Clinical trial NCT01931956: Real World Expanded Multicenter Study of the MitraClip® System (REALISM)
Official title: A Continued Access Registry of the Evalve® MitraClip® System: EVEREST II Real World Expanded Multicenter Study of the MitraClip System (REALISM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Keywords: Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Mitral Valve
Mitral Regurgitation (MR)
Mitral Valve Prolapse
Edge to Edge (E2E)
Alfieri Technique
MitraClip
Functional MR
Degenerative MR
Echocardiogram
Coronary Artery Disease (CAD)
Heart Failure
Heart Attack
EVEREST
EVEREST I
EVEREST II
REALISM
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 965
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Major Adverse Events
timeFrame: 30 days
measure: Number of Participants With Major Adverse Events
timeFrame: 12 months
measure: Number of Participants With 12-Month Efficacy
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With Serious Adverse Events
timeFrame: 30 days
measure: Number of Participants With Serious Adverse Events
timeFrame: 12 months
measure: Number of Participants With Clinically Significant Atrial Septal Defect (ASD)
timeFrame: 30 days
measure: Number of Participants With Clinically Significant Atrial Septal Defect (ASD)
timeFrame: 12 months
measure: Number of Participants With Major Adverse Events (MAE) in Patients Over 75 Years of Age
timeFrame: 30 days
measure: Number of Participants With Major Adverse Events in Patients Over 75 Years of Age
timeFrame: 12 Months
measure: Number of Participants With Major Adverse Events in Patients Over 75 Years of Age
timeFrame: 2 years
measure: Number of Participants With Major Adverse Events in Patients Over 75 Years of Age
timeFrame: 3 years
measure: Number of Participants With Major Adverse Events in Patients Over 75 Years of Age
timeFrame: 4 years
measure: Number of Participants With Major Adverse Events in Patients Over 75 Years of Age
timeFrame: 5 years
measure: Number of Participants With Acute Procedural Success
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure)
measure: Number of Participants With Procedural Success
timeFrame: 30 days
measure: Number of Participants With Clinical Durability
timeFrame: 12 months
measure: Number of Participants With Clip Implant Rate
timeFrame: On the day of index procedure (≤1 day)
measure: Procedure Time
timeFrame: On the day of index procedure
measure: Device Time
timeFrame: On the day of index procedure
measure: Fluoroscopy Duration
timeFrame: On the day of index procedure
measure: Number of Participants With MitraClip Devices Implanted
timeFrame: On the day of index procedure
measure: Post-Procedure Intensive Care Unit (ICU)/ Critical Care Unit (CCU)/ Post-anesthesia Care Unit (PACU) Duration
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure).
measure: Post-Procedure Length of Hospital Stay
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure).
measure: Number of Participants Experiencing Death
timeFrame: 12 months visit window (410 days)
measure: Number of Participants With Incidence of Discharge to a Nursing Home or Skilled Nursing Facility
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure)
measure: Number of Participants With Hospital Re-admissions
timeFrame: 30 days
measure: Number of Participants With Device Embolization or Single Leaflet Device Attachment (SLDA)
timeFrame: 0 to 5 years
measure: Number of Participants With Mitral Stenosis
timeFrame: 0 to 5 years
measure: Number of Participants With Mitral Regurgitation (MR) Severity
timeFrame: 30 days(Follow-up)
measure: Number of Participants With MR Severity
timeFrame: 12 months
measure: Number of Participants With MR Severity
timeFrame: 2 years
measure: Number of Participants With MR Severity
timeFrame: 3 years
measure: Number of Participants With MR Severity
timeFrame: 4 years
measure: Number of Participants With MR Severity
timeFrame: 5 years
measure: Number of Participants With Second Intervention to Place an Additional Mitraclip Device.
timeFrame: 139 days post the index procedure
measure: Number of Participants With Second Intervention to Place an Additional Mitraclip Device.
timeFrame: 5 years
measure: Number of Participants With New York Heart Association (NYHA) Functional Class
timeFrame: 30 days
measure: Number of Participants With NYHA Functional Class
timeFrame: 12 months
measure: Number of Participants With NYHA Functional Class
timeFrame: 2 years
measure: Number of Participants With NYHA Functional Class
timeFrame: 3 years
measure: Number of Participants With NYHA Functional Class
timeFrame: 4 years
measure: Number of Participants With NYHA Functional Class
timeFrame: 5 years
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: 12 months
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: 24 months
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: 36 months
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: 48 months
measure: Left Ventricular End-diastolic Volume (LVEDV)
timeFrame: 60 months
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: 12 months
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: 24 months
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: 36 months
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: 48 months
measure: Left Ventricular End-systolic Volume (LVESV)
timeFrame: 60 months
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: 12 months
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: 24 months
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: 36 months
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: 48 months
measure: Left Ventricular Internal Dimension Diastole (LVIDd)
timeFrame: 60 months
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 12 months
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 24 months
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 36 months
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 48 months
measure: Left Ventricular Internal Dimension Systole (LVIDs)
timeFrame: 60 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 24 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 36 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 48 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 60 months
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: 12 months
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: 24 months
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: 36 months
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: 48 months
measure: Septal-Lateral Annular Dimension Diastole (SLADd)
timeFrame: 60 months
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: At discharge (an average of ≤ 12.3 days post-index procedure) or 30 days
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: 12 months
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: 24 months
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: 36 months
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: 48 months
measure: Septal-Lateral Annular Dimension Systole (SLADs)
timeFrame: 60 months
Other outcomes:
measure: 36-Item Short Form Health Survey (SF-36) Quality of Life Change From Baseline to 30 Days
timeFrame: 30 days
measure: 36-Item Short Form Health Survey (SF-36) Quality of Life Change From Baseline to 12 Months
timeFrame: 12 months
measure: Change in 6-Minute Walk Test (6MWT)
timeFrame: At Baseline and 30 Days
measure: Change in 6-Minute Walk Test (6MWT)
timeFrame: At Baseline and 6 months
measure: Change in 6-Minute Walk Test (6MWT)
timeFrame: At Baseline and 12 months
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: Baptist Hospital of Miami, FL
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: St. Joseph's Hospital
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Indianapolis
country: United States
facility: The Care Group Medical Center (St. Vincent Hospital)
state: Indiana
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Houma
country: United States
facility: Terrebonne General Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Missoula
country: United States
facility: St. Patrick's Hospital & Health Science Center
state: Montana
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Charlotte
country: United States
facility: Carolina's Medical Center (Sanger Clinic)
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Heart Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Endeavor Health
name: Ted Feldman, M.D. Feldman, M.D.
role: STUDY_DIRECTOR
affiliation: Duke University
name: Donald D Glower Jr., MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.