The MAgnitude of Platelet Inhibition and the Pharmacokinetics of a 600 mg Loading Dose of Clopidogrel, in Different Patient CATegories (Stable Angina Versus Acute-coronary Syndromes Versus ST-elevated Myocardial Infarction).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 187
- 试验地点
- 1
- 主要终点
- Plasma concentrations of unchanged clopidogrel, its active thiol metabolite and its inactive carboxyl metabolite between the different patient groups after the administration of a 600 mg loading dose of clopidogrel.
研究概览
简要总结
Recent studies have demonstrated a marked interindividual variability of clopidogrel's capacity to inhibit platelet aggregation with a substantial proportion (11-34%) of the patients considered non-responders to clopidogrel treatment. Variable intestinal absorption is suggested to contribute to the inconsistencies in response to clopidogrel. However, little is known about intestinal absorption in subjects who had suffered from a stent thrombosis. The MAPCAT-study has been designed to investigate whether plasma pharmacokinetics (represented by Cmax, Tmax and the AUC) after a 600 mg loading dose are significantly different between subjects who have suffered a stent thrombosis and subjects who have not suffered a stent thrombosis.
详细描述
Objectives:
The first objective of the MAPCAT-study is to investigate whether plasma pharmacokinetics (Cmax, Tmax and AUC) of an additional 600 mg loading dose are impaired in patients with a history of stent thrombosis.
The second objective of the MAPCAT study is to investigate whether genetic polymorphisms in receptors, enzymes and ligands involved in the process of thrombosis and haemostasis as well in the conversion-process of clopidogrel into its metabolites do have influence on both the absolute magnitude of platelet inhibition and Cmax, Tmax and AUC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of a stent thrombosis in the period 2004-2008.
排除标准
- •Persistent acute ST-segment elevation
- •Successful revascularization during the qualifying hospitalization, prior to study entry
- •Acute pulmonary edema, hypotension, or evidence of cardiogenic shock
- •Clinically significant liver disease
- •End stage kidney disease requiring dialysis
- •Use at study entry of drugs that are strong inhibitors of cytochrome P450 3A4 and CYP3A5 (i.e. clarithromycin, erythromycin, itraconazole, ketoconazole)
- •Contraindications to antithrombotic/antiplatelet therapy
- •Failed coronary intervention in the previous 2 weeks
- •Malignancies
- •Increased risk of bleeding (previous stroke in the past months, active bleeding or bleeding diathesis, recent trauma or major surgery in the last month, suspected aortic dissection, oral anticoagulation therapy with coumarin derivate within 7 days, recent use of GPIIb/IIIa inhibitors within 14 days, severe uncontrolled hypertension >180 mmHg unresponsive to therapy)
- •Relevant hematologic deviations (haemoglobin <100g/L (6,2 mmol/L) or hematocrit <34%, platelet count <100 x 109 /L or platelet count > 600 x 109/L)
- •Known allergy to clopidogrel
- •Pregnancy (present or suspected)
- •uncontrolled hypertension at time of randomization
研究组 & 干预措施
stent thrombosis patients
Patients with a history of a stent thrombosis
干预措施: Clopidogrel (Drug)
Patients without a history of a stent thrombosis
Patients without a history of stent thrombosis
干预措施: Clopidogrel (Drug)
结局指标
主要结局
Plasma concentrations of unchanged clopidogrel, its active thiol metabolite and its inactive carboxyl metabolite between the different patient groups after the administration of a 600 mg loading dose of clopidogrel.
时间窗: 6 hours after the administration of a 600mg loading dose of clopidogrel
次要结局
- The magnitude of platelet reactivity as measured with several commercial available platelet function tests before and 6 hours after the ingestion of the loading dose.(platelet reactivity measured at baseline and 6 hours after a 600 mg clopidogrel loading dose.)
- Exploratory Endpoint: prevalence of various genetic polymorphisms that might influence the pharmacokinetics of clopidogrel(blood obtained for genetic sampeling at timepoint of first study blood collection)
研究者
J.M. ten Berg
Cardiologist, MD, PhD, FESC, FACC
St. Antonius Hospital