Randomization of Single vs Multiple Arterial Grafts

Coronary Artery Disease Clinical Trial

— ROMA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03217006
• Other study ID #: 1703018094
• Secondary ID: 1R01HL152021-01
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 7, 2018
• Est. completion date: January 1, 2030

Study information

• Verified date: April 2023
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4300
• Est. completion date: January 1, 2030
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Austria	Innsbruck (Medical University) Austria	Innsbruck
Austria	Krankenhaus Nord Vienna North Hospital	Vienna
Austria	MU Vienna Austria	Vienna
Brazil	Federal University of Sao Paulo	São Paulo
Canada	Hamilton General Hospital	Hamilton
Canada	London Health Sciences Ontario Canada	London
Canada	University Hospital of Montreal (CHUM)	Montréal
Canada	University of Ottawa Heart Institute Canada	Ottawa
Canada	Royal Victoria Hospital (McGill)	Quebec
Canada	Universite Laval Quebec (CRIUCPQ) Canada	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto
Canada	Toronto General Hospital	Toronto
Canada	St. Boniface General Hospital / WHRA	Winnipeg
China	Fuwai Hospital	Beijing
China	Jilin Heart Hospital	Changchun
China	Ruijin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai
China	National Taiwan University Hospital	Taiwan
China	Teda Hospital (TICH)	Tianjin
Croatia	University Hospital Dubrava	Zagreb
Czechia	General University Hospital, Prague	Prague
Germany	Duisburg Heart Center	Duisburg
Germany	Essen University	Duisburg
Germany	Düsseldorf University	Düsseldorf
Germany	University Hospital Erlangen	Erlangen
Germany	Giessen Hospital	Giessen
Germany	University Medical Center of Goettingen	Göttingen
Germany	Jena University Hospital	Jena
Germany	Heart Center (Herzzentrum)	Leipzig
Germany	HDZ NRW Bad	Oeynhausen
Germany	Robert-Bosch-Hospital	Stuttgart
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
Italy	Anthea Hospital	Bari
Italy	Fondazione Poliambulanza	Brescia
Italy	Maria Cecilia Hospital GVM	Cotignola
Italy	Universita' Cattolica del Sacro Cuore	Roma
Italy	European Hospital	Rome
Italy	Ospedale Le Molinette	Torino
Japan	Saitama Medical University	Saitama
Korea, Republic of	Severance Cardiovascular Hospital, Yonsei University College of Medicine	Sinchon-dong
Netherlands	MUMC Maastricht (University Medical Centre)	Maastricht
Poland	Medical University of Silesia (Katowice)	Katowice
Portugal	Hospitalar de Lisboa Central	Capuchos
Portugal	University Hospital (Praceta Mota Pinto)	Coimbra
Portugal	Centro Hospitalar e Universitário São João	Porto
Serbia	Dedinje Cardiovascular Institute	Belgrade
Singapore	National University of Singapore	Singapore
Spain	Hospital Univeritario Del Vinalopo	Alicante
Spain	Hospital Clinic de Barcelona (ICCV)	Barcelona
United States	University of Colorado	Boulder	Colorado
United States	NewYork-Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Nebraska Heart Hospital	Lincoln	Nebraska
United States	Icahn School of Medicine, Mount Sinai	New York	New York
United States	Lenox Hill Hospital (Northwell)	New York	New York
United States	NewYork-Presbyterian Queens	New York	New York
United States	Weil Cornell Medical College Department of Cardiothoracic Surgery	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Allegheny General Hospital (Cardiovascular Institute)	Pittsburgh	Pennsylvania
United States	Baystate Health	Springfield	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Canadian Institutes of Health Research (CIHR), National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Canada,  China,  Croatia,  Czechia,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Serbia,  Singapore,  Spain, 

References & Publications (22)

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Benedetto U, Gaudino M, Caputo M, Tranbaugh RF, Lau C, Di Franco A, Ng C, Girardi LN, Angelini GD. Right internal thoracic artery versus radial artery as the second best arterial conduit: Insights from a meta-analysis of propensity-matched data on long-term survival. J Thorac Cardiovasc Surg. 2016 Oct;152(4):1083-1091.e15. doi: 10.1016/j.jtcvs.2016.05.022. Epub 2016 May 28. — View Citation

Benedetto U, Raja SG, Albanese A, Amrani M, Biondi-Zoccai G, Frati G. Searching for the second best graft for coronary artery bypass surgery: a network meta-analysis of randomized controlled trialsdagger. Eur J Cardiothorac Surg. 2015 Jan;47(1):59-65; discussion 65. doi: 10.1093/ejcts/ezu111. Epub 2014 Mar 30. — View Citation

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Gaudino M, Puskas JD, Di Franco A, Ohmes LB, Iannaccone M, Barbero U, Glineur D, Grau JB, Benedetto U, D'Ascenzo F, Gaita F, Girardi LN, Taggart DP. Three Arterial Grafts Improve Late Survival: A Meta-Analysis of Propensity-Matched Studies. Circulation. 2017 Mar 14;135(11):1036-1044. doi: 10.1161/CIRCULATIONAHA.116.025453. Epub 2017 Jan 24. — View Citation

Harskamp RE, Alexander JH, Ferguson TB Jr, Hager R, Mack MJ, Englum B, Wojdyla D, Schulte PJ, Kouchoukos NT, de Winter RJ, Gibson CM, Peterson ED, Harrington RA, Smith PK, Lopes RD. Frequency and Predictors of Internal Mammary Artery Graft Failure and Subsequent Clinical Outcomes: Insights From the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV Trial. Circulation. 2016 Jan 12;133(2):131-8. doi: 10.1161/CIRCULATIONAHA.115.015549. Epub 2015 Dec 8. — View Citation

Hayward PA, Buxton BF. Mid-term results of the Radial Artery Patency and Clinical Outcomes randomized trial. Ann Cardiothorac Surg. 2013 Jul;2(4):458-66. doi: 10.3978/j.issn.2225-319X.2013.07.18. — View Citation

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 Association Task Force on Practice Guidelines. Circulation. 2011 Dec 6;124(23):e652-735. doi: 10.1161/CIR.0b013e31823c074e. Epub 2011 Nov 7. No abstract available. Erratum In: Circulation. 2011 Dec 20;124(25):e957. — View Citation

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. — View Citation

Lopes RD, Mehta RH, Hafley GE, Williams JB, Mack MJ, Peterson ED, Allen KB, Harrington RA, Gibson CM, Califf RM, Kouchoukos NT, Ferguson TB Jr, Alexander JH; Project of Ex Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) Investigators. Relationship between vein graft failure and subsequent clinical outcomes after coronary artery bypass surgery. Circulation. 2012 Feb 14;125(6):749-56. doi: 10.1161/CIRCULATIONAHA.111.040311. Epub 2012 Jan 11. — View Citation

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. — View Citation

Nasso G, Coppola R, Bonifazi R, Piancone F, Bozzetti G, Speziale G. Arterial revascularization in primary coronary artery bypass grafting: Direct comparison of 4 strategies--results of the Stand-in-Y Mammary Study. J Thorac Cardiovasc Surg. 2009 May;137(5):1093-100. doi: 10.1016/j.jtcvs.2008.10.029. Epub 2009 Feb 7. — View Citation

Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976 Dec;34(6):585-612. doi: 10.1038/bjc.1976.220. — View Citation

Serruys PW, Ong AT, van Herwerden LA, Sousa JE, Jatene A, Bonnier JJ, Schonberger JP, Buller N, Bonser R, Disco C, Backx B, Hugenholtz PG, Firth BG, Unger F. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial. J Am Coll Cardiol. 2005 Aug 16;46(4):575-81. doi: 10.1016/j.jacc.2004.12.082. — View Citation

Shavadia J, Norris CM, Graham MM, Verma S, Ali I, Bainey KR. Symptomatic graft failure and impact on clinical outcome after coronary artery bypass grafting surgery: Results from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Am Heart J. 2015 Jun;169(6):833-40. doi: 10.1016/j.ahj.2015.02.022. Epub 2015 Mar 13. — View Citation

Taggart DP, Altman DG, Gray AM, Lees B, Gerry S, Benedetto U, Flather M; ART Investigators. Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts. N Engl J Med. 2016 Dec 29;375(26):2540-9. doi: 10.1056/NEJMoa1610021. Epub 2016 Nov 14. — View Citation

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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. — View Citation

Zhang H, Wang ZW, Wu HB, Hu XP, Zhou Z, Xu P. Radial artery graft vs. saphenous vein graft for coronary artery bypass surgery : which conduit offers better efficacy? Herz. 2014 Jun;39(4):458-65. doi: 10.1007/s00059-013-3848-5. Epub 2013 Jun 21. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Outcome	A composite of death from any cause, any stroke, post discharge myocardial infarction and/or repeat revascularization.	> 72 hours after surgery and/or repeat revascularization
Secondary	30-day mortality	Death from any cause at 30-days	30 days post-operatively
Secondary	Major postoperative complications	Revision for bleeding, perioperative myocardial infarction, any stroke, need for dialysis, need for tracheostomy, and surgical site infection.	In-hospital stay, up to 30 days post-operatively
Secondary	Sternal wound complication	Wound drainage, skin separation, unstable sternum, and sternal dehiscence, infection	6 months post-operatively
Secondary	Composite Outcome of Death from any cause	A composite of death from any cause, post discharge myocardial infarction,stroke, and/or repeat revascularization	Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years.
Secondary	Stroke	Post discharge myocardial infarction and repeat revascularization considered as individual events	Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years.
Secondary	Cause-specific death (cardiac vs non-cardiac)	Death as either cardiac or non-cardiac in etiology	Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years
Secondary	Hospital readmissions	Hospital readmissions with specific causes	Analysis will be performed after 631 events. The investigators assume this will occur at a mean follow-up of 5 years