Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation

NCT00807040 | Completed Phase 2 Results DMC

• 4 other identifiers: GCO 08-1078-00002U01HL088942U01 HL088942-01-2595
• Study Type: interventional
• Target: 251
• Locations: 2 countries
• Sites: 21

Brief Summary

People with coronary artery disease (CAD) or people who have had a heart attack may develop a leak in the mitral valve of their heart and may therefore need to undergo surgery to fix the valve. The best way to fix the mitral valve remains undetermined. This study will evaluate whether it is better for people with severe mitral valve leakage to undergo a mitral valve replacement procedure or a mitral valve repair procedure.

Conditions

Mitral Valve Insufficiency; Coronary Artery Disease

Keywords

Ischemic Mitral Regurgitation; Mitral Valve Disease; Severe Mitral Regurgitation

Outcome Measures

Primary Outcomes (1)

• Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI)

  Measured at Month 12

Secondary Outcomes (1)

• All-cause Mortality

  Measured at Month 24

Study Arms (2)

Mitral Valve Repair with Annuloplasty

ACTIVE COMPARATOR

Participants will undergo mitral valve repair with annuloplasty and a sub-valvular procedure for severe tethering.

Procedure: Mitral Valve Repair with Annuloplasty

Mitral Valve Replacement

ACTIVE COMPARATOR

Participants will undergo mitral valve replacement and complete preservation of the sub-valvular apparatus.

Procedure: Mitral Valve Replacement

Interventions

Mitral Valve Repair with Annuloplasty PROCEDURE

The annuloplasty ring will be chosen by the surgeon. The ring is sized to the anterior leaflet and intertrigonal distance. A semi-rigid or rigid annuloplasty ring will be used, and if tethering is present, a subvalvar procedure will be performed.

Mitral Valve Repair with Annuloplasty

Mitral Valve Replacement PROCEDURE

Mitral valve replacement will include complete preservation of the subvalvar apparatus. The technique of preservation, choice of prosthetic valve, and technique of suture placement will be dependent on the surgeon's preference. The prosthetic valve will be tested for paravalvular leaks by using the left ventricular saline infusion test.

Mitral Valve Replacement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic severe ischemic mitral regurgitation (often with tethering as a major mechanism) in the judgment of the clinical site echocardiographer, assessed by transthoracic echocardiogram. Assessment of mitral regurgitation will be performed using an integrative method (Zoghbi W. et al. J. American Society of Echocardiography. 2003:16:777-802. see appendix). Quantitative guidelines as proposed would be: ERO ≥ 0.4 cmsq. If ERO \< 0.4, then the degree of mitral regurgitation will be guided by other color Doppler quantitative methods (jet area/left atrial area ratio, vena contracta, supportive criteria in an integrated fashion
• Eligible for surgical repair and replacement of mitral valve
• CAD with or without the need for coronary revascularization

You may not qualify if:

• Any evidence of structural (chordal or leaflet) mitral valve disease or ruptured papillary muscle
• Prior mitral valve repair
• Severe irreversible pulmonary hypertension in the judgment of the investigator
• Medically unable to undergo cardiopulmonary bypass (CPB)
• Inability to derive ERO and end-systolic volume index (ESVI) by transthoracic echocardiography
• Planned concomitant intra-operative procedures (with the exception of tricuspid valve repair, closure of patent foramen ovale \[PFO\] or atrial septal defect \[ASD\] or Maze procedure)
• Clinical signs of cardiogenic shock at the time of surgery
• Treatment with long-term intravenous inotropic therapy at the time of surgery
• ST segment elevation myocardial infarction (MI) requiring intervention in the 7 days before surgery
• Congenital heart disease (except PFO or ASD)
• Evidence of cirrhosis or liver synthetic failure
• Excessive surgical risk, as judged by the surgical investigator
• Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair compliance with the study, as judged by the investigator
• Therapy with an investigational intervention at the time of screening, or planning to enroll in an additional investigational intervention study during participation in this study
• Any concurrent disease with a life expectancy of less than 2 years

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (21)

University of Southern California

Los Angeles, California, 90033, United States

Location

Emory University

Atlanta, Georgia, 30383, United States

Location

Wellstar Kennestone Hospital

Marietta, Georgia, 30060, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

NIH Heart Center at Suburban Hospital

Bethesda, Maryland, 20892, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Einstein Heart Center

The Bronx, New York, 10467, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

East Carolina Heart Institute

Greenville, North Carolina, 27834, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor Research Institute

Plano, Texas, 75093, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, QC H4J 1C5, Canada

Location

Quebec Heart Institute/Laval Hopital

Québec, H7M 3L9, Canada

Location

Related Publications (7)

• Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, Smith PK, Hung JW, Blackstone EH, Puskas JD, Argenziano M, Gammie JS, Mack M, Ascheim DD, Bagiella E, Moquete EG, Ferguson TB, Horvath KA, Geller NL, Miller MA, Woo YJ, D'Alessandro DA, Ailawadi G, Dagenais F, Gardner TJ, O'Gara PT, Michler RE, Kron IL; CTSN. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med. 2014 Jan 2;370(1):23-32. doi: 10.1056/NEJMoa1312808. Epub 2013 Nov 18.

  PMID: 24245543 RESULT

• Bertrand PB, Overbey JR, Zeng X, Levine RA, Ailawadi G, Acker MA, Smith PK, Thourani VH, Bagiella E, Miller MA, Gupta L, Mack MJ, Gillinov AM, Giustino G, Moskowitz AJ, Gelijns AC, Bowdish ME, O'Gara PT, Gammie JS, Hung J; Cardiothoracic Surgical Trials Network (CTSN). Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation. J Am Coll Cardiol. 2021 Feb 16;77(6):713-724. doi: 10.1016/j.jacc.2020.11.066.

  PMID: 33573741 DERIVED

• Giustino G, Overbey J, Taylor D, Ailawadi G, Kirkwood K, DeRose J, Gillinov MA, Dagenais F, Mayer ML, Moskowitz A, Bagiella E, Miller M, Grayburn P, Smith PK, Gelijns A, O'Gara P, Acker M, Lala A, Hung J. Sex-Based Differences in Outcomes After Mitral Valve Surgery for Severe Ischemic Mitral Regurgitation: From the Cardiothoracic Surgical Trials Network. JACC Heart Fail. 2019 Jun;7(6):481-490. doi: 10.1016/j.jchf.2019.03.001.

  PMID: 31146872 DERIVED

• Ferket BS, Ailawadi G, Gelijns AC, Acker M, Hohmann SF, Chang HL, Bouchard, D, Meltzer DO, Michler RE, Moquete EG, Voisine P, Mullen JC, Lala A, Mack MJ, Gillinov AM, Thourani VH, Miller MA, Gammie JS, Parides MK, Bagiella E, Smith RL, Smith PK, Hung JW, Gupta LN, Rose EA, O'Gara PT, Moskowitz AJ, Cardiothoracic Surgical Trials Network (CTSN) Investigators. Cost-Effectiveness of Mitral Valve Repair Versus Replacement for Severe Ischemic Mitral Regurgitation: A Randomized Clinical Trial From the Cardiothoracic Surgical Trials Network. Circ Cardiovasc Qual Outcomes. 2018 Nov 14;11(11):e004466. doi: 10.1161/CIRCOUTCOMES.117.004466.

  PMID: 30785252 DERIVED

• Capoulade R, Zeng X, Overbey JR, Ailawadi G, Alexander JH, Ascheim D, Bowdish M, Gelijns AC, Grayburn P, Kron IL, Levine RA, Mack MJ, Melnitchouk S, Michler RE, Mullen JC, O'Gara P, Parides MK, Smith P, Voisine P, Hung J; Cardiothoracic Surgical Trials Network (CTSN) Investigators. Impact of Left Ventricular to Mitral Valve Ring Mismatch on Recurrent Ischemic Mitral Regurgitation After Ring Annuloplasty. Circulation. 2016 Oct 25;134(17):1247-1256. doi: 10.1161/CIRCULATIONAHA.115.021014.

  PMID: 27777294 DERIVED

• Goldstein D, Moskowitz AJ, Gelijns AC, Ailawadi G, Parides MK, Perrault LP, Hung JW, Voisine P, Dagenais F, Gillinov AM, Thourani V, Argenziano M, Gammie JS, Mack M, Demers P, Atluri P, Rose EA, O'Sullivan K, Williams DL, Bagiella E, Michler RE, Weisel RD, Miller MA, Geller NL, Taddei-Peters WC, Smith PK, Moquete E, Overbey JR, Kron IL, O'Gara PT, Acker MA; CTSN. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med. 2016 Jan 28;374(4):344-53. doi: 10.1056/NEJMoa1512913. Epub 2015 Nov 9.

  PMID: 26550689 DERIVED

• Kron IL, Hung J, Overbey JR, Bouchard D, Gelijns AC, Moskowitz AJ, Voisine P, O'Gara PT, Argenziano M, Michler RE, Gillinov M, Puskas JD, Gammie JS, Mack MJ, Smith PK, Sai-Sudhakar C, Gardner TJ, Ailawadi G, Zeng X, O'Sullivan K, Parides MK, Swayze R, Thourani V, Rose EA, Perrault LP, Acker MA; CTSN Investigators. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg. 2015 Mar;149(3):752-61.e1. doi: 10.1016/j.jtcvs.2014.10.120. Epub 2014 Nov 6.

  PMID: 25500293 DERIVED

Related Links

• Click here for the Cardiothoracic Surgical Trials Network Web site.

MeSH Terms

Conditions

Mitral Valve Insufficiency; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Alan Moskowitz, MD
• Organization: Icahn School of Medicine at Mount Sinai

alan.moskowitz@mountsinai.org

212-659-9568

Study Officials

• Timothy Gardner, MD

  Christiana Care Health Services

  STUDY CHAIR

• Patrick O'Gara, MD

  Brigham and Women's Hospital

  STUDY CHAIR

• Annetine C. Gelijns, Ph.D.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 10, 2008
• First Posted: December 11, 2008
• Study Start: December 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: March 1, 2014
• Last Updated: March 15, 2019
• Results First Posted: July 31, 2017

Record last verified: 2019-02

Locations

CA (3); US (18)