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

NCT ID: NCT00807040

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 251 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2014-03-31

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.

Detailed Description

CAD occurs when the arteries that supply blood to the heart become blocked as a result of plaque buildup. In severe cases, CAD can cause chest pain, shortness of breath, and heart attack. After a heart attack, some people may develop a leak in the mitral valve of the heart. This condition is known as ischemic mitral regurgitation (IMR), and it can cause blood to flow backward into the heart. If left untreated, severe IMR can lead to heart failure or serious heart rhythm irregularities, known as arrhythmias. People with severe mitral valve leakage routinely undergo one of two surgical procedures to fix the mitral valve: a mitral valve repair procedure, in which a surgical ring is used to repair the valve; or a mitral valve replacement procedure, in which the damaged valve is replaced with a new one. Currently, there is no consensus in the medical community as to which procedure is more beneficial. The purpose of this study is to determine whether people with severe mitral valve regurgitation should undergo a mitral valve repair procedure or a mitral valve replacement procedure.

This study will enroll people with CAD who have severe mitral regurgitation. At a baseline study visit, participants will undergo a physical examination; blood collection; neurocognitive tests; and questionnaires regarding medical history, medication history, and quality of life. In the operating room, participants will be randomly assigned to undergo either the mitral valve repair procedure or the mitral valve replacement procedure. Blood, urine, and tissue samples may be collected from participants after the surgery; this is optional and will only be done with prior approval from participants. All participants will attend study visits at Day 30 and Months 6, 12, and 24. At each visit, participants will take part in a medication history review, a physical examination, an echocardiogram, a cardiopulmonary exercise test, neurocognitive tests, and quality of life surveys.

Conditions

Mitral Valve Insufficiency; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Mitral Valve Repair with Annuloplasty

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

Group Type: ACTIVE_COMPARATOR

Mitral Valve Repair with Annuloplasty

Intervention Type: 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 Replacement

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

Group Type: ACTIVE_COMPARATOR

Mitral Valve Replacement

Intervention Type: 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.

Interventions

Mitral Valve Repair with Annuloplasty

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.

Intervention Type: PROCEDURE

Mitral Valve Replacement

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Pregnant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Alan Moskowitz

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timothy Gardner, MD

Role: STUDY_CHAIR

Christiana Care Health Services

Patrick O'Gara, MD

Role: STUDY_CHAIR

Brigham and Women's Hospital

Annetine C. Gelijns, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

University of Southern California

Los Angeles, California, United States

Emory University

Atlanta, Georgia, United States

Wellstar Kennestone Hospital

Marietta, Georgia, United States

University of Maryland

Baltimore, Maryland, United States

NIH Heart Center at Suburban Hospital

Bethesda, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Einstein Heart Center

The Bronx, New York, United States

Mission Hospital

Asheville, North Carolina, United States

Duke University

Durham, North Carolina, United States

East Carolina Heart Institute

Greenville, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor Research Institute

Plano, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

Montreal Heart Institute

Montreal, Quebec, Canada

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Quebec Heart Institute/Laval Hopital

Québec, , Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 24245543 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33573741 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31146872 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30785252 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27777294 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26550689 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25500293 (View on PubMed)

Related Links

http://www.ctsurgerynet.org/

Click here for the Cardiothoracic Surgical Trials Network Web site.

Other Identifiers

U01HL088942

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01 HL088942-01-2

Identifier Type: -

Identifier Source: secondary_id

595

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 08-1078-00002

Identifier Type: -

Identifier Source: org_study_id

NCT00919256

Identifier Type: -

Identifier Source: nct_alias