Real World Expanded Multicenter Study of the MitraClip® System (REALISM) (REALISM)

A Continued Access Registry of the Evalve® MitraClip® System: EVEREST II Real World Expanded Multicenter Study of the MitraClip System (REALISM)

Prospective, multicenter, continued access registry of the MitraClip® Cardiovascular Valve Repair System in the treatment of mitral valve regurgitation. Patients will undergo 30-day, 6-month, 12-month, 36-month and 60-month clinical follow-up. The study consists of two arms: a High Risk group (NCT01940120) and a Non-High Risk group (NCT00209274) . Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU).

Study Overview

• Status: Completed
• Conditions: Mitral Regurgitation; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Incompetence; Mitral Insufficiency
• Intervention / Treatment: Device: MitraClip® implant

Detailed Description

The EVEREST II REALISM study (REALISM study) is a continued access registry designed for continued data collection on the use of Abbott Vascular's MitraClip System (MitraClip® Device) under more "real world" conditions. After the completion of enrollment in the pivotal EVEREST II Randomized Controlled Trial (RCT) NCT00209274 and EVEREST II High Risk Registry Study NCT01940120, continued access to the technology was warranted to collect additional safety and effectiveness data on the MitraClip® Device. This continued access study was approved by FDA on November 21, 2008 (G030064). There are two arms (High Risk and Non-High Risk) in the REALISM study. Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU). Enrollment in the Non-High Risk arm of the study concluded on April 14, 2011 and enrollment in the High Risk arm concluded on December 19, 2013.

REALISM is a prospective, multi-center, 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). Patients with moderate-to-severe (3+) or severe (4+) mitral regurgitation (MR), as determined by the site from a transthoracic echocardiogram (TTE), were considered for enrollment in this study. The TTE and a transesophageal echocardiogram (TEE) are used to assess eligibility criteria for MR severity, valve anatomy and left ventricular parameters.

• Study Type: Interventional
• Enrollment (Actual): 965
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health Sciences Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami, FL
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • St. Joseph's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60201
      • Evanston Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • The Care Group Medical Center (St. Vincent Hospital)
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Terrebonne General Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Missoula, Montana, United States, 59802
      • St. Patrick's Hospital & Health Science Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Memorial Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolina's Medical Center (Sanger Clinic)
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina Heart Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor University Medical Center
    • Houston, Texas, United States, 77024
      • Memorial Hermann Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients screened in EVEREST II REALISM Study will first be screened for high risk (HR) status and enrolled into the HR arm if they meet eligibility for this arm of the study. If they do not meet eligibility for the HR arm, patients will be further screened for eligibility for enrollment into the non-high risk (NHR) arm.

Key Inclusion Criteria:

• The primary regurgitant jet originates from malcoaptation of the A2 and P2 scallops of the mitral valve (MV)
• Male or non-pregnant female
• Trans-septal catheterization is determined to be feasible by the treating physician

High Risk Arm:

• Predicted procedural mortality risk calculated using the STS surgical risk calculator of ≥12% or, in the judgment of a cardiac surgeon, the patient is considered a HR surgical candidate due to the presence of one of the following indications:

  1. Porcelain aorta or mobile ascending aortic atheroma
  2. Post-radiation mediastinum
  3. Previous mediastinitis
  4. Functional MR with EF <40
  5. Over 75 years old with EF<40
  6. Re-operation with patent grafts
  7. Two or more prior chest surgeries
  8. Hepatic cirrhosis
  9. Three or more of the following STS high risk factors 9.1 Creatinine >2.5 mg/dL 9.2 Prior chest surgery 9.3 Age over 75 9.4 EF<35
• Symptomatic moderate to severe (3+) or severe (4+) chronic MR and in the judgment of the investigator intervention to reduce MR is likely to provide symptomatic relief for the patient
• American Society of Anesthesiologists (ASA) physical status classification of ASA IV or lower

Non-High Risk Arm:

• Moderate to severe (3+) or severe (4+) chronic MV regurgitation and:

  1. Symptomatic with >25% LVEF and LVESD ≤55mm or, 2. Asymptomatic with one or more of the following: i. Left Ventricular Ejection Fraction (LVEF) 25% to 60% ii. Left Ventricular End-Systolic Diameter (LVESD) ≥40 mm iii. New onset of Atrial fibrillation (AFib) iv. Pulmonary arterial systolic pressure (PASP) >50 mmHg at rest or >60 mmHg with exercise

• Candidate for MV repair or replacement surgery, including cardiopulmonary bypass

Key Exclusion Criteria:

• Evidence of an Acute Myocardial Infarction (AMI) in the prior 12 weeks of the intended treatment
• In the judgment of the Investigator, the femoral vein cannot accommodate a 24 French scale (F) catheter or the presence of an inferior vena cava (IVC) filter would interfere with advancement of the catheter or ipsilateral Deep Venous Thrombus (DVT) is present
• MV orifice area <4.0 cm2

• If leaflet flail is present:

  1. Flail Width ≥15 mm, or
  2. Flail Gap ≥10 mm.

• If leaflet tethering is present:

  1. Vertical coaptation length <2 mm

• Leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in MR. This may include:

  1. Evidence of calcification in the grasping area of the A2 and/or P2 scallops
  2. Presence of a significant cleft of A2 or P2 scallops
  3. More than one anatomic criteria dimensionally near the exclusion limits
  4. Bileaflet flail or severe bileaflet prolapse
  5. Lack of both primary and secondary chordal support
• Hemodynamic instability (systolic pressure <90 mmHg without afterload reduction or cardiogenic shock or the need for inotropic support or intra-aortic balloon pump).
• Need for emergency surgery for any reason
• Prior MV surgery or valvuloplasty or any currently implanted mechanical prosthetic valve or currently implanted Ventricular assist device (VAD)
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation
• Active endocarditis or active rheumatic heart disease or leaflets degenerated from either endocarditis or rheumatic disease (i.e. noncompliant, perforated)
• History of bleeding diathesis or coagulopathy or subject will refuse blood transfusions
• Life expectancy <12 months
• Active infections requiring current antibiotic therapy
• Patients in whom transesophageal echocardiography (TEE) is contraindicated

High Risk Arm:

• EF <20%, and/or LVESD >60 mm

Non-High Risk Arm:

• The need for any other cardiac surgery
• Any endovascular therapeutic interventional or surgical procedure performed within 30 days prior to the index procedure
• Severe Left Ventricular (LV) dysfunction (EF <25% and/or LVESD >55mm)
• Severe mitral annular calcification
• Systolic anterior motion of the MV leaflet
• Hypertrophic cardiomyopathy
• History of a stroke or documented Transient Ischemic Attack (TIA) within the prior 6 months
• Upper GI bleeding within the prior 6 months
• Platelet count <75,000 cells/mm³
• Creatinine >2.5mg/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-High Risk; Includes patients who are candidate for mitral valve repair or replacement surgery, including cardiopulmonary bypass (i.e. non-high risk). The patients who are enrolled in this arm will undergo percutaneous mitral valve repair using MitraClip® implant. This arm was evaluated as a separate study NCT00209274.	Device: MitraClip® implant; Percutaneous mitral valve repair using MitraClip implant
Experimental: High Risk; Includes patients with a predicted procedural mortality risk calculated using the Society For Thoracic Surgeon (STS) surgical risk calculator of ≥12% or, in the judgment of a cardiac surgeon, the patient is considered a high risk surgical candidate due to the presence of pre-defined risk factors. The patients who are enrolled in this arm will undergo percutaneous mitral valve repair using MitraClip® implant. This arm was evaluated as a separate study NCT01940120.	Device: MitraClip® implant; Percutaneous mitral valve repair using MitraClip implant
Experimental: Compassionate Use; Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU). The objective of the Compassionate and Emergency Use Group of the EVEREST II REALISM study is to provide access to the MitraClip Device, in a non-commercial setting, for patients with serious or life-threatening conditions when conventional therapies have failed, are unsuitable, or unavailable. The patients who are enrolled in this arm will undergo percutaneous mitral valve repair using MitraClip® implant.	Device: MitraClip® implant; Percutaneous mitral valve repair using MitraClip implant
Experimental: Emergency Use; Patients that did not meet REALISM High Risk or Non-High Risk eligibility criteria were evaluated for consideration for either Emergency Use (EU) or Compassionate Use (CU). The objective of the Compassionate and Emergency Use Group of the EVEREST II REALISM study is to provide access to the MitraClip Device, in a non-commercial setting, for patients with serious or life-threatening conditions when conventional therapies have failed, are unsuitable, or unavailable. The patients who are enrolled in this arm will undergo percutaneous mitral valve repair using MitraClip® implant.	Device: MitraClip® implant; Percutaneous mitral valve repair using MitraClip implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major Adverse Events	A combined clinical endpoint of death, myocardial infarction (MI), re-operation for failed surgical repair or replacement, non-elective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, ventilation for greater than 48 hours, gastro-intestinal (GI) complication requiring surgery, new onset of permanent atrial fibrillation, septicemia and transfusion of 2 or more units of blood.	30 days
Number of Participants With Major Adverse Events	A combined clinical endpoint of death, myocardial infarction (MI), re-operation for failed surgical repair or replacement, non-elective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, ventilation for greater than 48 hours, GI complication requiring surgery, new onset of permanent atrial fibrillation, septicemia and transfusion of 2 or more units of blood.	12 months
Number of Participants With 12-Month Efficacy	Defined as freedom from: Surgery for Mitral Regurgitation (MR) or Valve Dysfunction, death, and MR > 2+ (moderate to severe (3+) or severe MR (4+)).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events	The definition of a serious adverse event is an event that is fatal or life threatening, results in persistent or significant disability, requires intervention to prevent permanent impairment/damage, or an event that results in congenital anomaly, malignancy, hospital admission or prolongation of hospitalization.	30 days
Number of Participants With Serious Adverse Events	The definition of a serious adverse event is an event that is fatal or life threatening, results in persistent or significant disability, requires intervention to prevent permanent impairment/damage, or an event that results in congenital anomaly, malignancy, hospital admission or prolongation of hospitalization.	12 months
Number of Participants With Clinically Significant Atrial Septal Defect (ASD)	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.	30 days
Number of Participants With Clinically Significant Atrial Septal Defect (ASD)	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.	12 months
Number of Participants With Major Adverse Events (MAE) in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	30 days
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	12 Months
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	2 years
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	3 years
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	4 years
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	MAE is defined as a combined clinical endpoint of Death (all cause), MI, Re-operation for Failed Surgical Repair or replacement, non-elective Cardiovascular Surgery for AEs, Stroke, Renal Failure, Deep Wound Infection, Ventilation for greater than 48 hours, GI complication requiring surgery, new onset of Permanent Afib, Septicemia, and transfusion of 2 or more units of blood. The occurrence of MAE is measured in patients over 75 years of age.	5 years
Number of Participants With Acute Procedural Success	Defined as successful implantation of the Clip(s) with resulting MR severity of 2+ or less as determined by the echocardiographic assessment at discharge. The 30-day echocardiogram will be used if the discharge echocardiogram is unavailable or uninterpretable, providing the patient has not undergone subsequent surgery after attempted clip.	At discharge (an average of ≤ 12.3 days post-index procedure)
Number of Participants With Procedural Success	Defined as successful implantation of the Clip(s) with resulting MR severity of 2+ of less at discharge or a 1 grade MR reduction at discharge accompanied by a 1 level reduction in NYHA at 30 days.	30 days
Number of Participants With Clinical Durability	Defined as the proportion of patients who have an acute reduction in MR severity of at least one grade (as measured by the discharge echocardiogram) that at 12 months have not required surgery for valve dysfunction and meet either of the following: 1) MR severity grade of 2+ or less or 2) a one grade reduction in MR severity compared to baseline accompanied by at least a one level reduction in NYHA at 12 months.	12 months
Number of Participants With Clip Implant Rate	Defined as the procedural rate of successful delivery and deployment of Clip implants with echocardiographic evidence of leaflet approximation and retrieval of the investigational delivery catheter.	On the day of index procedure (≤1 day)
Procedure Time	The mean procedure time is defined as the start time of the transseptal procedure to the time the steerable guide catheter (SGC) is removed.	On the day of index procedure
Device Time	Device time is defined as the time of insertion of the Steerable Guide Catheter (SGC) to the time the MitraClip delivery catheter is retracted into the SGC.	On the day of index procedure
Fluoroscopy Duration	Mean fluoroscopy duration during the MitraClip procedure.	On the day of index procedure
Number of Participants With MitraClip Devices Implanted	The distribution of number of MitraClip devices implanted in patients.	On the day of index procedure
Post-Procedure Intensive Care Unit (ICU)/ Critical Care Unit (CCU)/ Post-anesthesia Care Unit (PACU) Duration	Defined as the number of hours for which patients are in an intensive care unit or step down unit before discharge or moving to a standard care unit.	At discharge (an average of ≤ 12.3 days post-index procedure).
Post-Procedure Length of Hospital Stay	Defined as the number of days from the end of the procedure until the patient is discharged from the hospital. This does not include time in a nursing or skilled care facility.	At discharge (an average of ≤ 12.3 days post-index procedure).
Number of Participants Experiencing Death	Cardiac death is defined as any death in which a cardiac cause cannot be excluded. (This includes but is not limited to acute myocardial infarction, cardiac perforation/pericardial tamponade, arrhythmia or conduction abnormality,cerebrovascular accident within 30 days of the procedure or cerebrovascular accident suspected of being related to the procedure, death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery.) Non-cardiac death is defined as a death not due to cardiac causes (as defined above).	12 months visit window (410 days)
Number of Participants With Incidence of Discharge to a Nursing Home or Skilled Nursing Facility		At discharge (an average of ≤ 12.3 days post-index procedure)
Number of Participants With Hospital Re-admissions	Defined as re-admission of patients to the hospital following discharge from the Clip procedure.	30 days
Number of Participants With Device Embolization or Single Leaflet Device Attachment (SLDA)	A single leaflet device attachment (SLDA) is defined as attachment of one mitral valve leaflet to the MitraClip device.	0 to 5 years
Number of Participants With Mitral Stenosis	Mitral stenosis is a key safety consideration assessed after implantation of the MitraClip device. It is defined as Mitral Valve Area (MVA) less than 1.5 cm^2 as assessed by the Echocardiography Core Laboratory (ECL).	0 to 5 years
Number of Participants With Mitral Regurgitation (MR) Severity	Paired site-assessed Mitral regurgitation severity between baseline and 30 days using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	30 days(Follow-up)
Number of Participants With MR Severity	Paired site-assessed Mitral regurgitation severity between baseline and 12 months using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	12 months
Number of Participants With MR Severity	Paired site-assessed Mitral regurgitation severity between baseline and 2 years using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	2 years
Number of Participants With MR Severity	Paired site-assessed Mitral regurgitation severity between baseline and 3 years using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	3 years
Number of Participants With MR Severity	Paired site-assessed Mitral regurgitation severity between baseline and 4 years using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	4 years
Number of Participants With MR Severity	Paired site-assessed Mitral regurgitation severity between baseline and 5 years using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 2+ is moderate, 3+ is moderate-to-severe and 4+ is severe.	5 years
Number of Participants With Second Intervention to Place an Additional Mitraclip Device.	If residual MR was determined to be clinically unacceptable for patients who received only 1 clip during the index procedure, a second intervention to place an additional MitraClip device could be considered.	139 days post the index procedure
Number of Participants With Second Intervention to Place an Additional Mitraclip Device.	If residual MR was determined to be clinically unacceptable for patients who received only 1 clip during the index procedure, a second intervention to place an additional MitraClip device could be considered.	5 years
Number of Participants With New York Heart Association (NYHA) Functional Class	Paired NYHA data from baseline to 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.	30 days
Number of Participants With NYHA Functional Class	Paired NYHA data from baseline to 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.	12 months
Number of Participants With NYHA Functional Class	Paired NYHA data from baseline to 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.	2 years
Number of Participants With NYHA Functional Class	Paired NYHA data from baseline to 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.	3 years
Number of Participants With NYHA Functional Class	Paired NYHA data from baseline to 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.	4 years
Number of Participants With NYHA Functional Class	Paired NYHA data from baseline to 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.	5 years
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 12 months as determined by echo core laboratory.	12 months
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 24 months as determined by echo core laboratory.	24 months
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 36 months as determined by echo core laboratory.	36 months
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 48 months as determined by the echo core laboratory.	48 months
Left Ventricular End-diastolic Volume (LVEDV)	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 60 months as determined by echo core laboratory.	60 months
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 12 months as determined by echo core laboratory.	12 months
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 24 months as determined by echo core laboratory.	24 months
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 36 months as determined by echo core laboratory.	36 months
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 48 months as determined by echo core laboratory.	48 months
Left Ventricular End-systolic Volume (LVESV)	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 60 months as determined by echo core laboratory.	60 months
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 12 months as determined by echo core laboratory.	12 months
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 24 months as determined by echo core laboratory.	24 months
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 36 months as determined by echo core laboratory.	36 months
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 48 months as determined by echo core laboratory.	48 months
Left Ventricular Internal Dimension Diastole (LVIDd)	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 60 months as determined by echo core laboratory.	60 months
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 12 months as determined by echo core laboratory.	12 months
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 24 months as determined by echo core laboratory.	24 months
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 36 months as determined by echo core laboratory.	36 months
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 48 months as determined by echo core laboratory.	48 months
Left Ventricular Internal Dimension Systole (LVIDs)	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 60 months as determined by echo core laboratory.	60 months
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 12 months as determined by echo core laboratory.	12 months
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 24 months as determined by echo core laboratory.	24 months
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 36 months as determined by echo core laboratory.	36 months
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 48 months as determined by echo core laboratory.	48 months
Left Ventricular Ejection Fraction (LVEF)	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 60 months as determined by echo core laboratory.	60 months
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to 12 months as determined by echo core laboratory.	12 months
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to 24 months as determined by echo core laboratory.	24 months
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to 36 months as determined by echo core laboratory.	36 months
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to 48 months as determined by echo core laboratory.	48 months
Septal-Lateral Annular Dimension Diastole (SLADd)	Septal-Lateral Annular Dimension Diastole (SLADd) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in diastole. Paired SLADd data from baseline to 60 months as determined by echo core laboratory.	60 months
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to discharge or 30 days as determined by echo core laboratory.	At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to 12 months as determined by echo core laboratory.	12 months
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to 24 months as determined by echo core laboratory.	24 months
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to 36 months as determined by echo core laboratory.	36 months
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to 48 months as determined by echo core laboratory.	48 months
Septal-Lateral Annular Dimension Systole (SLADs)	Septal-Lateral Annular Dimension systole (SLADs) is the dimension across the mitral valve from the anterior annulus to the posterior annulus at the widest point in the center of the valve, measured in systole.Paired SLADs data from baseline to 60 months as determined by echo core laboratory.	60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
36-Item Short Form Health Survey (SF-36) Quality of Life Change From Baseline to 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.	30 days
36-Item Short Form Health Survey (SF-36) Quality of Life Change From Baseline to 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.	12 months
Change in 6-Minute Walk Test (6MWT)	Defined as a cardiopulmonary function test that measures a patient's exercise capacity by the distance he or she can walk in six minutes.	At Baseline and 30 Days
Change in 6-Minute Walk Test (6MWT)	Defined as a cardiopulmonary function test that measures a patient's exercise capacity by the distance he or she can walk in six minutes.	At Baseline and 6 months
Change in 6-Minute Walk Test (6MWT)	Defined as a cardiopulmonary function test that measures a patient's exercise capacity by the distance he or she can walk in six minutes.	At Baseline and 12 months

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Investigators: Study Director: Ted Feldman, M.D. Feldman, M.D., Northshore University Healthsystem; Study Director: Donald D Glower Jr., MD, Duke University

Publications and helpful links

General Publications

• Ailawadi G, Lim DS, Mack MJ, Trento A, Kar S, Grayburn PA, Glower DD, Wang A, Foster E, Qasim A, Weissman NJ, Ellis J, Crosson L, Fan F, Kron IL, Pearson PJ, Feldman T; EVEREST II Investigators. One-Year Outcomes After MitraClip for Functional Mitral Regurgitation. Circulation. 2019 Jan 2;139(1):37-47. doi: 10.1161/CIRCULATIONAHA.117.031733.
• Wang A, Sangli C, Lim S, Ailawadi G, Kar S, Herrmann HC, Grayburn P, Foster E, Weissman NJ, Glower D, Feldman T. Evaluation of renal function before and after percutaneous mitral valve repair. Circ Cardiovasc Interv. 2015 Jan;8(1):e001349. doi: 10.1161/CIRCINTERVENTIONS.113.001349.
• Grayburn PA, Roberts BJ, Aston S, Anwar A, Hebeler RF Jr, Brown DL, Mack MJ. Mechanism and severity of mitral regurgitation by transesophageal echocardiography in patients referred for percutaneous valve repair. Am J Cardiol. 2011 Sep 15;108(6):882-7. doi: 10.1016/j.amjcard.2011.05.013. Epub 2011 Jul 7.
• Pope NH, Lim S, Ailawadi G. Late calcific mitral stenosis after MitraClip procedure in a dialysis-dependent patient. Ann Thorac Surg. 2013 May;95(5):e113-4. doi: 10.1016/j.athoracsur.2012.10.067.
• Glower DD, Kar S, Trento A, Lim DS, Bajwa T, Quesada R, Whitlow PL, Rinaldi MJ, Grayburn P, Mack MJ, Mauri L, McCarthy PM, Feldman T. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study. J Am Coll Cardiol. 2014 Jul 15;64(2):172-81. doi: 10.1016/j.jacc.2013.12.062.
• Lim DS, Reynolds MR, Feldman T, Kar S, Herrmann HC, Wang A, Whitlow PL, Gray WA, Grayburn P, Mack MJ, Glower DD. Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation after transcatheter mitral valve repair. J Am Coll Cardiol. 2014 Jul 15;64(2):182-92. doi: 10.1016/j.jacc.2013.10.021. Epub 2013 Oct 31.

Helpful Links

• Web site listing study sites and describing mitral regurgitation, symptoms, clinical consequences and treatments
• Sponsor information

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2009
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: August 27, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Actual): December 4, 2018
• Last Update Submitted That Met QC Criteria: November 5, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Heart Failure; Mitral Regurgitation; MitraClip; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Incompetence; Mitral Insufficiency; Mitral Valve; Mitral Valve Prolapse; Alfieri Technique; Functional MR; Degenerative MR; Echocardiogram; Heart Attack; EVEREST; EVEREST I; EVEREST II; Coronary Artery Disease (CAD); Edge to Edge (E2E); REALISM; Mitral Regurgitation (MR)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 0401B; 0401 (Abbott Vascular)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes