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


OBJECTIVE
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).


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.


METHODS
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.
Ge
Junbo
J
Zhong Shan Hospital, Fudan University, Shanghai, China.
Zhu
Junren
J
Hong
Bum-Kee
BK
Boonbaichaiyapruck
Sarana
S
Goh
Yew Seong
YS
Hou
Charles Jia-Yin
CJ
Pinton
Philippe
P
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000208:ethnology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D044466:Asian People; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride; D012107:Research Design; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine