Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation
Trial status: Open for Enrollment
Why is this study being done?
Prospective, randomized, parallel-controlled, multicenter clinical evaluation of the MitraClip device for the treatment of clinically significant functional mitral regurgitation in symptomatic heart failure subjects who are treated per standard of care and who have been determined by the site's local heart team as not appropriate for mitral valve surgery. Eligible subjects will be randomized in a 1:1 ratio to the MitraClip device (Device group) or to no MitraClip device (Control group).
Who is eligible to participate?
1. Symptomatic functional MR (≥3+) due to cardiomyopathy of either ischemic or non-ischemic etiology determined by assessment of a qualifying transthoracic echocardiogram (TTE) obtained within 90 days and transesophageal echocardiogram (TEE) obtained within 180 days prior to subject registration, with MR severity based principally on the TTE study, and must be confirmed by the Echocardiography Core Lab (ECL). The ECL may request a transesophageal echocardiogram (TEE) to confirm MR etiology.
Note: Functional MR requires the presence of global or regional left ventricular wall motion abnormalities, which are believed to be the primary cause of the MR. If a flail leaflet or other evidence of degenerative MR is present, the subject is not eligible even if global or regional left ventricular systolic dysfunction is present.
Note: Qualifying TTE must be obtained after the subject has been stabilized on optimal therapy and at least 30 days after:
1. any change in guideline-directed medical therapy
2. revascularization and/or implant of Cardiac Resynchronization Therapy device (CRT or CRT-D) or reprogramming of an implanted CRT or CRT-D that results in increased biventricular pacing (from <92% to ≥92%)
2. In the judgment of the HF specialist investigator at the site, the subject has been adequately treated per applicable standards, including for coronary artery disease, left ventricular dysfunction, mitral regurgitation and heart failure (e.g., with cardiac resynchronization therapy, revascularization, and/or optimal medical therapy as appropriate. The Eligibility Committee must also concur that the subject has been adequately treated.
3. New York Heart Association (NYHA) Functional Class II, III or ambulatory IV.
4. The Local Site Heart Team (CT surgeon and HF specialist investigators) and the Central Eligibility Committee concur that surgery will not be offered as a treatment option and that medical therapy is the intended therapy for the subject, even if the subject is randomized to the Control group.
5. The subject has had at least one hospitalization for heart failure in the 12 months prior to subject registration and/or a corrected brain natriuretic peptide (BNP) ≥300 pg/ml or corrected n-Terminal pro- brain natriuretic peptide NT-proBNP ≥1500 pg/ml measured within 90 days prior to subject registration ("corrected" refers to a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m2 in BMI above a reference BMI of 20 kg/m2).
Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and at least 30 days after:
1. any change in guideline-directed medical therapy
2. revascularization and/or implant of Cardiac Resynchronization Therapy device (CRT or CRT-D) or reprogramming of an implanted CRT or CRT-D that results in increased biventricular pacing (from <92% to ≥92%).
6. Left Ventricular Ejection Fraction (LVEF) is ≥20% and ≤50% within 90 days prior to subject registration, assessed by the site using any one of the following methods: echocardiography, contrast left ventriculography, gated blood pool scan or cardiac magnetic resonance imaging (MRI).
7. The primary regurgitant jet is non-commissural, and in the opinion of the MitraClip implanting investigator can be successfully be treated by the MitraClip. If a secondary jet exists, it must be considered clinically insignificant.
8. Creatine Kinase-MB (CK-MB) obtained within prior 14 days < local laboratory Upper Limit of Normal (ULN).
9. Transseptal catheterization and femoral vein access is determined to be feasible by the MitraClip implanting investigator.
10. Age 18 years or older.
11. The subject or the subject's legal representative understands and agrees that should he/she be assigned to the Control group, he/she will be treated with medical therapy and conservative management without surgery and without the MitraClip, either domestically or abroad. If the subject would actively contemplate surgery and/or MitraClip if randomized to Control, he/she should not be registered in this trial.
12. 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.
1. Untreated clinically significant coronary artery disease requiring revascularization.
2. Coronary artery bypass grafting (CABG) within 30 days prior to subject registration.
3. Percutaneous coronary intervention within 30 days prior to subject registration.
4. Tricuspid valve disease requiring surgery.
5. Aortic valve disease requiring surgery.
6. Cerebrovascular accident within 30 days prior to subject registration.
7. Severe symptomatic carotid stenosis (> 70% by ultrasound).
8. Carotid surgery within 30 days prior to subject registration.
9. American College of Cardiology /American Heart Association (ACC/AHA) Stage D heart failure.
10. Presence of any of the following:
- Estimated pulmonary artery systolic pressure (PASP) > 70 mm Hg assessed by site based on echocardiography or right heart catheterization, unless active vasodilator therapy in the cath lab is able to reduce the pulmonary vascular resistance (PVR) to < 3 Wood Units or between 3 and 4.5 Wood Units with v wave less than twice the mean of the pulmonary capillary wedge pressure
- 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
- Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis)
- Hemodynamic instability requiring inotropic support or mechanical heart assistance.
11. Physical evidence of right-sided congestive heart failure with echocardiographic evidence of moderate or severe right ventricular dysfunction.
12. Implant of any Cardiac Resynchronization Therapy (CRT) or Cardiac Resynchronization Therapy with cardioverter-defibrillator (CRT-D) within the last 30days prior to subject registration.
13. Mitral valve orifice area < 4.0 cm2 assessed by site based on a transthoracic echocardiogram (TTE) within 90 days prior to subject registration.
14. Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR by the MitraClip. This evaluation is based on transesophageal echocardiogram (TEE) evaluation of the mitral valve within 180 days prior to subject registration and includes:
- Insufficient mobile leaflet available for grasping with the MitraClip device
- Evidence of calcification in the grasping area
- Presence of a significant cleft in the grasping area
- Lack of both primary and secondary chordal support in the grasping area
- Leaflet mobility length < 1 cm
15. Hemodynamic instability defined as systolic 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.
16. Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
17. Life expectancy < 12 months due to non-cardiac conditions.
18. Modified Rankin Scale ≥ 4 disability.
19. Status 1 heart transplant or prior orthotopic heart transplantation.
20. Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure.
21. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
22. Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated).
23. Active infections requiring current antibiotic therapy.
24. Subjects in whom transesophageal echocardiography (TEE) is contraindicated or high risk.
25. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically.
26. Pregnant or planning pregnancy within next 12 months.
Note: Female patients of childbearing age should be instructed to use safe contraception (e.g. intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release. It is accepted in certain cases to include subjects having a sterilized regular partner or subjects using a double barrier contraceptive method. However, this should be explicitly justified in special circumstances arising from the study design, product characteristics and/or study population.
27. Currently participating in an investigational drug or another device study that has not reached its primary endpoint. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
28. 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.