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

September 28, 2015 updated by: First Affiliated Hospital of Harbin Medical University

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: clopidogrel
To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel.
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)
Other Names:
  • low-dose ticagrelor(22.5 mg twice daily)
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)
Other Names:
  • clopidogrel (75mg once daily)
Experimental: low-dose ticagrelor
To observe the safety and efficacy of low-dose ticagrelor in Chinese patients withStable Coronary Artery Disease
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)
Other Names:
  • low-dose ticagrelor(22.5 mg twice daily)
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)
Other Names:
  • clopidogrel (75mg once daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
P2Y12 reaction units (PRU)
Time Frame: up to 5 months
up to 5 months

Secondary Outcome Measures

Outcome Measure
Time Frame
inhibition of platelet aggregation (IPA)
Time Frame: up to 5 months
up to 5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Harbin Medical University

Investigators

  • Principal Investigator: Yue Li, MD, Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Anticipated)

October 1, 2015

Study Completion (Anticipated)

November 1, 2015

Study Registration Dates

First Submitted

July 21, 2015

First Submitted That Met QC Criteria

August 3, 2015

First Posted (Estimate)

August 4, 2015

Study Record Updates

Last Update Posted (Estimate)

September 30, 2015

Last Update Submitted That Met QC Criteria

September 28, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCAD-201523

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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