Findings Published From REDUCE FMR Study of Cardiac Dimensions' Carillon System

September 12, 2019—Cardiac Dimensions announced the publication of findings from the REDUCE FMR clinical study of its Carillon mitral contour system. The study by Klaus K. Witte, MD, et al is available online in Journal of the American College of Cardiology: Heart Failure.

The Carillon system is a right heart transcatheter mitral valve repair device designed to treat the primary cause of functional mitral regurgitation (FMR) in patients with MR grades 2+, 3+, and 4+. The Carillon mitral contour system has European CE Mark approval. In the United States, the Carillon system is currently being studied in a pivotal trial and is limited to investigational use.

According to the company, the REDUCE FMR study was a blinded, multicenter, randomized, sham-controlled clinical trial that enrolled 120 patients at 31 sites in the European Union, Australia, and New Zealand. Patients on optimal heart failure medical therapy with FMR were randomized 3:1 to receive treatment with the Carillon device or a nonimplant sham procedure.

The primary endpoint was change in mitral regurgitant volume at 1 year, as assessed by a blinded vascular core lab at the Cleveland Clinic in Cleveland, Ohio. Secondary endpoints included change in left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) as compared to baseline, major adverse events, and heart failure hospitalizations at 1 year.

The study met its primary endpoint, while enrolling a less severe patient population, noted the company.

Cardiac Dimensions reported that key results from the REDUCE FMR study include:

• Treatment with the Carillon device resulted in a statistically significant reduction of mitral regurgitant volume compared with the control group (decrease of 7.1 mL/beat vs an increase of 3.3 mL/beat; P = .049).
• Treatment with the Carillon device induced a significant reduction of left ventricular volumes compared with the control group (LVEDV, decrease of 10.4 mL vs an increase of 6.5 mL [P = .03]; LVESV, decrease of 6.2 mL vs an increase of 6.1 mL [P = .04]).
• Significant improvements in regurgitant volume and LVEDV were observed across all MR grades with the absolute improvement in both measures the greatest in patients with MR grades 3+ and 4+ after 12 months (reduction of mitral regurgitant volume, 12.8 ± 21.6 [n=15]; change in LVEDV, –26.9 ± 16.3 [n=13]; and change in LVESV, –17.5 ± 18.9 [n=13]).
• Patients treated with the Carillon device had a significant improvement in 6-minute walk distance at 12 months compared with baseline (P = .002), whereas patients in the control group did not (P = .29).
• Patients in the Carillon treatment group had a significant improvement in New York Heart Association class at 12 months compared with baseline (P = .002), whereas patients allocated to the control group did not (P = .75).
• The Carillon device showed a positive safety profile with a similar incidence of major adverse events between groups through the follow-up period.
• Treatment with the Carillon device enabled patients to experience 48% fewer repeat (> 1) heart failure hospitalizations during follow-up (11% vs 21%; P = .23).

Dr. Witte, a cardiologist at Leeds Teaching Hospital NHS Trusts in Leeds, United Kingdom, and a top enroller in the study, commented in the company’s announcement, “The Carillon system is the first mitral valve repair device to demonstrate a significant reduction in regurgitant volume and favorable LV remodeling, indicating a size reduction of the left ventricle. The convincing 1-year data shows the Carillon system can slow the progression of heart failure and will provide hope to many of my patients.”

Professor Horst Sievert, MD, a Principal Investigator of the REDUCE-FMR study, stated, "We know that MR in the context of heart failure is strongly associated with increased morbidity and mortality. Carillon provides an option to treat a large portion of FMR patients with a minimally invasive treatment that doesn't compromise the valve leaflets. Patients across a wide spectrum of MR grade and New York Heart Association class benefited from Carillon treatment, experiencing significant improvements in MR and favorable remodeling of the left ventricle. Heart failure is a progressive disease, and we need options that allow for progressive treatment.” Prof. Sievert is Director and Founder of the Cardiovascular Center Frankfurt in Frankfurt, Germany.

Prof. Sievert first presented the REDUCE-FMR findings at TCT 2018, the 30th annual Transcatheter Cardiovascular Therapeutics scientific symposium held September 21–25 in San Diego, California.