Clinical trial NCT00807040: Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation
Official title: Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mitral Valve Insufficiency
Coronary Artery Disease
Keywords: Ischemic Mitral Regurgitation
Mitral Valve Disease
Severe Mitral 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: 251
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: 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.

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

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: All-cause Mortality
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: Saint 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: 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
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 C. Gelijns, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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: 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.
citation: 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.
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: 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.
citation: 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.