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

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.

Trial registration: ClinicalTrials.gov identifier: NCT00830960.

Key words::

• Acute coronary syndrome
• Clopidogrel
• Platelet
• Prasugrel

Transparency

Declaration of funding

This study is sponsored by Daiichi Sankyo Co. Ltd (Tokyo, Japan) and Eli Lilly and Company (Indianapolis, IN).

Declaration of financial/other relationships

E.K. has declared that he is an employee of Daiichi Sankyo. T.W., G.G., K.W., X.W.C., and P.P. have declared that they are employees of Eli Lilly and Company.

Peer reviewers may receive honoraria from CMRO for their review work. The peer reviewers have declared no relevant financial relationships.

Acknowledgements

The TACE study team consists of Junbo Ge; Junren Zhu; Bum-Kee Hong; Sarana Boonbaichaiyapruck; Yew Seong Goh; Charles Jia-Yin Hou; Teena Maree West; Gabrielle Louise Gallagher; Eiji Kawakatsu; Kenneth J. Winters; Xiao Wen Chen; Philippe Pinton. Teena Maree West, Gabrielle Louise Gallagher, Kenneth J Winters, Xiao Wen Chen, and Philippe Pinton are all employees of Eli Lilly and Company. Eiji Kawakatsu is an employee of Daiichi Sankyo Co. Ltd, Tokyo, Japan. The authors thank Amber Burns (Eli Lilly and Company) for editorial assistance.