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.
研究概览
详细说明
研究类型
注册 (实际的)
联系人和位置
学习地点
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Saint-etienne、法国、42000
- CHU de Saint-Etienne
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
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
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
干预/治疗 |
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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
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
adrenergic component of the platelet response
大体时间: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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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
VASP-CMF
大体时间: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
大体时间: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
大体时间: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
大体时间: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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合作者和调查者
调查人员
- 首席研究员:Jerome VARVAT, MD、CHU de Saint-Etienne
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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