Carillon Mitral Contour System® for Reducing Functional Mitral Regurgitation (REDUCE FMR)

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Mitral Valve Insufficiency
• Intervention / Treatment: Device: Carillon Mitral Contour System

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Prince Charles
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia
      • Royal Prince Alfred
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Prahran, Victoria, Australia, 3181
      • Alfred Health
• Czechia
  • Olomouc, Czechia
    • Olomouc University Hospital
  • Prague, Czechia
    • Na Homolce Hospital
  • Prague, Czechia
    • Institut klinické a experimentální medicíny (IKEM)
• France
  • Caen, France, 14000
    • Hôpital privé Saint-Martin
  • Montpellier, France
    • Clinique du Millénaire
  • Paris, France
    • European Hospital Georges Pompidou
  • Rouen, France
    • Hopital Charles Nicolle
  • Rouen, France, 76000
    • Clinique Saint-Hilaire
  • Toulouse, France, 31059
    • CHU Rangueil
  • Auvergne
    • Clermont Ferrand, Auvergne, France
      • Pôle Santé République
• Germany
  • Berlin, Germany, 12203
    • Charité Universitätsmedizin Berlin
  • Bochum, Germany, 44791
    • Augusta Kranken-Anstalt GmbH
  • Frankfurt, Germany
    • Cardio Vascular Center Frankfurt
  • Frankfurt, Germany
    • Klinikum Frankfurt Höchst GmbH
  • Frankfurt am Main, Germany
    • University Hospital Frankfurt
  • Freiburg, Germany
    • Universitäts-Herzzentrum Freiburg
  • Lübeck, Germany
    • Sana Kliniken Lubeck
  • Recklinghausen, Germany, 45661
    • Elisabeth Krankenhaus GmbH
  • North Rhine-Westphalia
    • Lüdenscheid, North Rhine-Westphalia, Germany, 58515
      • Märkische Kliniken GmbH, Klinikum Lüdenscheid
• Netherlands
  • Maastricht, Netherlands, 6202 AZ
    • Maastricht University Medical Centre
• New Zealand
  • Grafton, New Zealand, 1030
    • Auckland City Hospital
• Poland
  • Poznan, Poland
    • Poznan University of Medical Sciences
• United Kingdom
  • Newcastle upon Tyne, United Kingdom
    • Freeman Hospital
  • Middlesex
    • Harefield, Middlesex, United Kingdom, UB9 6JH
      • Harefield Hospital
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS2 9LN
      • Leeds Teaching Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Optimized stable medical therapy
Experimental: Treatment Group; Implantation of the Carillon Mitral Contour System	Device: Carillon Mitral Contour System; Percutaneous mitral valve repair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Baseline Regurgitant Volume Associated With the Carillon Device Relative to the Control Population at 12 Months	The primary echocardiographic index and primary endpoint of the REDUCE FMR study was Regurgitant Volume (RV) in the ITT population (N=120). RV was analyzed for the ITT patient population calculated as the mean change per randomization group among subjects with evaluable data. Between group comparisons were performed using the Students' t-test.	Baseline and 12 months
Difference in the Rate of Major Adverse Events Between Treatment (Carillon) and Control Groups	Cumulative number of events for Death, Myocardial Infarction, Cardiac Perforation, Device embolization, and surgical or percutaneous intervention related to device.	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Heart Failure Hospitalizations Between Treatment (Carillon) and Control Groups	A diagnosis of acute decompensated heart failure hospitalization (ADHF) requires an in-hospital stay that includes at least one calendar date change and requires intravenous or mechanical heart failure treatment. The length of hospital stay will be calculated from admission to discharge to home or other disposition. The diagnosis of ADHF will be based on: Symptoms of worsening heart failure such as increased shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, fatigue, decreased exercise tolerance or history of weight gain;; Physical examination evidence such as neck vein distention, the presence of a third heart sound, bilateral pulmonary rales, worsening ascites or pedal edema, hypotension or signs of worsening end-organ perfusion; and/or; Laboratory evidence, which may include pulmonary congestion on chest x-ray, elevated natriuretic peptide level, worsening oxygenation or respiratory acidosis.	Baseline and 12 months
Change in Six-minute Walk Distance Between Treatment (Carillon) and Control Groups	Subjects had 6-MWT conducted at baseline and each follow-up visit. The subject walked as far as they could within a 6-minute period. They were allowed to rest. The distance (in whole meters) was captured at each visit.	Baseline and 12 Months
Change in Left Ventricular Volumes Between Treatment (Carillon) and Control Groups	The volume of the left ventricle will be measured by a blinded echosonographer ajdn submitted to the core lab for blinded analysis. The ventricle will be measured as systole and diastole.	Baseline and 12 Months

Collaborators and Investigators

• Sponsor: Cardiac Dimensions Pty Ltd
• Collaborators: Menzies Institute for Medical Research
• Investigators: Principal Investigator: Horst Sievert, MD, Cardio Vascular Center; Principal Investigator: David Kaye, MD, The Alfred

Publications and helpful links

General Publications

• Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC, Levy WC, Mauri L, Feldman T, Kwong RY, Kaye DM, Duffy SJ, Tubler T, Degen H, Brandt MC, Van Bibber R, Goldberg S, Reuter DG, Hoppe UC. Percutaneous mitral annuloplasty for functional mitral regurgitation: results of the CARILLON Mitral Annuloplasty Device European Union Study. Circulation. 2009 Jul 28;120(4):326-33. doi: 10.1161/CIRCULATIONAHA.109.849885. Epub 2009 Jul 13.
• Siminiak T, Wu JC, Haude M, Hoppe UC, Sadowski J, Lipiecki J, Fajadet J, Shah AM, Feldman T, Kaye DM, Goldberg SL, Levy WC, Solomon SD, Reuter DG. Treatment of functional mitral regurgitation by percutaneous annuloplasty: results of the TITAN Trial. Eur J Heart Fail. 2012 Aug;14(8):931-8. doi: 10.1093/eurjhf/hfs076. Epub 2012 May 21.
• Siminiak T, Hoppe UC, Schofer J, Haude M, Herrman JP, Vainer J, Firek L, Reuter DG, Goldberg SL, Van Bibber R. Effectiveness and safety of percutaneous coronary sinus-based mitral valve repair in patients with dilated cardiomyopathy (from the AMADEUS trial). Am J Cardiol. 2009 Aug 15;104(4):565-70. doi: 10.1016/j.amjcard.2009.04.021. Epub 2009 May 29.
• Witte KK, Lipiecki J, Siminiak T, Meredith IT, Malkin CJ, Goldberg SL, Stark MA, von Bardeleben RS, Cremer PC, Jaber WA, Celermajer DS, Kaye DM, Sievert H. The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation. JACC Heart Fail. 2019 Nov;7(11):945-955. doi: 10.1016/j.jchf.2019.06.011. Epub 2019 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): January 8, 2020

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimated): December 25, 2014

Study Record Updates

• Last Update Posted (Actual): August 5, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Functional mitral regurgitation; Secondary mitral regurgitation; Percutaneous mitral repair
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Heart Failure; Mitral Valve Insufficiency
• Other Study ID Numbers: CVP 1627-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No