Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable CAD.

Sponsor
First Affiliated Hospital of Harbin Medical University (Other)
Overall Status
Completed
CT.gov ID
NCT03679091
Collaborator
(none)
36
1
2
6
6

Study Details

Study Description

Brief Summary

Ticagrelor has been demonstrated to provide a more rapid and more powerful inhibition of platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients. However, current guidelines recommend ticagrelor 90 mg twice daily might not be suitable for patients of Chinese. Therefore, the investigators performed this study to observe the efficacy of 60-mg ticagrelor in comparison to 75-mg clopidogrel in Chinese patients with stable CAD.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the established standard of care in ACS patients. Although a popular P2Y12 receptor inhibitor, clopidogrel is not the most potent antiplatelet agent due to its metabolic activation. Metabolic activation of clopidogrel depends on multiple cytochrome P450 (CYP) enzymes, including CYP2C19, which can delay the onset of its activity; in addition, some populations carry a reduced-function allele of the CYP2C19 gene. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles in these patients. A recent study indicated that Asians might have different adverse event profiles (thrombophilia and bleeding) and "therapeutic window" compared with white subjects, suggesting that regional differences may influence the altered response of clopidogrel to the onset of thrombotic events.

Ticagrelor is an orally administered, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with ACS. Guidelines give a recommendation on the use of dual antiplatelet therapy (DAPT) support ticagrelor 90 mg twice daily over clopidogrel 75 mg daily in addition to aspirin in ACS patients with or without ST-segment elevation. Increasing evidence indicated that Asian patients showed higher active metabolite exposure rates and stronger pharmacodynamic responses than their Caucasian subjects when treated with the same oral doses of prasugrel .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 in healthy subjects and patients with stable coronary artery disease, respectively .In our previous study, the investigators found that half-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose ticagrelor and exerted significantly stronger effects than clopidogrel in patients with ACS and one-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than clopidogrel in patients with stable CAD. Furthermore, standard-dose ticagrelor (180mg loading dose [LD], then 90mg twice daily) has a significant increase in the risk of bleeding and incidence rate of dyspnea, and that higher discontinuation rates due to adverse effects compared to clopidogrel. A recent study demonstrated 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. Notably, poor drug metabolism of clopidogrel is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 reduced-function alleles. The data suggested that a low dose of ticagrelor might be more appropriate for Chinese patients.

The objectives of this study were to evaluate the effects of ticagrelor (60.0mg daily) in comparison to clopidogrel (75mg daily) on platelet reactivity in Chinese patients with stable CAD.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Low-dose of Ticagrelor and Standard-dose Clopidogrel on Platelet Effects in Chinese Patients With Stable Coronary Artery Disease: a Randomized, Single-blind, Crossover Clinical Study
Actual Study Start Date :
Aug 29, 2018
Actual Primary Completion Date :
Feb 28, 2019
Actual Study Completion Date :
Feb 28, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: low-dose ticagrelor

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

Drug: low-dose ticagrelor
low-dose ticagrelor (60.0 mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of clopidogrel (75mg once daily).

Drug: Clopidogrel
clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of low-dose ticagrelor (60.0 mg once daily).

Active Comparator: clopidogrel

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

Drug: low-dose ticagrelor
low-dose ticagrelor (60.0 mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of clopidogrel (75mg once daily).

Drug: Clopidogrel
clopidogrel (75mg once daily) for 7 days,followed by a 2-week washout period then a 7 days crossover phase of low-dose ticagrelor (60.0 mg once daily).

Outcome Measures

Primary Outcome Measures

  1. The platelet inhibition ratio. [up to 2 months]

    Verifynow was used to measure platelet inhibition ratio.

Secondary Outcome Measures

  1. The platelet aggregation ratio. [up to 2 months]

    Light transmission aggregometry method was used to measure platelet aggregation ratio.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Patients were eligible to participate if they were aged ≥18 years and ≤ 75 Years

  • Subjects had documented stable CAD (defned as stable angina pectoris and objective evidence of CAD, a previous MI, or previous revascularization with percutaneous coronary intervention or coronary artery bypass grafting)

  • Women were required to be postmenopausal or surgically sterile

  • Patients who were taking clopidogrel or ticagrelor were required to discontinue these agents at least 14 days before randomization

Exclusion Criteria:
  • Acute coronary syndrome (ACS)

  • planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists other than the study medication, or anticoagulant therapy during the study period

  • platelet count <10*10^4/ul

  • 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

  • allergy to aspirin, ticagrelor or clopidogrel

  • diabetes patients

Contacts and Locations

Locations

Site City State Country Postal Code
1 VerifyNow Harbin California China 150001

Sponsors and Collaborators

  • First Affiliated Hospital of Harbin Medical University

Investigators

  • Principal Investigator: Yue Li, professor, First Affiliated Hospital of Harbin Medical University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Yue LI, Professor, First Affiliated Hospital of Harbin Medical University
ClinicalTrials.gov Identifier:
NCT03679091
Other Study ID Numbers:
  • CHD-201845
First Posted:
Sep 20, 2018
Last Update Posted:
Dec 21, 2021
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Yue LI, Professor, First Affiliated Hospital of Harbin Medical University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 21, 2021