Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET)

Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET Trial): Does Ticagrelor Improve Graft Patency After Coronary Bypass?

Saphenous vein graft disease remains an unresolved medical problem. Many vein grafts occlude in the first year after bypass surgery, leading to adverse cardiovascular outcomes, including recurrent angina, myocardial infarction, and the need for repeat coronary intervention. While aspirin is the standard antiplatelet treatment after CABG surgery, 10-20% of vein grafts continue to occlude despite contemporary secondary preventative therapy. Compared to aspirin and other antiplatelet therapies like clopidogrel, ticagrelor treatment leads to a more pronounced platelet inhibition, and may substantially improve graft patency following CABG compared to aspirin. No data has yet to be collected regarding the impact of ticagrelor on saphenous vein graft patency following CABG. In this context, the investigators seek to compare vein graft patency between patients randomized to receive aspirin therapy, the current standard of care, or ticagrelor treatment, starting in the early postoperative period, and continuing for 2 years after CABG.

Study Overview

• Status: Completed
• Conditions: Saphenous Vein Graft Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: Aspirin

Detailed Description

This clinical trial will be a randomized double-blind study focusing on ticagrelor antiplatelet therapy as a means of improving vein graft patency after CABG. Patients will be eligible if they have received at least 1 vein bypass graft at time of surgery. Patients will be randomized to receive either aspirin 81 mg bid or ticagrelor 90 mg bid. The aspirin and ticagrelor medications will be prepared in blinded capsules. Patients recovering from surgery will be eligible for study randomization within the first 5 postoperative days. Treatment will continue for 1 year, at which time patients will undergo a CT coronary angiogram to assess graft patency. Patients will then be invited to continue participating in the trial for 1 more year, and a repeat CT coronary angiogram will be performed at the 2 year postoperative time-point.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • University of Ottawa Heart Institute
• United States
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male patients aged 18-90 years
3. Patients undergoing first-time CABG with at least 1 saphenous vein graft, irrespective of concurrent valve surgery

Exclusion Criteria:

1. Inability to provide informed consent
2. Pregnancy or seeking pregnancy
3. Patients undergoing redo-CABG
4. Serum creatinine >1.8 mg/dL (need for contrast with CT coronary angiogram)
5. Hypersensitivity or allergy to aspirin or ticagrelor
6. Anticipated need for postoperative anticoagulation with coumadin, dabigatran or rivaroxaban (mechanical valve, chronic atrial fibrillation, DVT/PE)
7. History of gastrointestinal hemorrhage
8. Active pathological bleeding
9. History of intracranial hemorrhage
10. Severe hepatic impairment
11. Current or anticipated use of strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazadone, ritonavir, and atazanavir)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin; One aspirin 81 mg capsule 2 times per day	Drug: Aspirin
Active Comparator: Ticagrelor; One ticagrelor 90 mg capsule 2 times per day	Drug: Ticagrelor; Other Names: Brillinta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saphenous Vein Graft Occlusion	The primary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft occlusion 1 year after surgery, as assessed by computed tomography (CT) coronary angiography.	1 year after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saphenous Vein Graft Stenosis	The secondary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft stenosis, defined as >50% narrowing of the graft, 1 year after surgery, as assessed by computed tomography (CT) coronary angiography.	1 year after surgery

Collaborators and Investigators

• Sponsor: Boca Raton Regional Hospital
• Collaborators: AstraZeneca; Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: Alexander Kulik, MD MPH, Boca Raton Regional Hospital

Publications and helpful links

General Publications

• Kulik A, Abreu AM, Boronat V, Kouchoukos NT, Ruel M. Impact of ticagrelor versus aspirin on graft patency after CABG: Rationale and design of the TARGET (ticagrelor antiplatelet therapy to reduce graft events and thrombosis) randomized controlled trial (NCT02053909). Contemp Clin Trials. 2018 May;68:45-51. doi: 10.1016/j.cct.2018.03.008. Epub 2018 Mar 15.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: February 1, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Coronary artery disease; Secondary prevention; Antiplatelet therapy; Saphenous vein graft disease; Coronary artery bypass graft surgery; Graft patency
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: Brilinta ISSBRIL0220