Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting (CABG) Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation

NCT ID: NCT00806988

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2015-05-31

Brief Summary

Coronary artery bypass grafting (CABG) is a procedure that people with coronary artery disease (CAD) may undergo to increase blood flow to the heart. During a CABG procedure, people who have a leak in one of the valves in the heart-the mitral valve-may at the same time undergo a procedure that repairs the valve. This study will evaluate whether people with moderate mitral valve leakage would be better off undergoing CABG plus the mitral valve repair procedure or undergoing CABG alone.

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. CABG is one treatment option for people with CAD. During a CABG procedure, a healthy artery or vein from another part of the body is connected to the blocked coronary artery. Blood flow is then routed around the blockage to the heart.

After a heart attack, some people may have a leak in the mitral valve of the heart. This condition is known as ischemic mitral regurgitation (IMR) and is associated with poor health outcomes, including worsening heart failure. In people with severe mitral valve leakage, the CABG procedure and a mitral valve repair procedure are routinely performed together; however, in people with only moderate valve leakage, there is no consensus in the medical community as to whether the mitral valve repair procedure is beneficial at the time of CABG. The purpose of this study is to determine whether people with moderate mitral valve regurgitation should undergo a mitral valve repair procedure in addition to CABG or undergo CABG alone.

This study will enroll people with CAD who require a CABG procedure and have moderate 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 CABG surgery and the mitral valve repair procedure or only CABG surgery. 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 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

Participants will undergo CABG and a mitral valve repair procedure.

Group Type: ACTIVE_COMPARATOR

Mitral Valve Repair

Intervention Type: PROCEDURE

Surgical techniques for mitral valve repair may need to be adjusted at the discretion of the surgeon, as based on intra-operative findings that may not be previously recognized in the pre-operative evaluation. The common elements for mitral annuloplasty planned as part of this study include the following:

1. All procedures will be performed with cardiopulmonary bypass (CPB) and with moderate hypothermia. Cannulation will be central with aortic cannulation for arterial inflow from the cardiopulmonary bypass circuit. Right atrial or bicaval (inferior and superior vena cava) drainage cannulas will be employed.

2. The heart will be arrested with cardioplegia.

3. A complete annular ring shall be placed unless specifically contraindicated by intra-operative findings. Additional repair of the mitral apparatus itself will be based on intra-operative findings.

CABG

Intervention Type: PROCEDURE

CABG will be performed using standard surgical techniques. Conduit selection and harvesting methods will not be prescribed, except that utilization of the left internal mammary artery (LIMA) is recommended when a left anterior descending (LAD) graft is indicated. The technical details of bypass grafting will not be prescribed. Complete revascularization will be performed, within the judgment of the surgical investigator.

CABG

Participants will undergo CABG.

Group Type: ACTIVE_COMPARATOR

CABG

Intervention Type: PROCEDURE

CABG will be performed using standard surgical techniques. Conduit selection and harvesting methods will not be prescribed, except that utilization of the left internal mammary artery (LIMA) is recommended when a left anterior descending (LAD) graft is indicated. The technical details of bypass grafting will not be prescribed. Complete revascularization will be performed, within the judgment of the surgical investigator.

Interventions

Mitral Valve Repair

Surgical techniques for mitral valve repair may need to be adjusted at the discretion of the surgeon, as based on intra-operative findings that may not be previously recognized in the pre-operative evaluation. The common elements for mitral annuloplasty planned as part of this study include the following:

1. All procedures will be performed with cardiopulmonary bypass (CPB) and with moderate hypothermia. Cannulation will be central with aortic cannulation for arterial inflow from the cardiopulmonary bypass circuit. Right atrial or bicaval (inferior and superior vena cava) drainage cannulas will be employed.

2. The heart will be arrested with cardioplegia.

3. A complete annular ring shall be placed unless specifically contraindicated by intra-operative findings. Additional repair of the mitral apparatus itself will be based on intra-operative findings.

Intervention Type: PROCEDURE

CABG

CABG will be performed using standard surgical techniques. Conduit selection and harvesting methods will not be prescribed, except that utilization of the left internal mammary artery (LIMA) is recommended when a left anterior descending (LAD) graft is indicated. The technical details of bypass grafting will not be prescribed. Complete revascularization will be performed, within the judgment of the surgical investigator.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Moderate mitral regurgitation 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 between 0.2 cmsq to 0.39 cmsq. If ERO < 0.2, 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
• CAD that is amenable to CABG and a clinical indication for revascularization
• Age ≥ 18 years

Exclusion Criteria

• Any evidence of structural (chordal or leaflet) mitral valve disease
• Inability to derive ERO and end-systolic volume index (ESVI) by transthoracic echocardiography
• Planned concomitant intra-operative procedures (with the exception of closure of patent foramen ovale [PFO] or atrial septal defect [ASD]or Maze procedure or left atrial appendage excision)
• Prior surgical or percutaneous mitral valve repair
• Contraindication to cardiopulmonary bypass (CPB)
• Clinical signs of cardiogenic shock at the time of surgery
• Treatment with chronic intravenous inotropic therapy at the time of surgery
• Severe, irreversible pulmonary hypertension in the judgment of the investigator
• 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
• Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair compliance with the study, in the judgment of 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 the study
• Any concurrent disease with a life expectancy of less than 2 years
• Pregnancy at the time of randomization

• 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 Gelijns, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Alan Moskowitz, MD

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

Baystate Medical Center

Springfield, 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

University of Alberta Hospital

Edmonton, Alberta, Canada

University of Toronto Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Saint Michael's Hospital

Toronto, Ontario, Canada

University of Toronto, Toronto General Hospital

Toronto, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Quebec Heart Institute/Laval Hopital

Québec, Quebec, Canada

Aarhus University Hospital

Aarhus N, , Denmark

Countries

United States; Canada; Denmark

References

Smith PK, Puskas JD, Ascheim DD, Voisine P, Gelijns AC, Moskowitz AJ, Hung JW, Parides MK, Ailawadi G, Perrault LP, Acker MA, Argenziano M, Thourani V, Gammie JS, Miller MA, Page P, Overbey JR, Bagiella E, Dagenais F, Blackstone EH, Kron IL, Goldstein DJ, Rose EA, Moquete EG, Jeffries N, Gardner TJ, O'Gara PT, Alexander JH, Michler RE; Cardiothoracic Surgical Trials Network Investigators. Surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med. 2014 Dec 4;371(23):2178-88. doi: 10.1056/NEJMoa1410490. Epub 2014 Nov 18.

Reference Type: RESULT

PMID: 25405390 (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)

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)

Michler RE, Smith PK, Parides MK, Ailawadi G, Thourani V, Moskowitz AJ, Acker MA, Hung JW, Chang HL, Perrault LP, Gillinov AM, Argenziano M, Bagiella E, Overbey JR, Moquete EG, Gupta LN, Miller MA, Taddei-Peters WC, Jeffries N, Weisel RD, Rose EA, Gammie JS, DeRose JJ Jr, Puskas JD, Dagenais F, Burks SG, El-Hamamsy I, Milano CA, Atluri P, Voisine P, O'Gara PT, Gelijns AC; CTSN. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med. 2016 May 19;374(20):1932-41. doi: 10.1056/NEJMoa1602003. Epub 2016 Apr 3.

Reference Type: DERIVED

PMID: 27040451 (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

594

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 08-1078-00003

Identifier Type: -

Identifier Source: org_study_id

NCT00838786

Identifier Type: -

Identifier Source: nct_alias