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Platelet Reactivity in Stent Thrombosis Patients (MAPCAT)

Primary Purpose

Coronary Artery Stent Thrombosis

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Clopidogrel
Sponsored by
St. Antonius Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Coronary Artery Stent Thrombosis focused on measuring clopidogrel, pharmacokinetics, platelet function tests, platelet reactivity

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St Antonius Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

stent thrombosis patients

Patients without a history of a stent thrombosis

Arm Description

Patients with a history of a stent thrombosis

Patients without a history of stent thrombosis

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Exploratory Endpoint: prevalence of various genetic polymorphisms that might influence the pharmacokinetics of clopidogrel

Full Information

First Posted
November 12, 2009
Last Updated
August 22, 2011
Sponsor
St. Antonius Hospital
Collaborators
University of Cologne
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1. Study Identification

Unique Protocol Identification Number
NCT01012544
Brief Title
Platelet Reactivity in Stent Thrombosis Patients
Acronym
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).
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Antonius Hospital
Collaborators
University of Cologne

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Stent Thrombosis
Keywords
clopidogrel, pharmacokinetics, platelet function tests, platelet reactivity

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
187 (Actual)

8. Arms, Groups, and Interventions

Arm Title
stent thrombosis patients
Arm Type
Active Comparator
Arm Description
Patients with a history of a stent thrombosis
Arm Title
Patients without a history of a stent thrombosis
Arm Type
Active Comparator
Arm Description
Patients without a history of stent thrombosis
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
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
Primary Outcome Measure Information:
Title
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.
Time Frame
6 hours after the administration of a 600mg loading dose of clopidogrel
Secondary Outcome Measure Information:
Title
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.
Time Frame
platelet reactivity measured at baseline and 6 hours after a 600 mg clopidogrel loading dose.
Title
Exploratory Endpoint: prevalence of various genetic polymorphisms that might influence the pharmacokinetics of clopidogrel
Time Frame
blood obtained for genetic sampeling at timepoint of first study blood collection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.M. ten Berg, MD, PhD
Organizational Affiliation
St Antonius center for platelet function research
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Antonius Hospital
City
Nieuwegein
State/Province
Utrecht
ZIP/Postal Code
3435CM
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
19806258
Citation
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.
Results Reference
background
PubMed Identifier
19458375
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. No abstract available.
Results Reference
background
PubMed Identifier
19371823
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.
Results Reference
background
PubMed Identifier
16689772
Citation
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.
Results Reference
background
PubMed Identifier
17112805
Citation
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.
Results Reference
background
PubMed Identifier
21382172
Citation
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.
Results Reference
derived

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Platelet Reactivity in Stent Thrombosis Patients

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