Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke "AAPIX"

Completed

Phase N/A Results N/A

Trial Description

Ischemic stroke (AIC) is the leading cause of non-traumatic disability in adults, the second leading cause of dementia and the third leading cause of death in France.
Clopidogrel is one of the recommended first line in the secondary prevention of AIC non cardioembolic origin. However recurrences occur in approximately 9% of patients receiving clopidogrel. Some studies in patients with coronary artery disease have made the connection between these treatment failures and non-biological response to clopidogrel. This non-biological response is found for approximately 30% to 50% of patients. Several mechanisms may explain this non-response. The most accepted mechanism is pharmacokinetic. Indeed, clopidogrel is a prodrug that requires intestinal absorption by P-glycoprotein (PGP) and a transformation by hepatic cytochrome into active metabolites. The genetic polymorphism of proteins involved in these two steps explain the low plasma concentration of active metabolites and thus the low efficacy of clopidogrel in some patients.
A new pharmacodynamic hypothesis suggests the involvement of platelet alpha 2-adrenergic receptors. The activation of these receptors potentiates signaling pathway P2Y12 receptor (channel inhibited by clopidogrel) and helps reduce platelet aggregation inhibiting response to clopidogrel.

Detailed Description

Interest in the biological response to clopidogrel in the AIC is innovative because few data are available in this area. In addition to testing a new pharmacodynamic hypothesis, we also wish to study and compare other measures of platelet function methods in order to be able to use commonly in treatment decisions.

Conditions

Interventions

  • Clopidogrel (Plavix┬«)Drug
    Other Names: Plavix
    Intervention Desc: 75 mg milligrams per days of PLAVIX
    ARM 1: Kind: Experimental
    Label: AVC
    Description: Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

Trial Design

  • Observation: Case-Only
  • Perspective: Prospective
  • Sampling: Non-Probability Sample

Trial Population

Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

Outcomes

Type Measure Time Frame Safety Issue
Primary adrenergic component of the platelet response 5 days after taking clopidogrel No
Secondary VASP-CMF After 5 days taking clopidogrel No
Secondary ELISA VASP After 5 days taking clopidogrel No
Secondary active metabolite of clopidogrel After 5 days taking clopidogrel No
Secondary Genotyping of MDR-1 and P450 2C19 After 5 days taking clopidogrel No

Biospecimen Retention:Samples With DNA - Blood DNA

Sponsors