NCT01235351

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 335 (actual)
• Sponsor: The TIMI Study Group · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Myocardial Infarction
• Percutaneous Coronary Intervention

Interventions

Type	Name	Description
DRUG	Clopidogrel	Clopidogrel 75 mg daily, 150 mg daily, 225 mg daily, and 300 mg daily based on genotype
DRUG	Clopidogrel	Clopidogrel 75 mg daily, 150 mg daily

Timeline

• Start date: 2010-10-01
• Primary completion: 2011-09-01
• Completion: 2011-09-01
• First posted: 2010-11-05
• Last updated: 2019-11-15
• Results posted: 2019-11-15

Locations

1 site across 1 country: United States