Evaluation of Antiplatelet Effects and Safety of Intraoperative Administration of Ticagrelor Versus Clopidogrel

Phase 4

• Conditions: Coronary Disease
• Interventions: Drug: Clopidogrel; Drug: Ticagrelor

• Registration Number: NCT02513004
• Lead Sponsor: Yongjian Wu

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.

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-14
• Study First Submitted QC: 2015-07-30
• Study First Posted: 2015-07-31
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-08
• Last Update Posted: 2017-02-09
• Primary Completion: 2017-03
• Study Completion: 2017-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clopidogrel	Clopidogrel	Patients will receive a loading dose of 300mg clopidogrel tablets (four 75mg capsules powdered) taken via nasogastric tube after LIMA-LAD bypass establishing, the close of thorax and before PCI procedure. Thereafter, the patients will take 75mg of clopidogrel capsules orally od. The total study period is 3 months.
Ticagrelor	Ticagrelor	Patients will receive first dose of 90mg ticagrelor tablets (powdered) taken via nasogastric tube after LIMA-LAD bypass establishing, the close of thorax and before PCI procedure, followed by 90mg of ticagrelor 12 hours after the first dose.Thereafter, the patients will take 90mg of ticagrelor orally bid, at approximately 12-hourly intervals. The total study period is 3 months.

Primary Outcome Measures

Name	Time	Method
1hourPRU	1hour	PRU measured by Verify NowTM P2Y12 assay at 1 hour after first dose of study drug administered as powder via a nasogastric tube after confirmation of LIMA-LAD graft patency during the HCR procedure in HCR patients.

Secondary Outcome Measures

Name	Time	Method
30min,1h,2h,6h,12h,24h PRU	30min,1h,2h,6h,12h,24h after first dose	PRU measured by Verify NowTM P2Y12 assay at 30min,1h, 2h，6h,12h,24h after first dose of study drugs.

Trial Locations

Locations (1)

Fuwai hospital; 🇨🇳 Beijing, Beijing, China