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| Name | Class |
|---|---|
| University of Cologne | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| stent thrombosis patients | Active Comparator | Patients with a history of a stent thrombosis |
|
| Patients without a history of a stent thrombosis | Active Comparator | Patients without a history of stent thrombosis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J.M. ten Berg, MD, PhD | St Antonius center for platelet function research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Antonius Hospital | Nieuwegein | Utrecht | 3435CM | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19806258 | Background | Elsenberg EH, van Werkum JW, van de Wal RM, Zomer AC, Bouman HJ, Verheugt FW, Berg JM, Hackeng CM. The influence of clinical characteristics, laboratory and inflammatory markers on 'high on-treatment platelet reactivity' as measured with different platelet function tests. Thromb Haemost. 2009 Oct;102(4):719-27. doi: 10.1160/TH09-05-0285. | |
| 19458375 |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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|
| blood obtained for genetic sampeling at timepoint of first study blood collection |
| Taubert D, Bouman HJ, van Werkum JW. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 May 21;360(21):2249-50; author reply 2251. doi: 10.1056/NEJMc090391. No abstract available. |
| 19371823 | Background | van Werkum JW, Heestermans AA, Zomer AC, Kelder JC, Suttorp MJ, Rensing BJ, Koolen JJ, Brueren BR, Dambrink JH, Hautvast RW, Verheugt FW, ten Berg JM. Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. J Am Coll Cardiol. 2009 Apr 21;53(16):1399-409. doi: 10.1016/j.jacc.2008.12.055. |
| 16689772 | Background | Heestermans AA, van Werkum JW, Schomig E, ten Berg JM, Taubert D. Clopidogrel resistance caused by a failure to metabolize clopidogrel into its metabolites. J Thromb Haemost. 2006 May;4(5):1143-5. doi: 10.1111/j.1538-7836.2006.01891.x. No abstract available. |
| 17112805 | Background | Taubert D, von Beckerath N, Grimberg G, Lazar A, Jung N, Goeser T, Kastrati A, Schomig A, Schomig E. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006 Nov;80(5):486-501. doi: 10.1016/j.clpt.2006.07.007. |
| 21382172 | Derived | Bouman HJ, van Werkum JW, Breet NJ, ten Cate H, Hackeng CM, ten Berg JM. A case-control study on platelet reactivity in patients with coronary stent thrombosis. J Thromb Haemost. 2011 May;9(5):909-16. doi: 10.1111/j.1538-7836.2011.04255.x. |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |