Coronary Artery Bypass Surgery (CABG) Off or On Pump Revascularization Study (CORONARY)

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ClinicalTrials.gov Identifier: NCT00463294

Recruitment Status : Completed

First Posted : April 20, 2007

Last Update Posted : September 16, 2016

Sponsor:

Collaborators:

McMaster University

University of Oxford

Instituto Dante Pazzanese de Cardiologia

Fu Wai Hospital, Beijing, China

Universidad de la Frontera

Fundación Cardiovascular de Colombia

Charles University, Czech Republic

Hopital Jean Minjoz

Centre for Chronic Disease Control, India

Ospedale Santa Croce-Carle Cuneo

Medical University of Gdansk

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Ankara University

Hotel Dieu Hospital

Centre hospitalier de l'Université de Montréal (CHUM)

SAL Hospital, Ahmedabad, India

Information provided by (Responsible Party):

Andre Lamy, Population Health Research Institute

Study Description

Brief Summary:

I. Main Research Question:

To compare the risks and benefits of Off-pump Coronary artery bypass surgery (CABG) to On-pump CABG and to determine if one is better than the other.
The purpose of this pilot study is also to see the rate of recruitment with expertise-based randomization across different hospital settings.

II. Small RCT studies and meta-analyses done so far have not been able to conclusively say which of the procedure is better. A large randomized study is required to establish the risks and benefits associated with both the off-pump and on-pump CABG surgical procedures.

III. The study will look at which of the two techniques reduce major risks associated with CABG.

Condition or disease	Intervention/treatment	Phase
the Efficacy and Safety of Off-pump CABG	Procedure: Coronary Artery Bypass Graft with the use of CPB Procedure: Coronary Artery Bypass Graft without the use of CPB	Phase 3

Show detailed description

Detailed Description:

Rationale and purpose of the study:

Coronary artery bypass grafting (CABG) surgery prolongs life-expectancy in patients with severe ischemic heart disease, especially those with left main, triple vessel disease or single/double vessel disease with stenosis of the proximal left anterior descending (LAD) artery. The perioperative mortality is about 2% with an additional 5% to 7% suffering complications such as myocardial infarction, stroke, renal failure, etc. The technique of operating on a beating heart (off-pump) for coronary artery bypass grafting surgery has been recently developed in the past few years in an effort to decrease the above perioperative complications typically related to cardiopulmonary bypass associated with on-pump CABG. While registries suggest that off-pump CABG may be superior, these data cannot fully control for differences in patient characteristics, which influence patient selection for specific procedures. The benefits of off-pump CABG compared with conventional on-pump CABG are unclear. The investigators therefore propose a large simple, international multicentre randomized controlled trial to definitively evaluate the efficacy and safety of off-pump CABG in the treatment of patients undergoing coronary artery surgery funded by CIHR, this pilot study will be a preliminary step towards a full trial.

Sample size:

The investigators examined the outcomes in the Canadian off-pump CABG Registry to identify a group of patients who represent a higher risk of cardiovascular events. Utilizing the inclusion criteria described below, this group of patients has accumulated the vast majority of outcomes in the Registry and represent more than 50% of patients in the Registry, therefore minimizing the sample size but still being representative. The cumulative event rate at 30 days (first co-primary outcome) for on-pump CABG is estimated as being 8.6% and the investigators expect a 33% relative risk reduction (RRR) for the off-pump CABG group. The sample calculated for the whole trial is 4700 patients.

Design/Methodology:

Trial design: This is a pilot randomized controlled trial comparing off-pump CABG versus on-pump CABG in 60 patients who will be undergoing isolated CABG.

Interventions: Patients eligible for CABG will be randomized to receive either an Off-pump CABG surgery or On-pump CABG surgery.

Randomization: After obtaining informed written consent patients will be allocated to either off-pump CABG or on-pump CABG by calling a 24-hour randomization telephone number. An expertise-based randomization will be used wherein a surgeon who is an expert in Off-pump surgery will operate on patients randomized to receive Off-pump surgery. Patients randomized to receive On-pump CABG will be operated on by a surgeon who is an expert in on-pump CABG surgery. To minimize bias stratified block randomization will used. For this pilot study randomization will be stratified to 3 centres and random block of 4 or 6.

The data adjudicators will be blinded to the study. Due to the nature of intervention, the operating surgeon, anesthetist, perfusionist, other operation room staff, intensive-care unit staff will not be blinded in this study.

Setting:

Patients will have either been seen in the emergency, outpatient or ICU and diagnosed with having single, double or triple coronary artery occlusion requiring an isolated CABG.

Study interventions:

Interventions: Patients eligible for CABG will be randomized to receive either an Off-pump CABG surgery or On-pump CABG surgery. A surgeon who is an expert in the assigned technique will perform the procedure.

Primary outcomes:

The occurrence of the composite of total mortality, stroke, nonfatal MI, or new renal failure at 30 days post CABG surgery AND
The occurrence of the composite of total mortality, stroke, nonfatal MI, new renal failure, or repeat coronary revascularization (i.e. coronary artery bypass surgery or percutaneous coronary intervention) over 5 years after randomization.

The secondary outcomes

The assessment of total costs and resources consumption at 30 days after CABG surgery AND
The assessment of total costs and resources consumption at 5 years after CABG surgery

Measurements:

The investigators will ascertain all events of interest through periodic and regular follow-up utilizing standardized definitions for all events, appropriate supporting documents will be obtained centrally.

CV death: all deaths are considered cardiovascular unless a specific non-cardiovascular cause is evident (e.g. malignancy).
Stroke: new acute focal neurological deficit (except for subarachnoid hemorrhage which may not be focal) thought to be of vascular origin with signs or symptoms lasting greater than 24 hours.
MI perioperative (within 24 hours of surgery): new pathologic Q waves with documented new wall motion abnormalities other than septal OR cardiac markers ³ 10 x ULN.
MI non-perioperative (later than 24 hours after surgery): ECG changes consistent with infarction (new significant Q waves in two contiguous leads in the absence of previous LVH or conduction abnormalities) or evolving ST-segment to T-wave changes in two contiguous leads or new left bundle branch block or ST segment elevation requiring thrombolysis or PCI AND cardiac markers (troponins or CKMB) in the necrosis range. Post-PCI MI are included into non-perioperative MI group but are defined as new pathologic Q waves with documented new wall motion abnormalities other than septal OR cardiac markers ³ 3 x ULN within 24 hours of PCI.
Renal failure: doubling of serum creatinine from pre-op baseline or requirement for renal replacement therapy (eg, dialysis, continuous hemofiltration, renal transplant). Hemofiltration or dialysis only during cardio-pulmonary bypass does not constitute a requirement for renal replacement therapy. Patients who receive dialysis within 1 month of the surgery are not eligible for this endpoint.
Repeated coronary revascularization: new CABG procedure or PCI associated with documented ischemia by stress testing (ECG, ECHO, or nuclear) AND graft failure or new culprit lesion (³ 70% luminal stenosis).

For other endpoints, the investigators have defined:

Recurrence of angina: new or chronic onset of typical chest pain with documented ischemia by stress testing (ECG, ECHO, or nuclear).
Blood transfusions: all blood bank products transfused within 24 hours of the CABG surgery.
Total mortality: all causes of mortality

Plan for data analysis:

The intention to treat principle, in which all participants will be included in their assigned treatment groups regardless of adherence, will guide all analyses. In the principle analysis, the time to the first occurrence of one of the components of the cluster of (cardiac death, stroke, nonfatal MI, new renal failure) will be presented by Kaplan-Meier survival curves and the comparisons between the two treatment groups will be performed by a log-rank test. The treatment effect as measured by the hazard ratio and 95% confidence interval will be derived by the Cox proportional hazards model. The investigators will also calculate the absolute risk reductions and the associated 95% confidence intervals, as well as the number needed to treat (NNT) with off-pump CABG to prevent one major cardiovascular event. Participants who prematurely discontinue follow-up before a major cardiovascular event will be censored as to their last follow-up data; this number is expected to be <1% given the relatively short period of follow-up after surgery.

In secondary analyses the investigators will determine and compare the incidence of major cardiovascular events (cardiac death, stroke, nonfatal MI, new renal dialysis) and revascularization procedures (i.e. coronary artery bypass surgery and percutaneous coronary intervention) using the same strategy. The effect of the two operative techniques on different sub-groups (i.e. patients with diabetes, renal failure, congestive heart failure, cerebrovascular disease, as well as patient left ventricular function, gender and ages will be conducted by stratified analysis through a Cox proportional hazards model. The test of interaction between each subgroup factor and the treatment group will be done by including a product term in the model already containing treatment and the subgroup factor. The length of hospital stay and length of ICU/CCU stay will be compared using a student's t-test. An events adjudication committee (blind to surgical allocation) will centrally review all suspected major outcomes listed above.

The investigators will also do subgroup analysis on different sub-groups (i.e. patients with diabetes, renal failure, congestive heart failure, cerebrovascular disease, as well as patient left ventricular function, gender and ages will be examined for consistency and coherence)

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	4752 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	CABG Off or On Pump Revascularization Study (CORONARY)
Study Start Date :	October 2007
Actual Primary Completion Date :	March 2012
Actual Study Completion Date :	September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Coronary Artery Bypass Surgery

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: On Pump Arm	Procedure: Coronary Artery Bypass Graft with the use of CPB Coronary Artery Bypass Graft (CABG) using median sternotomy, CPB, cardioplegia and complete cross-clamp and no associated or concomitant surgical procedures Other Name: ON Pump CABG
Experimental: Off Pump Arm	Procedure: Coronary Artery Bypass Graft without the use of CPB Coronary Artery Bypass Graft (CABG) with no associated or concomitant surgical procedures, using median sternotomy and without CPB and cardioplegia Other Name: OFF Pump

Outcome Measures

Primary Outcome Measures :

First Co-Primary Outcome [ Time Frame: 30 days post CABG surgery ]
The occurrence of the composite of total mortality, stroke, nonfatal MI, or new renal failure at 30 days post CABG surgery
Second co-primary outcome [ Time Frame: 5 years after CABG ]
The occurrence of the composite of total mortality, stroke, nonfatal MI, new renal failure, or repeat coronary revascularization (i.e. coronary artery bypass surgery or percutaneous coronary intervention) over 5 years after randomization.

Secondary Outcome Measures :

The assessment of total costs and resources consumption at 30 days after CABG surgery [ Time Frame: 30 days after CABG surgery ]
The assessment of total costs and resources consumption at 5 years after CABG surgery [ Time Frame: 5 years after CABG surgery ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	21 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients who have been diagnosed with coronary artery disease (single, double or triple disease) will be eligible if they:

require isolated CABG with median sternotomy
are able to give their informed written consent
are> 21 years of age and
have one or more of the following risk factors:
- ≥ 70 years
- peripheral vascular disease (previous peripheral bypass or amputation or ABI <0.80)
- Cerebrovascular disease (history of stroke, TIA)
- Renal insufficiency (creatinine above upper limit of normal)
- >60 years of age and one of the following:
  - diabetes (oral hypoglycemic agent and/or insulin)
  - urgent revascularization (waiting in hospital)
  - LV ejection fraction <35%
  - current or recent smoker.
- 55-59 years of age and two of the following:
  - diabetes (oral hypoglycemic agent and/or insulin)
  - urgent revascularization (waiting in hospital)
  - LV ejection fraction <35%
  - current or recent smoker.

Exclusion Criteria:

Patients will be excluded if they have one of the following:

concomitant cardiac procedure associated with CABG,
contra-indications to off-pump CABG or on-pump CABG (calcified aorta, intramuscular LAD, calcified coronaries, small target vessels)
concomitant life-threatening disease likely to limit life expectancy to less than 2 years,
prior enrollment in this trial
emergency CABG surgery (immediate revascularization for hemodynamic instability) OR
redo CABG.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00463294

Locations

Show 52 study locations

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Argentina
Fundacion Medica de rio negro y neuquen
Rio Negro, Argentina
Brazil
Beneficencia Portuguesa de Sao Paulo
Sao Paulo,, CEP, Brazil, 01323.001
Instituto Dante Pazzanese de Cardiologia
Sao Paulo, CEP, Brazil, 04012-909
Hospital Sao Francisco Complexo Hospitalar Santa Casa
Porto Alegre, RS, Brazil, 90020-090
Irmande Santa Casa De Misericordia De Curtiba
Curitiba Parana, Brazil, 80010030
Braile Clinica de Servicos de Assistencia Medico
Sao Jose do Rio Preto, Brazil, 15091-450
Irmandade da Santa Casa de Misericordia de Sao Paulo
Sao Paulo, Brazil, 01221-020
Federal University of Sao Paulo School of Medicine
Sao Paulo, Brazil, 04024-002
Instituto do Coracao do Hospital das Clinicas da
Sao Paulo, Brazil, 05403-00
Hospital Mario Covas
Sao Paulo, Brazil, 09190-615
Santa Casa de Misericordia de Marilia
Sao Paulo, Brazil, 17515-000
Associação do Sanátorio Sírio
São Paulo, Brazil, 04038-030
Canada, Alberta
Foothills Medical Centre
Calgary, Alberta, Canada, T2N 2T9
Canada, Ontario
Hamilton General Hospital
Hamilton, Ontario, Canada, L8L 2X2
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Hotel-Dieu du CHUM
Montreal, Quebec, Canada, H2W 1T8
Chile
Hospital Regional Temuco
Temuco, IX Region, Chile
Instituto Nacional del Torax
Santiago, Chile
China
ChaoYang Hospital
Beijing, China
FuWai Hospital
Beijing, China
Nanjing First Hospital
Nanjing, China
Colombia
Fundacion Cardioinfantil
Bogota, Colombia
Fundacion Valle Del Lili
Cali, Colombia
Czech Republic
Charles University Hospital
Hradec Kralove, Czech Republic, 50005
Kardiochirurgicke centrum
Ostrava-Poruba, Czech Republic, 708 52
University Hospital Pilsen
Pilsen, Czech Republic, 304 60
Fakultni nemocnice Kralovske Vinohrady (FNKV)
Prague, Czech Republic, 100 34
University Hospital Motol
Praha, Czech Republic, 150 00
Nemocnice Podlesi
Trinec, Czech Republic, 739 61
France
Service de chirurgie thoracique et cardio-vasculaire
Besancon, France, 25030
India
Nizam's Institute of Medical Sciences
Hyderabad, Andhra Pradesh, India, 500 082
SAL Hospital and Medical Institute
Ahmedabad, Gujarat, India, 380054
Amrita Institute of Medical Sciences and Research Center
Cochin, Kerala, India, 682 026
G.Kuppuswamy Naidu Memorial Hospital
Coimbatore, TamilNadu, India, 641 037
SAL Hospital
Ahmedabad, India
International Center of Cardiovascular and Thoracic Diseases
Chennai Tamil Nadu, India, 600101
Sanjay Gandhi PGIMS
Lucknow, India, 226 014
All India Institute of Medical Sciences
New Delhi, India, 110016
Escorts Heart Institute and Research Centre
Noida, India, 201307
Italy
Ospedale S. Croce
Cuneo, Italy, 12100
Ospedale Niguarda - Ca Granda
Milano, Italy, 20162
Poland
Jagiellonian University
Krakow, Poland, 31-202
Turkey
Alp Aslan
Ankara, Turkey
Erol Senor
Ankara, Turkey
Ruchan Akar
Ankara, Turkey
Sertap Aykut Aka
Ankara, Turkey
Volkan Sinci
Ankara, Turkey
United Kingdom
Basildon and Thurrock University Hospital NHS FT
Basildon, Essex, United Kingdom, SS16 5NL
Royal Infirmary of Edinburgh
Edinburgh, EU, United Kingdom, 16 4SU
The John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU

Sponsors and Collaborators

Population Health Research Institute

McMaster University

University of Oxford

Instituto Dante Pazzanese de Cardiologia

Fu Wai Hospital, Beijing, China

Universidad de la Frontera

Fundación Cardiovascular de Colombia

Charles University, Czech Republic

Hopital Jean Minjoz

Centre for Chronic Disease Control, India

Ospedale Santa Croce-Carle Cuneo

Medical University of Gdansk

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Ankara University

Hotel Dieu Hospital

Centre hospitalier de l'Université de Montréal (CHUM)

SAL Hospital, Ahmedabad, India

Investigators

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Principal Investigator:	Lamy Andre, MD, MSc	McMaster University
Principal Investigator:	Salim Yusuf, MD, DPhil	Population Health Research Institute
Principal Investigator:	David Taggart, MD	University of Oxford

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Straka Z, Piegas LS, Avezum A, Akar AR, Lanas Zanetti F, Jain AR, Noiseux N, Padmanabhan C, Bahamondes JC, Novick RJ, Tao L, Olavegogeascoechea PA, Airan B, Sulling TA, Whitlock RP, Ou Y, Gao P, Pettit S, Yusuf S; CORONARY Investigators. Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting. N Engl J Med. 2016 Dec 15;375(24):2359-2368. Epub 2016 Oct 23.

Lamy A, Tong W, Devereaux PJ, Gao P, Gafni A, Singh K, Taggart D, Straka Z, Akar AR, Piegas L, Ou Y, Yusuf S. The cost implications of off-pump versus on-pump coronary artery bypass graft surgery at one year. Ann Thorac Surg. 2014 Nov;98(5):1620-5. doi: 10.1016/j.athoracsur.2014.06.046. Epub 2014 Sep 24.

Garg AX, Devereaux PJ, Yusuf S, Cuerden MS, Parikh CR, Coca SG, Walsh M, Novick R, Cook RJ, Jain AR, Pan X, Noiseux N, Vik K, Stolf NA, Ritchie A, Favaloro RR, Parvathaneni S, Whitlock RP, Ou Y, Lawrence M, Lamy A; CORONARY Investigators. Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial. JAMA. 2014 Jun 4;311(21):2191-8. doi: 10.1001/jama.2014.4952. Erratum in: JAMA. 2014 Jul 2;312(1):97.

Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, Straka Z, Piegas LS, Akar AR, Jain AR, Noiseux N, Padmanabhan C, Bahamondes JC, Novick RJ, Vaijyanath P, Reddy SK, Tao L, Olavegogeascoechea PA, Airan B, Sulling TA, Whitlock RP, Ou Y, Pogue J, Chrolavicius S, Yusuf S; CORONARY Investigators. Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year. N Engl J Med. 2013 Mar 28;368(13):1179-88. doi: 10.1056/NEJMoa1301228. Epub 2013 Mar 11.

Garg AX, Devereaux PJ, Yusuf S, Cuerden MS, Parikh CR, Coca SG, Walsh M, Cook RJ, Whitlock RP, Noiseux N, Novick RJ, Ou Y, Lamy A; CORONARY Investigators. Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY): kidney substudy analytic protocol of an international randomised controlled trial. BMJ Open. 2012 Apr 18;2(2):e001080. doi: 10.1136/bmjopen-2012-001080. Print 2012.

Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, Straka Z, Piegas LS, Akar AR, Jain AR, Noiseux N, Padmanabhan C, Bahamondes JC, Novick RJ, Vaijyanath P, Reddy S, Tao L, Olavegogeascoechea PA, Airan B, Sulling TA, Whitlock RP, Ou Y, Ng J, Chrolavicius S, Yusuf S; CORONARY Investigators. Off-pump or on-pump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012 Apr 19;366(16):1489-97. doi: 10.1056/NEJMoa1200388. Epub 2012 Mar 26.

Lamy A, Devereaux PJ, Prabhakaran D, Hu S, Piegas LS, Straka Z, Paolasso E, Taggart D, Lanas F, Akar AR, Jain A, Noiseux N, Ou Y, Chrolavicius S, Ng J, Yusuf S. Rationale and design of the coronary artery bypass grafting surgery off or on pump revascularization study: a large international randomized trial in cardiac surgery. Am Heart J. 2012 Jan;163(1):1-6. doi: 10.1016/j.ahj.2011.10.007.

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Responsible Party:	Andre Lamy, Cardiac Surgeon, Population Health Research Institute
ClinicalTrials.gov Identifier:	NCT00463294
Other Study ID Numbers:	PHRI-065
First Posted:	April 20, 2007 Key Record Dates
Last Update Posted:	September 16, 2016
Last Verified:	September 2016

Keywords provided by Andre Lamy, Population Health Research Institute:


CABG On-pump Off-pump

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