Escalating Clopidogrel by Involving a Genetic Strategy - Thrombolysis In Myocardial Infarction 56

Phase 2

Completed

Conditions: Myocardial Infarction
Percutaneous Coronary Intervention

Interventions: Drug: Clopidogrel

Registration Number: NCT01235351

Lead Sponsor: The TIMI Study Group

Brief Summary: To determine whether higher as compared with lower maintenance doses of clopidogrel can adequately improve the degree of platelet inhibition in carriers of a reduced-function CYP2C19 allele.

Detailed Description: Clopidogrel blocks the P2Y12 ADP receptor on platelets and has been shown to reduce cardiovascular events in acute coronary syndrome (ACS) patients.However, inter-patient variability in the pharmacodynamic response to clopidogrel is well recognized, and patients with lesser degrees of platelet inhibition in response to clopidogrel have been shown to be at increased risk of cardiovascular events.

One potential source of this variability is the metabolism of clopidogrel, which is a pro-drug requiring biotransformation to become an active antiplatelet compound. Cytochrome P-450 (CYP) enzymes play a role in the metabolism, and carriers of reduced-function genetic variants in CYP2C19 (\~30% of the population) have lower active clopidogrel metabolite levels, diminished platelet inhibition, and higher rates of adverse cardiovascular events as compared with non-carriers in the setting of treatment with standard maintenance doses of clopidogrel.

Aim: To determine whether higher as compared with lower maintenance doses of clopidogrel can adequately improve the degree of platelet inhibition in carriers of a reduced-function CYP2C19 allele.

Hypotheses: The primary hypothesis is that subjects who carry a reduced-function CYP2C19 allele will have improvement in platelet inhibition with higher maintenance doses of clopidogrel.The secondary hypothesis is that higher maintenance doses of clopidogrel in carriers of a reduced-function CYP2C19 allele will result in similar platelet inhibition as compared to a standard maintenance dose of clopidogrel in non-carriers.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 335

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Clopidogrel - for CYP2C19*2 carriers	Clopidogrel	Clopidogrel for CYP2C19\*2 gene carriers
Clopidogrel - for CYP2C19*2 non-carriers	Clopidogrel	Clopidogrel for CYP2C19\*2 gene NON-carriers

Primary Outcome Measures

Name	Time	Method
Comparisons of Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation Platelet Reactivity Index (PRI)	Approximately every 2 weeks for 8 weeks	The outcome measurement was on-treatment PRI determined through flow cytometric assessment of phosphorylation status of VASP.

Secondary Outcome Measures