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

• ClinicalTrials.gov Identifier: NCT03142152
• Recruitment Status: Recruiting
• First Posted: May 5, 2017
• Last Update Posted: February 28, 2024
• Sponsor: Cardiac Dimensions, Inc.
• Information provided by (Responsible Party): Cardiac Dimensions Pty Ltd ( Cardiac Dimensions, Inc. )

Tracking Information

• First Submitted Date: May 2, 2017
• First Posted Date: May 5, 2017
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: January 1, 2018
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2023)

• Primary Safety Objective - Freedom from Major Adverse Events [ Time Frame: 12 months ]
  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%.
• Primary Efficacy Objective 1 - Hierarchical Clinical Composite [ Time Frame: 24 months ]
  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.)

Original Primary Outcome Measures (submitted: May 3, 2017)

• Primary Safety Objective - Freedom from Major Adverse Events [ Time Frame: 12 months ]
  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%.
• Primary Efficacy Objective 1 - Hierarchical Clinical Composite [ Time Frame: 12 months ]
  To demonstrate that the Carillon Mitral Contour System (Intervention) group is superior to the Control group on the hierarchical composite endpoint of death, time to first heart failure hospitalization, and improvement in six-minute walk distance. The endpoint will use the Win Ratio analysis method for composite endpoints employing the Finkelstein-Schoenfeld methodology.
• Primary Efficacy Objective 2 - Change in Regurgitant Volume [ Time Frame: 12 months ]
  To demonstrate a significantly greater decrease from baseline in Regurgitant Volume (assessed by the Echocardiography Core Laboratory) associated with the Carillon Mitral Contour System (Intervention group) relative to the Control group

Current Secondary Outcome Measures (submitted: March 15, 2023)

• Secondary Efficacy Objective 1- Regurgitant Volume [ Time Frame: 12 months ]
  To compare regurgitant volume change relative to control from baseline through 12 months of follow up
• Secondary Efficacy Objective 2 - Change in LV End-diastolic Volume [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 3 - Change in LV End-Systolic Volume [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 4 - Change in 6 Minute Walk Distance [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 5 - Change in KCCQ [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 6 - Change in NYHA Classification [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 7 - Percent days lost due to HFH or CV death [ Time Frame: 12 months of follow-up, and any available data up to 24 months ]
  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.
• Secondary Efficacy Objective 8 - Incidence of alternative therapy and all-cause mortality [ Time Frame: 12 months of follow-up, and any available data up to 24 months ]
  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
• Secondary Efficacy Objective 9 - Total number of HFH [ Time Frame: 12 months of follow-up, and any available data up to 24 months ]
  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
• Secondary Safety Objective - Freedom from peri-procedural Major Adverse Events [ Time Frame: 30 days or hospital discharge date, whichever is longer ]
  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%.

Original Secondary Outcome Measures (submitted: May 3, 2017)

• Secondary Safety Objective - Freedom from peri-procedural Major Adverse Events [ Time Frame: 30 days or hospital discharge date, whichever is longer ]
  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%.
• Secondary Efficacy Objective 1 - Freedom from Major Adverse Events [ Time Frame: 12 months ]
  To assess the relative risk reduction of heart failure hospitalizations in the Intervention group relative to the Control group, from the time of the index procedure to a minimum of twelve (12) months.
• Secondary Efficacy Objective 2 - Change in 6 Minute Walk Distance [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 3 - Change in LV End-Systolic Volume [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 4 - Change in Kansas City Cardiomyopathy Score (Quality of Life measure) [ Time Frame: 12 months ]
  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.
• Secondary Efficacy Objective 5 - Change in New York Heart Association Classification [ Time Frame: 12 months ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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, 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

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 Names:

  • Carillon
  • Percutaneous mitral valve repair
• Other: Guideline Directed Heart Failure Medication
  Heart failure medication per ACC/AHA guidelines

Study Arms

• Experimental: Intervention Group
  Carillon Mitral Contour System and Guideline Directed Heart Failure Medication
  Interventions:

  • Device: Carillon Mitral Contour System
  • Other: Guideline Directed Heart Failure Medication
• Active Comparator: Control Group
  Guideline Directed Heart Failure Medication
  Intervention: Other: Guideline Directed Heart Failure Medication

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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 10, 2021): 300
• Original Estimated Enrollment (submitted: May 3, 2017): 400
• Estimated Study Completion Date: December 31, 2030
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Angie Swenson; (425) 605-5900; aswenson@cardiacdimensions.com

• Listed Location Countries: France, Greece, Poland, United States
• Removed Location Countries: Czechia, United Kingdom

Administrative Information

• NCT Number: NCT03142152
• Other Study ID Numbers: CVP 1670-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cardiac Dimensions Pty Ltd ( Cardiac Dimensions, Inc. )
• Original Responsible Party: Cardiac Dimensions Pty Ltd
• Current Study Sponsor: Cardiac Dimensions, Inc.
• Original Study Sponsor: Cardiac Dimensions Pty Ltd
• Collaborators: Not Provided

Investigators

• Principal Investigator: Samir Kapadia, MD; The Cleveland Clinic
• Principal Investigator: Randall Starling, MD; The Cleveland Clinic

• PRS Account: Cardiac Dimensions Pty Ltd
• Verification Date: February 2024