The EMPOWER Trial - The Carillon® Mitral Contour System® in Treating Heart Failure With at Least Mild FMR
Study Details
Study Description
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 at least mild functional regurgitation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 as well as a review by a Central Review Committee to determine appropriateness for the implant procedure. On the day of the procedure, 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. With the distal aspect of the device anchored, incremental tension will be applied to plicate the peri-annular tissue. After the proximal anchor of the implant is locked in place, safety 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 Intervention group (without device placement) to ensure that 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. Any additional therapies which are required to treat symptomatic or advancing disease subjects will be reviewed by a Central Review Committee for endpoint evaluation as long as the subject was treated >6months after randomization so that all subjects may remain on the trial for the entire 5 years of follow up.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention Group Carillon Mitral Contour System and Guideline Directed Heart Failure Medication |
Device: Carillon Mitral Contour System
The CARILLON implant (mXE2) 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:
Other: Guideline Directed Heart Failure Medication
Heart failure medication per ACC/AHA guidelines
|
| Active Comparator: Control Group Guideline Directed Heart Failure Medication |
Other: Guideline Directed Heart Failure Medication
Heart failure medication per ACC/AHA guidelines
|
Outcome Measures
Primary Outcome Measures
- Primary Safety Objective - Freedom from Major Adverse Events [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 [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, transplant or LVAD, percutaneous or surgical mitral valve intervention, heart failure hospitalization, Improvement in KCCQ, and improvement in six-minute walk distance at 12 months.
Secondary Outcome Measures
- Secondary Efficacy Objective 1- Regurgitant Volume [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 [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 [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 [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 [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 [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 [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 [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 [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 [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%.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of ischemic or non-ischemic cardiomyopathy
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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.
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NYHA Class II, III, or IVa
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Six Minute Walk distance ≥ 150 meters and ≤ 450 meters
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Left Ventricular Ejection Fraction ≤ 50%
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LVEDD ≥ 60 mm and LVESD ≤ 70 mm Note: As assessed by Imaging Core Laboratory.
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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
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Guideline directed heart failure medication regimen.
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Age ≥ 18 years old
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CARILLON implant can be sized and placed in accordance with the IFU
-
The subject or the subject's legal representative 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:
-
Recipient of intravenous positive-inotrope infusion or intra-aortic balloon pump support within the past 30 days
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Heart failure hospitalization within the past 30 days
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Anticipated need of left ventricular assist device within twelve (12) months
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Class I indication for cardiac resynchronization therapy (CRT), or anticipated need for CRT within twelve (12) months
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Primary renal dysfunction or compromised renal function as reflected by an estimated Glomerular Filtration Rate (eGFR) < 30 ml/min, as assessed by MDRD formula, or patients on dialysis
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Heart transplant candidate or prior orthotopic heart transplantation
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Unlikely to benefit from annular reduction therapy
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Presence of a mechanical or bio-prosthetic mitral valve or, mitral valve annuloplasty, or leaflet repair device
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Hypertrophic cardiomyopathy, infiltrative cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis
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Echocardiographic documentation of non-compaction cardiomyopathy as assessed by the Imaging Core Laboratory
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Pre-existing device (e.g., pacing lead) in coronary sinus (CS) / great cardiac vein (GCV)
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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
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Severe tricuspid regurgitation associated with right ventricular dysfunction and enlargement, as assessed by the Imaging Core Laboratory
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Severe mitral annular calcification
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Severe aortic stenosis
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Not a candidate for right internal jugular venous cannulation
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Hospitalization in past 30 days due to myocardial infarction, coronary artery bypass graft surgery or unstable angina
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Cerebral vascular event within the past 30 days
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Hospitalization in the past 30 days for coronary angioplasty or stent placement or ICD implant
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Pulmonary embolus or deep vein thrombosis within the past six (6) months
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Expected to require any cardiac surgery, including surgery for coronary artery disease (CAD) or valve disease within one (1) year
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Expected to require any percutaneous coronary intervention within 30 days of the index procedure.
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Hemodynamic instability defined as sustained systolic blood pressure < 90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or intra-aortic balloon pump or other hemodynamic support device
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Presence of left atrial appendage (LAA) clot or presence of LAA occluder
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Anemia defined as hemoglobin < 9.0 mg/dL
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Currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints
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Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically
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Active infections requiring current antibiotic therapy
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Chronic, severe, medical conditions or pathology, other than heart failure, that will prevent likely survival beyond twelve (12) months
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Female subjects pregnant or planning to become pregnant in the next five (5) years
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Subjects unable to perform the required study assessments (e.g., 6 minute walk test)
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Any other medical condition that, in the judgment of the Investigator, makes the patient a poor candidate for this study
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Subjects belonging to a vulnerable population per investigator's judgment or subject has any kind of disorder that compromises his/her ability to give written informed consent and/or comply with the study procedures
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dignity Health Research Institute at Mercy Gilbert and Chandler Regional Medical Centers | Gilbert | Arizona | United States | 85297 |
| 2 | Banner University Hospital- Phoenix | Phoenix | Arizona | United States | 85006 |
| 3 | Banner University Tuscon | Tucson | Arizona | United States | 85724 |
| 4 | Loma Linda University Health | Loma Linda | California | United States | 92354 |
| 5 | UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 6 | Foundation for Cardiovascular Medicine | San Diego | California | United States | 92122 |
| 7 | University of California- San Francisco | San Francisco | California | United States | 94143 |
| 8 | Yale | New Haven | Connecticut | United States | 06520 |
| 9 | Medstar | Washington | District of Columbia | United States | 20010 |
| 10 | Delray Medical Center | Delray Beach | Florida | United States | 33484 |
| 11 | Baptist Hospital of Miami | Miami | Florida | United States | 33101 |
| 12 | University of Miami | Miami | Florida | United States | 33136 |
| 13 | Cleveland Clinic- Weston | Weston | Florida | United States | 33331 |
| 14 | Piedmont Heart Institute | Atlanta | Georgia | United States | 30309 |
| 15 | Carle Foundation Hospital | Champaign | Illinois | United States | 61801 |
| 16 | Rush University | Chicago | Illinois | United States | 60612 |
| 17 | NorthShore University Health System | Evanston | Illinois | United States | 60201 |
| 18 | Prairie Heart Institute | Springfield | Illinois | United States | 62701 |
| 19 | University of Kentucky Medical Center | Lexington | Kentucky | United States | 40536 |
| 20 | Ochsner Health System | New Orleans | Louisiana | United States | 70121 |
| 21 | Maine Medical Center | Scarborough | Maine | United States | 04074 |
| 22 | St. Elizabeths | Boston | Massachusetts | United States | 02135 |
| 23 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02145 |
| 24 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 25 | University of Michigan | Ann Arbor | Michigan | United States | 48859 |
| 26 | Beaumont Health | Royal Oak | Michigan | United States | 48073 |
| 27 | Ascension St. Marys Research Institute | Saginaw | Michigan | United States | 48601 |
| 28 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 29 | Dartmouth Hitchcock Medical Center | Hanover | New Hampshire | United States | 03756 |
| 30 | Columbia University Medical Center | New York | New York | United States | 10027 |
| 31 | New York Presbyterian- Weill Cornell Medical College | New York | New York | United States | 10065 |
| 32 | Vassar Brothers- Hudson Valley Cardiovascular Practice | Poughkeepsie | New York | United States | 12601 |
| 33 | UNC- Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 34 | Lindner Research Center at the Christ Hospital | Cincinnati | Ohio | United States | 45219 |
| 35 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 36 | Oklahoma Heart Hospital | Oklahoma City | Oklahoma | United States | 73120 |
| 37 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822 |
| 38 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19014 |
| 39 | UPMC Presbyterian | Pittsburgh | Pennsylvania | United States | 15213 |
| 40 | Centennial Medical Center | Nashville | Tennessee | United States | 37203 |
| 41 | Henrico Doctors Hospital | Henrico | Virginia | United States | 23229 |
| 42 | Sentara Norfolk General | Norfolk | Virginia | United States | 23501 |
| 43 | University of Washington | Seattle | Washington | United States | 98112 |
| 44 | Pole Sante Republique | Clermont Ferrand | France | ||
| 45 | European Interbalkan Medical Center | Thessaloníki | Greece | ||
| 46 | Centrum Medyczne Hcp | Poznan | Poland | 61-485 | |
| 47 | Uniwersytecki Szpital Kliniczny | Wroclaw | Poland | ||
| 48 | Leeds Teaching Hospital NHS | Leeds | United Kingdom |
Sponsors and Collaborators
- Cardiac Dimensions, Inc.
Investigators
- Principal Investigator: Samir Kapadia, MD, The Cleveland Clinic
- Principal Investigator: Randall Starling, MD, The Cleveland Clinic
- Principal Investigator: Marc Gillinov, MD, The Cleveland Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
- Lipiecki J, Siminiak T, Sievert H, Müller-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.
- Schofer J, Siminiak T, Haude M, Herrman JP, Vainer J, Wu JC, Levy WC, Mauri L, Feldman T, Kwong RY, Kaye DM, Duffy SJ, Tübler 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.
- CVP 1670-01