Platelet Reactivity in Stent Thrombosis Patients

NCT01012544 | Completed Phase 4

• 1 other identifier: MAPCAT01
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Coronary Artery Stent Thrombosis

Keywords

clopidogrel; pharmacokinetics; platelet function tests; platelet reactivity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

stent thrombosis patients

ACTIVE COMPARATOR

Patients with a history of a stent thrombosis

Drug: Clopidogrel

Patients without a history of a stent thrombosis

ACTIVE COMPARATOR

Patients without a history of stent thrombosis

Drug: Clopidogrel

Interventions

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

Also known as: Plavix

Patients without a history of a stent thrombosis; stent thrombosis patients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a history of a stent thrombosis in the period 2004-2008.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Antonius Hospital: lead
• University of Cologne: collaborator

Study Sites (1)

St Antonius Hospital

Nieuwegein, Utrecht, 3435CM, Netherlands

Location

Related Publications (6)

• 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.

  PMID: 19806258 BACKGROUND

• 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.

  PMID: 19458375 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.

  PMID: 19371823 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.

  PMID: 16689772 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.

  PMID: 17112805 BACKGROUND

• 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.

  PMID: 21382172 DERIVED

MeSH Terms

Interventions

Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• J.M. ten Berg, MD, PhD

  St Antonius center for platelet function research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist, MD, PhD, FESC, FACC

Study Record Dates

• First Submitted: November 12, 2009
• First Posted: November 13, 2009
• Study Start: April 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 23, 2011

Record last verified: 2011-08

Locations

NL (1)