Pivotal Study of a Percutaneous Mitral Valve Repair System

Not Applicable

Completed

Conditions: Mitral Valve Incompetence
Mitral Valve Regurgitation
Mitral Regurgitation
Mitral Insufficiency
Mitral Valve Insufficiency

Interventions: Procedure: Mitral valve repair or replacement surgery
Device: Percutaneous mitral valve repair using MitraClip implant

Registration Number: NCT00209274

Lead Sponsor: Abbott Medical Devices

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 279

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Mitral valve repair or replacement surgery	Mitral valve repair or replacement surgery. The calculated sample size was 93 patients in the control arm.
1	Percutaneous mitral valve repair using MitraClip implant	Percutaneous mitral valve repair using MitraClip implant. The calculated sample size was 186 patients in the device arm

Primary Outcome Measures

Name	Time	Method
Number of Participants With Major Adverse Events (MAE)	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).	12 months

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Dysrhythmia	12 months
Cardiac Index (CI)	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.
Number of Participants With Clip Implant Rate	Day 0	Defined as the rate of successful implantation of MitraClip(s).
Number of Participants With Acute Procedural Success	30 Days	Defined as successful MitraClip implantation with resulting MR of 2+ or less.
Number of Participants With MAE: Surgery After Device and First Time Surgery Control	30 days
Number of Participants With Major Adverse Events (MAE)	12 months.
Number of Participants With Thrombosis.	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 Clinically Significant Atrial Septal Defect (ASD)	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.
Mitral Valve Area by Planimetry Index	24 months	Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.
Number of Participants With Major Vascular Complications	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 Bleeding Complications.	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.
Number of Participants With Hemolysis	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 Clinically Significant Atrial Septal Defect (ASD).	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.
Mitral Valve Area by Pressure Half-time Index	24 months	Defined as mitral valve area divided by body surface area as measured by core lab echocardiography.
Post-procedure Length of Hospital Stay	30 Days
Post-procedure Intensive Care Unit (ICU) / Critical Care Unit (CCU) Duration	30 Days
Number of Participants With Incidence of Discharge to a Nursing Home or Skilled Nursing Facility/Hospital	30 Days
Number of Participants With Incidence of Hospital Readmissions for Congestive Heart Failure (CHF).	30 days
Number of Participants With Durability of the MitraClip Device and Surgery.	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 Death and Mitral Valve Surgery/Re-operation	5 years	Durability estimates: Freedom from Death and Mitral Valve Surgery/Re-operation
Number of Participants With Non-cerebral Thromboembolism.	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.
Mitral Valve Area by Pressure Half-time	5 years	Mitral valve area as measured by core lab echocardiography.
Number of Participants With Mitral Valve Stenosis	5 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.
Mitral Valve Area by Planimetry	5 years	Mitral valve area as measured by core lab echocardiography.
Number of Participants With New Coumadin (Warfarin) Usage	12 months
Number of Participants With Freedom From Death, Mitral Valve Surgery/Re-operation and MR > 2+	3 years	Durability estimates: Freedom from Death, Mitral Valve Surgery/Re-operation and MR \> 2+
Transvalvular Mitral Valve Gradient	At Discharge (≤ 14 days following index procedure)	Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.
Transvalvular Mitral Mean Pressure Gradient (Mean MVG)	5 years	Defined as the mean pressure gradient across the mitral valve as measured by echocardiography.
Number of Participants With Hospital Re-admissions	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 for both the Device and Control groups.
Number of Participants With Freedom From Mitral Valve Surgery/Re-operation	5 years	Durability estimates: Freedom from Mitral Valve Surgery/Re-operation
Number of Participants With Incidence of Mitral Valve Replacement	24 months
Freedom From All-Cause Mortality	5 years
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	24 months
Left Ventricular Ejection Fraction (LVEF)	5 years	LVEF as determined by the core echo laboratory.
Number of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease.	5 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 MitraClip Device Embolization/Single Leaflet Device Attachment	12 months to 5 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 MR Severity	5 years	MR Severity of 0: None,1+: Mild, 2+: Moderate, 3+: Moderate-to-Severe, 4+: Severe
Left Ventricular Status- Left Ventricular End-diastolic Volume (LVEDV), Left Ventricular End-systolic Volume (LVESV)	30 days	Left Ventricular Status includes 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	5 years	Left Ventricular Status includes LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), as determined by the core echo laboratory at 5 years.
Left Ventricular Internal Dimension Systole (LVIDs)	5 years	Left Ventricular internal dimension systole (LVIDs) as determined by the core echo laboratory.
Left Ventricular Internal Dimension Diastole (LVIDd)	5 years	Left Ventricular internal dimension diastole (LVIDd) as determined by the core echo laboratory at 5 years.
Percentage of Participants With New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV	5 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.	Day 0
Cardiac Index	24 months	Defined as cardiac output divided by body surface area, as measured by core lab echocardiography.
Regurgitant Volume	24 months	Regurgitant volume as determined by the core echo laboratory.
Number of Participants With Acute Surgical Success	30 Days	Defined as successful mitral valve repair or replacement surgery.
Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation.	12 months
Number of Participants With Freedom From Surgery for Valve Dysfunction, Death, and Moderate to Severe (3+) or Severe (4+) Mitral Regurgitation (MR).	24 months
New York Heart Association (NYHA) Functional Class Cardiac Disease: NYHA Functional Class III or IV	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.
Short Form (SF)-36 Quality of Life Questionnaire.	12 months	The SF-36 is a multidimensional, patient-reported survey containing 36 questions on a 0-100 scale measuring physical (Physical Component Score) \& mental health status (Mental Component Score) 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.
Cardiac Output	24 months	Cardiac output as measured by core lab echocardiography.
Regurgitant Fraction (RF)	30 Days	RF is defined as the percentage of the left ventricular (LV) stroke volume that regurgitates into the left atrium.
Regurgitant Fraction	24 months	Regurgitant fraction is defined as the percentage of the left ventricular (LV) stroke volume that regurgitates into the left atrium.
Number of Participants With Successful Clip Implant and Acute Procedural Success	30 days	Acute procedural success is defined as MR severity ≤ 2 at discharge or 1 grade MR reduction at discharge accompanied by 1 level NYHA reduction.
Number of Participants With Mitral Valve Repair Success.	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 Procedural Freedom From In-hospital MAE	Day 30
Number of Participants With MAE in Patients Over 75 Years of Age.	12 months
Number of Participants With Endocarditis.	12 months	Defined as a diagnosis of endocarditis based on the Duke criteria. Infection in the lining of the heart, of the valves, or of the muscles of the heart. Signs of endocarditis may include persistent positive blood cultures and/or valvular structural abnormality and vegetations as seen using echocardiography.