Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

COAPT Clinical Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Evalve
Sponsor:
Collaborator:
Abbott Vascular
Information provided by (Responsible Party):
Evalve
ClinicalTrials.gov Identifier:
NCT01626079
First received: June 20, 2012
Last updated: December 16, 2014
Last verified: December 2014
  Purpose

The purpose of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial is to confirm the safety and effectiveness of the MitraClip System for the treatment of moderate-to-severe or severe functional mitral regurgitation (FMR) 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. This randomized controlled trial will provide the opportunity to strengthen or add labeling claims regarding safety and clinical benefits of the MitraClip System for symptomatic heart failure patients with moderate-to-severe or severe functional mitral regurgitation.


Condition Intervention Phase
Mitral Regurgitation
Mitral Valve Regurgitation
Device: MitraClip System
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation

Resource links provided by NLM:


Further study details as provided by Evalve:

Primary Outcome Measures:
  • Primary safety endpoint [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Composite of Single Leaflet Device Attachment (SLDA), device embolizations, endocarditis requiring surgery, Echocardiography Core Laboratory confirmed mitral stenosis requiring surgery, LVAD implant, heart transplant, and any device related complications requiring non-elective cardiovascular surgery.

  • Primary effectiveness endpoint [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Recurrent heart failure (HF) hospitalizations


Secondary Outcome Measures:
  • A composite of all-cause death, stroke, MI, or non-elective cardiovascular surgery for device related complications in the Device group [ Time Frame: 30 days post-procedure in the Device group ] [ Designated as safety issue: Yes ]
  • All-cause mortality [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Mitral Regurgitation severity [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in distance walked on the 6 Minute Walk Test (6MWT distance or 6MWD) [ Time Frame: 12 months over baseline ] [ Designated as safety issue: No ]
    The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

  • Change in quality of life (QoL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: 12 months over baseline ] [ Designated as safety issue: No ]
  • Change in Left Ventricular End Diastolic Volume (LVEDV) [ Time Frame: 12 months over baseline ] [ Designated as safety issue: No ]
  • New York Heart Association (NYHA) Functional Class I/II [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA CLASS)

    Class I: Patients with cardiac disease but without resulting limitations of physical activity.

    Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III: Patients with cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.

    Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.


  • Recurrent hospitalizations - all cause [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Hierarchical composite of death and recurrent HF hospitalization hospitalization (analyzed when the last subject completes 12 months of follow-up) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Device or Procedure-Related Adverse Events [ Time Frame: Within and after 30 days of the procedure ] [ Designated as safety issue: Yes ]
    Device or procedure-related adverse events are defined as adverse events that are adjudicated by the Clinical Events Committee as possibly, probably or definitely device and/or procedure-related, regardless of the temporal relationship to the MitraClip procedure. Device or procedure-related adverse events will be broken down into those that occur within 30 days of the procedure and those that occur after 30 days of the procedure. Examples of device-related adverse events are: myocardial perforation, Single Leaflet Device Attachment, embolization of the MitraClip device or MitraClip System components, iatrogenic atrial septal defect, mitral valve stenosis, need for mitral valve replacement instead of repair due at least in part to the MitraClip procedure or the presence of the MitraClip device.

  • Implant Rate [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Defined as the rate of successful delivery and deployment of the MitraClip device(s) with echocardiographic evidence of leaflet approximation and retrieval of the delivery catheter

  • Device Procedure Time [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Defined as the time elapsed from the start of the transseptal procedure to the time the Steerable Guide Catheter is removed

  • Total Procedure Time [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Defined as the time elapsed from the first of any of the following: intravascular catheter placement, anesthesia or sedation, or transesophageal echocardiogram (TEE), to the removal of the last catheter and TEE

  • Device Time [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Defined as the time the Steerable Guide Catheter is placed in the intra-atrial septum until the time the MitraClip Delivery System (CDS) is retracted into the Steerable Guide Catheter

  • Fluoroscopy duration [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Defined as the duration of exposure to fluoroscopy during the MitraClip procedure

  • MR Severity Grade [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • MR Severity Grade [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Effective Regurgitant Orifice Area [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Regurgitant Volume [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Regurgitant Fraction [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Left Ventricle End Diastolic Volume (LVEDV) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Volume (LVESV) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Diastolic Dimension (LVEDD) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Left Ventricular End Systolic Dimension (LVESD) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Right Ventricular Systolic Pressure (RVSP) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Mitral Valve Area [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Mean Mitral Valve Gradient [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Systolic Anterior Motion of the mitral valve (present or absent) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Cardiac Output [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: At discharge (or 30 days if discharge echocardiogram is not available) ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Forward Stroke Volume [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the components of the primary safety composite [ Time Frame: 12 months in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the components of the primary safety composite [ Time Frame: 24 months in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the components of the primary safety composite [ Time Frame: 3 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the components of the primary safety composite [ Time Frame: 4 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the components of the primary safety composite [ Time Frame: 5 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the primary safety composite [ Time Frame: 24 months in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the primary safety composite [ Time Frame: 3 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the primary safety composite [ Time Frame: 4 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from the primary safety composite [ Time Frame: 5 years in Device group ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular mortality [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular mortality [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular mortality [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from HF related hospitalization [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from HF related hospitalization [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from HF related hospitalization [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from HF related hospitalization [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from HF related hospitalization [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular hospitalization [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular hospitalization [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular hospitalization [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular hospitalization [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from cardiovascular hospitalization [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality or HF related hospitalization [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality or HF related hospitalization [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality or HF related hospitalization [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality or HF related hospitalization [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Kaplan-Meier freedom from all-cause mortality or HF related hospitalization [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • NYHA Functional Class [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Six-Minute Walk Test Distance (6MWD) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • 6MWD [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • 6MWD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 6MWD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 6MWD [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Change in 6MWD from baseline [ Time Frame: Between baseline and 30 days ] [ Designated as safety issue: No ]
  • Change in 6MWD from baseline [ Time Frame: Between baseline and 6 months ] [ Designated as safety issue: No ]
  • Change in 6MWD from baseline [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
  • Change in 6MWD from baseline [ Time Frame: Between baseline and 24 months ] [ Designated as safety issue: No ]
  • Kansas City Cardiomyopathy Questionnaire (KCCQ) QoL scores [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • KCCQ QoL scores [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • KCCQ QoL scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • KCCQ QoL scores [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • KCCQ QoL scores [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Change in KCCQ QoL scores from baseline [ Time Frame: Between baseline and 30 days ] [ Designated as safety issue: No ]
  • Change in KCCQ QoL scores from baseline [ Time Frame: Between baseline and 6 months ] [ Designated as safety issue: No ]
  • Change in KCCQ QoL scores from baseline [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
  • Change in KCCQ QoL scores from baseline [ Time Frame: Between baseline and 24 months ] [ Designated as safety issue: No ]
  • SF-36 QoL scores [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • SF-36 QoL scores [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • SF-36 QoL scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • SF-36 QoL scores [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • SF-36 QoL scores [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Change in SF-36 QoL scores from baseline [ Time Frame: Between baseline and 30 days ] [ Designated as safety issue: No ]
  • Change in SF-36 QoL scores from baseline [ Time Frame: Between baseline and 6 months ] [ Designated as safety issue: No ]
  • Change in SF-36 QoL scores from baseline [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
  • Change in SF-36 QoL scores from baseline [ Time Frame: Between baseline and 24 months ] [ Designated as safety issue: No ]
  • Mitral valve surgery (including type of surgery), new use of CRT, new use of single or dual chamber pacemaker, permanent LVAD implant, heart transplant, additional MitraClip device intervention in Device group [ Time Frame: Through 5 years ] [ Designated as safety issue: No ]
  • De novo MitraClip device intervention in Control group [ Time Frame: Through 5 years ] [ Designated as safety issue: No ]
  • Responder analysis for 6MWD [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 24 meters and 50 meters (difference in proportion of responders between Device and Control groups)

  • Responder analysis for 6MWD [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 24 meters and 50 meters (difference in proportion of responders between Device and Control groups)

  • Responder analysis for LVEDV Index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)

  • Responder analysis for LVEDV Index [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)

  • Responder analysis for LVEDV Index [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)

  • Responder analysis for LVEDV Index [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)

  • Responder analysis for LVEDV Index [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 12 ml/m2 (difference in proportion of responders between Device and Control groups)

  • Responder analysis for QoL (KCCQ) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 5 points (difference in proportion of responders between Device and Control groups)

  • Responder analysis for QoL (KCCQ) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Where responder is defined as alive and experiencing an improvement of 5 points (difference in proportion of responders between Device and Control groups)

  • Each subscale for QoL (KCCQ) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    difference in means between Device and Control groups

  • Each subscale for QoL (KCCQ) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    difference in means between Device and Control groups

  • Length of index hospitalization for MitraClip procedure (Device group) [ Time Frame: Before MitraClip procedure on day 0 ] [ Designated as safety issue: No ]
  • Number of hospitalizations and reason for hospitalization (i.e. heart failure, cardiovascular, non-cardiovascular) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    in each of the Device and Control groups

  • Number of hospitalizations and reason for hospitalization (i.e. heart failure, cardiovascular, non-cardiovascular) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    in each of the Device and Control groups

  • Number of days alive and out of hospital [ Time Frame: From the time of randomization to 12 months ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days alive and out of hospital [ Time Frame: From the time of randomization to 24 months ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days alive and out of hospital [ Time Frame: From the time of randomization to 3 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days alive and out of hospital [ Time Frame: From the time of randomization to 4 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days alive and out of hospital [ Time Frame: From the time of randomization to 5 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days hospitalized from the "Treatment" visit [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days hospitalized from the "Treatment" visit [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days hospitalized from the "Treatment" visit [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days hospitalized from the "Treatment" visit [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Number of days hospitalized from the "Treatment" visit [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    difference in medians between Device and Control groups

  • Proportion of alive time in hospital [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Proportion of alive time in hospital [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Proportion of alive time in hospital [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Proportion of alive time in hospital [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Proportion of alive time in hospital [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Proportion of subjects living in the baseline location [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Proportion of subjects living in the baseline location [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Proportion of subjects living in the baseline location [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Proportion of subjects living in the baseline location [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Proportion of subjects living in the baseline location [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Mitral valve replacement rates [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Mitral valve replacement rates [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Mitral valve replacement rates [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Mitral valve replacement rates [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • Mitral valve replacement rates [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    summarized and compared between Device and Control groups

  • New onset of permanent atrial fibrillation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • New onset of permanent atrial fibrillation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • New onset of permanent atrial fibrillation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • New onset of permanent atrial fibrillation [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • New onset of permanent atrial fibrillation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Mitral stenosis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory

  • Mitral stenosis [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory

  • Mitral stenosis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory

  • Mitral stenosis [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory

  • Mitral stenosis [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory

  • Clinically significant atrial septal defect (ASD) that requires intervention [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Clinically significant atrial septal defect (ASD) that requires intervention [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Clinically significant atrial septal defect (ASD) that requires intervention [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Clinically significant atrial septal defect (ASD) that requires intervention [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Clinically significant atrial septal defect (ASD) that requires intervention [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Device-related complications in Device group subjects and Control group subjects who undergo the MitraClip procedure [ Time Frame: Through 5 years ] [ Designated as safety issue: No ]
  • Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP levels) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • BNP or NT-proBNP levels [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • BNP or NT-proBNP levels [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Modified Rankin Scale Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

    0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead


  • Modified Rankin Scale Score [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

    0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead


  • Modified Rankin Scale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

    0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead


  • Modified Rankin Scale Score [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    MODIFIED RANKIN SCALE SCORE DESCRIPTIONS:

    0- No symptoms at all; 1- No significant disability despite symptoms; able to carry out all usual duties and activities; 2- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- Moderate disability; requiring some help, but able to walk without assistance; 4- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5- Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- Dead


  • Major bleeding [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic Research Consortium (BARC) definition

  • Prolonged ventilation [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Defined as pulmonary insufficiency requiring ventilatory support for greater than 48 hours post-catheterization

  • Average dosages of Guideline Directed Medical Therapy (GDMT) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Average dosages of GDMT [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 30 days ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 6 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 24 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 3 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 4 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT and GDMT dosage from baseline [ Time Frame: Between baseline and 5 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 30 days ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 6 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 24 months ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 3 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 4 years ] [ Designated as safety issue: No ]
  • The number and reasons for any changes in GDMT from baseline that result in a greater than 100% increase or greater than 50% decrease in dose [ Time Frame: Between baseline and 5 years ] [ Designated as safety issue: No ]
  • Cardiopulmonary exercise (CPX) testing [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    A substudy endpoint will utilize peak oxygen consumption oxygen uptake (VO2) as a parameter for cardiopulmonary exercise testing on a total of at least 50 and up to 100 subjects.

  • Cardiopulmonary exercise (CPX) testing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A substudy endpoint will utilize peak oxygen consumption oxygen uptake (VO2) as a parameter for cardiopulmonary exercise testing on a total of at least 50 and up to 100 subjects.

  • Cardiopulmonary exercise (CPX) testing: mean changes in peak VO2 [ Time Frame: Between baseline and 12 months ] [ Designated as safety issue: No ]
    Mean changes in peak VO2 (ml/kg/min) will be summarized at 12 months from baseline for the subset of patients who complete a CPX test at baseline and 12 months. A comparison of change from baseline between Device and Control groups will be presented.

  • Health Economic Data [ Time Frame: Through 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 430
Study Start Date: August 2012
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MitraClip System
Percutaneous mitral valve repair using MitraClip System
Device: MitraClip System
Percutaneous mitral valve repair using MitraClip System
Other Names:
  • MitraClip device
  • MitraClip
No Intervention: Control Group
Patients with mitral regurgitation managed non-surgically based on standard hospital clinical practice.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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, 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 including Guideline Directed Medical Therapy (GDMT) and at least 30 days after:

    1. a greater than 100% increase or greater than 50% decrease in dose of GDMT
    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 GDMT. 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 GDMT and at least 30 days after:

    1. a greater than 100% increase or greater than 50% decrease in dose of GDMT
    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).

    Note: The method must provide a quantitative readout (not a visual assessment).

  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.
  13. Left Ventricular End Systolic Dimension (LVESD) is ≤ 70 mm assessed by site based on a transthoracic echocardiographic (TTE) obtained within 90 days prior to subject registration.

Exclusion Criteria:

  1. Chronic Obstructive Pulmonary Disease (COPD) requiring continuous home oxygen therapy or chronic outpatient oral steroid use.
  2. Untreated clinically significant coronary artery disease requiring revascularization.
  3. Coronary artery bypass grafting (CABG) within 30 days prior to subject registration.
  4. Percutaneous coronary intervention within 30 days prior to subject registration.
  5. Transcatheter aortic valve replacement (TAVR) within 30 days prior to subject registration.
  6. Tricuspid valve disease requiring surgery or transcatheter intervention.
  7. Aortic valve disease requiring surgery.
  8. Cerebrovascular accident within 30 days prior to subject registration.
  9. Severe symptomatic carotid stenosis (> 70% by ultrasound).
  10. Carotid surgery or stenting within 30 days prior to subject registration.
  11. American College of Cardiology /American Heart Association (ACC/AHA) Stage D heart failure.
  12. 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.
  13. Physical evidence of right-sided congestive heart failure with echocardiographic evidence of moderate or severe right ventricular dysfunction as assessed by site.
  14. Implant of any Cardiac Resynchronization Therapy (CRT) or Cardiac Resynchronization Therapy with cardioverter-defibrillator (CRT-D) within the last 30days prior to subject registration.
  15. Mitral valve orifice area < 4.0 cm2 assessed by site based on a transthoracic echocardiogram (TTE) within 90 days prior to subject registration.
  16. 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
  17. 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.
  18. Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months.
  19. Life expectancy < 12 months due to non-cardiac conditions.
  20. Modified Rankin Scale ≥ 4 disability.
  21. Status 1 heart transplant or prior orthotopic heart transplantation.
  22. Prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure.
  23. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
  24. Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated).
  25. Active infections requiring current antibiotic therapy.
  26. Subjects in whom transesophageal echocardiography (TEE) is contraindicated or high risk.
  27. Known hypersensitivity or contraindication to procedural medications which cannot be adequately managed medically.
  28. 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.

  29. 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.
  30. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01626079

Contacts
Contact: Denise Mansfield 408-845-0546 denise.mansfield@av.abbott.com
Contact: Robin Eckert 408-845-8170 robin.eckert@av.abbott.com

  Hide Study Locations
Locations
United States, Arizona
Banner Good Samaritan Hospital Recruiting
Phoenix, Arizona, United States, 85006
Contact: Tim Byrne, DO       timothybyrne1@mac.com   
Principal Investigator: Tim Byrne, DO         
United States, California
Scripps Green Hospital Recruiting
La Jolla, California, United States, 92037
Contact: Matthew Price, MD    858-554-9905    price.matthew@scrippshealth.org   
Principal Investigator: Matthew Price, MD         
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Saibal Kar, MD    310-423-3978    karsk@cshs.org   
Principal Investigator: Saibal Kar, MD         
University California Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Jason Rogers, MD    916-734-3764    jason.rogers@ucdmc.ucdavis.edu   
Principal Investigator: Jason Rogers, MD         
Kaiser Permanente Recruiting
San Francisco, California, United States, 94115
Contact: Jacob Mishell, MD    415-833-6016    jacob.mishell@kp.org   
Principal Investigator: Jacob Mishell, MD         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Alan Yeung, MD       ayeung@stanford.edu   
Principal Investigator: Alan Yeung, MD         
Principal Investigator: Craig D Miller, MD         
United States, Colorado
Univ of Colorado Hospital Recruiting
Denver, Colorado, United States, 80045
Contact: Andreas Brieke, MD    303-724-2102    Andreas.brieke@ucdenver.edu   
Principal Investigator: Andreas Brieke, MD         
United States, Connecticut
Yale - New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: John Forrest, MD       john.k.forrest@yale.edu   
Principal Investigator: John Forrest, MD         
United States, District of Columbia
Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Lowell Satler, MD       satlerlowell@gmail.com   
Principal Investigator: Lowell Satler, MD         
United States, Florida
Mount Sinai Hospital Recruiting
Miami, Florida, United States, 33140
Contact: Nirat Beohar, MD    305-674-2754    Nirat.Beohar@msmc.com   
Principal Investigator: Nirat Beohar, MD         
Florida Hospital Recruiting
Orlando, Florida, United States, 32803
Contact: Andy Taussig, MD    321-499-4178    astaussig@aol.com   
Principal Investigator: Andy Taussig, MD         
Sarasota Memorial Hospital Recruiting
Sarasota, Florida, United States, 34239
Contact: Ricardo Yaryura, MD    941-917-2225    Sdobson@intercoastalmedical.com   
Principal Investigator: Ricardo Yaryura, MD         
Tallahassee Memorial Recruiting
Tallahassee, Florida, United States, 32308
Contact: Wayne Batchelor, MD    850-216-0120    wabat@southern-med.com   
Principal Investigator: Wayne Batchelor, MD         
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Vasilis Babaliaros, MD    404-712-0131    vbabali@emory.edu   
Principal Investigator: Vasilis Babaliaros, MD         
Piedmont Hospital Recruiting
Atlanta, Georgia, United States, 30309
Contact: Vivek Rajagopal, MD    404-605-2800    vivek.rajagopal@piedmont.org   
Principal Investigator: Vivek Rajagopal, MD         
St. Joseph's Hospital - Atlanta Recruiting
Atlanta, Georgia, United States, 30342
Contact: Louis Heller, MD    770-962-0399    lhellermd@aol.com   
Principal Investigator: Louis Heller, MD         
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Mark J Ricciardi, MD    312-695-4965    mricciar@nmff.org   
Principal Investigator: Patrick McCarthy, MD         
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Clifford Kavinsky, MD       clifford_j_kavinsky@rush.edu   
Principal Investigator: Clifford Kavinsky, MD         
NorthShore University Health Systems Recruiting
Evanston, Illinois, United States, 60201
Contact: Ted Feldman, MD       tfeldman@tfeldman.org   
Principal Investigator: Ted Feldman, MD         
United States, Indiana
St. Vincent Medical Group Recruiting
Indianapolis, Indiana, United States, 46290
Contact: James Hermiller, MD       jhermill@thecaregroup.com   
Principal Investigator: James Hermiller, MD         
United States, Iowa
Iowa Heart Center Recruiting
Des Moines, Iowa, United States, 50266
Contact: Magdi Ghali, MD    515-633-3600    mghali@iowaheart.com   
Principal Investigator: Magdi Ghali, MD         
United States, Kansas
KU Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Mark Wiley, MD       mawiley@mac.md   
Principal Investigator: Mark Wiley, MD         
United States, Kentucky
St. Joseph's Hospital - Lexington, KY Recruiting
Lexington, Kentucky, United States, 40504
Contact: Robert Salley, MD    859-977-0898    robertsalley@catholichealth.net   
Principal Investigator: Robert Salley, MD         
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Steven Jenkins, MD       sjenkins@ochsner.org   
Principal Investigator: Steven Jenkins, MD         
United States, Maine
Maine Medical Center Recruiting
Portland, Maine, United States, 04102
Contact: Mirle Kellet, Jr, MD    207-662-2414    kellem@mmc.org   
Principal Investigator: Mirle Kellet, Jr, MD         
United States, Maryland
University of Maryland Baltimore Recruiting
Baltimore, Maryland, United States, 21201
Contact: Mark Vesley, MD    410-328-5842    mvesely@medicine.umaryland.edu   
Contact: James Gammie, MD       jsgammiemd@gmail.com   
Principal Investigator: Mark Vesley, MD         
Principal Investigator: James Gammie, MD         
United States, Massachusetts
Brigham Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Andy Eisenhauer, MD    857-307-1991    AEISENHAUER@PARTNERS.ORG   
Principal Investigator: Andy Eisenhauer, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Igor Palacios, MD    617-726-8424    ipalacios@partners.org   
Principal Investigator: Igor Palacios, MD         
United States, Michigan
University of Michigan Hospitals Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Steven Bolling, MD       sbolling@med.umich.edu   
Principal Investigator: Steven Bolling, MD         
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Adam Greenbaum, M.D    313-916-3875    AGREENB1@hfhs.org   
Principal Investigator: Adam Greenbaum, M.D         
William Beaumont Hospital Recruiting
Royal Oak, Michigan, United States, 48073-6796
Contact: George Hanzel, MD    248-898-5242    ghanzel@beaumont.edu   
Principal Investigator: George Hanzel, MD         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Wesley Pedersen, MD    612-863-3925    wesley.pedersen@allina.com   
Principal Investigator: Wesley Pedersen, MD         
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Charanjit Rihal, MD    507-255-2440    rihal@mayo.edu   
Principal Investigator: Charanjit Rihal, MD         
United States, Missouri
St. Luke's Mid America Recruiting
Kansas City, Missouri, United States, 64111
Contact: Kenneth Huber, MD       khuber@saint-lukes.org   
Principal Investigator: Kenneth Huber, MD         
Washington University Medical Center Recruiting
St. Louis, Missouri, United States, 63110
Contact: John Lasala, MD, PhD    314-362-3729    jlasala@dom.wustl.edu   
Principal Investigator: John Lasala, MD, PhD         
United States, Montana
St. Patrick Hospital Recruiting
Missoula, Montana, United States, 59802
Contact: Mark Sanz, MD    406-329-5615    msanz@ihimontana.org   
Contact: Tod J Maddux, MD       jtmaddux@ihimontana.org   
Principal Investigator: Mark Sanz, MD         
Principal Investigator: Tod J Maddux, MD         
United States, Nebraska
Nebraska Heart Institute Recruiting
Lincoln, Nebraska, United States, 68526
Contact: Omar Nass, MD       onass@neheart.com   
Principal Investigator: Omar Nass, MD         
United States, New Jersey
Cooper Research Institute Recruiting
Camden, New Jersey, United States, 08103
Contact: Janah Aji, MD       aji-janah@cooperhealth.edu   
Principal Investigator: Janah Aji, MD         
Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07960
Contact: Robert Kipperman, MD    973-467-0005    rkipperman@okheart.com   
Principal Investigator: Robert Kipperman, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: William Gray, MD    212-305-7060    wg2131@mail.cumc.columbia.edu   
Principal Investigator: William Gray, MD         
Mount Sinai Hospital - NY Recruiting
New York, New York, United States, 10029
Contact: Samin Sharma, MD    212-427-1540    samin.sharma@mountsinai.org   
Contact: David Adams, MD       david.adams@mountsinai.org   
Principal Investigator: Samin Sharma, MD         
Principal Investigator: David Adams, MD         
NY Presbyterian Hospital Recruiting
New York, New York, United States, 10065
Contact: Chiu S Wong, MD       scwong@med.cornell.edu   
Principal Investigator: Chiu S Wong, MD         
NYU Medical Center Recruiting
New York, New York, United States, 10016
Contact: James Slater, MD    212-263-5656    james.slater@nyumc.org   
Principal Investigator: James Slater, MD         
St. Francis Hospital Recruiting
Roslyn, New York, United States, 11576
Contact: Andrew D Berke, MD       aberke.md@gmail.com   
Principal Investigator: Andrew D Berke, MD         
United States, North Carolina
Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Michael J Rinaldi, MD    704-355-4794    Michael.Rinaldi@carolinashealthcare.org   
Principal Investigator: Michael J Rinaldi, MD         
Duke University Hospital Recruiting
Durham, North Carolina, United States, 27710
Contact: Andrew Wang, MD    919-681-6197    a.wang@duke.edu   
Principal Investigator: Andrew Wang, MD         
East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Contact: Ramesh Daggubati, MD       daggubatir@ecu.edu   
Principal Investigator: Ramesh Daggubati, MD         
United States, Ohio
Lindner Center at Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Ian Sarembock, MD    513-585-1777    sarembock@ohioheart.org   
Principal Investigator: Ian Sarembock, MD         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Samir Kapadia, MD    216-444-6697    kapadis@ccf.org   
Principal Investigator: Samir Kapadia, MD         
Ohio Health Research Institute/Riverside Methodist Hospital Recruiting
Columbus, Ohio, United States, 43214-3907
Contact: Steven Yakubov, MD    614-566-1250    steven.yakubov@gmail.com   
Principal Investigator: Steven Yakubov, MD         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Juan Crestanello, MD    614-293-8866    juan.crestanello@osumc.edu   
Principal Investigator: Juan Crestanello, MD         
United States, Oklahoma
Oklahoma Heart Hospital Recruiting
Oklahoma City, Oklahoma, United States, 73120
Contact: Mohammad Ghani, MD    405-608-3800    mghani@ohkeart.com   
Contact: John Williams, MD       jwilliams@okheart.com   
Principal Investigator: Mohammad Ghani, MD         
Principal Investigator: John Williams, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Saurabh Gupta, MD       guptasa@ohsu.edu   
Principal Investigator: Saurabh Gupta, MD         
Providence St. Vincent Medical Center Recruiting
Portland, Oregon, United States, 97225
Contact: Ethan Korngold, MD    503-216-0900    Ethan.Korngold@providence.org   
Principal Investigator: Ethan Korngold, MD         
United States, Pennsylvania
Hospital of University Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Howard C Herrmann, MD    215-662-2180    howard.herrmann@uphs.upenn.edu   
Principal Investigator: Howard C Herrmann, MD         
Temple University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Howard Cohen, MD    215-707-2230    howard.cohen@tuhs.temple.edu   
Principal Investigator: Howard Cohen, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Anson Jay C Smith, M.D.    412-647-8117    smithaj@upmc.edu   
Principal Investigator: Anson Jay C Smith, M.D.         
Pinnacle Health at Harrisburg Hospital Recruiting
Wormleysburg, Pennsylvania, United States, 17043
Contact: Brijeshwar Maini, MD    717-731-0101    bmaini@pinnaclehealth.org   
Principal Investigator: Brijeshwar Maini, MD         
United States, Tennessee
St. Thomas Hospital Recruiting
Nashville, Tennessee, United States, 37205
Contact: Evelio Rodriguez, MD    615-222-5500    evelio.rodriguez@stthomas.org   
Principal Investigator: Evelio Rodriguez, MD         
Vanderbilt University Hospital Recruiting
Nashville, Tennessee, United States, 37232-7235
Contact: Joseph Fredi, MD       joseph.fredi@vanderbilt.edu   
Principal Investigator: Joseph Fredi, MD         
United States, Texas
Seton Heart Institute Recruiting
Austin, Texas, United States, 78705
Contact: Osvaldo S Gigliotti, MD       OSGigliotti@seton.org   
Principal Investigator: Osvaldo S Gigliotti, MD         
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75204
Contact: Paul Grayburn, MD       paulgr@baylorhealth.edu   
Contact: Michael Mack, MD    214-820-7358    michael.mack@baylorhealth.edu   
Principal Investigator: Paul Grayburn, MD         
Principal Investigator: Michael Mack, MD         
Memorial Hermann Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Richard Smalling, MD, PhD    713-500-6559    richard.w.smalling@uth.tmc.edu   
Principal Investigator: Richard Smalling, MD, PhD         
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Neal Kleiman, MD    713-441-1100    nkleiman@tmhs.org   
Principal Investigator: Neal Kleiman, MD         
University of Texas Health Science Center at SA Recruiting
San Antonio, Texas, United States, 78229-3900
Contact: Steven R Bailey, MD       baileys@uthscsa.edu   
Principal Investigator: Steven R Bailey, MD         
United States, Utah
Intermountain Medical Center Recruiting
Murray, Utah, United States, 84107
Contact: Brian Whisenant, MD    801-507-4700    brian.whisenant@imail.org   
Principal Investigator: Brian Whisenant, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Scott D Lim, MD    434-982-1058    sl9pc@virginia.edu   
Principal Investigator: Scott D Lim, MD         
United States, Washington
Swedish Medical Center Recruiting
Seattle, Washington, United States, 98122
Contact: Paul Huang, MD       Paul.Huang@swedish.org   
Principal Investigator: Paul Huang, MD         
United States, Wisconsin
Aurora St. Luke's Medical Center Recruiting
Milwaukee, Wisconsin, United States, 53215
Contact: Tanvir Bajwa, MD    414-219-7666    doris.payne@aurora.org   
Principal Investigator: Tanvir Bajwa, MD         
Sponsors and Collaborators
Evalve
Abbott Vascular
Investigators
Principal Investigator: Michael Mack, MD Baylor Health Care System
Principal Investigator: Gregg Stone, MD Columbia University Medical Center / New York-Presbyterian Hospital
Principal Investigator: William T Abraham, MD The Ohio State University Heart Center
Principal Investigator: JoAnn Lindenfeld, MD University of Colorado, Denver
  More Information

Additional Information:
No publications provided

Responsible Party: Evalve
ClinicalTrials.gov Identifier: NCT01626079     History of Changes
Other Study ID Numbers: 11-512
Study First Received: June 20, 2012
Last Updated: December 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Evalve:
Functional Mitral Regurgitation
Mitral Valve Regurgitation
Symptomatic Heart Failure
Functional MR
MitraClip
Mitral Valve Insufficiency

Additional relevant MeSH terms:
Mitral Valve Insufficiency
Cardiovascular Diseases
Heart Diseases
Heart Valve Diseases

ClinicalTrials.gov processed this record on February 27, 2015