Timing of Coronary Artery Bypass Surgery Among Patients With Acute Coronary Syndromes Initially on Ticagrelor

Study Overview
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Brief Summary
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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.

Official Title
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Reassessment of Anti-Platelet Therapy Using InDividualized Strategies -Ticagrelor in Patients With Acute Coronary Syndromes Treated by Coronary Artery Bypass Graft Surgery - A Pharmacodynamic and Clinical Study to Decrease Bleeding Risks and Ischemic Complications - The RAPID-TITRATE CABG Study

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Procedure: Early CABG (Day 2-3 after ticagrelor discontinuation)
* Procedure: Delayed CABG (Day 5-7 after ticagrelor discontinuation)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early CABG<br>Patients to undergo early CABG | Procedure: Early CABG (Day 2-3 after ticagrelor discontinuation)<br>* Timing for CABG after ticagrelor discontinuation<br>|
| Active Comparator: Delayed CABG<br>Patients to undergo delayed CABG | Procedure: Delayed CABG (Day 5-7 after ticagrelor discontinuation)<br>* Timing for CABG after ticagrelor discontinuation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe-massive bleeding | Class 3 or 4 UDPB (universal definition for peri-operative bleeding) | 24 hours post CABG | 
| 12-hour chest tube drainage | Chest tube drainage in the first 12 hours after bypass surgery | 12 hours post CABG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other major bleeding criteria (BARC) | Bleeding Academic Research Consortium (BARC) CABG-related (Type 4) bleeding | 48 hours post CABG | 
| Other major bleeding criteria (TIMI) | TIMI major/minor CABG bleeding | 48 hours post CABG | 
| Other major bleeding criteria (CABG related life threatening bleed) | CABG-related life-threatening bleed including: cardiac tamponade, all intracranial bleeding | 48 hours post CABG | 
| Transfusion (RBC) | Red Blood Cell (RBC) transfusion (in Units) | 48 hours post CABG | 
| Transfusion (Platelet) | Platelet transfusion (in Units) | 48 hours post CABG | 
| Peri-operative biomarker rise | CK, troponin rise post CABG | 48 hours post CABG | 
| 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). | MACE defined as composite of cardiovascular death, recurrent myocardial infarction, stroke, refractory ischemia, or urgent unplanned revascularization | 6 months and 1 year | 
| 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). | cardiovascular death, recurrent myocardial infarction, stroke, refractory ischemia, or urgent unplanned revascularization | 6 months and 1 year | 
| P2Y12 Reactivity Units (PRU) as a continuous variable | Platelet Function as Measured by VerifyNow P2Y12 assay | Baseline (at CABG), 24, 48, 72 hours post CABG | 
| ADP-induced Aggregation (AU) as a continuous variable | Platelet Function as Measured by Multiplate analyzer | Baseline (at CABG), 24, 48, 72 hours post CABG | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute coronary syndrome, coronary artery bypass surgery, ticagrelor, antiplatelet therapy, platelet function testing