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Trial registered on ANZCTR


Registration number
ACTRN12613001362785
Ethics application status
Not yet submitted
Date submitted
5/12/2013
Date registered
12/12/2013
Date last updated
12/12/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Do new blood-thinning treatments commenced after cardiac surgery keep By-Pass Grafts open longer ?
Scientific title
The effect of postoperative Aspirin and Clopidogrel versus Aspirin and Ticagrelor on coronary graft patency in patients undergoing primary isolated coronary artery bypass surgery (CABG) post acute coronary syndrome (ACS) presentation
Secondary ID [1] 283569 0
Nil
Universal Trial Number (UTN)
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Graft Patency following Coronary Artery Bypass Graft (CABG) post Acute Coronary Syndrome (ACS) 290473 0
Condition category
Condition code
Cardiovascular 290865 290865 0 0
Coronary heart disease
Surgery 291050 291050 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients who are undergoing isolated CABG following an ACS presentation at Waikato hospital Hamilton NZ and the Austin hospital Melbourne Australia will be eligible for randomisation and will be approached to consider participation
After CABG patients will be randomised to receive enteric coated Aspirin 100 mg orally daily and either Ticagrelor 90 mg orally twice daily or Clopidogrel 75 mg orally daily for 12 months post CABG. Post-operatively dual anti-platelet treatment will be commenced within 12 hours of the procedure, once the cardiac surgeon assessment indicates bleeding /drainage is less that 50 ml/hour
The study drug initial dose after surgery is going to be the maintenance dose, 75 mg orally daily for clopidogrel and 90 mg orally twice dailiy for ticagrelor. Compliance will be assessed by phone follow up
Intervention code [1] 288262 0
Treatment: Drugs
Comparator / control treatment
- The control/comparator treatment arm is active treatment, clopidogrel and aspirin
Control group
Active

Outcomes
Primary outcome [1] 290862 0
Coronary Graft patency 12 months following CABG as measured by multi slice computed tomography coronary angiography
Timepoint [1] 290862 0
12 months
Secondary outcome [1] 305489 0
1. Total Mortality
Timepoint [1] 305489 0
12 months
Secondary outcome [2] 305490 0
bleeding
Bleeding is the primary safety endpoint. Bleeding complications will be assessed using the TIMI Bleeding Criteria (15-18)
2.3.1 Non-CABG Related Bleeding:

1. Major
Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI)
Clinically overt signs of hemorrhage associated with a drop in hemoglobin of 50 g/L or greater or a 15% or more absolute decrease in haematocrit
Fatal bleeding (bleeding that directly results in death within 7 d)

2. Minor
Clinically overt (including imaging), resulting in hemoglobin drop of 30 to <50 g/L or 10% or greater decrease in haematocrit
No observed blood loss: 40 g/L or greater decrease in the haemoglobin concentration or =12% decrease in haematocrit
Any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined above
Requiring intervention (medical practitioner-guided medical or surgical treatment to stop or treat bleeding, including temporarily or permanently discontinuing or changing the dose of a medication or study drug)
Leading to or prolonging hospitalization
Prompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging)
3. Minimal
Any overt bleeding event that does not meet the criteria above
Any clinically overt sign of haemorrhage (including imaging) associated with a <30 g/L decrease in haemoglobin concentration or <9% decrease in haematocrit

2.3.2 Bleeding in the Setting of CABG:
Fatal bleeding (bleeding that directly results in death)
Perioperative intracranial bleeding
Reoperation after closure of the sternotomy incision for the purpose of controlling bleeding
Transfusion of 5 U or more PRBCs or whole blood within a 48-h period; cell saver transfusion will not be counted in calculations of blood products.
Chest tube output >2 L within a 24-h period
Timepoint [2] 305490 0
12 months
Secondary outcome [3] 305926 0
2. Presentations with symptomatic graft failure (acute coronary syndrome or angina)
Timepoint [3] 305926 0
12 months
Secondary outcome [4] 305927 0
3 The occurrence of major adverse cardiac events (MACE), defined as follows:
1. Cardiovascular death
2. Myocardial infarction (Post operative incidence of myocardial infarction will be assessed by serial cardiac enzymes (High sensitive Troponin T) at day 1, 3, 5 and post discharge myocardial infarction will be assessed by either hospital visit for myocardial infarction reported by patient or hospital admission for myocardial infarction reported by cardiologist) .
The 3rd universal definition of post CABG MI (Type 5) will be used for post CABG events .
The 3rd universal definition of MI (Type I) will be used outside of peri/post operative period .
Timepoint [4] 305927 0
12 months
Secondary outcome [5] 305928 0
3. The need for revascularization (repeat operation or angioplasty reported by patient or cardiologist) through 12 months after CABG.
Timepoint [5] 305928 0
12 months
Secondary outcome [6] 305929 0
4. Combined MACE (CV death,MI,revascularization)
Timepoint [6] 305929 0
12 months
Secondary outcome [7] 305930 0
5. Assessment of platelet function with VERIFY-NOW assay at Day 5 post CABG and Pre CT Coronary angiography
Timepoint [7] 305930 0
Day 5 post op and 12 months

Eligibility
Key inclusion criteria
Patients undergoing primary isolated CABG post ACS presentation
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous CABG
Platelet count <100x 109/l
need for concomitant valve surgery or aneurysm resection
Need for post op warfarin
profuse post op bleeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Consent will be sought and obtained pre op. Patient will be randomised post op using pre randomisation via sequentially numbered envelopes. Treatment will not be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistics book.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
each participating centre will be supplied with 100 sealed envelopes in sequential order
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
According to previous studies, the combination of aspirin and clopidogrel has a graft occlusion rate of about 10% at 1 year after CABG. We estimate that a 5% difference between 2 arms can be reliably detected with a power of 80%, if we have 435 coronary grafts in each arm (2 sided T test with a p-value <0.05). In addition, expecting a 10% drop out rates, we estimate 175 patients in each arm (average of three grafts per patient).
The analysis will be based on an estimate of the proportion of failed grafts within each patient and compare these patient graft failure proportions between treatments using a non-parametric test like Wilcoxon.
Analysis will be performed on an intention to treat AND treatment received at time CT
The effect on power compared to a potentially biased Chi-square test is very limited. Based on simulations from the assumptions listed by Prof. Devlin in his proposal, would the power to detect a reduction from 10% graft failure to 5% with 165 patients per arm and 3 grafts / patient in mean, be over 80% with large probability and such a study would deliver a significant result at a 5% level with an observed absolute reduction of 2.5 percentage points.
One note is that for a study this large is probably a parametric approach like a t-test or z-test acceptable approximations, but picky statistical peer reviewers might frown upon such an approach.
Continuous variables will be expressed as mean (SD) or median (interquartile range [IQR]), and categorical variables reported as number (percentage). The significance of any difference between treatment groups in the proportion of patients with =1 occluded graft or with a secondary outcome will be assessed using Fisher exact test, and continuous variables (chest tube output, transfusion) assessed using 2-sample t tests. The significance of any differences between randomized treatment groups in the total numbers of occluded bypass grafts will be assessed by logistic regression using the generalized estimating equations method for non-independent outcomes. A 2-sided P value < .05 will be considered statistically significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/02/2014
Actual
Date of last participant enrolment
Anticipated
20/11/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment outside Australia
Country [1] 5580 0
New Zealand
State/province [1] 5580 0

Funding & Sponsors
Funding source category [1] 288252 0
Commercial sector/Industry
Name [1] 288252 0
AstraZenica Limited
Global Commercial Organisation New Zealand
Country [1] 288252 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Pembroke Street
Hamilton
3240
Country
New Zealand
Secondary sponsor category [1] 286969 0
None
Name [1] 286969 0
Address [1] 286969 0
Country [1] 286969 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 290155 0
New Zealand Health and Disability Ethics Committee
Ethics committee address [1] 290155 0
Ethics committee country [1] 290155 0
New Zealand
Date submitted for ethics approval [1] 290155 0
10/12/2013
Approval date [1] 290155 0
Ethics approval number [1] 290155 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44210 0
A/Prof Gerry Devlin
Address 44210 0
Cardiology Department
Waikato Hospital
Private Bag 3200
Pembroke St
Hamilton 3240
Country 44210 0
New Zealand
Phone 44210 0
+64 7 839 8899
Fax 44210 0
+64 7 839 7140
Email 44210 0
Gerard.Devlin@waikatodhb.health.nz
Contact person for public queries
Name 44211 0
Gerry Devlin
Address 44211 0
Cardiology Department
Waikato Hospital
Private Bag 3200
Pembroke St
Hamilton 3240
Country 44211 0
New Zealand
Phone 44211 0
+64 7 839 8899
Fax 44211 0
Email 44211 0
Gerard.Devlin@waikatodhb.health.nz
Contact person for scientific queries
Name 44212 0
Gerry Devlin
Address 44212 0
Cardiology Department
Waikato Hospital
Private Bag 3200
Pembroke St
Hamilton 3240
Country 44212 0
New Zealand
Phone 44212 0
+64 7 839 8899
Fax 44212 0
Email 44212 0
Gerard.Devlin@waikatodhb.health.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo The study results found that dual anti platelet th... [More Details]

Documents added automatically
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