Acute Coronary Syndrome
Conditions
Keywords
acute coronary syndrome, coronary artery bypass surgery, ticagrelor, antiplatelet therapy, platelet function testing
Brief summary
Ticagrelor, a more potent P2Y12 inhibitor, has been shown to reduce major adverse cardiac events (MACE) in acute coronary syndromes (ACS). It is increasingly used as a first line therapy in ACS. However, more potent P2Y12 inhibition has been associated with increased bleeding. This may be of particular concern for patients with ACS who require coronary artery bypass surgery (CABG). In particular, the timing for cessation of ticagrelor before proceeding to CABG is unclear. RAPID TITRATE CABG is a randomized vanguard study to evaluate the feasibility and preliminary safety of a strategy of early versus delayed CABG in ACS patients initially treated with ticagrelor and to identify potential mechanisms underlying benefits or complications of early bypass surgery.
Interventions
PROCEDUREEarly CABG (Day 2-3 after ticagrelor discontinuation)
Timing for CABG after ticagrelor discontinuation
PROCEDUREDelayed CABG (Day 5-7 after ticagrelor discontinuation)
Timing for CABG after ticagrelor discontinuation
Sponsors
Canadian Institutes of Health Research (CIHR)
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ACS patient referred for CABG and have received \>= 1 dose of ticagrelor before decision for CABG made
Exclusion criteria
Patients are excluded if they: * refuse consent for enrollment * are deemed to require immediate CABG (Day 0 or day 1) * have a ST-elevation myocardial infarction (STEMI )initially treated with primary PCI * are undergoing concurrent valve surgery * are intolerant or allergic to aspirin * have been on an oral anticoagulant (including a vitamin K antagonist or a NOAC) * received adjuvant therapy with a glycoprotein IIbIIIa inhibitor * have a co-morbidity with life-expectancy of \< 1 year * have active bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severe-massive bleeding | 24 hours post CABG | Class 3 or 4 UDPB (universal definition for peri-operative bleeding) |
| 12-hour chest tube drainage | 12 hours post CABG | Chest tube drainage in the first 12 hours after bypass surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Other major bleeding criteria (CABG related life threatening bleed) | 48 hours post CABG | CABG-related life-threatening bleed including: cardiac tamponade, all intracranial bleeding |
| Transfusion (RBC) | 48 hours post CABG | Red Blood Cell (RBC) transfusion (in Units) |
| Transfusion (Platelet) | 48 hours post CABG | Platelet transfusion (in Units) |
| Peri-operative biomarker rise | 48 hours post CABG | CK, troponin rise post CABG |
| Other major bleeding criteria (BARC) | 48 hours post CABG | Bleeding Academic Research Consortium (BARC) CABG-related (Type 4) bleeding |
| Number of Patients with Individual Components of Major Adverse Cardiovascular Events (MACE) (To be collected but blinded to investigators,as this data will be carried from the vanguard study into a future definitive clinical trial). | 6 months and 1 year | cardiovascular death, recurrent myocardial infarction, stroke, refractory ischemia, or urgent unplanned revascularization |
| P2Y12 Reactivity Units (PRU) as a continuous variable | Baseline (at CABG), 24, 48, 72 hours post CABG | Platelet Function as Measured by VerifyNow P2Y12 assay |
| ADP-induced Aggregation (AU) as a continuous variable | Baseline (at CABG), 24, 48, 72 hours post CABG | Platelet Function as Measured by Multiplate analyzer |
| Number of Patients with Major Adverse Cardiovascular Events (MACE) (To be collected but blinded to investigators,as this data will be carried from the vanguard study into a future definitive clinical trial). | 6 months and 1 year | MACE defined as composite of cardiovascular death, recurrent myocardial infarction, stroke, refractory ischemia, or urgent unplanned revascularization |
| Other major bleeding criteria (TIMI) | 48 hours post CABG | TIMI major/minor CABG bleeding |
Countries
Canada
Outcome results
None listed