Cardiovascular Diseases, Functional Mitral Regurgitation, Heart Diseases, Heart Failure, Heart Valve Diseases, Mitral Valve Insufficiency
Conditions
Keywords
Functional Mitral Regurgitation, Percutaneous Mitral Valve Repair, Percutaneous Mitral Valve Annuloplasty, Coronary Sinus Annuloplasty, Secondary Mitral Regurgitation, Functional MR, FMR
Brief summary
The objective of this prospective, randomized, double- blinded (patient and assessors), sham-controlled clinical trial is to assess the safety and efficacy of the CMCS in treating heart failure with functional regurgitation (FMR).
Detailed description
A total of 300 subjects will be randomized at up to 100 investigational sites in the United States, Canada, and Europe. 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 the Carillon implant 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 implant 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.
Interventions
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.
OTHERGuideline Directed Heart Failure Medication
Heart failure medication per ACC/AHA guidelines
Sponsors
Cardiac Dimensions, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Symptomatic heart failure with functional (secondary) mitral regurgitation of at least 1+ (mild) severity 2. NYHA II, III, or IV 3. Six Minute Walk distance ≥ 100 meters and ≤ 600 meters 4. Left Ventricular Ejection Fraction ≤ 50% 5. LVEDD: * ≥ 55 mm (women) * ≥ 57 mm (men) 6. LVESD ≤ 75 mm 7. Corrected NT-proBNP \> 1200 pg/ml measured within 60 days of randomization, and/or one or more heart failure hospitalizations within one year prior to consent or one or more outpatient visits for intensification of heart failure therapy within one year prior to consent. 8. Optimal Guideline directed heart failure medical therapy assessed by the Central Review Committee 9. Age ≥ 18 years old 10. Carillon implant can be sized and placed in accordance with the IFU 11. The subject has been informed of the nature of the trial and agrees to its provisions, including the possibility of randomization to the Control group and returning for all required post-procedure follow-up visits, and has provided written informed consent
Exclusion criteria
1. Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty, or leaflet repair device 2. 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) 3. Severe tricuspid regurgitation associated with right ventricular dysfunction and enlargement 4. Severe mitral annular calcification 5. Severe aortic stenosis 6. Expected to require any cardiac surgery, including surgery for coronary artery disease (CAD) or valve disease within one (1) year 7. Chronic, severe, medical conditions or pathology, other than heart failure, that will prevent likely survival beyond twelve (12) months or any other medical condition that, in the judgement of the Investigator or Central Review Committee, makes the patient a poor candidate for this study * An entire list of eligibility is available in the clinical investigational plan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Objective - Freedom from Major Adverse Events | 12 months | 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%. |
| Primary Efficacy Objective 1 - Hierarchical Clinical Composite | 24 months | To demonstrate that the CMCS (Intervention) group is superior to the Control group on the hierarchical composite endpoint of death, Cardiac transplantation or LVAD implantation, unplanned percutaneous or surgical mitral valve intervention, unplanned heart failure hospitalization, change in KCCQ overall summary score, and change in six-minute walk distance at 24 months (analyzed when the last subject completes 12 months of follow-up.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Objective 1- Regurgitant Volume | 12 months | To compare regurgitant volume change relative to control from baseline through 12 months of follow up in patients with at least MR grade 2+ at baseline |
| Secondary Efficacy Objective 2 - Change in LV End-diastolic Volume | 12 months | To compare the change from baseline left ventricular end-diastolic volume (LVEDV) relative to the Control group. |
| Secondary Efficacy Objective 3 - Change in NYHA | 12 months | To compare the change from baseline in New York Heart Association (NYHA) Classification, relative to Control, at twelve (12) months |
| Secondary Efficacy Objective 4 - Hierarchical Clinical Composite | 12 months | To compare the first four components of the hierarchical primary efficacy endpoint, relative to Control, analyzed when the last subject completes 12 months of follow up and use all available data up to twenty-four (24) months |
| Secondary Efficacy Objective 5 - Heart Failure Hospitalizations | 12 months of follow-up, and any available data up to 24 months | 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 |
| Exploratory Secondary Endpoint 1 - Change in Six-Minute Walk Distance | 12 months | To compare the change improvement from baseline in six-minute walk distance (6MWD), relative to Control, at twelve (12) months |
| Exploratory Secondary Endpoint 2 - Change in KCCQ | 12 months | To compare the change from baseline, relative to the Control group, in the Overall Summary Score (OSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ), at twelve (12) months |
| Exploratory Secondary Endpoint 3 - Change in LV End-systolic Volume | 12 months | To compare the change from baseline in left ventricular end-systolic volume (LVESV), relative to Control, at twelve (12) months |
| Exploratory Secondary Endpoint 4 - days lost due to HFH and CV death | 12 months of follow-up, and any available data up to 24 months | 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 |
| Exploratory Secondary Endpoint 5 - Alternative Therapies | 12 months of follow-up, and any available data up to 24 months | 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 |
Countries
Canada, France, Greece, Italy, Poland, Spain, United Kingdom, United States
Contacts
CONTACTHank Hauser
PRINCIPAL_INVESTIGATORSamir Kapadia, MD
The Cleveland Clinic
PRINCIPAL_INVESTIGATORRandall Starling, MD
The Cleveland Clinic
Outcome results
None listed