The CARILLON Trial - Assessment of the Carillon® Mitral Contour System® in Treating Functional Mitral Regurgitation Associated With Heart Failure
The CARILLON Trial - Assessment of the Carillon® Mitral Contour System® in Treating Functional Mitral Regurgitation 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 subjects with
 functional mitral regurgitation (FMR) associated with heart failure, compared to a randomized
 Control group which is medically managed according to heart failure guidelines.
A total of 352 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 as well as a review by a Central Review
 Committee to determine appropriateness for the implant procedure. On the day of the
 procedure, 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.
 With the distal aspect of the device anchored, incremental tension will be applied to plicate
 the peri-annular tissue. After the proximal anchor of the implant is locked in place, safety
 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
 Intervention group (without device placement) to ensure that 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 for an additional three (3) years, for a total of five (5) years. Any additional
 therapies which are required to treat symptomatic or advancing disease subjects will be
 reviewed by a Central Review Committee for endpoint evaluation as long as the subject was
 treated >6months after randomization so that all subjects may remain on the trial for the
 entire 5 years of follow up.
Inclusion Criteria:

 1. Diagnosis of ischemic or non-ischemic cardiomyopathy

 2. Symptomatic functional (secondary) mitral regurgitation defined as both: - 2+
 (Moderate), 3+ (Moderate/Severe), or 4+ (Severe).

 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.

 3. NYHA Class II, III, or IV

 4. Six Minute Walk distance ≥ 150 meters and ≤ 450 meters

 5. Left Ventricular Ejection Fraction ≤ 50%

 6. LVESD ≤ 70 mm Note: As assessed by Imaging Core Laboratory.

 7. Corrected BNP of > 300 pg/ml, or corrected NT-proBNP > 1500 pg/ml, or one or more
 heart failure hospitalizations within one year prior to consent

 8. Guideline directed heart failure medication regimen.

 9. Age ≥ 18 years old

 10. CARILLON implant can be sized and placed in accordance with the IFU

 11. The subject or the subject's legal representative 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. Recipient of intravenous positive-inotrope infusion or intra-aortic balloon pump
 support within the past 30 days

 2. Heart failure hospitalization within the past 30 days

 3. Anticipated need of left ventricular assist device within twelve (12) months

 4. Class I indication for cardiac resynchronization therapy (CRT), or anticipated need
 for CRT within twelve (12) months

 5. Primary renal dysfunction or compromised renal function as reflected by an estimated
 Glomerular Filtration Rate (eGFR) < 30 ml/min, as assessed by MDRD formula, or
 patients on dialysis

 6. Heart transplant candidate or prior orthotopic heart transplantation

 7. Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty,
 or leaflet repair device.

 8. Hypertrophic cardiomyopathy, infiltrative cardiomyopathy, restrictive cardiomyopathy
 or constrictive pericarditis

 9. Echocardiographic documentation of non-compaction cardiomyopathy as assessed by the
 Imaging Core Laboratory

 10. Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein
 (GCV)

 11. 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

 12. Severe tricuspid regurgitation associated with right ventricular dysfunction and
 enlargement, as assessed by the Imaging Core Laboratory

 13. Severe mitral annular calcification

 14. Severe aortic stenosis

 15. Not a candidate for right internal jugular venous cannulation

 16. Hospitalization in past 30 days due to myocardial infarction, coronary artery bypass
 graft surgery or unstable angina

 17. Cerebral vascular event within the past 30 days

 18. Hospitalization in the past 30 days for coronary angioplasty or stent placement or ICD
 implant

 19. Pulmonary embolus or deep vein thrombosis within the past six (6) months

 20. Expected to require any cardiac surgery, including surgery for coronary artery disease
 (CAD) or valve disease within one (1) year

 21. Expected to require any percutaneous coronary intervention within 30 days of the index
 procedure.

 22. Hemodynamic instability defined as sustained systolic blood pressure < 90 mmHg with or
 without afterload reduction, cardiogenic shock or the need for inotropic support or
 intra-aortic balloon pump or other hemodynamic support device

 23. Presence of left atrial appendage (LAA) clot or presence of LAA occluder

 24. Anemia defined as hemoglobin < 9.0 mg/dL

 25. Currently participating in an investigational drug or device study that has not
 completed the primary endpoint or that clinically interferes with the current study
 endpoints

 26. Known hypersensitivity or contraindication to procedural medications which cannot be
 adequately managed medically

 27. Active infections requiring current antibiotic therapy

 28. Chronic, severe, medical conditions or pathology, other than heart failure, that will
 prevent likely survival beyond twelve (12) months

 29. Female subjects pregnant or planning to become pregnant in the next five (5) years

 30. Subjects unable to perform the required study assessments (e.g., 6 minute walk test)

 31. Any other medical condition that, in the judgment of the Investigator, makes the
 patient a poor candidate for this study

 32. Subjects belonging to a vulnerable population per investigator's judgment or subject
 has any kind of disorder that compromises his/her ability to give written informed
 consent and/or comply with the study procedures