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

Sponsor
Population Health Research Institute (Other)
Overall Status
Completed
CT.gov ID
NCT00463294
Collaborator
McMaster University (Other), University of Oxford (Other), Instituto Dante Pazzanese de Cardiologia (Other), Fu Wai Hospital, Beijing, China (Other), Universidad de La Frontera (Other), Fundación Cardiovascular de Colombia (Other), Charles University, Czech Republic (Other), Hopital Jean Minjoz (Other), Centre for Chronic Disease Control, India (Other), Ospedale Santa Croce-Carle Cuneo (Other), Medical University of Gdansk (Other), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Ankara University (Other), Hotel Dieu Hospital (Other), Centre hospitalier de l'Université de Montréal (CHUM) (Other), SAL Hospital, Ahmedabad, India (Other)
4,752
Enrollment
52
Locations
2
Arms
107
Duration (Months)
91.4
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

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.

  1. 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.

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

Condition or Disease Intervention/Treatment Phase
  • Procedure: Coronary Artery Bypass Graft with the use of CPB
  • Procedure: Coronary Artery Bypass Graft without the use of CPB
 Phase 3

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

Study Type:
Interventional
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 :
Oct 1, 2007
Actual Primary Completion Date :
Mar 1, 2012
Actual Study Completion Date :
Sep 1, 2016

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 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. First Co-Primary Outcome [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

    2. Second co-primary outcome [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

    1. The assessment of total costs and resources consumption at 30 days after CABG surgery [30 days after CABG surgery]

    2. The assessment of total costs and resources consumption at 5 years after CABG surgery [5 years after CABG surgery]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

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

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Andre Lamy, Cardiac Surgeon, Population Health Research Institute
    ClinicalTrials.gov Identifier:
    NCT00463294
    Other Study ID Numbers:
    • PHRI-065
    First Posted:
    Apr 20, 2007
    Last Update Posted:
    Sep 16, 2016
    Last Verified:
    Sep 1, 2016
    Keywords provided by Andre Lamy, Cardiac Surgeon, Population Health Research Institute
    CABG
    On-pump
    Off-pump

    Study Results

    No Results Posted as of Sep 16, 2016