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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
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment
Brain Ischemia Ischemic Attack Drug: 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 Design

Study Type : Observational
Actual Enrollment : 91 participants
Observational Model: Case-Only
Time Perspective: Prospective
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
Primary Completion Date : December 2015
Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Group/Cohort Intervention/treatment
AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
Drug: Clopidogrel
75 mg milligrams per days of PLAVIX
Other Name: PLAVIX(R)


Outcome Measures

Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. VASP-CMF [ Time Frame: After 5 days taking clopidogrel ]
    Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method

  2. ELISA VASP [ Time Frame: After 5 days taking clopidogrel ]
    Platelet reactivity index (PRI-ELISA) using ELISA VASP

  3. active metabolite of clopidogrel [ Time Frame: After 5 days taking clopidogrel ]
    Rate of residual plasma active metabolite of clopidogrel (R-130964)

  4. 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
Blood DNA

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01955642


Locations
France
CHU de Saint-Etienne
Saint-etienne, France, 42000
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Groupe de Recherche sur la Thrombose
Investigators
Principal Investigator: Jerome VARVAT, MD CHU de Saint-Etienne
More Information

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT01955642     History of Changes
Other Study ID Numbers: 1208094
2013-000313-20 ( EudraCT Number )
First Posted: October 7, 2013    Key Record Dates
Last Update Posted: December 31, 2015
Last Verified: December 2015

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Clopidogrel
Brain Ischemia
Ischemic attack
Biological response to clopidogrel

Additional relevant MeSH terms:
Ischemia
Brain Ischemia
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors