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Pivotal Study of a Percutaneous Mitral Valve Repair System (EVERESTIIRCT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Evalve
ClinicalTrials.gov Identifier:
NCT00209274
First received: September 13, 2005
Last updated: August 2, 2017
Last verified: June 2017
  Purpose
EVEREST II Randomized Controlled Trial (RCT) is a prospective, multi-center, randomized study of the MitraClip® System in the treatment of mitral valve regurgitation, randomizing patients to MitraClip or mitral valve surgery. The EVEREST II High Risk Registry (HRR) study is a prospective multi-center study of the MitraClip System for the treatment of mitral valve regurgitation in high surgical risk patients. Enrollment in the RCT and HRR is closed. A continued access prospective, multi-center study (REALISM) of the MitraClip System in a surgical population (non-high risk arm) and a high surgical risk population (high risk arm) is ongoing. Enrollment in the non-high risk arm of REALISM is closed. Enrollment in the high risk arm of REALISM is ongoing. Patients enrolled in EVEREST II undergo 30-day, 6-month, 12-month, 18-month and 24-month clinical and echocardiographic follow-up, and then annually for 5 years.

Condition Intervention
Mitral Valve Insufficiency Mitral Valve Regurgitation Mitral Valve Incompetence Mitral Regurgitation Mitral Insufficiency Device: Percutaneous mitral valve repair using MitraClip implant Procedure: Mitral valve repair or replacement surgery

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pivotal Study: A Study of the Evalve Cardiovascular Valve Repair System - Endovascular Valve Edge-to-Edge REpair STudy (EVERESTIIRCT)

Further study details as provided by Evalve:

Primary Outcome Measures:
  • Number of Participants With Major Adverse Events (MAE) [ Time Frame: 30 days ]
    Defined as a combined clinical endpoint of death, myocardial infarction, reoperation for failed surgical repair or replacement, nonelective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, ventilation for greater than 48 hours, gastrointestinal (GI) complication requiring surgery, new onset of permanent atrial fibrillation, septicemia, and transfusion of 2 or more units of blood.

  • Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR). [ Time Frame: 12 months ]

Secondary Outcome Measures:
  • Number of Participants With Clip Implant Rate [ Time Frame: Day 0 ]
    Defined as the rate of successful implantation of MitraClip(s).

  • Number of Participants With Mitral Valve Stenosis [ Time Frame: 30 days ]
    Defined as a mitral valve planimetered orifice area of less than 1.5 cm^2 as measured by echocardiography.

  • Number of Participants With Acute Surgical Success [ Time Frame: 30 Days ]
    Defined as successful mitral valve repair or replacement surgery.

  • Number of Participants With Acute Procedural Success [ Time Frame: 30 Days ]
    Defined as successful MitraClip implantation with resulting MR of 2+ or less.

  • Number of Participants With Procedural Success [ Time Frame: 30 days ]
    Defined as successful implant of the Clip(s) with resulting MR severity ≤ 2 at discharge or 1 grade MR reduction at discharge accompanied by 1 level NYHA reduction.

  • Regurgitant Volume [ Time Frame: 30 Days ]
    Regurgitant volume as determined by the core echo laboratory. In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

  • Regurgitant Fraction [ Time Frame: 30 Days ]
    Regurgitant fraction as determined by the core echo laboratory. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

  • Number of Participants With Mitral Valve Repair Success. [ Time Frame: 12 months ]
    Defined as freedom from mitral valve replacement surgery for Valve Dysfunction, death, re-operation, and MR > 2+ at 12 months.

  • Number of Participants With Incidence of Hospital Readmissions for Congestive Heart Failure (CHF). [ Time Frame: 30 days ]
  • Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation. [ Time Frame: 12 months ]
  • Number of Participants With Mitral Valve Stenosis [ Time Frame: 12 months ]
    Defined as a mitral valve planimetered orifice area of less than 1.5 cm^2 as measured by echocardiography.

  • Short Form (SF)-36 Quality of Life Questionnaire. [ Time Frame: 30 days ]

    The SF-36 is a multidimensional, patient-reported survey containing 36 questions on a 0-100 scale measuring physical (Physical Component Score PCS) & mental health status (Mental Component Score MCS) in relation to 8 health concepts: physical functioning, role limitations due to physical or emotional health, bodily pain, general health perceptions, vitality, social functioning, & general mental health. Responses to each of the SF-36 items are scored and expressed as a score on a 0-100 scale (0% in a domain represents the poorest possible QOL&100% indicates full QOL).Higher scores represent better self-perceived health.

    The physical & mental functions were assessed by the Physical Component Summary (PCS) score & Mental Component Summary (MCS) score. Normal PCS and MCS scores vary depending on the demographics of the population studied. The PCS&MCS norms for 65-75 year old are 44 & 52, respectively while the norms for CHF population are 31 & 46, respectively.


  • Short Form (SF)-36 Quality of Life Questionnaire. [ Time Frame: 12 months ]

    The SF-36 is a multidimensional, patient-reported survey containing 36 questions on a 0-100 scale measuring physical (Physical Component Score PCS) & mental health status (Mental Component Score MCS) in relation to 8 health concepts: physical functioning, role limitations due to physical or emotional health, bodily pain, general health perceptions, vitality, social functioning, & general mental health. Responses to each of the SF-36 items are scored and expressed as a score on a 0-100 scale (0% in a domain represents the poorest possible QOL&100% indicates full QOL).Higher scores represent better self-perceived health.

    The physical & mental functions were assessed by the Physical Component Summary (PCS) score & Mental Component Summary (MCS) score. Normal PCS and MCS scores vary depending on the demographics of the population studied. The PCS&MCS norms for 65-75 year old are 44 & 52, respectively while the norms for CHF population are 31 & 46, respectively.


  • Number of Participants With Durability of the MitraClip Device and Surgery. [ Time Frame: 12 months ]

    Device group: Freedom from death, surgery for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.

    Control group: Freedom from death, re-operation for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.


  • Regurgitant Volume [ Time Frame: 12 months ]
    Regurgitant volume as determined by the core echo laboratory.

  • Regurgitant Fraction [ Time Frame: 12 months ]
    Regurgitant fraction as determined by the core echo laboratory. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

  • Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR). [ Time Frame: 24 months ]
  • Number of Participants With Freedom From Mitral Valve Surgery/Re-operation [ Time Frame: 12 months ]
    Durability estimates: Freedom from Mitral Valve Surgery/Re-operation

  • Number of Participants With Durability of the MitraClip Device and Surgery. [ Time Frame: 12-18 months ]

    Device group: Freedom from death, surgery for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.

    Control group: Freedom from death, re-operation for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.


  • Number of Participants With Procedural Freedom From MAE. [ Time Frame: Day 0 ]
  • Number of Participants With Freedom From Death, Mitral Valve Surgery/Re-operation and MR > 2+ [ Time Frame: 12 months ]
    Durability estimates: Freedom from Death, Mitral Valve Surgery/Re-operation and MR > 2+

  • Number of Participants With Freedom From Death and Mitral Valve Surgery/Re-operation [ Time Frame: 12 months ]
    Durability estimates: Freedom from Death and Mitral Valve Surgery/Re-operation

  • Number of Participants With Mitral Valve Stenosis [ Time Frame: 24 months ]
    Defined as a mitral valve planimetered orifice area of less than 1.5 cm^2 as measured by echocardiography.

  • Number of Participants With MitraClip Device Embolization/Single Leaflet Device Attachment [ Time Frame: 12 months ]
    Device Embolization is defined as the complete detachment of the MitraClip Device from one or both mitral leaflets. Single leaflet device attachment (SLDA) is defined as attachment of one mitral valve leaflet to the MitraClip device. The control group did not receive the MitraClip device.

  • Number of Participants With Mitral Valve Repair Success. [ Time Frame: 24 months ]
    Defined as freedom from mitral valve replacement surgery for Valve Dysfunction, death, re-operation, and MR > 2+ at 12 months.

  • Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation. [ Time Frame: 24 months ]
  • Regurgitant Fraction [ Time Frame: 24 months ]
    Regurgitant fraction as determined by the core echo laboratory. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

  • Regurgitant Volume [ Time Frame: 24 months ]
    Regurgitant volume as determined by the core echo laboratory.

  • Number of Participants With Freedom From Death and Mitral Valve Surgery/Re-operation [ Time Frame: 24 months ]
    Durability estimates: Freedom from Death and Mitral Valve Surgery/Re-operation

  • Number of Participants With Durability of the MitraClip Device and Surgery. [ Time Frame: 18-24 months ]

    Device group: Freedom from death, surgery for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.

    Control group: Freedom from death, re-operation for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.


  • Number of Participants With Durability of the MitraClip Device and Surgery. [ Time Frame: 24 months-3 year ]

    Device group: Freedom from death, surgery for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.

    Control group: Freedom from death, re-operation for mitral valve dysfunction and MR > 2+ at the end of each follow-up interval.


  • Number of Participants With Freedom From Mitral Valve Surgery/Re-operation [ Time Frame: 24 months ]
    Durability estimates: Freedom from Mitral Valve Surgery/Re-operation

  • Number of Participants With Freedom From Death, Mitral Valve Surgery/Re-operation and MR > 2+ [ Time Frame: 3 years ]
    Durability estimates: Freedom from Death, Mitral Valve Surgery/Re-operation and MR > 2+

  • Number of Participants With Freedom From Death, Mitral Valve Surgery/Re-operation and MR > 2+ [ Time Frame: 24 months ]
    Durability estimates: Freedom from Death, Mitral Valve Surgery/Re-operation and MR > 2+

  • Number of Participants With Freedom From Mitral Valve Surgery/Re-operation [ Time Frame: 3 years ]
    Durability estimates: Freedom from Mitral Valve Surgery/Re-operation

  • Number of Participants With Freedom From Death and Mitral Valve Surgery/Re-operation [ Time Frame: 3 years ]
    Durability estimates: Freedom from Death and Mitral Valve Surgery/Re-operation

  • Number of Participants With Mitral Valve Stenosis [ Time Frame: 3 years ]
    Defined as a mitral valve (MV) planimetered orifice area of less than 1.5 cm^2 as measured by echocardiography. A "confirmed" case of MV stenosis is defined as Echocardiography Core Lab (ECL) measured mitral valve orifice area < 1.5 cm^2. A "conservative" case of MV stenosis is defined as stenosis suspected by the site, based on hemodynamic measurements or clinical symptoms.

  • Number of Participants With Mitral Valve Stenosis [ Time Frame: 4 years ]
    Defined as a mitral valve (MV) planimetered orifice area of less than 1.5 cm^2 as measured by echocardiography. A "confirmed" case of MV stenosis is defined as Echocardiography Core Lab (ECL) measured mitral valve orifice area < 1.5 cm^2. A "conservative" case of MV stenosis is defined as stenosis suspected by the site, based on hemodynamic measurements or clinical symptoms.

  • Number of Participants With MitraClip Device Embolization/Single Leaflet Device Attachment [ Time Frame: 12 months to 4 years ]
    Device Embolization is defined as the complete detachment of the MitraClip Device from one or both mitral leaflets. Single leaflet device attachment (SLDA) is defined as attachment of one mitral valve leaflet to the MitraClip device. The control group did not receive the MitraClip device

  • Number of Participants With MitraClip Device Embolization/Single Leaflet Device Attachment [ Time Frame: 12 months to 3 years ]
    Device Embolization is defined as the complete detachment of the MitraClip Device from one or both mitral leaflets. Single leaflet device attachment (SLDA) is defined as attachment of one mitral valve leaflet to the MitraClip device. The control group did not receive the MitraClip device

  • Freedom From All-Cause Mortality [ Time Frame: 12 months ]
  • Freedom From All-Cause Mortality [ Time Frame: 24 months ]
  • Freedom From All-Cause Mortality [ Time Frame: 3 years ]
  • Freedom From All-Cause Mortality [ Time Frame: 4 years ]
  • Number of Participants With MR Severity [ Time Frame: 30 days ]

    MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe.

    "Discharge" refers to each individual patient's date of hospital discharge. The discharge date varies for each patient, but in general, discharge occurs before 30-days follow-up. A 30-day echocardiogram will be used if the discharge echocardiogram is unavailable or otherwise uninterpretable.


  • Number of Participants With MR Severity [ Time Frame: 12 months ]
    MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe

  • Number of Participants With MR Severity [ Time Frame: 24 months ]
    MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe

  • Number of Participants With MR Severity [ Time Frame: 3 years ]
    MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe

  • Number of Participants With MR Severity [ Time Frame: 4 years ]
    MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe

  • Left Ventricular Status- LVEDV, LVESV [ Time Frame: 30 days ]
    Left Ventricular Status is defined a including Left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), as determined by the core echo laboratory at 30 days or hospital discharge, whichever is longer.

  • Left Ventricular Status- LVEDV, LVESV [ Time Frame: 12 months ]
    Left Ventricular Status is defined as including LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV),as determined by the core echo laboratory at 12 months.

  • Left Ventricular Status- LVEDV, LVESV [ Time Frame: 24 months ]
    Left Ventricular Status is defined as including LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), as determined by the core echo laboratory at 24 months.

  • Left Ventricular Status- LVEDV, LVESV [ Time Frame: 3 years ]
    Left Ventricular Status is defined as including LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), as determined by the core echo laboratory at 24 months.

  • Left Ventricular Status- LVEDV, LVESV [ Time Frame: 4 years ]
    Left Ventricular Status is defined as including LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), as determined by the core echo laboratory at 24 months.

  • Left Ventricular Status- LVEF [ Time Frame: 30 days ]
    LVEF as determined by the core echo laboratory at 30 days or hospital discharge, whichever is longer.

  • Left Ventricular Status- LVEF [ Time Frame: 12 months ]
    LVEF as determined by the core echo laboratory.

  • Left Ventricular Status- LVEF [ Time Frame: 24 months ]
    LVEF as determined by the core echo laboratory.

  • Left Ventricular Status- LVEF [ Time Frame: 3 years ]
    LVEF as determined by the core echo laboratory.

  • Left Ventricular Status- LVEF [ Time Frame: 4 years ]
    LVEF as determined by the core echo laboratory.

  • Number of Participants With Endocarditis. [ Time Frame: 30 days ]
    Defined as a diagnosis of endocarditis based on the Duke criteria.From The American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Patients with Valvular Heart Disease, Journal of the American College of Cardiology (JACC), Vol 32, No.5, November 1, 1998: pg1541, Table 21.

  • Left Ventricular Internal Dimension Systole (LVIDs) [ Time Frame: 30 days ]
    Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Systole (LVIDs) [ Time Frame: 12 months ]
    Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Systole (LVIDs) [ Time Frame: 2 years ]
    Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Systole (LVIDs) [ Time Frame: 3 years ]
    Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Systole (LVIDs) [ Time Frame: 4 years ]
    Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Diastole (LVIDd) [ Time Frame: 30 days ]
    Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory.

  • Left Ventricular Internal Dimension Diastole (LVIDd) [ Time Frame: 12 months ]
    Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory at 12 months.

  • Left Ventricular Internal Dimension Diastole (LVIDd) [ Time Frame: 24 months ]
    Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory at 24 months.

  • Left Ventricular Internal Dimension Diastole (LVIDd) [ Time Frame: 3 years ]
    Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory at 24 months.

  • Left Ventricular Internal Dimension Diastole (LVIDd) [ Time Frame: 4 years ]
    Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory at 24 months.

  • Number of Participants With Non-cerebral Thromboembolism. [ Time Frame: 30 days ]
    Defined as any thrombus or thromboembolism in the vasculature (excluding central nervous system events) or on the investigational device or any commercially available implant used during surgery confirmed by standard clinical and laboratory testing and which requires treatment.

  • Post-procedure Length of Hospital Stay [ Time Frame: 30 Days ]
  • Number of Participants With Hemolysis [ Time Frame: 30 days ]

    Defined as new onset of anemia associated with laboratory evidence of red cell destruction. Diagnosed when plasma free hemoglobin is greater than 40 mg/dL on repeat measures within 24 hours or on one measure if intervention is initiated based on other clinical symptoms. Reported as major or minor as defined below:

    Major: Requires intervention with red blood cell transfusion or other hematocrit increasing measures in the absence of other obvious bleeding.

    Minor: Does not require intervention.


  • Number of Participants With Major Bleeding Complications. [ Time Frame: 30 days ]
    Major Bleeding Complications defined as procedure related bleeding that requires a transfusion of ≥2 units of blood products and/or surgical intervention at 30 days or hospital discharge, whichever is longer.

  • Number of Participants With Thrombosis. [ Time Frame: 30 days ]
    Defined as evidence of the formation of an independently moving thrombus on any part of the MitraClip or any commercially available implant used during surgery by echocardiography or fluoroscopy.

  • Number of Participants With Clinically Significant Atrial Septal Defect (ASD). [ Time Frame: 30 days ]
    Defined as a significant residual atrial septal opening. Reported as clinically significant if intervention is performed for the primary purpose of repairing the ASD. If cardiac surgery is indicated for reasons other than residual ASD (e.g., residual MR) and the ASD is repaired at the same time, this does not meet the definition of clinically significant ASD.

  • Number of Participants With Non-cerebral Thromboembolism. [ Time Frame: 12 months ]
    Defined as any thrombus or thromboembolism in the vasculature (excluding central nervous system events) or on the investigational device or any commercially available implant used during surgery confirmed by standard clinical and laboratory testing and which requires treatment.

  • Number of Participants With Major Adverse Events (MAE) [ Time Frame: 12 months. ]
  • Number of Participants With Major Vascular Complications [ Time Frame: 12 months ]

    Vascular Complications defined as the occurrence of any of the following resulting through 30 days or hospital discharge, whichever is longer:

    • Hematoma at access site >6 cm;
    • Retroperitoneal hematoma;
    • Arteriovenous (AV) fistula;
    • Symptomatic peripheral ischemia / nerve injury or the clinical signs or symptoms lasting >48 hours;
    • Vascular Surgical Repair at catheter access sites;
    • Pulmonary embolism;
    • Ipsilateral deep vein thrombus; or
    • Access site-related infection requiring intravenous antibiotics and/or extended hospitalization.

  • Number of Participants With Major Vascular Complications [ Time Frame: 30 days ]

    Vascular Complications defined as the occurrence of any of the following resulting through 30 days or hospital discharge, whichever is longer:

    • Hematoma at access site >6 cm;
    • Retroperitoneal hematoma;
    • Arteriovenous (AV) fistula;
    • Symptomatic peripheral ischemia / nerve injury or the clinical signs or symptoms lasting >48 hours;
    • Vascular Surgical Repair at catheter access sites;
    • Pulmonary embolism;
    • Ipsilateral deep vein thrombus; or
    • Access site-related infection requiring intravenous antibiotics and/or extended hospitalization.

  • Number of Participants With Major Bleeding Complications. [ Time Frame: 12 months ]
    Major Bleeding Complications defined as procedure related bleeding that requires a transfusion of ≥2 units of blood products and/or surgical intervention at 12 months.

  • Post-procedure Intensive Care Unit (ICU) / Critical Care Unit (CCU) Duration [ Time Frame: 30 Days ]
  • Number of Participants With MAE in Patients Over 75 Years of Age. [ Time Frame: 12 months ]
  • Number of Participants With Hemolysis [ Time Frame: 12 months ]

    Defined as new onset of anemia associated with laboratory evidence of red cell destruction. Diagnosed when plasma free hemoglobin is greater than 40 mg/dL on repeat measures within 24 hours or on one measure if intervention is initiated based on other clinical symptoms. Reported as major or minor as defined below:

    Major: Requires intervention with red blood cell transfusion or other hematocrit increasing measures in the absence of other obvious bleeding.

    Minor: Does not require intervention.


  • Number of Participants With Thrombosis. [ Time Frame: 12 months ]
    Defined as evidence of the formation of an independently moving thrombus on any part of the MitraClip or any commercially available implant used during surgery by echocardiography or fluoroscopy.

  • Number of Participants With Endocarditis. [ Time Frame: 12 months ]
    Defined as a diagnosis of endocarditis based on the Duke criteria. From The American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Patients with Valvular Heart Disease, Journal of the American College of Cardiology (JACC), Vol 32, No.5, November 1, 1998: pg1541, Table 21.

  • Number of Participants With Clinically Significant Atrial Septal Defect (ASD) [ Time Frame: 12 months ]
    Defined as a significant residual atrial septal opening. Reported as clinically significant if intervention is performed for the primary purpose of repairing the ASD. If cardiac surgery is indicated for reasons other than residual ASD (e.g., residual MR) and the ASD is repaired at the same time, this does not meet the definition of clinically significant ASD.

  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: Baseline ]

    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. They 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.


  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: 30 days ]
    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. They 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.

  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: 12 months ]

    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. They 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.


  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: 24 months ]

    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. They 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.


  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: 3 years ]

    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. They 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.


  • Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease. [ Time Frame: 4 years ]

    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. They 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.


  • New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV [ Time Frame: 30 days ]

    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. They 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.


  • New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV [ Time Frame: 12 months ]

    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. They 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.


  • New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV [ Time Frame: 2 years ]

    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. They 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.


  • New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV [ Time Frame: 3 years ]

    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. They 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.


  • New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV [ Time Frame: 4 years ]

    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. They 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.


  • Number of Participants With Procedural Freedom From In-hospital MAE [ Time Frame: Day 30 ]
  • Number of Participants With MAEa Surgery After Device and First Time Surgery Control [ Time Frame: 30 days ]
  • Number of Participants With MAE in Patients Over 75 Years of Age. [ Time Frame: 30 days ]
  • Number of Participants With Dysrhythmia [ Time Frame: 30 days ]
  • Number of Participants With Dysrhythmia [ Time Frame: 12 months ]
  • Number of Participants With Hospital Re-admissions [ Time Frame: 30 days ]
    Defined as re-admission to the hospital for any reason. The endpoint was intended to capture each time a patient was re-admitted to the hospital for any reason and was to be reported as a rate through 30 days and 12 months for both the Device and Control groups.

  • Number of Participants With New Coumadin (Warfarin) Usage [ Time Frame: 30 days ]
  • Number of Participants With New Coumadin (Warfarin) Usage [ Time Frame: 12 months ]
  • Cardiac Output [ Time Frame: 30 days ]
    Cardiac output as measured by core lab echocardiography.

  • Cardiac Index [ Time Frame: 30 days ]
    Defined as cardiac index (cardiac output divided by body surface area) as measured by core lab echocardiography.

  • Number of Participants With Incidence of Discharge to a Nursing Home or Skilled Nursing Facility/Hospital [ Time Frame: 30 Days ]
  • Mitral Valve Area by Planimetry Index [ Time Frame: 30 Days ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Mitral Valve Area by Planimetry [ Time Frame: 30 Days ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Transvalvular Mitral Valve Gradient [ Time Frame: Discharge (≤ 14 days following index procedure] ]
    Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: 30 days ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time Index [ Time Frame: 30 Days ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Number of Participants With Incidence of Mitral Valve Replacement [ Time Frame: 12 months ]
  • Cardiac Output [ Time Frame: 12 months ]
    Cardiac output as measured by core lab echocardiography.

  • Cardiac Index (CI) [ Time Frame: 12 months ]
    Defined as cardiac output divided by body surface area as measured by core lab echocardiography. CI is a normalization of cardiac output to take into account the effect of body size on cardiac output requirements.

  • Mitral Valve Area by Planimetry Index [ Time Frame: 12 months ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Mitral Valve Area by Planimetry [ Time Frame: 12 months ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time Index [ Time Frame: 12 months ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: 12 months ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Transvalvular Mitral Mean Pressure Gradient (Mean MVG) [ Time Frame: 12 months ]
    Defined as the mean pressure gradient across the mitral valve as measured by Echocardiography Core Laboratory (ECL).

  • Mitral Valve Area by Planimetry [ Time Frame: 24 months ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: 24 months ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Planimetry Index [ Time Frame: 24 months ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time Index [ Time Frame: 24 months ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Transvalvular Mitral Mean Pressure Gradient (Mean MVG) [ Time Frame: 24 months ]
    Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.

  • Number of Participants With Incidence of Mitral Valve Replacement [ Time Frame: 24 months ]
  • Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR) in Intention to Treat Strategy Cohort [ Time Frame: 24 months ]
  • Cardiac Output [ Time Frame: 24 months ]
    Cardiac output as measured by core lab echocardiography.

  • Cardiac Index [ Time Frame: 24 months ]
    Defined as cardiac index (cardiac output divided by body surface area) as measured by core lab echocardiography.

  • Mitral Valve Area by Planimetry [ Time Frame: 3 years ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: 3 years ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Transvalvular Mitral Mean Pressure Gradient (Mean MVG) [ Time Frame: 4 year ]
    Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.

  • Transvalvular Mitral Mean Pressure Gradient (Mean MVG) [ Time Frame: 3 year ]
    Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.

  • Mitral Valve Area by Planimetry [ Time Frame: 4 years ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: 4 years ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Pressure Half-time [ Time Frame: At Discharge (≤14 days of index procedure) ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Mitral Valve Area by Planimetry [ Time Frame: At Baseline and Discharge (≤14 days of index procedure) ]
    Defined as mitral valve area as measured by core lab echocardiography.


Enrollment: 279
Study Start Date: August 2005
Study Completion Date: December 2014
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Percutaneous mitral valve repair using MitraClip implant. The calculated sample size was 186 patients in the device arm
Device: Percutaneous mitral valve repair using MitraClip implant
MitraClip Implant
Other Name: MitraClip
Active Comparator: 2
Mitral valve repair or replacement surgery. The calculated sample size was 93 patients in the control arm.
Procedure: Mitral valve repair or replacement surgery
Repair or replacement of mitral valve

Detailed Description:

Prospective, multi-center, randomized study of the safety and effectiveness of an endovascular approach to the treatment of mitral valve regurgitation using the Evalve Cardiovascular Valve Repair System (MitraClip® implant).

A minimum of 279 evaluable patients randomized 2:1 to MitraClip or mitral valve surgery, respectively, are required to test the primary safety and effectiveness endpoints of the RCT. Enrollment in the RCT is now complete. 60 roll-in patients were enrolled under EVEREST II RCT.

38 clinical sites throughout the US and Canada have participated in the RCT and HRR. 37 US sites are participating in REALISM.

The RCT is powered to test the hypothesis MitraClip has both superiority of safety and non-inferiority of effectiveness compared to mitral valve repair or replacement surgery. The HRR is powered to show lower mortality at 30 days with the MitraClip than predicted surgical mortality.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion/Exclusion Criteria:

Patients with Grade 3 (moderate to severe) or Grade 4 (severe) mitral regurgitation (MR) based on American Society of Echocardiography guidelines:

  • Are 18 years or older.
  • Symptomatic
  • If asymptomatic, must have new onset of atrial fibrillation, pulmonary hypertension, or evidence of left ventricular dysfunction
  • Are candidates for mitral valve surgery
  • Are candidates for transseptal catheterization
  • Primary regurgitant jet must originate from malcoaptation of the A2 and P2 scallops of the mitral valve
  • Appropriate valve anatomy for MitraClip
  • Does not need other cardiac surgery or any emergency surgery
  • Did not experience myocardial infarction in prior 12 weeks or endovascular procedure in prior 30 days
  • Mitral valve orifice area ≥ 4 cm2
  • Do not have renal insufficiency
  • Echocardiographic evidence of intracardiac mass, thrombus or vegetation
  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: NCT00209274

Locations
United States, Illinois
Evanston Northwestern Healthcare
Evanston, Illinois, United States, 60201
Sponsors and Collaborators
Evalve
Investigators
Principal Investigator: Ted Feldman, M.D. NorthShore University HealthSystem Research Institute
Principal Investigator: Donald G Glower Jr., MD Duke University Medical Center, Department of Surgery
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Evalve
ClinicalTrials.gov Identifier: NCT00209274     History of Changes
Other Study ID Numbers: Protocol #0401
Study First Received: September 13, 2005
Results First Received: December 6, 2013
Last Updated: August 2, 2017

Keywords provided by Evalve:
Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Mitral Valve
MR
Mitral Valve Prolapse
Edge to Edge (E2E)
Alfieri Technique
MitraClip
Functional MR
Degenerative MR
Echocardiogram
CAD - Coronary Artery Disease
Heart Failure
Heart Attack
EVEREST
EVEREST I
EVEREST II
REALISM

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

ClinicalTrials.gov processed this record on September 21, 2017