Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With NSTE-ACS

April 9, 2015 updated by: First Affiliated Hospital of Harbin Medical University

Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With Non-ST-Elevation Acute Coronary Syndrome: A Randomized 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. These recommendations are primarily based on large, randomized, Phase III clinical trials. 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 described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. Therefore, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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. These recommendations are primarily based on large, randomized, Phase III clinical trials. 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 described that East Asian patients have a higher prevalence of platelet reactivity during DAPT, but an ischaemic event rate following PCI or ACS is similar or even lower than white patients. Therefore, the antiplatelet treatment strategy that is most appropriate for East Asian patients is increasingly urgent. In Korea and Japan, it has been reported that low doses of ticagrelor had 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 (Cmax) and area under the plasma concentration-time curve (AUC) 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, we performed the current study to observe the different effects of low-dose ticagrelor (45 mg twice daily), conventional-dose ticagrelor (90 mg twice daily) and clopidogrel (75mg once daily) on high platelet reactivity (HPR) and IPA, and investigated the safety and efficacy of low-dose ticagrelor further in Chinese patients with non-ST-elevation ACS (NSTE-ACS).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Hongjie Xue, MD
  • Phone Number: 86-451-85555672
  • Email: xuehj@163.com

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • hospitalized for NSTE-ACS within the preceding 48 h

  • have one of the following additional criteria:

    1. ischemic symptoms at rest, lasting ≥10 minutes;
    2. horizontal or down-sloping ST segment depression ≥0.1 mV;
    3. cardiac troponin I (cTnI), marker associated with NSTE-ACS, local laboratory upper limit of normal values;
    4. underwent percutaneous coronary intervention (PCI); (5) a history of myocardial infarction.

Exclusion Criteria:

  • ST-elevation ACS;
  • planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
  • platelet count <100g/L;
  • 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;
  • aspirin, ticagrelor or clopidogrel allergies;
  • 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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: low-dose ticagrelor
To observe the safety and efficacy of low-dose ticagrelor in Chinese patients with non-ST-elevation acute coronary syndrome
Drug: low-dose ticagrelor
90 mg loading dose, then 45 mg twice daily for 5 days
Active Comparator: conventional-dose ticagrelor
To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose ticagrelor.
Drug: conventional-dose ticagrelor
180 mg loading dose, then 90 mg twice daily for 5 days
Active Comparator: clopidogrel
To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel.
Drug: Clopidogrel
300 mg loading dose, then 75 mg once daily for 5 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
the differences in mean inhibition of platelet aggregation or inhibition ratio (%)
Time Frame: before dosing (baseline) and up to 12 hours after the last dose
After overnight fasting, venous blood samples of all subjects were taken for pharmacodynamic measurements before dosing (baseline) and 12 hours after the last dose. VerifyNow P2Y12 (Accumetrics, SanDiego, CA), a whole-blood, cartridge-based and point-of-care turbidometric assay, was performed to test platelet aggregation at baseline and 12 hours after the last dose, and the results were reported in P2Y12 reaction units (PRU). With this assay, a higher PRU reflects greater adenosine-diphosphate-mediated platelet reactivity (PR). High-platelet reactivity (HPR) was defined as a PRU>208. Blood samples were placed in 3.2% sodium citrate (Greiner Bio-One Vacuette North America, Inc, Monroe, NC) for this assay. Additionally, inhibition of platelet aggregation (IPA) calculated by VerifyNow assays was similar to light transmittance aggregometry.
before dosing (baseline) and up to 12 hours after the last dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Number of bleeding events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
Number of difficulty breathing events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
number of ventricular pauses
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
number of myocardial infarction events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
number of death events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
number of stroke events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)
number of severe recurrent ischemia events
Time Frame: throughout the study (from baseline to 12 hours after the last dose)
throughout the study (from baseline to 12 hours after the last dose)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 26, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACS-1

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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