Clinical trial NCT01641510: PRAsugrel or clopIdogrel In Acute Coronary SyndromE With CYP2C19 GENEtic Variants
Official title: Phase 3 Study Comparing the Efficacy and Safety of Prasugrel and Clopidogrel in Acute Coronary Syndrome Patients With CYP2C19 Polymorphism Who Undergo Percutaneous Coronary Intervention.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Coronary Syndromes
Keywords: reduced-function CYP2C19 allele
high platelet reactivity
clopidogrel
prasugrel
Lead sponsor: Dong-A University
Sponsor class: OTHER
First posted: 2012-07-16
Enrollment: 70
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The investigators hypothesize that reduced loading dose of prasugrel followed by reduced maintenance dose of prasugrel in acute coronary syndrome patients with CYP2C19 polymorphism undergoing percutaneous coronary intervention might exhibit lower platelet reactivity 24 hours and 30 days later which is associated with major adverse cardiovascular events.

Detailed description: Antiplatelet treatment is recommended worldwide for the secondary prevention and clopidogrel is an essential drug. But clopidogrel has limited value because of its pharmacodynamic interpatient variability and delayed onset time.

It is well known that patients who carry a common reduced-function CYP2C19 allele have a lower level of active metabolite of clopidogrel, diminished platelet inhibition, and furthermore, higher rate of major adverse cardiovascular events than noncarriers.

To achieve maximum plateau more rapidly and reduce the rate of high on-treatment platelet reactivity, higher loading dose of clopidogrel, up to 600 mg, is recommended. Although, however, the higher loading dose of clopidogrel, many patients still remain as non-responder.

Incidence of patients with clopidogrel resistance, especially CYP2C19\*2 and \*3, which encounter loss function, is higher in Eastern Asian peoples than Western peoples. Some studies report incidence rate of clopidogrel resistance in Eastern Asian peoples up to 99%.

However, the metabolism is not influenced by the presence of CYP2C19 genetic variation and prasugrel shows potent platelet inhibition. Although prasugrel exhibit potent platelet inhibition, recent reports describe the possible over inhibition of platelet especially in the East Asian people.

The investigators are going to compare the efficacy and safety of loading dose of prasugrel 30 mg which is lower than conventional loading dose followed by 5 mg/day which is also lower than conventional maintenance dose for 30 days and loading dose of clopidogrel 600 mg followed by 75 mg/day for 30 days.

Eligibility criteria: Inclusion Criteria:

* Acute coronary syndrome
* Patients planned to undergo percutaneous transluminal coronary angioplasty
* Patients who agreed to the experimental plan which was permitted by IRB

Exclusion Criteria:

* Low body weight (\< 50kg)
* History of stroke or transient ischemic attack
* History of upper gastrointestinal bleeding in recent 6 months
* Renal dysfunction defined by serum creatinine \> 2.5 mg/dl
* Severe hepatic dysfunction defined by Child-Pugh criteria B or C
* Bleeding tendency
* Anticoagulation treatment including warfarin
* Thrombocytopenia defined by platelet \< 100,000/ml
* Anemia defined by hemoglobin \< 10 g/dl
* Contraindication for antiplatelet treatment or anticoagulation treatment
* History of administer glycoprotein IIb/IIIa inhibitor in recent 24hrs or planned to

Primary outcomes:
measure: HPR 1 day
timeFrame: 24 hours after PCI
Secondary outcomes:
measure: MACE
timeFrame: 30 days
measure: Bleeding
timeFrame: 30 days
measure: HPRs
timeFrame: 4 hours after PCI, 30 days after PCI
measure: HPR by VASP at 24 hours
timeFrame: 24 hours from PCI
measure: HPR by VASP at 30 days
timeFrame: 30 days from PCI
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: DongA University Hospital
Study officials:
affiliation: Director, Regional Clinical Trial Center
name: Moo Hyun Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: