Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- adrenergic component of the platelet response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consent signed
- •Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
- •normal standard biological tests
排除标准
- •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
研究组 & 干预措施
AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
干预措施: Clopidogrel (Drug)
结局指标
主要结局
adrenergic component of the platelet response
时间窗: 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)
次要结局
- VASP-CMF(After 5 days taking clopidogrel)
- ELISA VASP(After 5 days taking clopidogrel)
- active metabolite of clopidogrel(After 5 days taking clopidogrel)
- Genotyping of MDR-1 and P450 2C19(After 5 days taking clopidogrel)