Clinical trial NCT05380063: Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting
Official title: Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting in Patients Without Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Disease
Coronary Artery Bypass Grafting
Dual Antiplatelet Therapy
Bleeding
Myocardial Infarction
Myocardial Ischemia
Angina Pectoris
Keywords: Coronary Artery Bypass Grafting
Ticagrelor
Aspirin
Dual Antiplatelet Therapy
De-escalated Dual Antiplatelet Therapy
Great Saphenous Vein
Bleeding
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2022-05-18
Enrollment: 2300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting trial (TOP-CABG trial) is a multicenter, randomized, double-blind, non-inferiority, parallel controlled trial. The aim of TOP-CABG is to investigate whether de-escalated dual antiplatelet therapy (De-DAPT) is non-inferior to dual antiplatelet therapy (DAPT) in efficacy on inhibiting great saphenous vein (SVG) graft occlusion and is superior in reducing bleeding events in patients accepting coronary artery bypassing grafting.

Detailed description: After informed consent, at least 10 centers and 2,300 eligible admissions will be recruited. Eligible patients would be randomized (1:1) in double-blind manner (patients and treating physicians) to dual antiplatelet therapy (DAPT) group (ticagrelor 90mg bid and aspirin 100 mg qd for 12 month) and de-escalated DAPT (De-DAPT) group (90mg bid and aspirin 100 mg qd for first 3 months, and then aspirin 100 mg qd and placebo for 9 months).

Eligibility criteria: Inclusion criteria

1. Patients 18-80 of age. 2. Patients undergo planned CABG for the first time with ≥1 SVGs 3. Patients with written informed consent. Exclusion criteria

1. Concomitant valve (excluding aortic bioprosthesis), aorta, or rhythm surgery during the same session.
2. Patients undergo emergency CABG.
3. Patients with single coronary artery disease.
4. Patients with cardiogenic shock and hemodynamic instability.
5. Patients with sick sinus syndrome, 2nd or 3rd atrioventricular block.
6. Patients with contraindications for coronary computed tomography angiography or coronary angiography (eg. contrast allergy).
7. Use of other antiplatelet drugs than aspirin or ticagrelor (clopidogrel, prasugrel, etc) and unable to discontinue this medication after CABG, in the treating physician's or the investigator's opinion.
8. Patients who take oral anticoagulants before CABG and have to use anticoagulants after surgery.
9. Contraindication for the use of ticagrelor or aspirin (ie. history of bleeding diathesis within 3 months prior presentation, severe gastrointestinal bleeding within 1year prior presentation, peptic ulcer without gastrointestinal bleeding in past 3 years or history of intracranial hemorrhage, allergy, severe gastrointestinal reaction caused by aspirin).
10. Placement of a drug-eluting stent in a coronary or cerebral artery within 6 months of CABG or placement of a bare-metal stent in a coronary or cerebral artery within 1 month of CABG
11. Thrombocytopenia before CABG (\< 100 x 109/L).
12. patients with severe renal function impairment requiring dialysis or active liver disease, including patients with unexplained persistent elevated transaminase or any transaminase more than 3 times the normal limit.
13. Use of strong inhibitors of CYP3A4
14. Patients who have to use methotrexate and ibuprofen.
15. Patients with active malignant tumors with increase in bleeding risk in the investigator's opinion
16. Pregnant patients, patients who have given birth within the past 90 days, or who are breastfeeding.
17. Premenopausal women who do not take adequate contraception. Adequate contraception refers to the adoption of at least two reliable methods of contraception, one of which must be a barrier method of contraception.
18. CABG volume of the surgeon less than 50.

Primary outcomes:
measure: 100% great saphenous vein (SVG) grafts occlusions
timeFrame: During 0-day to 1-year after CABG
measure: Bleeding events
timeFrame: During 0-day to 1-year after CABG
Secondary outcomes:
measure: SVG Failure
timeFrame: During 0-day to 1-year after CABG
measure: Graft stenosis and occlusion
timeFrame: During 0-day to 1-year after CABG
measure: MACCE episodes
timeFrame: Within 1-year after CABG
Other outcomes:
measure: Subgroup analysis 1 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 2 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 3 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 4 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 5 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 6 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 7 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 8 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 9 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 10 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 11 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 12 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 13 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 14 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 15 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 16 for primary outcome
timeFrame: 1 year
measure: Subgroup analysis 17 for primary outcome
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Fuwai Hospital
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Shengshou Hu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Xin Yuan, PhD
role: STUDY_CHAIR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Qing Chu, PhD
role: STUDY_DIRECTOR
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Kai Chen
role: STUDY_DIRECTOR
References: