Effects of Different Doses of Ticagrelor on Platelet Aggregation and Endothelial Function in Diabetic Patients With Stable Coronary Artery Disease

February 20, 2017 updated by: First Affiliated Hospital of Harbin Medical University

Effects of Different Doses of Ticagrelor and Standard-dose Clopidogrel on Platelet Aggregation and Endothelial Function in Diabetic Patients With Stable Coronary Artery Disease

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 have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. However, few East Asian patients 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. But it is still not clear whether a low dose of ticagrelor is superior to clopidogrel in diabetic patients with stable coronary disease.

Recent studies found that antiplatelet drugs might have anti-inflammatory effects and protect endothelial function. ACS patients treated by ticagrelor had a significantly higher increase in levels of circulating progenitor cells compared to those treated by clopidogrel, suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug. This may prompt the regression of blood vessels and the endothelium stability. But it is not very clear that the effect of low-dose ticagrelor on vascular endothelial function in diabetic patients with stable coronary artery disease.

Therefore, the investigators performed this randomized, single-blind clinical trial to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet aggregation and endothelial function in diabetic 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 have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. However, few East Asian patients 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. In Korea and Japan, it has been recently reported that low doses of ticagrelor might have a more potent inhibition of platelet aggregation 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 diabetic patients with stable coronary disease. 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 patients with coronary heart disease. 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.

Recent studies found that antiplatelet drugs might have anti-inflammatory effects and protect endothelial function. ACS patients treated by ticagrelor had a significantly higher increase in levels of circulating progenitor cells compared to those treated by clopidogrel, suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug. This may prompt the regression of blood vessels and the endothelium stability. But it is not very clear that the effect of low-dose ticagrelor on vascular endothelial function in diabetic patients with stable coronary artery disease.

Therefore, the investigators performed this randomized, single-blind clinical trial to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet aggregation and endothelial function in diabetic patients with stable coronary artery disease.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • China
      • Harbin, China
        • Recruiting
        • Endothelial Function detection by brachial artery ultrasound
        • Contact:
  • United States
    • California
      • San Diego, California, United States, 92101-92117

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:

  1. 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）
  2. Diabetes

Exclusion Criteria:

  1. ACS
  2. planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, aspirin 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. ticagrelor or clopidogrel allergies

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ticagrelor 22.5 mg
Ticagrelor (22.5 mg, twice daily, oral) treatment for 1 month.
Drug: ticagrelor
Different doses of ticagrelor (22.5/45/90 mg, twice daily, oral) treatment for 1 month
Experimental: Ticagrelor 45 mg
Ticagrelor (45 mg, twice daily, oral) treatment for 1 month.
Drug: ticagrelor
Different doses of ticagrelor (22.5/45/90 mg, twice daily, oral) treatment for 1 month
Experimental: Ticagrelor 90 mg
Ticagrelor (90 mg, twice daily, oral) treatment for 1 month.
Drug: ticagrelor
Different doses of ticagrelor (22.5/45/90 mg, twice daily, oral) treatment for 1 month
Active Comparator: Clopidogrel
Clopidogrel (75mg, once daily, oral) treatment for 1 month.
Drug: clopidogrel
Standard dose of clopidogrel (75 mg, once daily, oral) treatment for 1 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Inhibition of platelet aggregation
Time Frame: up to 1 month
up to 1 month

Secondary Outcome Measures

Outcome Measure
Time Frame
Endothelial Function
Time Frame: up to 1 month
up to 1 month

Collaborators and Investigators

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

Sponsor

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

August 1, 2016

Primary Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

August 31, 2016

First Submitted That Met QC Criteria

August 31, 2016

First Posted (Estimate)

September 5, 2016

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

February 20, 2017

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCAD-20160901

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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