Clinical trial NCT02415803: Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With NSTE-ACS
Official title: Safety and Efficacy of Low-Dose Ticagrelor in Chinese Patients With Non-ST-Elevation Acute Coronary Syndrome: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non ST Segment Elevation Acute Coronary Syndrome
Keywords: low-dose ticagrelor
clopidogrel
Chinese patients with NSTE-ACS
platelet reactivity
inhibition of platelet aggregation
Lead sponsor: First Affiliated Hospital of Harbin Medical University
Sponsor class: OTHER
First posted: 2015-04-14
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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).

Eligibility criteria: 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.

Primary outcomes:
measure: the differences in mean inhibition of platelet aggregation or inhibition ratio (%)
timeFrame: before dosing (baseline) and up to 12 hours after the last dose
Secondary outcomes:
measure: Number of bleeding events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: Number of difficulty breathing events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: number of ventricular pauses
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: number of myocardial infarction events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: number of death events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: number of stroke events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
measure: number of severe recurrent ischemia events
timeFrame: throughout the study (from baseline to 12 hours after the last dose)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: VerifyNow
state: California
Study officials:
References: