|January 17, 2013
|July 26, 2013
|August 2016 (final data collection date for primary outcome measure)
|Hierarchical composite of all-cause mortality and recurrent heart failure hospitalizations [ Time Frame: two years ] [ Designated as safety issue: Yes ]
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.
|Same as current
|Complete list of historical versions of study NCT01772108 on ClinicalTrials.gov Archive Site
- 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 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- Mitral regurgitation severity reduction to mild or mild-to-moderate at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in Left Ventricular End Diastolic Volume (LVEDV) at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in Left Ventricular End Systolic Volume (LVESV) at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in 6 Minute Walk Test (6MWT) distance at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in Quality of Life (QoL) score, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ), at 12 months over baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- New York Heart Association (NYHA) Functional Class I/II at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
|Same as current
|A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation
|A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation
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.
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 is 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.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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
- Experimental: MitraClip Device
Subjects randomized to the Device group will undergo the MitraClip procedure in addition to optimal standard medical therapy
Intervention: Device: MitraClip
- No Intervention: Control
Subjects randomized to the Control group will receive optimal standard of care therapy alone
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- Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 Sep 23;52(13):e1-142. No abstract available.
- Feldman T, Foster E, Glower DG, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV, Massaro JM, Mauri L; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011 Apr 14;364(15):1395-406. Epub 2011 Apr 4.
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|August 2016 (final data collection date for primary outcome measure)
- 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
- 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
|18 Years to 90 Years
||Piotr Ponikowski, MD, PhD
||Military Hospital, Medical University, Wroclaw, Poland