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

Coronary Artery Disease Clinical Trial

Official title:

Safety and Efficacy of Low-dose Ticagrelor in Chinese Patients With Stable Coronary Artery Disease: a Randomized, Single-blind, Crossover Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02514642
• Other study ID #: SCAD-201523
• Status: Recruiting
• Phase: Phase 4
• First received: July 21, 2015
• Last updated: September 28, 2015
• Start date: July 2015
• Est. completion date: November 2015

Study information

• Verified date: July 2015
• Source: First Affiliated Hospital of Harbin Medical University
• Contact: Meijiao He, MM
• Phone: 86-451 -85555673
• Email: hemeijiao99[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• 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)
• 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)

Locations

Country	Name	City	State
United States	VerifyNow	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Harbin Medical University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P2Y12 reaction units (PRU)		up to 5 months	Yes
Secondary	inhibition of platelet aggregation (IPA)		up to 5 months	Yes