Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With NSTE-ACS

NCT ID: NCT02415803

Last Updated: 2015-04-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31

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. These recommendations are primarily based on large, randomized, Phase III clinical trials. 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 described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).

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. These recommendations are primarily based on large, randomized, Phase III clinical trials. 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 described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. In Korea and Japan, it has been reported that low doses of ticagrelor had 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 (Cmax) and area under the plasma concentration-time curve (AUC) 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, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).

Conditions

Non ST Segment Elevation Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

low-dose ticagrelor

To observe the safety and efficacy of low-dose ticagrelor in Chinese patients with non-ST-elevation acute coronary syndrome

Group Type: EXPERIMENTAL

low-dose ticagrelor

Intervention Type: DRUG

90 mg loading dose, then 45 mg twice daily for 5 days

conventional-dose ticagrelor

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

Group Type: ACTIVE_COMPARATOR

conventional-dose ticagrelor

Intervention Type: DRUG

180 mg loading dose, then 90 mg twice daily for 5 days

clopidogrel

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

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

300 mg loading dose, then 75 mg once daily for 5 days

Interventions

low-dose ticagrelor

90 mg loading dose, then 45 mg twice daily for 5 days

Intervention Type: DRUG

conventional-dose ticagrelor

180 mg loading dose, then 90 mg twice daily for 5 days

Intervention Type: DRUG

Clopidogrel

300 mg loading dose, then 75 mg once daily for 5 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• hospitalized for NSTE-ACS within the preceding 48 h
• have one of the following additional criteria:

1. ischemic symptoms at rest, lasting ≥10 minutes;

2. horizontal or down-sloping ST segment depression ≥0.1 mV;

3. cardiac troponin I (cTnI), marker associated with NSTE-ACS, local laboratory upper limit of normal values;

4. underwent percutaneous coronary intervention (PCI); (5) a history of myocardial infarction.

Exclusion Criteria

• ST-elevation ACS;
• planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
• platelet count <100g/L;
• creatinine clearance rate < 30ml/min;
• diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction < 40%);
• a history of bleeding tendency;
• aspirin, ticagrelor or clopidogrel allergies;
• 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

Locations

VerifyNow

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yue Li, MD

Role: CONTACT

ly99ly@vip.163.com

86-451-85555673

Hongjie Xue, MD

Role: CONTACT

xuehj@163.com

86-451-85555672

Facility Contacts

Jing Shi, MM

Role: primary

customerservice@accriva.com

518-393-2200

Other Identifiers

ACS-1

Identifier Type: -

Identifier Source: org_study_id