Prasugrel versus clopidogrel in Asian patients with acute coronary syndromes: design and rationale of a multi-dose, pharmacodynamic, phase 3 clinical trial

Curr Med Res Opin. 2010 Sep;26(9):2077-85. doi: 10.1185/03007995.2010.502048.

Abstract

Background: Prasugrel is a third generation thienopyridine that is more potent, rapid in onset, and consistent in inhibition of platelets than clopidogrel. However, early prasugrel dose-ranging studies and the subsequent phase 3 TRITON-TIMI 38 trial were conducted primarily in Caucasian populations.

Objectives: The current clinical study is designed to confirm superior inhibition of platelet aggregation with prasugrel versus clopidogrel in the treatment of Asian subjects with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Research design and methods: This is a phase 3, randomized, double-blind, multi-dose, four-arm parallel, multinational clinical trial. East and Southeast Asian patients (N = 715) with moderate- to high-risk ACS undergoing PCI will be randomized to one of three prasugrel dosing regimens (60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD) or clopidogrel (300 mg LD/75 mg MD) for 90 days.

Main outcome measures: The primary endpoint is inhibition of platelet aggregation measured by the point-of-care Accumetrics VerifyNow P2Y12 device, and the primary analysis will be performed in a hierarchical manner for descending doses of prasugrel. Additional key endpoints include major adverse cardiovascular events, non-coronary artery bypass-graft (CABG) surgery-related TIMI bleeding, and genetic analyses of cytochrome P450 polymorphisms.

Conclusions: This study is a phase 3, multi-dose, pharmacodynamic comparison of prasugrel versus clopidogrel in Asian patients with ACS undergoing PCI. It is the first study designed to investigate prasugrel therapy specifically in Asian ACS subjects, and will inform which doses of prasugrel are effective and safe for patients of Asian ethnicity.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / ethnology
  • Adolescent
  • Adult
  • Aged
  • Algorithms
  • Asian People
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prasugrel Hydrochloride
  • Research Design
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects
  • Thiophenes / pharmacokinetics*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Young Adult

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine