Clinical trial NCT04124120: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Diseases
Coronary Artery Disease
Coronary Artery Bypass Grafting
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: New York Presbyterian Hospital
name: Sunnybrook Health Sciences Centre
name: Cedars-Sinai Medical Center
name: Columbia University
name: Duke University
First posted: 2019-10-11
Enrollment: 2000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients undergoing coronary artery bypass surgery will be in one of two groups. One group will receive a single arterial graft and the second group will receive two or more arterial grafts.
Primary purpose: TREATMENT

Brief summary: 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 grfating (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 grfating (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 2,000 women randomized 1:1 to MAG or SAG (690 from the parent ROMA trial + 1,310 from ROMA:Women). 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 2,000 women randomized 1:1 to MAG or SAG (690 from the parent ROMA trial + 1,310 from ROMA:Women). 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.

Eligibility criteria: Inclusion Criteria:

1. Women patients ≥18 years old.
2. Isolated coronary artery bypass grafting.
3. Primary (first time) cardiac surgery procedure.
4. 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

Primary outcomes:
measure: 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.
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Primary outcome for aim 2: Disease-specific quality of life
timeFrame: Postoperatively, minimum 2.5 year follow-up
Secondary outcomes:
measure: Death from any cause, any stroke, non-procedural myocardial infarction, and repeat revascularization.
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Death from cardiac cause, any stroke, non-procedural myocardial infarction, repeat revascularization and hospital readmission for acute coronary syndrome or heart failure.
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Death from any cause
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Stroke
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Non-procedural myocardial infarction
timeFrame: > 48 hours postoperatively, minimum 2.5 year follow-up
measure: Repeat revascularization
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Readmission for acute coronary syndrome
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Readmission for heart failure
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Generic quality of life according to the Short Form Health Survey (SF-12v2)
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Generic quality of life according to EuroQuol-5D (EQ-5D)
timeFrame: Postoperatively, minimum 2.5 year follow-up
measure: Mental and physical health symptoms according to PROMIS instruments
timeFrame: Postoperatively, minimum 2.5 year follow-up
Other outcomes:
measure: Other recorded outcomes (safety endpoints)
timeFrame: Within 30 days of surgery or during index hospitalization, whichever is longer.
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Springfield
country: United States
facility: Baystate Health
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Hospital
state: Nebraska
city: Omaha
country: United States
facility: Methodist Physicians Health
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Englewood
country: United States
facility: Englewood Health
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Brooklyn
country: United States
facility: NewYork-Presbyterian Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Queens
country: United States
facility: New York Presbyterian Queens
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
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: Zanesville
country: United States
facility: Genesis Healthcare System
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Galveston
country: United States
facility: The University of Texas Medical Health Branch at Galveston
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Clayton
country: Australia
facility: Victorian Heart Hospital
city: Melbourne
country: Australia
facility: The University of Melbourne
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Innsbruck Medical University
city: Linz
country: Austria
facility: Kepler University Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Krankenhaus Nord Vienna North Hospital
city: Porto Alegre
country: Brazil
facility: Institute of Cardiology Porto Alegre
city: São Paulo
country: Brazil
facility: Heart Institute University of São Paulo
city: Vila Mariana
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Saint John
country: Canada
facility: Horizon Health Network - Saint John Regional Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: NL Health Services
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montréal
country: Canada
facility: University Hospital of Montreal
state: Quebec
city: Montréal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Ste Foy
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
city: Montréal
country: Canada
facility: Hopital Sacre-Coeur
city: New Westminster
country: Canada
facility: Fraser Clinical Trials
city: Beijing
country: China
facility: Fuwai Hospital China
state: Beijing
city: Changchun
country: China
facility: Jilin Heart Hospital China
state: Jilin
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: Teda Hospital Tianjin China
state: Tianjin
city: Zagreb
country: Croatia
facility: University Hospital Dubrava
city: Hradec Králové
country: Czechia
facility: University Hradec Králové
city: Nové Město
country: Czechia
facility: General University Hospital, Prague
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Bad Krozingen Freiburg
state: Baden-Wuerttemberg
city: Bad Oeynhausen
country: Germany
facility: HDZ NRW Bad Oeynhausen Germany
city: Berlin
country: Germany
facility: Deutsches Herzzentrum der Charite
city: Duisburg
country: Germany
facility: Duisburg Heart Center
city: Düsseldorf
country: Germany
facility: Dusseldorf University
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: Essen University
city: Frankfurt
country: Germany
facility: Frankfurt University
city: Gießen
country: Germany
facility: University Hospital of Giessen and Marburg
city: Göttingen
country: Germany
facility: University Medical Center of Göttingen
city: Jena
country: Germany
facility: Jena University Hospital
city: Leipzig
country: Germany
facility: Heart Center Herzzentrum, Leipzig
city: Stuttgart
country: Germany
facility: Robert-Bosch-Hospital Stuttgart Germany
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Coimbatore
country: India
facility: G Kuppuswamy Naidu Memorial Hospital (GKNM)
state: Tamil Nadu
city: Hyderabad
country: India
facility: Star Hospitals - Hyderabad, India
state: Telangana
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Bari
country: Italy
facility: Anthea Hospital
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni of Bergamo
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
city: Cotignola
country: Italy
facility: Maria Cecilia Hospital GVM
city: Florence
country: Italy
facility: Careggi University Hospital
city: Roma
country: Italy
facility: European Hospital
city: Roma
country: Italy
facility: Universita' Cattolica del Sacro Cuore
city: Torino
country: Italy
facility: Ospedale Le Molinette, Torino
city: Bunkyō-Ku
country: Japan
facility: Tokyo Medical and Dental University
state: Tokyo
city: Saitama
country: Japan
facility: Saitama Medical University Japan
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seúl
country: Korea, Republic of
facility: Severance Cardiovascular Hospital, Yonsei University College of Medicine
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: South Holland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Skopje
country: North Macedonia
facility: Acibadem-Sistina Hospital
city: Gdańsk
country: Poland
facility: Medical University Gdansk
city: Katowice
country: Poland
facility: Medical University of Silesia
city: Zabrze
country: Poland
facility: Zbigniew Religa Lower Silesian Heart Disease Centre
city: Coimbra
country: Portugal
facility: University Hospital Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental
city: Porto
country: Portugal
facility: Centro Hospitalar e Universitário Sao Joao
city: Porto
country: Portugal
facility: Centro Hospitalar e Universitário Sao João
city: Tomsk
country: Russian Federation
facility: National Research Medical Center of the Russian Academy of Sciences - Tomsk, Russia
city: Belgrade
country: Serbia
facility: Dedinje Cardiovascular Institute
city: Singapore
country: Singapore
facility: National University of Singapore
city: Elx
country: Spain
facility: Hospital Universitario del Vinalopo
state: Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico de San Carlos
city: Pamplona
country: Spain
facility: NavarraBiomed
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karonlinska University Hospital
city: Zhongzheng
country: Taiwan
facility: National Taiwan University Hospital
state: Taipei
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Trust
state: Lancashire
city: Multiple Locations
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
state: Oxford
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS Trust
state: Staffordshire
city: Cambridge
country: United Kingdom
facility: Royal Papworth NHS Foundation Trust
city: Clydebank
country: United Kingdom
facility: NHS Golden Jubilee
city: Edinburgh
country: United Kingdom
facility: The Royal Infirmary of Edinburgh
city: Hull
country: United Kingdom
facility: Hull University Hospitals
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: St George's University Hospitals
city: Manchester
country: United Kingdom
facility: Manchester University NHS Trust
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton NHS Trust
Study officials:
affiliation: Weill Medical College of Cornell University
name: Mario Gaudino, Prof/PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Stephen Fremes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Ruth Masterson Creber, RN, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai
name: C. Noel Bairey Merz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Karla Ballman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Sean O'Brien, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
citation: 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.
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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; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; Society of Cardiovascular Anesthesiologists; Society of Thoracic Surgeons. 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. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011 Dec 6;58(24):e123-210. doi: 10.1016/j.jacc.2011.08.009. Epub 2011 Nov 7. No abstract available.
citation: 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 Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available.
citation: 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.
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.