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

Tracking Information
First Submitted Date	September 27, 2013
First Posted Date	October 7, 2013
Last Update Posted Date	December 31, 2015
Study Start Date	September 2013
Actual Primary Completion Date	December 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: October 4, 2013)	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)
Original Primary Outcome Measures	Same as current
Change History	Complete list of historical versions of study NCT01955642 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: October 4, 2013)	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
Original Secondary Outcome Measures	Same as current
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	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
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 Type	Observational
Study Design	Observational Model: Case-Only; Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	Retention: Samples With DNA; Description: Blood DNA
Sampling Method	Non-Probability Sample
Study Population	Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
Condition	Brain Ischemia; Ischemic Attack
Intervention	Drug: Clopidogrel; 75 mg milligrams per days of PLAVIX; Other Name: PLAVIX(R)
Study Groups/Cohorts	AVC; Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications; Intervention: Drug: Clopidogrel
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Actual Enrollment; (submitted: December 30, 2015)	91
Original Estimated Enrollment; (submitted: October 4, 2013)	80
Actual Study Completion Date	December 2015
Actual Primary Completion Date	December 2015 (Final data collection date for primary outcome measure)
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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	France
Removed Location Countries
Administrative Information
NCT Number	NCT01955642
Other Study ID Numbers	1208094; 2013-000313-20 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Centre Hospitalier Universitaire de Saint Etienne
Study Sponsor	Centre Hospitalier Universitaire de Saint Etienne
Collaborators	Groupe de Recherche sur la Thrombose
Investigators	Principal Investigator: Jerome VARVAT, MD CHU de Saint-Etienne
PRS Account	Centre Hospitalier Universitaire de Saint Etienne
Verification Date	December 2015