The primary aim of this MAPCAT-study is to investigate whether pharmacokinetics of clopidogrel differ significantly betwen different clinical scenarios. A second aim is to study specifically whether genetic polymorfisms influence these…
ID
Source
Brief title
Condition
- Platelet disorders
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) To investigate whether platelet function is significantly different between
patients with a history of stent thrombosis and controls (stable anginga and
ACS) .
2) To investigate whether plasma pharmacokinetics (represented by Cmax, Tmax
and the AUC) of unchanged clopidogrel and its active thiol metabolite and its
inactive carboxyl metabolite are significantly different between patients with
a history of stent thrombosis and controls (stable angina and ACS) .
Secondary outcome
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.
Background summary
Patients undergoing a percutaneous coronary intervention (PCI), are on aspirin
and clopidogrel to prevent (secondary) thrombotic complications. Still, in 1-3%
of these patients receiving dual antiplatelet therapy, a (subacute) stent
thrombosis (ST) occurs. 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. Our primary hypothesis is that
patients with a history of stent thrombosis exhibit a significantly higher
magnitude of platelet reactivity as compared to controls. In addition, we
hypothesized that patients with a history of stent thrombosis are less capable
to generate the active metabolite of clopidogrel. Thus far a clear trend
between 60 cases and 40 controls was seen in an interim analysis. We expect
that including 100 patients per group, will show a significant difference
between both groups.
Furthermore it is widely known that medication and comorbidity (like diabetes
mellitus) can influence the period after a PCI and the occurence of
complications. To investigate these influences, it is necessary to make several
subanalyses between the several subgroups in our MAPCAT-database.
Study objective
The primary aim of this MAPCAT-study is to investigate whether pharmacokinetics
of clopidogrel differ significantly betwen different clinical scenarios. A
second aim is to study specifically whether genetic polymorfisms influence
these pharmacokinetics. We request to increase the number of cases and controls
to 100 patients per group, because thus far a clear trend between 60 cases and
40 controls was seen in an interim analysis. We expect that including 100
patients per group, will show a significant difference between both groups.
Furthermore, we would like to subanalyze the different subgroups that are
represented in the MAPCAT (for example diabetes mellitus, use of proton pump
inhibitors and/or use of calcium channel blockers).
Study design
This is a single center, observational study.
Study burden and risks
The risk associated with participiation in this amendement is conform the
original studyprotocol. Venapuncture at different timepoints has a negligible
risk of hemorrhage as well as the loadingdose of clopidogrel has a slight risk
of hemorrhage.
Koekoekslaan 1
3435 CM Nieuwegein
NL
Koekoekslaan 1
3435 CM Nieuwegein
NL
Listed location countries
Age
Inclusion criteria
Group 1: Patients with a history of a stent thrombosis in the period 2002-2009.
Group 2: Patients with ACS or stable AP.
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 ( aemoglobin <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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005749-12-NL |
| CCMO | NL15115.100.06 |