Timing of Coronary Artery Bypass Surgery Among Patients With Acute Coronary Syndromes Initially on Ticagrelor (RAPID CABG)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Procedure: Early CABG (Day 2-3 after ticagrelor discontinuation); Procedure: Delayed CABG (Day 5-7 after ticagrelor discontinuation)

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y4W7
      • University of Ottawa Heart Institute
  • Quebec
    • Montreal, Quebec, Canada, H1T1C8
      • Montreal Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Derek So, MD FRCPC FACC, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): April 9, 2021
• Study Completion (Actual): March 9, 2022

Study Registration Dates

• First Submitted: January 6, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimated): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: acute coronary syndrome; ticagrelor; coronary artery bypass surgery; antiplatelet therapy; platelet function testing
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: 20150656

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO