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

Brain Ischemia Clinical Trial

— AAPIX  

Official title:

Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955642
• Other study ID #: 1208094
• Secondary ID: 2013-000313-20
• Status: Completed
• Phase: N/A
• First received: September 27, 2013
• Last updated: December 30, 2015
• Start date: September 2013
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: French Data Protection AuthorityFrance: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Brain Ischemia
• Ischemia
• Ischemic Attack

Intervention

Drug:
• Clopidogrel
75 mg milligrams per days of PLAVIX

Locations

Country	Name	City	State
France	CHU de Saint-Etienne	Saint-etienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Groupe de Recherche sur la Thrombose

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	adrenergic component of the platelet response	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)	5 days after taking clopidogrel	No
Secondary	VASP-CMF	Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method	After 5 days taking clopidogrel	No
Secondary	ELISA VASP	Platelet reactivity index (PRI-ELISA) using ELISA VASP	After 5 days taking clopidogrel	No
Secondary	active metabolite of clopidogrel	Rate of residual plasma active metabolite of clopidogrel (R-130964)	After 5 days taking clopidogrel	No
Secondary	Genotyping of MDR-1 and P450 2C19	Genotyping of MDR-1 and P450 2C19	After 5 days taking clopidogrel	No