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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-000313-20 | EudraCT Number |
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| Name | Class |
|---|---|
| Groupe de Recherche sur la Thrombose | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVC | Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | 75 mg milligrams per days of PLAVIX |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| VASP-CMF | Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method | After 5 days taking clopidogrel |
| ELISA VASP | Platelet reactivity index (PRI-ELISA) using ELISA VASP |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
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| Name | Affiliation | Role |
|---|---|---|
| Jerome VARVAT, MD | CHU de Saint-Etienne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Saint-Etienne | Saint-Etienne | 42000 | France |
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| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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Blood DNA
| After 5 days taking clopidogrel |
| active metabolite of clopidogrel | Rate of residual plasma active metabolite of clopidogrel (R-130964) | After 5 days taking clopidogrel |
| Genotyping of MDR-1 and P450 2C19 | Genotyping of MDR-1 and P450 2C19 | After 5 days taking clopidogrel |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |