A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation

Randomised Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients With Clinically Significant Functional Mitral Regurgitation

To study the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with New York Heart Association (NYHA) Functional Class II to Class IV chronic heart failure.

The trial is designed to provide additional evidence regarding appropriate recommendations for use of the MitraClip System for patients with chronic heart failure and clinically significant functional mitral regurgitation. Additionally, the trial will collect evidence regarding health economics of the MitraClip System for use in this patient population.

Key Inclusion Criteria:

• Clinically significant functional mitral regurgitation (moderate-to-severe or severe MR) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
• Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization.
• Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 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 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
• Ambulatory patient with symptomatic congestive heart failure (CHF) in NYHA functional class II to IV (despite optimal standard of care therapy as assessed within 30 days preceding randomization) and with LVEF 20% to 50%. Note: LVEF needs to be determined by one of the following methods: transthoracic echocardiography (TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance) within 90 days prior to randomization
• Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness

Key Exclusion Criteria:

• Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).
• Status 1 heart transplant or prior orthotropic heart transplantation.
• Introduction of a new heart failure drug class within the last 2 weeks prior to randomization.
• Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Note:Acute coronary syndrome (ACS) is defined as an ACS that requires an intervention. Increased troponin without acute symptoms and chest pain is not defined as ACS.
• Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.
• Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD)) within 90 day 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 the preferred therapeutic option for the subject
• Renal replacement therapy
• 6-Minute Walk Test (6MWT) distance > 475 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