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

September 15, 2016 updated by: Andre Lamy, Population Health Research Institute

CABG Off or On Pump Revascularization Study (CORONARY)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

4752

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

  1. require isolated CABG with median sternotomy
  2. are able to give their informed written consent
  3. are> 21 years of age and

  4. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • OFF Pump

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
5 years after CABG

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Population Health Research Institute

Collaborators

Charles University, Czech Republic
Centre hospitalier de l'Université de Montréal (CHUM)
McMaster University
University of Oxford
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Fundación Cardiovascular de Colombia
Centre for Chronic Disease Control, India
Instituto Dante Pazzanese de Cardiologia
Medical University of Gdansk
Ankara University
Fu Wai Hospital, Beijing, China
Hotel Dieu Hospital
Universidad de La Frontera
Ospedale Santa Croce-Carle Cuneo
Hopital Jean Minjoz
SAL Hospital, Ahmedabad, India

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

April 18, 2007

First Submitted That Met QC Criteria

April 19, 2007

First Posted (Estimate)

April 20, 2007

Study Record Updates

Last Update Posted (Estimate)

September 16, 2016

Last Update Submitted That Met QC Criteria

September 15, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • PHRI-065

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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