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

This study has been completed.
Sponsor:
Collaborator:
Groupe de Recherche sur la Thrombose
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:
NCT01955642
First received: September 27, 2013
Last updated: December 30, 2015
Last verified: December 2015
History of Changes

September 27, 2013
December 30, 2015
September 2013
December 2015   (final data collection date for primary outcome measure)
adrenergic component of the platelet response [ Time Frame: 5 days after taking clopidogrel ] [ Designated as safety issue: No ]
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)
Same as current
Complete list of historical versions of study NCT01955642 on ClinicalTrials.gov Archive Site
  • VASP-CMF [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method
  • ELISA VASP [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Platelet reactivity index (PRI-ELISA) using ELISA VASP
  • active metabolite of clopidogrel [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Rate of residual plasma active metabolite of clopidogrel (R-130964)
  • Genotyping of MDR-1 and P450 2C19 [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Genotyping of MDR-1 and P450 2C19
Same as current
Not Provided
Not Provided
 
Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke
Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors

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.
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.
Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
Blood DNA
Non-Probability Sample
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
  • Brain Ischemia
  • Ischemic Attack
Drug: Clopidogrel
75 mg milligrams per days of PLAVIX
Other Name: PLAVIX(R)
AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
Intervention: Drug: Clopidogrel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
December 2015
December 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01955642
1208094, 2013-000313-20
No
Not Provided
Not Provided
Centre Hospitalier Universitaire de Saint Etienne
Centre Hospitalier Universitaire de Saint Etienne
Groupe de Recherche sur la Thrombose
Principal Investigator: Jerome VARVAT, MD CHU de Saint-Etienne
Centre Hospitalier Universitaire de Saint Etienne
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP