A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation

Study Overview
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Brief Summary
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This trial is a randomized study of the MitraClip device in heart failure patients with clinically significant functional mitral regurgitation. A hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations is hypothesized to occur at a lower rate with the use of the MitraClip device in addition to optimal standard medical therapy compared to optimal standard of care therapy alone.

Detailed Description
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This study is a clinical evaluation of the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with chronic heart failure. The objective was to further study the safety and effectiveness of the MitraClip System for the treatment of clinically significant functional mitral regurgitation in New York Heart Association Functional Class III or IV chronic heart failure patients. Due to lower than expected recruitment rate, Abbott Vascular sponsorship of the trial was terminated early.

Official Title
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A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Device: MitraClip


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 years and 90 years old Clinically significant functional mitral regurgitation (moderate-to-severe or severe mitral regurgitation), as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Assessed by the investigator to be on optimal standard of care therapy for heart failure for at least 4 weeks with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization Documented New York Heart Association Class III or Class IV heart failure, despite optimal standard of care therapy, within 90 days preceding randomization Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of at least 350 pg/mL for BNP or at least 1400 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Left ventricular ejection fraction (LVEF) ≥15% and ≤40% determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Left ventricular end diastolic diameter (LVEDD) ≥55 mm determined by transthoracic echocardiogram within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness Subject agrees to return for all required post-procedure follow-up visits The subject has been informed of the nature of the study and agrees to the study's provisions, including the possibility of randomization to the Control group, and has provided written informed consent as approved by the respective clinical site's Ethics Committee Exclusion Criteria: Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative mitral regurgitation), as determined by transesophageal echocardiography Status 1 heart transplant or prior orthotopic heart transplantation Introduction of a new heart failure drug class within the last 4 weeks prior to randomization Cardiovascular hospitalization within the last 2 weeks immediately prior to randomization Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery or atrial fibrillation ablation within 90 days prior to randomization Implant of any rhythm management device (i.e., pacemaker, Cardiac Resynchronization Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD) within 90 days prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization Need for any cardiovascular surgery Mitral valve surgery is considered a therapeutic option for the subject Renal replacement therapy Uncontrolled hypertension (i.e., BP >180 mmHg systolic and/or >105 mmHg diastolic) or hypotension (i.e., BP <90 mmHg systolic) Unstable angina pectoris as judged by the investigator, other clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias 6MWT distance >450 meters Mitral Valve Area (MVA) by planimetry <4.0 cm2; if MVA by planimetry is not measurable, pressure half-time measurement is acceptable; MVA must be confirmed by the Echocardiography Core Laboratory Leaflet anatomy which may preclude MitraClip device implantation, proper device positioning on the leaflets, or sufficient reduction in mitral regurgitation that may include: Evidence of calcification in the grasping area Presence of significant cleft in the grasping area Lack of both primary and secondary chordal support in the grasping area Prior mitral valve surgery Coaptation length ≤2 mm Leaflet mobility length <1 cm Presence of an IVC filter in the femoral vein that would interfere with the delivery catheter, or ipsilateral deep vein thrombosis (DVT) is present Contraindication to transseptal catheterization Subjects in whom transesophageal echocardiography is contraindicated Echocardiographic evidence of intracardiac mass, thrombus, or vegetation Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated) Presence of any of the following: Severe aortic stenosis (aortic valve area <1.0 cm2) or severe aortic regurgitation Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis) Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non-ischemic etiology Hemodynamic instability requiring inotropic support or mechanical heart circulatory support Active infections requiring current antibiotic therapy Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically Severe right ventricular failure or severe tricuspid regurgitation History of bleeding diathesis or coagulopathy or subject who refuses blood transfusions Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to randomization and be adherent to an accepted method of contraception Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the investigator Currently participating in another therapeutic or interventional heart failure trial, or in any trial of an unapproved drug or device (Subjects participating in observational studies or registries may be considered as eligible) Subject belongs 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 to comply with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MitraClip Device<br>Subjects randomized to the Device group will undergo the MitraClip procedure in addition to optimal standard medical therapy. | Device: MitraClip<br>* The MitraClip System includes a MitraClip device, a Steerable Guide Catheter, and a MitraClip Delivery System that enables placement of the MitraClip device on the mitral valve leaflets<br>|
| No Intervention: Control<br>Subjects randomized to the Control group will receive optimal standard of care therapy alone. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations | The analysis will be carried out when the last patient completes 12-month follow-up. All follow-up, up to 24 months, will be included in the analysis. | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause mortality, stroke, myocardial infarction, new need for renal replacement therapy, and non-elective cardiovascular surgery for device related complications in the Device group at 30 days |  | 30 days | 
| Mitral regurgitation severity reduction to mild or mild-to-moderate at 12 months |  | 12 months | 
| Change in Left Ventricular End Diastolic Volume (LVEDV) at 12 months over baseline |  | 12 months | 
| Change in Left Ventricular End Systolic Volume (LVESV) at 12 months over baseline |  | 12 months | 
| Change in 6 Minute Walk Test (6MWT) distance at 12 months over baseline |  | 12 months | 
| Change in Quality of Life (QoL) score, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ), at 12 months over baseline |  | 12 months | 
| New York Heart Association (NYHA) Functional Class I/II at 12 months |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Valve Diseases