Ignite Creation Date:
2024-05-05 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00463294
Status:
COMPLETED
Last Update Posted:
2016-09-16
First Post:
2007-04-18
Brief Title:
Coronary Artery Bypass Surgery CABG Off or On Pump Revascularization Study
Sponsor:
Population Health Research Institute
Organization:
Population Health Research Institute
Study Overview
Official Title:
CABG Off or On Pump Revascularization Study CORONARY
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CORONARY
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
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
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 singledouble 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 86 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
DesignMethodology
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 ie 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 eg 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 ie coronary artery bypass surgery and percutaneous coronary intervention using the same strategy The effect of the two operative techniques on different sub-groups ie 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 ICUCCU stay will be compared using a students 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 ie 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
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 singledouble 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 86 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
DesignMethodology
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 ie 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 eg 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 ie coronary artery bypass surgery and percutaneous coronary intervention using the same strategy The effect of the two operative techniques on different sub-groups ie 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 ICUCCU stay will be compared using a students 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None