitral valve intervention, heart failure hospitalization, Improvement in KCCQ, and improvement in six-minute walk distance at 24 months (analyzed when the last subject completes 12 months of follow-up.) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Objective 1- Regurgitant Volume | To compare regurgitant volume change relative to control from baseline through 12 months of follow up | 12 months | 
| Secondary Efficacy Objective 2 - Change in LV End-diastolic Volume | To demonstrate an improvement from baseline in the parameter left ventricular end-diastolic volume (LVEDV) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group. | 12 months | 
| Secondary Efficacy Objective 3 - Change in LV End-Systolic Volume | To demonstrate an improvement from baseline in the parameter left ventricular end-systolic volume (LVESV) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group. | 12 months | 
| Secondary Efficacy Objective 4 - Change in 6 Minute Walk Distance | To demonstrate a significantly greater improvement from baseline in six-minute walk distance associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group. | 12 months | 
| Secondary Efficacy Objective 5 - Change in KCCQ | To demonstrate the improvement from baseline in the overall summary score of the Kansas City Cardiomyopathy Questionnaire (KCCQ) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group. | 12 months | 
| Secondary Efficacy Objective 6 - Change in NYHA Classification | To demonstrate the improvement in the proportion of patients who improve by at least one NYHA class from baseline associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group. | 12 months | 
| Secondary Efficacy Objective 7 - Percent days lost due to HFH or CV death | To compare percent days lost due to HFH and CV death, relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months. | 12 months of follow-up, and any available data up to 24 months | 
| Secondary Efficacy Objective 8 - Incidence of alternative therapy and all-cause mortality | To compare the incidence of need for alternative therapy and all-cause mortality (superiority test if HR < 1), relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months | 12 months of follow-up, and any available data up to 24 months | 
| Secondary Efficacy Objective 9 - Total number of HFH | To compare total number of HFH, relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months | 12 months of follow-up, and any available data up to 24 months | 
| Secondary Safety Objective - Freedom from peri-procedural Major Adverse Events | Freedom from a composite of major adverse events (defined as Death, Myocardial Infarction, Device Embolization, Vessel Erosion, Cardiac Perforation, and occurrence of cardiac surgery or percutaneous coronary intervention) in the Intervention group is greater than 80%. | 30 days or hospital discharge date, whichever is longer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional Mitral Regurgitation, Percutaneous Mitral Valve Repair, Percutaneous Mitral Valve Annuloplasty, Coronary Sinus Annuloplasty, Secondary Mitral Regurgitation, Functional MR, FMR