Platelet Reactivity in Stent Thrombosis Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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).

Conditions
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Coronary Artery Stent Thrombosis

Intervention / Treatment
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* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a history of a stent thrombosis in the period 2004-2008. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: stent thrombosis patients<br>Patients with a history of a stent thrombosis | Drug: Clopidogrel<br>* both arms of the study (patients with a history of stent thrombosis as well as patients who did not suffer from a stent thrombosis) will be given a 600 mg loading dose of clopidogrel<br>* Other names: Plavix;|
| Active Comparator: Patients without a history of a stent thrombosis<br>Patients without a history of stent thrombosis | Drug: Clopidogrel<br>* both arms of the study (patients with a history of stent thrombosis as well as patients who did not suffer from a stent thrombosis) will be given a 600 mg loading dose of clopidogrel<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 6 hours after the administration of a 600mg loading dose of clopidogrel | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clopidogrel, pharmacokinetics, platelet function tests, platelet reactivity