Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03679091
Recruitment Status : Recruiting
First Posted : September 20, 2018
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Yue LI, First Affiliated Hospital of Harbin Medical University

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
Platelet Reactivity Drug: low-dose ticagrelor Drug: Clopidogrel 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 29, 2018
Estimated Primary Completion Date : February 28, 2019
Estimated Study Completion Date : August 29, 2019

Resource links provided by the National Library of Medicine


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).




Primary Outcome Measures :
  1. The platelet inhibition ratio. [ Time Frame: up to 2 months ]
    Verifynow was used to measure platelet inhibition ratio.


Secondary Outcome Measures :
  1. The platelet aggregation ratio. [ Time Frame: up to 2 months ]
    Light transmission aggregometry method was used to measure platelet aggregation ratio.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03679091


Contacts
Layout table for location contacts
Contact: Yue Li, professor 86-451-85555673 ly99ly@vip.163.com

Locations
Layout table for location information
China, California
VerifyNow Recruiting
Harbin, California, China, 150001
Contact: Meijiao He, doctor    518-393-2200    customerservice@accriva.com   
Contact: Jing Shi, Professor    86-451-85555672    yidashijing@163.com   
Sponsors and Collaborators
First Affiliated Hospital of Harbin Medical University
Investigators
Layout table for investigator information
Principal Investigator: Yue Li, professor First Affiliated Hospital of Harbin Medical University

Layout table for additonal information
Responsible Party: Yue LI, Professor, First Affiliated Hospital of Harbin Medical University
ClinicalTrials.gov Identifier: NCT03679091     History of Changes
Other Study ID Numbers: CHD-201845
First Posted: September 20, 2018    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yue LI, First Affiliated Hospital of Harbin Medical University:
Ticagrelor
clopidogrel
coronary artery disease
platelet reactivity

Additional relevant MeSH terms:
Layout table for MeSH terms
Platelet Aggregation Inhibitors
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Clopidogrel
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs