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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Evalve
ClinicalTrials.gov Identifier:
NCT00209274
First received: September 13, 2005
Last updated: September 17, 2013
Last verified: September 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Evalve:

Primary Outcome Measures:
  • Freedom from surgery for valve dysfunction, death, and moderate to severe (3+) or severe (4+) mitral regurgitation (MR). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Major adverse events (MAE) [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Major adverse events (MAE) [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
  • Major bleeding complications. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    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

  • Non-cerebral thromboembolism. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    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.

  • Endocarditis. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    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

  • Thrombosis. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    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.

  • Hemolysis. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]

    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.


  • Clinically significant Atrial septal defect (ASD). [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    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.

  • Mitral Valve stenosis. [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]
    Defined as a mitral valve planimetered orifice area of less than 1.5 cm2 as measured by echocardiography.

  • New York Heart Association (NYHA) functional class cardiac disease. [ Time Frame: 30 days, 6 months and 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Acute procedural success [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Defined as successful MitraClip implantation with resulting MR of 2+ or less.

  • Post-procedure length of hospital stay. [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
  • Post-procedure intensive care unit (ICU) / critical care unit (CCU)/(post-anesthesia care unit) PACU duration. [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
  • Short Form (SF)-36 Quality of Life questionnaire. [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: No ]
  • MAE in patients over 75 years of age. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Mitral valve repair success. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Defined as freedom from mitral valve replacement surgery for Valve Dysfunction, death, re-operation, and MR > 2+ at 12 months.

  • Procedural success [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.

  • Freedom from surgery for valve dysfunction, death, and moderate to severe (3+) or severe (4+) mitral regurgitation. [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]
  • Clip implant rate [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    defined as the rate of successful implantation of MitraClip(s).

  • Procedural freedom from MAE. [ Time Frame: Day 0 ] [ Designated as safety issue: Yes ]
  • Acute surgical success [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Defined as successful mitral valve repair or replacement.

  • Left Ventricular Status [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: No ]
    Left Ventricular Status is defined a including including Left ventricular (LV) ejection fraction (EF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV internal dimension systole (LVIDs), and LV internal dimension diastole (LVIDd) as determined by the core echo laboratory at 30 days or hospital discharge, whichever is longer, and 12 months.

  • Incidence of hospital readmissions for congestive heart failure (CHF). [ Time Frame: 12 months pre- versus post-MitraClip ] [ Designated as safety issue: No ]
  • Number of days hospitalized for CHF. [ Time Frame: 12 months pre- versus post-MitraClip ] [ Designated as safety issue: No ]
  • 6 Minute Walk Test. [ Time Frame: 30 days, 6 months, 12 months ] [ Designated as safety issue: No ]
  • Major vascular [ Time Frame: 30 days and 12 months. ] [ Designated as safety issue: Yes ]

    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.


Other Outcome Measures:
  • Cardiac output [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: No ]
    Cardiac output as measured by core lab echocardiography

  • Cardiac index [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: No ]
    Defined as cardiac index (cardiac output divided by body surface area) as measured by core lab echocardiography

  • Incidence of new Coumadin (warfarin) usage [ Time Frame: 30 days and 6 months ] [ Designated as safety issue: No ]
  • Incidence of discharge to a nursing home or skilled nursing facility. [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
  • Mitral valve index [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.

  • Mitral valve area [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Defined as mitral valve area as measured by core lab echocardiography.

  • Transvalvular flow gradient [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Peak and Mean

  • Regurgitant volume [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Regurgitant volume as determined by the core echo laboratory.

  • Regurgitant fraction [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
    Regurgitant fraction as determined by the core echo laboratory.

  • Incidence of mitral valve replacement [ Time Frame: 30 Days and 12 months ] [ Designated as safety issue: No ]
  • Hospital re-admissions [ Time Frame: 30 Days and 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1317
Study Start Date: May 2005
Estimated 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 expected number of patients in the device arm is 186 (172 evaluable)
Device: Percutaneous mitral valve repair using MitraClip implant
MitraClip Implant
Other Name: MitraClip
Active Comparator: 2
Mitral valve repair or replacement surgery.The expected number of patients in the active comparator arm is 93 (86 evaluable).
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
Genders Eligible for Study:   Both
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

Additional Information:
Publications:

Additional 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, Protocol #0401
Study First Received: September 13, 2005
Last Updated: September 17, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

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 August 28, 2014