The EMPOWER Trial - The Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild FMR

Heart Failure Clinical Trial

Official title:

Assessment of the Carillon Mitral Contour System® in Treating Heart Failure With at Least Mild Functional Mitral Regurgitation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03142152
• Other study ID #: CVP 1670-01
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: December 31, 2030

Study information

• Verified date: May 2024
• Source: Cardiac Dimensions Pty Ltd
• Contact: Angie Swenson
• Phone: (425) 605-5900
• Email: aswenson[@]cardiacdimensions.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

A total of 300 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of ischemic or non-ischemic cardiomyopathy

2. Symptomatic functional (secondary) mitral regurgitation of at least 1+ (Mild) severity 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 = 100 meters and = 600 meters

5. Left Ventricular Ejection Fraction = 50%

6. LVEDD = 57 mm and LVESD = 75 mm

7. Corrected BNP of = 300 pg/ml, or corrected NT-proBNP = 1200 pg/ml, or one or more heart failure hospitalizations within six months prior to consent

8. Guideline directed heart failure medication regimen.

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), as assessed by the Imaging Core Laboratory

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

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Functional Mitral Regurgitation
• Heart Diseases
• Heart Failure
• Heart Valve Diseases
• Mitral Valve Insufficiency

Intervention

Device:
• Carillon Mitral Contour System
The Carillon implant is designed to be deployed, tensioned, and locked in the coronary vein in order to reshape the mitral annulus and thus reduce mitral annular dilation and mitral regurgitation.

Other:
• Guideline Directed Heart Failure Medication
Heart failure medication per ACC/AHA guidelines

Locations

Country	Name	City	State
France	Pole Sante Republique	Clermont Ferrand
Greece	European Interbalkan Medical Center	Thessaloníki
Poland	Poznan University of Medical Sciences	Poznan
United States	Albany Medical College,	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Augusta University Research Institute	Augusta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	St. Elizabeths	Boston	Massachusetts
United States	Deborah Heart & Lung	Browns Mills	New Jersey
United States	University at Buffalo	Buffalo	New York
United States	Carle Foundation Hospital	Champaign	Illinois
United States	Rush University	Chicago	Illinois
United States	Lindner Research Center at the Christ Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mount Carmel	Columbus	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Kettering Health Research Institute	Dayton	Ohio
United States	Advocate Good Samaritan	Downers Grove	Illinois
United States	Hackensack University Medical Center	Edison	New Jersey
United States	NorthShore University Health System	Evanston	Illinois
United States	Methodist Le Bonheur Healthcare	Germantown	Tennessee
United States	Dignity Health Research Institute at Mercy Gilbert and Chandler Regional Medical Centers	Gilbert	Arizona
United States	Henrico Doctors Hospital	Henrico	Virginia
United States	Cardiovascular Institute South	Houma	Louisiana
United States	UT Health Houston	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	Penn Medicine Lancaster General Health	Lancaster	Pennsylvania
United States	Keck School of Medicine of USC	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Wellstar Health System,	Marietta	Georgia
United States	Baptist Hospital of Miami	Miami	Florida
United States	Advocate Aurora Research Institute	Milwaukee	Wisconsin
United States	Community Healthcare System	Munster	Indiana
United States	Intermountain Medical Center	Murray	Utah
United States	Midwest Cardiovascular Institute (MCI)	Naperville	Illinois
United States	Naples Heart Institute	Naples	Florida
United States	Centennial Medical Center	Nashville	Tennessee
United States	Ochsner Health System	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Sentara Norfolk General	Norfolk	Virginia
United States	Oklahoma Heart Hospital	Oklahoma City	Oklahoma
United States	Advent Health Hospital	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Cardiovascular Research Center,	Phoenix	Arizona
United States	Banner Health - Phoenix	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Providence Heart Institute	Portland	Oregon
United States	Vassar Brothers- Hudson Valley Cardiovascular Practice	Poughkeepsie	New York
United States	Stanford University	Redwood City	California
United States	Carilion Hospital	Roanoke	Virginia
United States	William Beaumont Health	Royal Oak	Michigan
United States	Ascension St. Marys Research Institute	Saginaw	Michigan
United States	CentraCare Heart and Vascular	Saint Cloud	Minnesota
United States	Scripps Health	San Diego	California
United States	University of California- San Francisco	San Francisco	California
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Prairie Heart Institute	Springfield	Illinois
United States	Tallahassee Research Institute, Inc	Tallahassee	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Tuscon	Tucson	Arizona
United States	Tucson Medical Center Health	Tucson	Arizona
United States	Saint Francis Hospital,	Tulsa	Oklahoma
United States	Medstar	Washington	District of Columbia
United States	Cardiovascular Research Institute of Kansas	Wichita	Kansas
United States	Lankenau Institute for Medical Research	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Cardiac Dimensions, Inc.

Countries where clinical trial is conducted

United States,  France,  Greece,  Poland, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Safety Objective - Freedom from Major Adverse Events	Freedom from a composite of major adverse events (defined as Device Embolization, Vessel Erosion, Cardiac Perforation, and occurrence of cardiac surgery or percutaneous coronary intervention) in the Intervention group is greater than performance goal of 90%.	12 months
Primary	Primary Efficacy Objective 1 - Hierarchical Clinical Composite	To demonstrate that the Carillon Mitral Contour System (Intervention) group is superior to the Control group on the hierarchical composite endpoint of death, transplant or LVAD, percutaneous or surgical mitral valve intervention, heart failure hospitalization, Improvement in KCCQ, and improvement in six-minute walk distance at 24 months (analyzed when the last subject completes 12 months of follow-up.)	24 months
Secondary	Secondary Efficacy Objective 1- Regurgitant Volume	To compare regurgitant volume change relative to control from baseline through 12 months of follow up	12 months
Secondary	Secondary Efficacy Objective 2 - Change in LV End-diastolic Volume	To demonstrate an improvement from baseline in the parameter left ventricular end-diastolic volume (LVEDV) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group.	12 months
Secondary	Secondary Efficacy Objective 3 - Change in LV End-Systolic Volume	To demonstrate an improvement from baseline in the parameter left ventricular end-systolic volume (LVESV) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group.	12 months
Secondary	Secondary Efficacy Objective 4 - Change in 6 Minute Walk Distance	To demonstrate a significantly greater improvement from baseline in six-minute walk distance associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group.	12 months
Secondary	Secondary Efficacy Objective 5 - Change in KCCQ	To demonstrate the improvement from baseline in the overall summary score of the Kansas City Cardiomyopathy Questionnaire (KCCQ) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group.	12 months
Secondary	Secondary Efficacy Objective 6 - Change in NYHA Classification	To demonstrate the improvement in the proportion of patients who improve by at least one NYHA class from baseline associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group.	12 months
Secondary	Secondary Efficacy Objective 7 - Percent days lost due to HFH or CV death	To compare percent days lost due to HFH and CV death, relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months.	12 months of follow-up, and any available data up to 24 months
Secondary	Secondary Efficacy Objective 8 - Incidence of alternative therapy and all-cause mortality	To compare the incidence of need for alternative therapy and all-cause mortality (superiority test if HR < 1), relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months	12 months of follow-up, and any available data up to 24 months
Secondary	Secondary Efficacy Objective 9 - Total number of HFH	To compare total number of HFH, relative to Control, analyzed when the last subject completes 12 months of follow-up and use all available data up to 24 months	12 months of follow-up, and any available data up to 24 months
Secondary	Secondary Safety Objective - Freedom from peri-procedural Major Adverse Events	Freedom from a composite of major adverse events (defined as Death, Myocardial Infarction, Device Embolization, Vessel Erosion, Cardiac Perforation, and occurrence of cardiac surgery or percutaneous coronary intervention) in the Intervention group is greater than 80%.	30 days or hospital discharge date, whichever is longer