Clinical trial NCT00806988: 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
Official title: Surgical Interventions for Moderate Ischemic Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitral Valve Insufficiency
Coronary Artery Disease
Keywords: Ischemic Mitral Regurgitation
Mitral Valve Regurgitation
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Canadian Institutes of Health Research (CIHR)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2008-12-11
Enrollment: 301
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Degree of Left Ventricular Remodeling, as Assessed by Left Ventricular End Systolic Volume Index (LVESVI)
timeFrame: Measured at Month 12
Secondary outcomes:
measure: Major Adverse Cardiac Event, Including Death, Stroke, Worsening Heart Failure (+1 New York Heart Association [NYHA] Class), Congestive Heart Failure Hospitalization, or Mitral Valve Re-intervention
timeFrame: Measured at Month 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Bethesda
country: United States
facility: NIH Heart Center at Suburban Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: St Louis
country: United States
facility: Washington University
state: Missouri
city: Bronx
country: United States
facility: Montefiore Einstein Heart Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University
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: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Plano
country: United States
facility: Baylor Research Institute
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Toronto
country: Canada
facility: University of Toronto Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Saint Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto, Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
city: Quebec
country: Canada
facility: Quebec Heart Institute/Laval Hopital
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Christiana Care Health Services
name: Timothy Gardner, MD
role: STUDY_CHAIR
affiliation: Brigham and Women's Hospital
name: Patrick O'Gara, MD
role: STUDY_CHAIR
affiliation: Icahn School of Medicine at Mount Sinai
name: Annetine Gelijns, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Alan Moskowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.