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

Not Applicable

Completed

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

Interventions: Device: MitraClip® implant

Registration Number: NCT01931956

Lead Sponsor: Abbott Medical Devices

Brief Summary: 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).

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 965

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Non-High Risk	MitraClip® implant	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.
Compassionate Use	MitraClip® implant	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.
High Risk	MitraClip® implant	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.
Emergency Use	MitraClip® implant	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Major Adverse Events	12 months	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.
Number of Participants With 12-Month Efficacy	12 months	Defined as freedom from: Surgery for Mitral Regurgitation (MR) or Valve Dysfunction, death, and MR \> 2+ (moderate to severe (3+) or severe MR (4+)).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Major Adverse Events in Patients Over 75 Years of Age	5 years	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.
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.
Number of Participants With Procedural Success	30 days	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.
Number of Participants With Clinical Durability	12 months	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.
Device Time	On the day of index procedure	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.
Fluoroscopy Duration	On the day of index procedure	Mean fluoroscopy duration during the MitraClip procedure.
Number of Participants With Major Adverse Events (MAE) in Patients Over 75 Years of Age	30 days	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.
Post-Procedure Intensive Care Unit (ICU)/ Critical Care Unit (CCU)/ Post-anesthesia Care Unit (PACU) Duration	At discharge (an average of ≤ 12.3 days post-index procedure).	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.
Post-Procedure Length of Hospital Stay	At discharge (an average of ≤ 12.3 days post-index procedure).	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.
Number of Participants With Device Embolization or Single Leaflet Device Attachment (SLDA)	0 to 5 years	A single leaflet device attachment (SLDA) is defined as attachment of one mitral valve leaflet to the MitraClip device.
Number of Participants With Mitral Regurgitation (MR) Severity	30 days(Follow-up)	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.
Number of Participants With Acute Procedural Success	At discharge (an average of ≤ 12.3 days post-index procedure)	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.
Number of Participants With Clip Implant Rate	On the day of index procedure (≤1 day)	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.
Septal-Lateral Annular Dimension Diastole (SLADd)	60 months	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.
Septal-Lateral Annular Dimension Systole (SLADs)	60 months	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.
Number of Participants Experiencing Death	12 months visit window (410 days)	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).
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 MR Severity	5 years	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.
Left Ventricular Ejection Fraction (LVEF)	60 months	Paired Left Ventricular Ejection Fraction (LVEF) data from baseline to 60 months as determined by echo core laboratory.
Number of Participants With Hospital Re-admissions	30 days	Defined as re-admission of patients to the hospital following discharge from the Clip procedure.
Number of Participants With Second Intervention to Place an Additional Mitraclip Device.	5 years	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.
Number of Participants With NYHA Functional Class	5 years	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.
Number of Participants With New York Heart Association (NYHA) Functional Class	30 days	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.
Left Ventricular Internal Dimension Systole (LVIDs)	60 months	Paired Left Ventricular internal dimension systole (LVIDs) data from baseline to 60 months as determined by echo core laboratory.
Number of Participants With Mitral Stenosis	0 to 5 years	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).
Left Ventricular End-diastolic Volume (LVEDV)	60 months	Paired Left ventricular end-diastolic volume (LVEDV) data from baseline to 60 months as determined by echo core laboratory.
Left Ventricular End-systolic Volume (LVESV)	60 months	Paired Left ventricular end-systolic volume (LVESV) data from baseline to 60 months as determined by echo core laboratory.
Left Ventricular Internal Dimension Diastole (LVIDd)	60 months	Paired Left Ventricular internal dimension diastole (LVIDd) data from baseline to 60 months as determined by echo core laboratory.
Number of Participants With Serious Adverse Events	12 months	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.
Procedure Time	On the day of index procedure	The mean procedure time is defined as the start time of the transseptal procedure to the time the steerable guide catheter (SGC) is removed.
Number of Participants With MitraClip Devices Implanted	On the day of index procedure	The distribution of number of MitraClip devices implanted in patients.

Trial Locations

Locations (38): Baptist Hospital of Miami, FL
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Miami, Florida, United States
Rush University Medical Center
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Chicago, Illinois, United States
William Beaumont Hospital
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Royal Oak, Michigan, United States
St. Patrick's Hospital & Health Science Center
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Missoula, Montana, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Swedish Medical Center
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Seattle, Washington, United States
Maine Medical Center
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Portland, Maine, United States
Washington University School of Medicine
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Saint Louis, Missouri, United States
El Camino Hospital
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Mountain View, California, United States
Evanston Hospital
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Evanston, Illinois, United States
Washington Hospital Center
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Washington, District of Columbia, United States
St. Joseph's Hospital
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Atlanta, Georgia, United States
Terrebonne General Medical Center
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Houma, Louisiana, United States
The Care Group Medical Center (St. Vincent Hospital)
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Indianapolis, Indiana, United States
Shawnee Mission Medical Center
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Shawnee Mission, Kansas, United States
Morristown Memorial Hospital
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Morristown, New Jersey, United States
Columbia University Medical Center
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New York, New York, United States
Lenox Hill Hospital
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New York, New York, United States
East Carolina Heart Institute
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Greenville, North Carolina, United States
Cleveland Clinic Foundation
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Cleveland, Ohio, United States
Baylor University Medical Center
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Dallas, Texas, United States
Intermountain Medical Center
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Murray, Utah, United States
University of Virginia Health System
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Charlottesville, Virginia, United States
New York Presbyterian Hospital
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New York, New York, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Piedmont Hospital
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Atlanta, Georgia, United States
St. Francis Hospital
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Roslyn, New York, United States
New York University Medical Center
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New York, New York, United States
Memorial Hermann Hospital
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Houston, Texas, United States
Minneapolis Heart Institute
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Minneapolis, Minnesota, United States
Medical University of South Carolina
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Charleston, South Carolina, United States
St. Luke's Medical Center
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Milwaukee, Wisconsin, United States
University of Colorado Health Sciences Center
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Aurora, Colorado, United States
University of California Davis Medical Center
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Sacramento, California, United States
Oklahoma Heart Hospital
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Oklahoma City, Oklahoma, United States
Duke University Medical Center
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Durham, North Carolina, United States
University of Texas Health Science Center
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San Antonio, Texas, United States
Carolina's Medical Center (Sanger Clinic)
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Charlotte, North Carolina, United States