Randomization of Single vs Multiple Arterial Grafts

Official title

Randomized Comparison of the Clinical Outcome of Single Versus Multiple Arterial Grafts: the ROMA Trial

Overview

The primary hypothesis of ROMA is that in patients undergoing primary isolated non-emergent coronary artery bypass surgery (CABG), the use of two or more arterial grafts compared to a single arterial graft is associated with a reduction in the composite outcome of death from any cause, any stroke, post discharge myocardial infarction and/or repeat revascularization. The secondary hypothesis is that in patients undergoing primary isolated non-emergent CABG, the use of two or more arterial grafts compared to a single arterial graft is associated with improved survival. Prospective event-driven unblinded randomized multicenter trial of at least 4,300 subjects enrolled in at least 25 international centers. Patients will be randomized to a single arterial graft (SAG) or multiple arterial grafts (MAG). Patients will be randomized in a 1:1 fashion between the two groups. Permuted block randomization with random blocks stratified by the center and the type of second arterial graft will be used to provide treatment distribution in equal proportion.

Detailed description

In the 1980's, it was recognized that long-term survival was enhanced in patients undergoing coronary surgery when the left anterior descending (LAD) was grafted with a left internal thoracic artery (ITA) rather than a saphenous vein (1). This difference was predicated, at least in part, due to greater and more durable patency of the left ITA compared to an increased early occlusion rate and later progressive atherosclerosis of saphenous vein grafts (SVG) (2).

For more than 20 years it has generally been accepted that patients who receive multiple arterial grafts (AGs) at the time of coronary artery bypass surgery (CABG) have increased postoperative survival compared to those who receive only one AG, especially over the long term (3-5). The current United States and European Guidelines encourage the use of AGs in patients with a long life expectancy (6, 7). Last year, a position paper from the Society of Thoracic Surgeons strongly recommended a wider use of AGs (8).

The putative mechanism underlying the AG hypothesis is greater patency. In line with the original findings of improved LAD graft patency with ITA vs. SVG, data from randomized control trials (RCTs) as well as observational studies and a network meta-analysis (9) have demonstrated that the patency of the RA, as well as the right ITA, exceed that of a SVG, providing mechanistic basis to support the AG hypothesis.

ROMA is a two arm event driven randomized multi-centre trial aimed at evaluating the impact of the use of one ITA vs two or more AGs for CABG on a composite of death from any cause, any stroke, post discharge myocardial infarction and/or repeat revascularization. The trial is powered to detect a 20% relative reduction in the primary outcome with 90% power at 5% alpha.

The primary aim is to conduct a multicenter international randomized control trial to test the hypothesis that the use of a two or more AGs compared to a single arterial graft is associated with a reduction in the composite outcome of death from any cause, any stroke, post discharge myocardial infarction and/or repeat revascularization.

The secondary aim is to conduct a multicenter international randomized control trial to test the hypothesis that the use of two or more AGs compared to a single arterial graft is associated with improved survival.

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

• Composite Outcome [Time frame: > 72 hours after surgery and/or repeat revascularization]

Secondary outcome measures (7)

• 30-day mortality [Time frame: 30 days post-operatively]
• Major postoperative complications [Time frame: In-hospital stay, up to 30 days post-operatively]
• Sternal wound complication [Time frame: 6 months post-operatively]
• Composite Outcome of Death from any cause [Time frame: Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years.]
• Stroke [Time frame: Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years.]
• Cause-specific death (cardiac vs non-cardiac) [Time frame: Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years]
• Hospital readmissions [Time frame: Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years]

Eligibility criteria

Inclusion criteria

• Primary isolated CABG patients with disease of the left main coronary artery and/or of the left anterior descending and the circumflex coronary system with or without disease of the right coronary artery.

Exclusion criteria

• Age > 70 years
• Single graft
• Emergency operation
• Evolving myocardial infarction within 48 hours of surgery
• Left ventricular ejection fraction of < 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 reduce 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 · 11 centers

• University of Colorado — Boulder
• Baystate Health — Springfield
• Nebraska Heart Hospital — Lincoln
• University of Nebraska Medical Center — Omaha
• NewYork-Presbyterian Brooklyn Methodist Hospital — Brooklyn
• Icahn School of Medicine, Mount Sinai — New York
• Weil Cornell Medical College Department of Cardiothoracic Surgery — New York
• Lenox Hill Hospital (Northwell) — New York
• … and 3 more centers

Germany · 11 centers

• Duisburg Heart Center — Duisburg
• Essen University — Duisburg
• Düsseldorf University — Düsseldorf
• University Hospital Erlangen — Erlangen
• Giessen Hospital — Giessen
• University Medical Center of Goettingen — Göttingen
• Jena University Hospital — Jena
• Heart Center (Herzzentrum) — Leipzig
• … and 3 more centers

Canada · 9 centers

• Hamilton General Hospital — Hamilton
• London Health Sciences Ontario Canada — London
• University Hospital of Montreal (CHUM) — Montreal
• University of Ottawa Heart Institute Canada — Ottawa
• Royal Victoria Hospital (McGill) — Québec
• Universite Laval Quebec (CRIUCPQ) Canada — Québec
• Sunnybrook Health Sciences Centre — Toronto
• Toronto General Hospital — Toronto
• … and 1 more center

Italy · 6 centers

• Anthea Hospital — Bari
• Fondazione Poliambulanza — Brescia
• Maria Cecilia Hospital GVM — Cotignola
• Universita' Cattolica del Sacro Cuore — Roma
• European Hospital — Rome
• Ospedale Le Molinette — Torino

China · 5 centers

• Fuwai Hospital — Beijing
• Jilin Heart Hospital — Changchun
• Ruijin Hospital Shanghai Jiao Tong University School of Medicine — Shanghai
• National Taiwan University Hospital — Taiwan
• Teda Hospital (TICH) — Tianjin

Austria · 3 centers

• Innsbruck (Medical University) Austria — Innsbruck
• Krankenhaus Nord Vienna North Hospital — Vienna
• MU Vienna Austria — Vienna

Portugal · 3 centers

• Hospitalar de Lisboa Central — Capuchos
• University Hospital (Praceta Mota Pinto) — Coimbra
• Centro Hospitalar e Universitário São João — Porto

Spain · 2 centers

• Hospital Univeritario Del Vinalopo — Alicante
• Hospital Clinic de Barcelona (ICCV) — Barcelona

Brazil · 1 center

• Federal University of Sao Paulo — São Paulo

Croatia · 1 center

• University Hospital Dubrava — Zagreb

Czechia · 1 center

• General University Hospital, Prague — Prague

Japan · 1 center

• Saitama Medical University — Saitama

Netherlands · 1 center

• MUMC Maastricht (University Medical Centre) — Maastricht

Poland · 1 center

• Medical University of Silesia (Katowice) — Katowice

Serbia · 1 center

• Dedinje Cardiovascular Institute — Belgrade

Singapore · 1 center

• National University of Singapore — Singapore

South Korea · 1 center

• Severance Cardiovascular Hospital, Yonsei University College of Medicine — Sinchŏn-dong

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. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Assoc PMID 22064599
• 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: NCT03217006 · 1703018094 · 1R01HL152021-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗