Clinical trial NCT02513004: Evaluation of Antiplatelet Effects and Safety of Intraoperative Administration of Ticagrelor Versus Clopidogrel
Official title: Evaluation of Antiplatelet Effects and Safety of Intraoperative Administration of Ticagrelor Versus Clopidogrel in Patients Undergoing "One-stop" Hybrid Coronary Revascularization
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Disease
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
First posted: 2015-07-31
Enrollment: 60
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: This study is designed to test the hypothesis that the onset of the antiplatelet effect 90mg-first-dose of ticagrelor will be more rapid and greater than 300mg-loading-dose of clopidogrel evaluated by P2Y12 reaction units measured by Verify NowTM P2Y12 assay at 1 hour in patients undergoing one-stop Hybrid coronary revascularization(HCR).

Detailed description: This is a single-center, randomized, active-controlled, open-label, prospective study, and the study is designed to test the hypothesis that the onset of the antiplatelet effect 90mg-first-dose of ticagrelor will be more rapid and greater than 300mg-loading-dose of clopidogrel evaluated by P2Y12 reaction units (PRU) measured by Verify NowTM P2Y12 assay at 1 hour in patients undergoing one-stop HCR. The first dose of study drug (ticagrelor 90mg or clopidogrel 300 mg) will be administered as powder via a nasogastric tube after conﬁrmation of left internal mammal artery to left anterior descending coronary antery (LIMA-LAD) graft patency during the HCR procedure. Approximately 60 patients will enrol for the study. Patients will be randomized equally (ratio 1:1) to the two treatment arms of this study. The anticipated duration of the study is approximately 15 months, including an anticipated enrolment period of 12 months and follow-up period of 3months.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. A patient who is considered as ethnic Chinese
3. 80years \>aged\> 18years, male or female
4. Patient is willing to perform HCR with the following conditions: Multi-vessel coronary artery disease with unfavorable left anterior descending coronary artery (LAD) for percutaneous coronary intervetion (PCI) (i.e., chronic total occlusion, excessive tortuosity, severely diffuse lesion), unprotected left main coronary artery disease, and non-LAD lesions were technically feasible for PCI with a drug-eluting stent (DES) .Limitations to traditional coronary artery bypass graft (CABG), such as pre-existing organ dysfunction, heavily calciﬁed proximal aorta, or lack of suitable graft conduits

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study
2. Previous enrolment or randomization in the present study
3. Participation in another clinical study with an investigational product during the last 30 days
4. Contraindication or other reason that clopidogrel or ticagrelor should not be administered (eg, hypersensitivity, active bleeding, moderate or severe liver disease, history of previous intracranial bleed, GI bleed within the past 6 months, major surgery within 30 days)
5. With coagulation disorder
6. With uric acid nephropathy
7. History of intolerance or allergy to acetylsalicylic acid (ASA) or clopidogrel or ticagrelor
8. Patient has a coronary artery bypass graft (CABG) history.
9. left subclavian artery and LIMA stenosis
10. buried intramyocardial LAD
11. need for a concomitant operation (e.g., valve repair or replacement)
12. overt congestive heart failure
13. Unsuccessful LIMA-LAD graft
14. hemodynamic instability
15. other conditions rendering PCI unsuitable (e.g., fresh thrombus, coronary vessel diameter \<1.5 mm)
16. Platelet count less than 100\*10\^9/L
17. Haemoglobin (Hb) level less than 110g/L
18. White blood cell count less than 4\*10\^12/L
19. Recent (within 30 days of dosing) blood donation
20. Fibrinolytic therapy in the 24 hours prior to randomisation, or planned fibrinolytic treatment following randomisation (eg, for ST-segment elevation myocardial infarction or pulmonary embolism)
21. P2Y12 receptor inhibitor therapy in 7 days before HCR surgery.
22. Nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and prostacyclins (PGI2) therapy that cannot be stopped
23. Increased risk of bradycardic events (eg, no pacemaker and known sick sinus syndrome, second degree atrioventricular block, third degree atrioventricular block or previous documented syncope suspected to be due to bradycardia).
24. Concomitant oral or intravenous therapy (see examples below) with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers within 14 days of study treatment or cannot be stopped for the course of the study.

    Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice.

    Substrates with narrow therapeutic index: cyclosporine, quinidine. Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine. The sponsor should be consulted for enrolment with any concomitant medicines which are suspected of undergoing strong drug-drug interaction
25. Any other condition which in the opinion of the investigator, may either put the patient at risk or influence the result of the study (e.g., cardiogenic shock or active cancer)
26. Moderate or severe renal disease;
27. Moderate or severe chronic lung disease or asthma;
28. Pregnancy or lactation

Primary outcomes:
measure: 1hourPRU
timeFrame: 1hour
Secondary outcomes:
measure: 30min,1h,2h,6h,12h,24h PRU
timeFrame: 30min,1h,2h,6h,12h,24h after first dose
Other outcomes:
measure: safety assessed by the bleeding risk of ticagrelor compared with clopidogrel in the peri-operative and in-hospital period and 3 months follow-up.
timeFrame: 3 monthes
Locations:
city: Beijing
country: China
facility: Fuwai hospital
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Yongjian Wu, Professor
role: PRINCIPAL_INVESTIGATOR
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