Platelet Reactivity in Stent Thrombosis Patients

Coronary Artery Stent Thrombosis Clinical Trial

— MAPCAT  

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01012544
• Other study ID #: MAPCAT01
• Status: Completed
• Phase: Phase 4
• First received: November 12, 2009
• Last updated: August 22, 2011
• Start date: April 2009
• Est. completion date: December 2009

Study information

• Verified date: August 2011
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 187
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Coronary Artery Stent Thrombosis
• Thrombosis

Intervention

Drug:
• Clopidogrel
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

Locations

Country	Name	City	State
Netherlands	St Antonius Hospital	Nieuwegein	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
St. Antonius Hospital	University of Cologne

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

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. — View Citation

Heestermans AA, van Werkum JW, Schömig 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. — View Citation

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. — View Citation

Taubert D, von Beckerath N, Grimberg G, Lazar A, Jung N, Goeser T, Kastrati A, Schömig A, Schömig E. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006 Nov;80(5):486-501. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	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	No