Clinical trial NCT01955642: Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke
Official title: Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Brain Ischemia
Ischemic Attack
Keywords: Clopidogrel
Brain Ischemia
Ischemic attack
Biological response to clopidogrel
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Groupe de Recherche sur la Thrombose
First posted: 2013-10-07
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

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.

Eligibility criteria: 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

Primary outcomes:
measure: adrenergic component of the platelet response
timeFrame: 5 days after taking clopidogrel
Secondary outcomes:
measure: VASP-CMF
timeFrame: After 5 days taking clopidogrel
measure: ELISA VASP
timeFrame: After 5 days taking clopidogrel
measure: active metabolite of clopidogrel
timeFrame: After 5 days taking clopidogrel
measure: Genotyping of MDR-1 and P450 2C19
timeFrame: After 5 days taking clopidogrel
Other outcomes:
Locations:
city: Saint-etienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: CHU de Saint-Etienne
name: Jerome VARVAT, MD
role: PRINCIPAL_INVESTIGATOR
References: