Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke (AAPIX)
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|ClinicalTrials.gov Identifier: NCT01955642|
Recruitment Status : Completed
First Posted : October 7, 2013
Last Update Posted : December 31, 2015
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.
|Condition or disease||Intervention/treatment|
|Brain Ischemia Ischemic Attack||Drug: Clopidogrel|
|Study Type :||Observational|
|Actual Enrollment :||91 participants|
|Official Title:||Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors|
|Study Start Date :||September 2013|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
75 mg milligrams per days of PLAVIX
Other Name: PLAVIX(R)
- adrenergic component of the platelet response [ Time Frame: 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)
- VASP-CMF [ Time Frame: After 5 days taking clopidogrel ]Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method
- ELISA VASP [ Time Frame: After 5 days taking clopidogrel ]Platelet reactivity index (PRI-ELISA) using ELISA VASP
- active metabolite of clopidogrel [ Time Frame: After 5 days taking clopidogrel ]Rate of residual plasma active metabolite of clopidogrel (R-130964)
- Genotyping of MDR-1 and P450 2C19 [ Time Frame: After 5 days taking clopidogrel ]Genotyping of MDR-1 and P450 2C19
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01955642
|CHU de Saint-Etienne|
|Saint-etienne, France, 42000|
|Principal Investigator:||Jerome VARVAT, MD||CHU de Saint-Etienne|