Comparison of the Outcomes of Single vs Multiple Arterial Grafts in Women

Official title

Randomized Comparison of the Outcomes of Single vs Multiple Arterial Grafts in Women (ROMA:Women) Trial

Overview

The central hypothesis of ROMA:Women is that the use of multiple arterial grafting (MAG) will improve clinical outcomes and quality of life (QOL) compared to single arterial grafting (SAG). The specific aims of ROMA:Women are: Aim 1: Determine the impact of MAG vs SAG on major adverse cardiac and cerebrovascular events in women undergoing coronary artery bypass grafting (CABG). The investigators will compare major adverse cardiac and cerebrovascular events (death, stroke, non-procedural myocardial infarction, repeat revascularization, and hospital readmission for acute coronary syndrome or heart failure) in a cohort of 2,300 women randomized 1:1 to MAG or SAG. Differences by important clinical and surgical subgroups (patients younger or older than 70 years, diabetics, racial and ethnic minorities, on vs off pump CABG, type of arterial grafts used) will also be evaluated. The women enrolled in the ongoing ROMA trial (anticipated to be approximately 690) will be included in ROMA:Women, increasing efficiency and reducing enrollment time. Hypothesis 1.0. MAG will reduce the incidence of major adverse cardiac and cerebrovascular events. Hypothesis 1.1. The improvement with MAG will be consistent across key subgroups. Aim 2: Determine the impact of MAG vs SAG on generic and disease-specific QOL, physical and mental health symptoms in women undergoing CABG. The investigators will compare generic (SF-12, EQ-5D) and disease-specific (Seattle Angina Questionnaire) QOL and physical and mental health symptoms (PROMIS-29) in a sub-cohort of 500 women randomized 1:1 to MAG or SAG (including those enrolled in ROMA:QOL). Differences by important subgroups (as defined above) will also be evaluated. Hypothesis 2.0. MAG will improve generic and disease-specific QOL compared to SAG. Hypothesis 2.1. MAG will improve physical and mental health symptoms compared to SAG. Hypothesis 2.2. The improvement with MAG will be consistent across key subgroups.

Detailed description

ROMA:Women will leverage the infrastructure and the existing women population of the ROMA trial. ROMA:Women has two key Aims. In Aim 1, the investigators will compare major adverse cardiac and cerebrovascular events (death, stroke, non-procedural myocardial infarction, repeat revascularization and hospital readmission for acute coronary syndrome or heart failure) in a cohort of 2,300 women randomized 1:1 to MAG or SAG. In Aim 2, the investigators will compare generic (SF-12, EQ-5D) and disease-specific (Seattle Angina Questionnaire) QOL and physical and mental health symptoms (PROMIS-29) in a sub-cohort of 500 women randomized 1:1 to MAG or SAG. Differences by important subgroups (patients younger or older than 70 years, diabetics, racial and ethnic minorities, on vs off pump CABG, type of arterial grafts used) will also be evaluated.

ROMA:Women is a two-arm, international, multi-center, randomized clinical trial nested in the ROMA trial. ROMA:Women will include all the women enrolled in the parent ROMA trial and will leverage the existing ROMA infrastructure including clinical trial unit, database, case report forms (CRF), randomization system, site training resources, informed consent forms (ICF), regulatory approvals, Central Events Review Committee (CEC) processes/personnel, network of participating sites, site PIs, and study coordinators. The planned randomization procedure, interventions and treatment arms, outcome assessments and follow-up protocol of ROMA:Women are identical to those of the currently ongoing parent ROMA trial. The sites participating in ROMA will continue enrollment of women after the completion of the ROMA trial and additional sites will also be opened to reach the target sample size of ROMA:Women.

Interventions

• Procedure Single arterial graft
  This interventions consists of patients receiving the left internal thoracic artery to the left anterior descending coronary artery of the heart. In addition to the left internal thoracic artery patients will receive venous grafts for all additional grafting.
• Procedure Multiple arterial grafting
  This intervention consists of the patient receiving the left internal thoracic artery to the left anterior descending coronary artery of the heart. The second arterial graft (right internal thoracic artery or radial artery) will be directed to the major branch of the circumflex. Additional grafts will include saphenous veins or arterial conduits.

Primary outcome measures

• Primary outcome for aim 1: Death from any cause, any stroke, non-procedural myocardial infarction, repeat revascularization and hospital readmission for acute coronary syndrome or heart failure. [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Primary outcome for aim 2: Disease-specific quality of life [Time frame: Postoperatively, minimum 2.5 year follow-up]

Secondary outcome measures (11)

• Death from any cause, any stroke, non-procedural myocardial infarction, and repeat revascularization. [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Death from cardiac cause, any stroke, non-procedural myocardial infarction, repeat revascularization and hospital readmission for acute coronary syndrome or heart failure. [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Death from any cause [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Stroke [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Non-procedural myocardial infarction [Time frame: > 48 hours postoperatively, minimum 2.5 year follow-up]
• Repeat revascularization [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Readmission for acute coronary syndrome [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Readmission for heart failure [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Generic quality of life according to the Short Form Health Survey (SF-12v2) [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Generic quality of life according to EuroQuol-5D (EQ-5D) [Time frame: Postoperatively, minimum 2.5 year follow-up]
• Mental and physical health symptoms according to PROMIS instruments [Time frame: Postoperatively, minimum 2.5 year follow-up]

Eligibility criteria

Inclusion criteria

• Women patients ≥18 years old.
• Isolated coronary artery bypass grafting.
• Primary (first time) cardiac surgery procedure.
• Significant disease of the left main coronary artery or of the left anterior descending and the circumflex coronary system with or without disease of the right coronary artery.

Exclusion criteria

• Male gender
• Single graft
• Emergency operation
• Myocardial infarction within 72 hours of surgery
• Left ventricular ejection fraction < 35%
• Any concomitant cardiac or non-cardiac procedure
• Previous cardiac surgery
• Preoperative severe end-organ dysfunction (dialysis, liver failure, respiratory failure), cancer or any co-morbidity that reduces life expectancy to less than 5 years.
• Inability to use the saphenous vein or to use both radial and right internal thoracic arteries
• Anticipated need for coronary thrombo-endarterectomy
• Planned hybrid revascularization

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 42 centers

• Cedars-Sinai Medical Center — Los Angeles
• Pomona Valley Hospital Medical Center — Pomona
• University of California, San Francisco — San Francisco
• University of Colorado — Aurora
• Hartford Hospital — Hartford
• Yale University Hospital — New Haven
• Emory University — Atlanta
• University of Chicago — Chicago
• … and 34 more centers

United Kingdom · 18 centers

Center list to be confirmed — check the primary protocol.

Canada · 16 centers

• Mazankowski Alberta Heart Institute — Edmonton
• St. Boniface General Hospital — Winnipeg
• Horizon Health Network - Saint John Regional Hospital — Saint John
• Newfoundland and Labrador Health Services — St. John's
• Health Sciences North — Greater Sudbury
• Hamilton General Hospital — Hamilton
• London Health Sciences — London
• University of Ottawa Heart Institute — Ottawa
• … and 8 more centers

Germany · 16 centers

• Universitäts-Herzzentrum Bad Krozingen Freiburg — Bad Krozingen
• HDZ NRW Bad Oeynhausen Germany — Bad Oeynhausen
• Deutsches Herzzentrum der Charite — Berlin
• … and 13 more centers

Italy · 8 centers

Center list to be confirmed — check the primary protocol.

Austria · 5 centers

• Medical University of Graz — Graz
• Innsbruck Medical University — Innsbruck
• Kepler University Hospital — Linz
• Medical University of Vienna — Vienna
• Krankenhaus Nord Vienna North Hospital — Vienna

China · 4 centers

• Fuwai Hospital China — Beijing
• Jilin Heart Hospital China — Changchun
• Ruijin Hospital Shanghai Jiao Tong University School of Medicine — Shanghai
• Teda Hospital Tianjin China — Tianjin

Spain · 4 centers

Center list to be confirmed — check the primary protocol.

Brazil · 3 centers

• Institute of Cardiology Porto Alegre — Porto Alegre
• Heart Institute University of São Paulo — São Paulo
• Instituto Dante Pazzanese de Cardiologia — Vila Mariana

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Poland · 3 centers

Center list to be confirmed — check the primary protocol.

Portugal · 3 centers

Center list to be confirmed — check the primary protocol.

Australia · 2 centers

• Victorian Heart Hospital — Clayton
• The University of Melbourne — Melbourne

Czechia · 2 centers

• University Hradec Králové — Hradec Králové
• General University Hospital, Prague — New Town

Denmark · 2 centers

• Aalborg University Hospital — Aalborg
• Rigshospitalet — Copenhagen

India · 2 centers

Center list to be confirmed — check the primary protocol.

Japan · 2 centers

Center list to be confirmed — check the primary protocol.

South Korea · 2 centers

Center list to be confirmed — check the primary protocol.

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Croatia · 1 center

• University Hospital Dubrava — Zagreb

Israel · 1 center

Center list to be confirmed — check the primary protocol.

North Macedonia · 1 center

Center list to be confirmed — check the primary protocol.

Russia · 1 center

Center list to be confirmed — check the primary protocol.

Serbia · 1 center

Center list to be confirmed — check the primary protocol.

Singapore · 1 center

Center list to be confirmed — check the primary protocol.

Taiwan · 1 center

Center list to be confirmed — check the primary protocol.

Publications

• Loop FD, Lytle BW, Cosgrove DM, Stewart RW, Goormastic M, Williams GW, Golding LA, Gill CC, Taylor PC, Sheldon WC, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med. 1986 Jan 2;314(1):1-6. doi: 10.1056/NEJM198601023140101. PMID 3484393
• Tatoulis J, Buxton BF, Fuller JA. Patencies of 2127 arterial to coronary conduits over 15 years. Ann Thorac Surg. 2004 Jan;77(1):93-101. doi: 10.1016/s0003-4975(03)01331-6. PMID 14726042
• Lytle BW, Blackstone EH, Loop FD, Houghtaling PL, Arnold JH, Akhrass R, McCarthy PM, Cosgrove DM. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg. 1999 May;117(5):855-72. doi: 10.1016/S0022-5223(99)70365-X. PMID 10220677
• Taggart DP, D'Amico R, Altman DG. Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet. 2001 Sep 15;358(9285):870-5. doi: 10.1016/S0140-6736(01)06069-X. PMID 11567701
• Yi G, Shine B, Rehman SM, Altman DG, Taggart DP. Effect of bilateral internal mammary artery grafts on long-term survival: a meta-analysis approach. Circulation. 2014 Aug 12;130(7):539-45. doi: 10.1161/CIRCULATIONAHA.113.004255. Epub 2014 Jun 10. PMID 24916209
• Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, Cigarroa JE, Disesa VJ, Hiratzka LF, Hutter AM Jr, Jessen ME, Keeley EC, Lahey SJ, Lange RA, London MJ, Mack MJ, Patel MR, Puskas JD, Sabik JF, Selnes O, Shahian DM, Trost JC, Winniford MD; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surge PMID 22070836
• Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial PMID 25173339
• Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik J, Rosengart T, Kappetein AP, Thourani VH, Firestone S, Mitchell JD; Society of Thoracic Surgeons. The Society of Thoracic Surgeons Clinical Practice Guidelines on Arterial Conduits for Coronary Artery Bypass Grafting. Ann Thorac Surg. 2016 Feb;101(2):801-9. doi: 10.1016/j.athoracsur.2015.09.100. Epub 2015 Dec 8. PMID 26680310

Identifiers

NCT: NCT04124120 · 1703018094-ROMA-Women

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗