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

Completed

• Conditions: Brain Ischemia; Ischemic Attack
• Interventions: Drug: Clopidogrel

• Registration Number: NCT01955642
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-27
• Study First Submitted QC: 2013-10-04
• Study First Posted: 2013-10-07
• Status Verified: 2015-12
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Last Update Submitted: 2015-12-30
• Last Update Posted: 2015-12-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

Inclusion Criteria

• Consent signed
• Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
• normal standard biological tests

Exclusion Criteria

• Need to continue aspirin therapy
• Patients with a recurrence of clopidogrel AIC
• Patient already tacking clopidogrel
• Drugs interfering with the adrenergic system alpha blockers, alpha 2 receptor agonists (alpha-methyldopa) and alpha2 receptor inhibitors (Mianserin, Mirtazapine, yohimbine)
• Contra indication of clopidogrel and / or any of its excipients

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
AVC	Clopidogrel	Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

Primary Outcome Measures

Name	Time	Method
adrenergic component of the platelet response	5 days after taking clopidogrel	adrenergic component of the platelet response is estimated by the difference between the maximum percentage of platelet aggregation by light transmission aggregometry (LTA) with the addition of ADP(adenosine diphosphate) + ADP versus selective agonist (epinephrine)

Secondary Outcome Measures

Name	Time	Method
VASP-CMF	After 5 days taking clopidogrel	Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method
ELISA VASP	After 5 days taking clopidogrel	Platelet reactivity index (PRI-ELISA) using ELISA VASP
active metabolite of clopidogrel	After 5 days taking clopidogrel	Rate of residual plasma active metabolite of clopidogrel (R-130964)
Genotyping of MDR-1 and P450 2C19	After 5 days taking clopidogrel	Genotyping of MDR-1 and P450 2C19

Trial Locations

Locations (1)

CHU de Saint-Etienne; 🇫🇷 Saint-etienne, France