Clinical trial NCT02053909: Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis
Official title: Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET Trial): Does Ticagrelor Improve Graft Patency After Coronary Bypass?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Saphenous Vein Graft Disease
Keywords: Saphenous vein graft disease
Coronary artery bypass graft surgery
Antiplatelet therapy
Coronary artery disease
Secondary prevention
Graft patency
Lead sponsor: Boca Raton Regional Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Ottawa Heart Institute Research Corporation
First posted: 2014-02-04
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Saphenous Vein Graft Occlusion
timeFrame: 1 year after surgery
Secondary outcomes:
measure: Saphenous Vein Graft Stenosis
timeFrame: 1 year after surgery
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Boca Raton Regional Hospital
name: Alexander Kulik, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.