Clinical trial NCT02325830: Carillon Mitral Contour System® for Reducing Functional Mitral Regurgitation
Official title: The REDUCE FMR Trial: Safety and Efficacy of the Carillon Mitral Contour System® in Reducing Functional Mitral Regurgitation (FMR) Associated With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitral Valve Insufficiency
Heart Failure
Keywords: Functional mitral regurgitation
Secondary mitral regurgitation
Percutaneous mitral repair
Lead sponsor: Cardiac Dimensions Pty Ltd
Sponsor class: INDUSTRY
Collaborators: name: Menzies Institute for Medical Research
First posted: 2014-12-25
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: With crossover for sham procedure patients who are eligible at time of 12 month follow up.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Baseline Regurgitant Volume Associated With the Carillon Device Relative to the Control Population at 12 Months
timeFrame: Baseline and 12 months
measure: Difference in the Rate of Major Adverse Events Between Treatment (Carillon) and Control Groups
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Rate of Heart Failure Hospitalizations Between Treatment (Carillon) and Control Groups
timeFrame: Baseline and 12 months
measure: Change in Six-minute Walk Distance Between Treatment (Carillon) and Control Groups
timeFrame: Baseline and 12 Months
measure: Change in Left Ventricular Volumes Between Treatment (Carillon) and Control Groups
timeFrame: Baseline and 12 Months
Other outcomes:
Locations:
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred
state: New South Wales
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Prahran
country: Australia
facility: Alfred Health
state: Victoria
city: Brisbane
country: Australia
facility: Prince Charles
city: Olomouc
country: Czechia
facility: Olomouc University Hospital
city: Prague
country: Czechia
facility: Institut klinické a experimentální medicíny (IKEM)
city: Prague
country: Czechia
facility: Na Homolce Hospital
city: Clermont Ferrand
country: France
facility: Pôle Sante République
state: Auvergne
city: Caen
country: France
facility: Hôpital Privé Saint-Martin
city: Montpellier
country: France
facility: Clinique du Millénaire
city: Paris
country: France
facility: European Hospital Georges Pompidou
city: Rouen
country: France
facility: Clinique Saint-Hilaire
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Toulouse
country: France
facility: CHU Rangueil
city: Lüdenscheid
country: Germany
facility: Märkische Kliniken GmbH, Klinikum Lüdenscheid
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: Augusta Kranken-Anstalt GmbH
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
city: Frankfurt
country: Germany
facility: Cardio Vascular Center Frankfurt
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst GmbH
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg
city: Lübeck
country: Germany
facility: Sana Kliniken Lübeck
city: Recklinghausen
country: Germany
facility: Elisabeth Krankenhaus GmbH
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Grafton
country: New Zealand
facility: Auckland City Hospital
city: Poznan
country: Poland
facility: Poznan University of Medical Sciences
city: Harefield
country: United Kingdom
facility: Harefield Hospital
state: Middlesex
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
state: Yorkshire
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Cardio Vascular Center
name: Horst Sievert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: David Kaye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.