Brain Ischemia | Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke
Brain Ischemia research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Clopidogrel75 mg milligrams per days of PLAVIX
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
AVCPatients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
Start Date: September 2013
Completed Date: December 2015
Primary Outcome: adrenergic component of the platelet response
Secondary Outcome: VASP-CMF
Study sponsors, principal investigator, and references
Principal Investigator: Jerome VARVAT, MD
Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne
Collaborator: Groupe de Recherche sur la Thrombose