Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke (AAPIX)
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.
調査の概要
詳細な説明
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Saint-etienne、フランス、42000
- Chu de Saint-Etienne
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
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75 mg milligrams per days of PLAVIX
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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adrenergic component of the platelet response
時間枠：5 days after taking clopidogrel
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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)
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5 days after taking clopidogrel
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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VASP-CMF
時間枠：After 5 days taking clopidogrel
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Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method
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After 5 days taking clopidogrel
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ELISA VASP
時間枠：After 5 days taking clopidogrel
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Platelet reactivity index (PRI-ELISA) using ELISA VASP
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After 5 days taking clopidogrel
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active metabolite of clopidogrel
時間枠：After 5 days taking clopidogrel
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Rate of residual plasma active metabolite of clopidogrel (R-130964)
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After 5 days taking clopidogrel
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Genotyping of MDR-1 and P450 2C19
時間枠：After 5 days taking clopidogrel
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Genotyping of MDR-1 and P450 2C19
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After 5 days taking clopidogrel
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協力者と研究者
捜査官
- 主任研究者：Jerome VARVAT, MD、Chu de Saint-Etienne
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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