Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke (AAPIX)
This study has been completed.
Sponsor:
Centre Hospitalier Universitaire de Saint Etienne
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
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Purpose
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 | Intervention |
|---|---|
|
Brain Ischemia Ischemic Attack |
Drug: Clopidogrel |
| Study Type: | Observational |
| Study Design: | 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 |
Resource links provided by NLM:
Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:
Primary Outcome Measures:
- 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)
Secondary Outcome Measures:
- 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
Biospecimen Retention: Samples With DNA
Blood DNA
| Enrollment: | 91 |
| Study Start Date: | September 2013 |
| Study Completion Date: | December 2015 |
| Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
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)
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01955642
Please refer to this study by its ClinicalTrials.gov identifier: 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 |
| Study First Received: | September 27, 2013 |
| Last Updated: | December 30, 2015 |
| Health Authority: | France: French Data Protection Authority France: Agence Nationale de Sécurité du Médicament et des produits de santé |
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 |
ClinicalTrials.gov processed this record on September 28, 2016