Carillon Mitral Contour System® for Reducing Functional Mitral Regurgitation

The REDUCE FMR Trial: Safety and Efficacy of the Carillon Mitral Contour System® in Reducing Functional Mitral Regurgitation (FMR) Associated With Heart Failure

The objective of this prospective, multi-center, randomized, double-blind trial is to assess the safety and efficacy of the Carillon Mitral Contour System in treating functional mitral regurgitation (FMR) associated with heart failure, compared to a randomized Control group which is medically managed according to heart failure guidelines.

The American Heart Association (AHA) estimates that there are more than 22 million people worldwide with heart failure. Functional mitral regurgitation, defined as the leakage of the mitral valve caused by global or regional changes in left ventricular geometry as well as mitral annular dilation, occurs as a consequence of heart failure. Cardiac Dimensions has developed proprietary technology designed to address functional mitral regurgitation in a minimally invasive manner.

Cardiac Dimensions plans to conduct a clinical trial of the Carillon Mitral Contour System in study subjects with functional mitral regurgitation. This study is a prospective, randomized parallel-group, double-blind, multi-center clinical trial designed to examine the safety and efficacy of the Carillon Mitral Contour System in study subjects with functional mitral regurgitation. The study will consent up to 180 subjects in order to randomize up to 120 subjects at 25 investigational sites in Europe and Australia/New Zealand. Subjects will be randomized into one of two study groups using a 3:1 (Treatment group : Control group) ratio.

Study subjects who are eligible for this clinical study and have consented to participating in the study will undergo multiple assessments prior to randomization to evaluate the eligibility (inclusion/exclusion) criteria. Subjects who meet all eligibility criteria will be randomized into one of two study groups (Treatment or Control).

Study subjects randomized to the Treatment group will undergo a venous angiogram 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 Carillon implant procedure begins. With the distal aspect of the device anchored, incremental tension will be applied to plicate the peri-annular tissue. A transesophageal or transthoracic echocardiogram will be obtained during the procedure to evaluate the effect on functional mitral regurgitation and to evaluate left ventricular function. After the proximal anchor of the implant is locked in place, safety (including assessment of coronary arterial flow) and efficacy will be reconfirmed prior to releasing the Carillon implant from the delivery system.

Subjects randomized to the Control group will experience an index procedure similar to the Treatment group, however, without device placement. To ensure that subjects randomized to the Control group will not be able to deduce the treatment assignment based on the type of intervention or time associated with the procedure, minimal interventional procedures, such as femoral arterial pressure monitoring and a jugular venous drip. If a recent (within the last 3 months for ischemic cardiomyopathy or 12 months for non-ischemic cardiomyopathy) coronary angiogram is available, this assessment may be precluded.

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), and twelve (12) months post-implant, to assess long-term safety, and functional and clinical status. (Reference Section 3.8-Study Follow-up Evaluations)

This study will provide for an independent Clinical Events Committee (CEC) and an independent Data Safety Monitoring Board (DSMB). The CEC will be responsible for adjudicating complications reported during the study that are related to study endpoints (objectives), the procedure or the device. The DSMB will review the safety data against the established criteria and in the context of other safety data accumulated to date and the continued validity of the study.

Inclusion Criteria:

• Diagnosis of dilated ischemic or non-ischemic cardiomyopathy
• Functional Mitral Regurgitation: 2+ (Moderate), 3+ (Moderate/Severe), or 4+ (Severe)
• New York Heart Association (NYHA) II, III, or IV
• Six Minute Walk distance of at least 150 meters and no farther than 450 meters
• Left Ventricular Ejection Fraction ≤ 50 %
• LV end diastolic dimension (LVEDD) >55mm or LVEDD/Body Surface Area (BSA) > 3.0cm/m2
• Stable heart failure medication regimen for at least three (3) months prior to index procedure

Exclusion Criteria:

• Hospitalization in past three (3) months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina
• Hospitalization in the past 30 days for coronary angioplasty or stent placement
• Subjects expected to require any cardiac surgery within one (1) year
• Subjects expected to require any percutaneous coronary intervention within 30 days of enrollment
• Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV), or anticipated need for CRT within twelve (12) months
• Presence of a coronary artery stent under the CS / GCV in the implant target zone
• Presence of left atrial appendage (LAA) clot.
• Presence of primary renal dysfunction or significantly compromised renal function as reflected by a serum creatinine > 2.2 mg/dL OR eGFR < 30 ml/min
• Inability to undertake a six-minute walk test due to physical restrictions/limitations
• Chronic severe pathology limiting survival to less than 12-months