Clinical trial NCT03142152: The EMPOWER Trial - The Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild FMR
Official title: Assessment of the Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild Functional Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Functional Mitral Regurgitation
Heart Failure
Mitral Valve Insufficiency
Heart Diseases
Cardiovascular Diseases
Heart Valve Diseases
Keywords: Functional Mitral Regurgitation
Percutaneous Mitral Valve Repair
Percutaneous Mitral Valve Annuloplasty
Coronary Sinus Annuloplasty
Secondary Mitral Regurgitation
Functional MR
FMR
Lead sponsor: Cardiac Dimensions Pty Ltd
Sponsor class: INDUSTRY
First posted: 2017-05-05
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this prospective, randomized, blinded clinical trial is to assess the safety and efficacy of the Carillon Mitral Contour System in treating heart failure with functional regurgitation (FMR).

Detailed description: A total of 300 subjects will be randomized at up to 75 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 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.

Subjects randomized to the Control group will experience an index procedure similar to the Intervention group (without device 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.

Eligibility criteria: 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 ≥ 57 mm and LVESD ≤ 75 mm
6. Corrected BNP of \> 300 pg/ml, or corrected NT-proBNP \> 1200 pg/ml, or one or more heart failure hospitalizations within one year prior to consent
7. Guideline directed heart failure medication regimen
8. Age 18 years old
9. Carillon implant can be sized and placed in accordance with the IFU
10. 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. Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV) or Class I indication for cardiac resynchronization therapy (CRT)
2. Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty, or leaflet repair device
3. 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)
4. Severe tricuspid regurgitation associated with right ventricular dysfunction and enlargement
5. Severe mitral annular calcification
6. Severe aortic stenosis
7. Expected to require any cardiac surgery, including surgery for coronary artery disease (CAD) or valve disease within one (1) year
8. 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 judgment of the Investigator, makes the patient a poor candidate for this study

   * An entire list of eligibility is available in the clinical investigational plan

Primary outcomes:
measure: Primary Safety Objective - Freedom from Major Adverse Events
timeFrame: 12 months
measure: Primary Efficacy Objective 1 - Hierarchical Clinical Composite
timeFrame: 24 months
Secondary outcomes:
measure: Secondary Efficacy Objective 1- Regurgitant Volume
timeFrame: 12 months
measure: Secondary Efficacy Objective 2 - Change in LV End-diastolic Volume
timeFrame: 12 months
measure: Secondary Efficacy Objective 3 - Change in LV End-Systolic Volume
timeFrame: 12 months
measure: Secondary Efficacy Objective 4 - Change in 6 Minute Walk Distance
timeFrame: 12 months
measure: Secondary Efficacy Objective 5 - Change in KCCQ
timeFrame: 12 months
measure: Secondary Efficacy Objective 6 - Change in NYHA Classification
timeFrame: 12 months
measure: Secondary Efficacy Objective 7 - Percent days lost due to HFH or CV death
timeFrame: 12 months of follow-up, and any available data up to 24 months
measure: Secondary Efficacy Objective 8 - Incidence of alternative therapy and all-cause mortality
timeFrame: 12 months of follow-up, and any available data up to 24 months
measure: Secondary Efficacy Objective 9 - Total number of HFH
timeFrame: 12 months of follow-up, and any available data up to 24 months
measure: Secondary Safety Objective - Freedom from peri-procedural Major Adverse Events
timeFrame: 30 days or hospital discharge date, whichever is longer
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Dignity Health Research Institute at Mercy Gilbert and Chandler Regional Medical Centers
state: Arizona
city: Phoenix
country: United States
facility: Banner Health - Phoenix
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center Health
state: Arizona
city: Tucson
country: United States
facility: Banner University Tuscon
state: Arizona
city: Long Beach
country: United States
facility: Memorial Care Hospital
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Redwood City
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Scripps Health
state: California
city: San Francisco
country: United States
facility: University of California- San Francisco
state: California
city: Littleton
country: United States
facility: South Denver Cardiology
state: Colorado
city: Washington
country: United States
facility: Medstar
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Advent Health Hospital
state: Florida
city: Palm Beach
country: United States
facility: Palm Beach Gardens Medical
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Augusta
country: United States
facility: Augusta University Research Institute
state: Georgia
city: Marietta
country: United States
facility: Wellstar Health System,
state: Georgia
city: Downers Grove
country: United States
facility: Advocate Good Samaritan
state: Illinois
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute (MCI)
state: Illinois
city: Springfield
country: United States
facility: Prairie Heart Institute
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Houma
country: United States
facility: Cardiovascular Institute South
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: St. Elizabeths
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saginaw
country: United States
facility: Ascension St. Marys Research Institute
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular
state: Minnesota
city: Browns Mills
country: United States
facility: Deborah Heart & Lung
state: New Jersey
city: Edison
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College,
state: New York
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Poughkeepsie
country: United States
facility: Vassar Brothers- Hudson Valley Cardiovascular Practice
state: New York
city: Cincinnati
country: United States
facility: Lindner Research Center at the Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Harrington Vascular
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Kettering Health Research Institute
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute Hospital
state: Oklahoma
city: Tulsa
country: United States
facility: Saint Francis Hospital,
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Portland
country: United States
facility: Providence Heart Institute
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Penn Medicine Lancaster General Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburg
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Institute of Medical Research
state: Pennsylvania
city: Sioux Falls
country: United States
facility: North Central Heart-Avera
state: South Dakota
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Henrico
country: United States
facility: Henrico Doctors Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Hospital
state: Virginia
city: Milwaukee
country: United States
facility: Advocate Aurora Research Institute
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: St Boniface Hospital - University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto, St Michael's Hospital
state: Ontario
city: Clermont Ferrand
country: France
facility: Pole Sante Republique
city: Lille
country: France
facility: Centre Hospitalier Universitaire De Lille
city: Lyon
country: France
facility: Hôpital Cardiologique Louis Pradel
city: Montpellier
country: France
facility: Clinique du Millènaire Montpelier
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
city: Thessaloníki
country: Greece
facility: European Interbalkan Medical Center
city: Poznan
country: Poland
facility: Poznan University of Medical Sciences
city: Leeds
country: United Kingdom
facility: St James University Hospital
Study officials:
affiliation: The Cleveland Clinic
name: Samir Kapadia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Randall Starling, 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: Lipiecki J, Siminiak T, Sievert H, Muller-Ehmsen J, Degen H, Wu JC, Schandrin C, Kalmucki P, Hofmann I, Reuter D, Goldberg SL, Haude M. Coronary sinus-based percutaneous annuloplasty as treatment for functional mitral regurgitation: the TITAN II trial. Open Heart. 2016 Jul 8;3(2):e000411. doi: 10.1136/openhrt-2016-000411. eCollection 2016.