Safety and Efficacy of Low-dose Ticagrelor in Chinese Patients With Stable Coronary Artery Disease

NCT ID: NCT02514642

Last Updated: 2015-09-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2015-11-30

Brief Summary

Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In Korea and Japan, it has been reported that low doses of ticagrelor might have a more potent inhibition of platelet aggregation (IPA) than clopidogrel (75 mg once daily) in healthy subjects and patients with stable coronary artery disease, respectively. But it is still not clear whether a low dose of ticagrelor is superior to clopidogrel in a large population of Chinese ACS patients. A recent study on pharmacokinetics and tolerability of ticagrelor has found that maximum plasma concentration and area under the plasma concentration-time curve of ticagrelor (90 mg twice daily) and its active metabolite (AR-C124910XX) tended to be approximately 40% higher in healthy Chinese volunteers compared with Caucasian subjects. This data also suggested that a low dose of ticagrelor might be more appropriate for Chinese ACS patients. In view of a large diurnal variation with a single daily dose, a lower dose twice daily may be a better choice for Chinese patients. Therefore, the investigators performed this randomized, single-blind, crossover clinical trial to observe the efficacy and safety of low-dose ticagrelor (22.5 mg twice daily) in comparison to clopidogrel (75mg once daily) in Chinese patients with stable coronary artery disease.

Detailed Description

Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy (DAPT) have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for patients who have an ACS with or without ST-segment elevation. However, few East Asian patients (or those of East Asian descent) have been included in these trials to assess the use of these drugs. In addition, a growing body of data supported that East Asian might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects. Furthermore, "East Asian paradox" phenomenon has been also described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following percutaneous coronary intervention (PCI) or ACS is similar or even lower than white patients. In Korea and Japan, it has been reported that low doses of ticagrelor might have a more potent inhibition of platelet aggregation (IPA) than clopidogrel (75 mg once daily) in healthy subjects and patients with stable coronary artery disease, respectively. But it is still not clear whether a low dose of ticagrelor is superior to clopidogrel in a large population of Chinese ACS patients. A recent study on pharmacokinetics and tolerability of ticagrelor has found that maximum plasma concentration and area under the plasma concentration-time curve of ticagrelor (90 mg twice daily) and its active metabolite (AR-C124910XX) tended to be approximately 40% higher in healthy Chinese volunteers compared with Caucasian subjects. This data also suggested that a low dose of ticagrelor might be more appropriate for Chinese ACS patients. In view of a large diurnal variation with a single daily dose, a lower dose twice daily may be a better choice for Chinese patients. Therefore, the investigators performed this randomized, single-blind, crossover clinical trial to observe the efficacy and safety of low-dose ticagrelor (22.5 mg twice daily) in comparison to clopidogrel (75mg once daily) in Chinese patients with stable coronary artery disease.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

low-dose ticagrelor

To observe the safety and efficacy of low-dose ticagrelor in Chinese patients withStable Coronary Artery Disease

Group Type: EXPERIMENTAL

low-dose ticagrelor

Intervention Type: DRUG

low-dose ticagrelor (22.5 mg twice daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of clopidogrel (75mg once daily)

Clopidogrel

Intervention Type: DRUG

clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of low-dose ticagrelor (22.5 mg twice daily)

clopidogrel

To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel.

Group Type: ACTIVE_COMPARATOR

low-dose ticagrelor

Intervention Type: DRUG

low-dose ticagrelor (22.5 mg twice daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of clopidogrel (75mg once daily)

Clopidogrel

Intervention Type: DRUG

clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of low-dose ticagrelor (22.5 mg twice daily)

Interventions

low-dose ticagrelor

low-dose ticagrelor (22.5 mg twice daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of clopidogrel (75mg once daily)

Intervention Type: DRUG

Clopidogrel

clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7days crossover phase of low-dose ticagrelor (22.5 mg twice daily)

Intervention Type: DRUG

Other Intervention Names

low-dose ticagrelor(22.5 mg twice daily); clopidogrel (75mg once daily)

Eligibility Criteria

Inclusion Criteria

• Stable Coronary Artery Disease

1. stable angina

2. low-risk unstable angina

3. variant angina

4. patients with asymptomatic with appropriate therapy（including percutaneous coronary intervention）.

Exclusion Criteria

1. ACS

2. planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period

3. platelet count <100g/L

4. creatinine clearance rate < 30ml/min

5. diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%)

6. a history of bleeding tendency

7. aspirin, ticagrelor or clopidogrel allergies

8. diabetes.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yue Li, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University

Locations

VerifyNow

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Meijiao He, MM

Role: CONTACT

Phone: 86-451 -85555673

Email: hemeijiao99@sina.com

Facility Contacts

Meijiao He, Master

Role: primary

Other Identifiers

SCAD-201523

Identifier Type: -

Identifier Source: org_study_id