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

Coronary Artery Disease Clinical Trial

— ROMA:Women  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04124120
• Other study ID #: 1703018094-ROMA-Women
• Status: Recruiting
• Phase: N/A
• Start date: April 17, 2023
• Est. completion date: March 2030

Study information

• Verified date: December 2023
• Source: Weill Medical College of Cornell University
• Contact: Mario Gaudino, Prof/PhD/MD
• Phone: 212.746.1812
• Email: mfg9004[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: March 2030
• Est. primary completion date: March 2030
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Bypass Grafting
• 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
Australia	The University of Melbourne	Melbourne
Austria	Medical University of Graz	Graz
Austria	Innsbruck Medical University	Innsbruck
Austria	Kepler University Hospital	Linz
Austria	Krankenhaus Nord Vienna North Hospital	Vienna
Austria	Medical University of Vienna	Vienna
Brazil	Institute of Cardiology Porto Alegre	Porto Alegre
Brazil	Heart Institute University of São Paulo	São Paulo
Brazil	Instituto Dante Pazzanese de Cardiologia	Vila Mariana
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences	London	Ontario
Canada	Hopital Sacre-Coeur	Montréal
Canada	Montreal Heart Institute	Montréal	Quebec
Canada	Royal Victoria Hospital	Montréal	Quebec
Canada	University Hospital of Montreal	Montréal	Quebec
Canada	Fraser Clinical Trials	New Westminster
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Horizon Health Network - Saint John Regional Hospital	Saint John	New Brunswick
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Ste Foy	Quebec
Canada	Health Sciences North	Sudbury	Ontario
Canada	Sunnybrook Health Sciences	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
China	Fuwai Hospital China	Beijing	Beijing
China	Jilin Heart Hospital China	Changchun	Jilin
China	Ruijin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Teda Hospital Tianjin China	Tianjin	Tianjin
Croatia	University Hospital Dubrava	Zagreb
Czechia	University Hradec Králové	Hradec Králové
Czechia	General University Hospital, Prague	Nové Mesto
Germany	Universitäts-Herzzentrum Bad Krozingen Freiburg	Bad Krozingen	Baden-Wuerttemberg
Germany	HDZ NRW Bad Oeynhausen Germany	Bad Oeynhausen
Germany	Deutsches Herzzentrum der Charite	Berlin
Germany	Duisburg Heart Center	Duisburg
Germany	Essen University	Duisburg
Germany	Dusseldorf University	Düsseldorf
Germany	University Hospital Erlangen	Erlangen
Germany	Frankfurt University	Frankfurt
Germany	University Hospital of Giessen and Marburg	Gießen
Germany	University Medical Center of Göttingen	Göttingen
Germany	Jena University Hospital	Jena
Germany	Heart Center Herzzentrum, Leipzig	Leipzig
Germany	Robert-Bosch-Hospital Stuttgart Germany	Stuttgart
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
India	G Kuppuswamy Naidu Memorial Hospital (GKNM)	Coimbatore	Tamil Nadu
India	Star Hospitals - Hyderabad, India	Hyderabad	Telangana
Israel	Rambam Health Care Campus	Haifa
Italy	Anthea Hospital	Bari
Italy	Fondazione Poliambulanza	Brescia
Italy	Maria Cecilia Hospital GVM	Cotignola
Italy	European Hospital	Roma
Italy	Universita' Cattolica del Sacro Cuore	Roma
Italy	Ospedale Le Molinette, Torino	Torino
Japan	Tokyo Medical and Dental University	Bunkyo-Ku	Tokyo
Japan	Saitama Medical University Japan	Saitama
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Cardiovascular Hospital, Yonsei University College of Medicine	Seúl
Netherlands	Maastricht University Medical Centre	Maastricht
North Macedonia	Acibadem-Sistina Hospital	Skopje
Poland	Medical University of Silesia	Katowice
Poland	Zbigniew Religa Lower Silesian Heart Disease Centre	Zabrze
Portugal	University Hospital Coimbra	Coimbra
Portugal	Centro Hospitalar Lisboa Ocidental	Lisboa
Portugal	Centro Hospitalar e Universitário Sao João	Porto
Russian Federation	National Research Medical Center of the Russian Academy of Sciences - Tomsk, Russia	Tomsk
Serbia	Dedinje Cardiovascular Institute	Belgrade
Singapore	National University of Singapore	Singapore
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario del Vinalopo	Elx	Alicante
Spain	Hospital Clinico de San Carlos	Madrid
Spain	NavarraBiomed	Pamplona
Sweden	Sahlgrenska University Hospital	Gothenburg
Taiwan	National Taiwan University Hospital	Zhongzheng	Taipei
United Kingdom	Hull University Hospitals	Hull
United Kingdom	University Hospitals of Leicester	Leicester
United Kingdom	St George's University Hospitals	London
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	NewYork-Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Englewood Health	Englewood	New Jersey
United States	Nebraska Heart Hospital	Lincoln	Nebraska
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Yale University Hospital	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine, Mount Sinai	New York	New York
United States	Lenox Hill Hospital	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	New York Presbyterian Queens	Queens	New York
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Baystate Health	Springfield	Massachusetts
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (6)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Cedars-Sinai Medical Center, Columbia University, Duke University, New York Presbyterian Hospital, Sunnybrook Health Sciences Centre

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  China,  Croatia,  Czechia,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  North Macedonia,  Poland,  Portugal,  Russian Federation,  Serbia,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (9)

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. — View 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. — 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

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. — 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

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

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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other recorded outcomes (safety endpoints)	30-day mortality and major postoperative complications (revision for bleeding, perioperative MI (<48 hours after surgery), need for dialysis, need for tracheostomy, and surgical site complications).	Within 30 days of surgery or during index hospitalization, whichever is longer.
Primary	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.	The primary outcome for aim 1 will be a composite of the first occurrence of death from any cause, any stroke, non-procedural myocardial infarction (>48 hours after surgery), repeat revascularization and hospital readmission for acute coronary syndrome or heart failure.	Postoperatively, minimum 2.5 year follow-up
Primary	Primary outcome for aim 2: Disease-specific quality of life	Assessed using the Seattle Angina Questionnaire (SAQ), a validated 19-item questionnaire that measures five domains related to coronary disease: angina frequency, physical limitations, quality of life, angina stability, and treatment satisfaction. Scores range from 0 to 100 with higher scores indicating fewer symptoms and better health status. The minimum clinically important difference on the SAQ is 5 points.; The primary endpoint for aim 2 is the absolute change in the Seattle Angina Questionnaire (SAQ) at 12 months compared to baseline.	Postoperatively, minimum 2.5 year follow-up
Secondary	Death from any cause, any stroke, non-procedural myocardial infarction, and repeat revascularization.	One of the secondary outcomes for aim 1: It will be a composite of the first occurrence of death from any cause, any stroke, non-procedural myocardial infarction (>48 hours after surgery), and repeat revascularization.; This is the primary outcome of the parent ROMA trial.	Postoperatively, minimum 2.5 year follow-up
Secondary	Death from cardiac cause, any stroke, non-procedural myocardial infarction, repeat revascularization and hospital readmission for acute coronary syndrome or heart failure.	Another secondary outcome for aim 1: It will be a composite of the first occurrence of death from cardiac cause, any stroke, non-procedural myocardial infarction (>48 hours after surgery), repeat revascularization, and hospital readmission for acute coronary syndrome or heart failure.	Postoperatively, minimum 2.5 year follow-up
Secondary	Death from any cause	Another secondary outcome for aim 1: Death will be considered to be cardiac unless a definite non-cardiac cause is identified.	Postoperatively, minimum 2.5 year follow-up
Secondary	Stroke	Another secondary outcome for aim 1: Based on the American Heart Association/American Stroke Association Expert Consensus stroke definition, stroke will be identified in case of: pathological, imaging, or other objective evidence of cerebral ischemic injury in a defined vascular distribution; OR; clinical evidence of cerebral ischemic injury based on symptoms persisting =24 hours or until death, and other etiologies excluded.	Postoperatively, minimum 2.5 year follow-up
Secondary	Non-procedural myocardial infarction	Another secondary outcome for aim 1: Based on the 4th Universal Definition, non-periprocedural myocardial infarction will be identified in case of detection of rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: symptoms of ischemia; electrocardiogram changes indicative of new ischemia (new ST-T changes or new left bundle branch block); development of pathological Q waves in the electrocardiogram; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.	> 48 hours postoperatively, minimum 2.5 year follow-up
Secondary	Repeat revascularization	Another secondary outcome for aim 1: Repeat revascularization will include any percutaneous or surgical revascularization on a grafted coronary artery after the initial operation.	Postoperatively, minimum 2.5 year follow-up
Secondary	Readmission for acute coronary syndrome	Another secondary outcome for aim 1: Prolonged ischemic symptoms at rest (usually =10 minutes in duration), or accelerating pattern of chest pain that occurs with a lower activity threshold (CCS class III or IV) considered to be myocardial ischemia upon final diagnosis resulting in an unscheduled visit to a healthcare facility resulting in an overnight stay generally within 24 hours of the most recent symptoms, cardiac biomarkers not meeting MI criteria, and ECG or angiographic evidence of ischemia.	Postoperatively, minimum 2.5 year follow-up
Secondary	Readmission for heart failure	Another secondary outcome for aim 1: While patients may have multiple simultaneous disease processes, for the outcome event of heart failure requiring hospitalization, the diagnosis of congestive heart failure would need to be the primary process. Heart failure (HF) requiring hospitalization is defined as an event that meets the following criteria: i. Requires hospitalization AND ii. Clinical symptoms of heart failure AND iii. Physical signs of heart failure AND iv. Need for additional/increased therapy AND v. No other non-cardiac etiology (such as chronic obstructive pulmonary disease, hepatic cirrhosis, acute renal failure, or venous insufficiency) and no other cardiac etiology (such as pulmonary embolus, cor pulmonale, primary pulmonary hypertension, or congenital heart disease) for signs or symptoms are identified.	Postoperatively, minimum 2.5 year follow-up
Secondary	Generic quality of life according to the Short Form Health Survey (SF-12v2)	Secondary outcomes for aim 2: The SF-12v12 measures eight dimensions of health: physical functioning, role limitations due to physical problems, bodily pain, vitality, general health perception, social function, role limitations due to emotional problems, and mental health. Scores for each domain range from 0 to 100 with higher scores indicating better health status.; The SF-12v2 has two summary measures: physical and mental self-perceived health with norm-based methods that standardize the score to a mean of 50 and standard deviation of 10.	Postoperatively, minimum 2.5 year follow-up
Secondary	Generic quality of life according to EuroQuol-5D (EQ-5D)	Secondary outcomes for aim 2: EQ-5D is a five-item instrument to assess health status in the following five dimensions: mobility, self-care, usual activity, pain or discomfort, and anxiety or depression. Individual domain scores will be converted to a summary index representing utility weights, which allow conduct of cost-effectiveness analyses.	Postoperatively, minimum 2.5 year follow-up
Secondary	Mental and physical health symptoms according to PROMIS instruments	Secondary outcomes for aim 2: Physical and mental health symptoms and physical functioning will be measured with standardized PROMIS instruments, including: Pain interference, Neuropathic Pain, Fatigue, Sleep disturbance, Depression, Anxiety, and Physical Function. A mean of 50 and a standard deviation of 10 represent the general population in the US.	Postoperatively, minimum 2.5 year follow-up