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

NCT02415803 | Unknown Phase 3 DMC

• 1 other identifier: ACS-1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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).

Conditions

Non ST Segment Elevation Acute Coronary Syndrome

Keywords

low-dose ticagrelor; clopidogrel; Chinese patients with NSTE-ACS; platelet reactivity; inhibition of platelet aggregation

Outcome Measures

Primary Outcomes (1)

• the differences in mean inhibition of platelet aggregation or inhibition ratio (%)

  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 Outcomes (7)

• Number of bleeding events

  throughout the study (from baseline to 12 hours after the last dose)

• Number of difficulty breathing events

  throughout the study (from baseline to 12 hours after the last dose)

• number of ventricular pauses

  throughout the study (from baseline to 12 hours after the last dose)

• number of myocardial infarction events

  throughout the study (from baseline to 12 hours after the last dose)

• number of death events

  throughout the study (from baseline to 12 hours after the last dose)

Study Arms (3)

low-dose ticagrelor

EXPERIMENTAL

To observe the safety and efficacy of low-dose ticagrelor in Chinese patients with non-ST-elevation acute coronary syndrome

Drug: low-dose ticagrelor

conventional-dose ticagrelor

ACTIVE COMPARATOR

To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose ticagrelor.

Drug: conventional-dose ticagrelor

clopidogrel

ACTIVE COMPARATOR

To observe the different safety and efficacy between low-dose ticagrelor and conventional-dose clopidogrel.

Drug: Clopidogrel

Interventions

low-dose ticagrelor DRUG

90 mg loading dose, then 45 mg twice daily for 5 days

low-dose ticagrelor

conventional-dose ticagrelor DRUG

180 mg loading dose, then 90 mg twice daily for 5 days

conventional-dose ticagrelor

Clopidogrel DRUG

300 mg loading dose, then 75 mg once daily for 5 days

clopidogrel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• hospitalized for NSTE-ACS within the preceding 48 h
• have one of the following additional criteria:
• ischemic symptoms at rest, lasting ≥10 minutes;
• horizontal or down-sloping ST segment depression ≥0.1 mV;
• cardiac troponin I (cTnI), marker associated with NSTE-ACS, local laboratory upper limit of normal values;
• underwent percutaneous coronary intervention (PCI); (5) a history of myocardial infarction.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead

Study Sites (1)

VerifyNow

San Diego, California, 92101-92117, United States

RECRUITING

MeSH Terms

Interventions

Ticagrelor; Clopidogrel

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Yue Li, MD

CONTACT

86-451-85555673; ly99ly@vip.163.com

Hongjie Xue, MD

CONTACT

86-451-85555672; xuehj@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: April 14, 2015
• Study Start: December 1, 2014
• Primary Completion: December 1, 2016
• Last Updated: April 14, 2015

Record last verified: 2014-12

Locations

US (1)