Healthy Volunteer Study of Clopidogrel and Rifampicin
The principal research question is: Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?
Clopidogrel is an antithrombotic drug in clinical use that reduces the risk of heart attack and coronary stent thrombosis. However some patients respond poorly to clopidogrel, at least partly because they fail to convert it effectively to its active form, and consequently are at higher risk of arterial thrombosis. Preliminary evidence indicates that the antibiotic rifampicin enhances the effectiveness of clopidogrel by increasing its conversion to its active form by the liver. We wish to study further the extent of rifampicin's effect on clopidogrel to see whether this might be useful in clinical practice.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Study of the Potentiation of the Effects of Clopidogrel by Rifampicin in Healthy Volunteers|
- Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin? [ Time Frame: All year ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Study Completion Date:||March 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
All subjects will receive Clopidogrel and Rifampicin.
Drug: Clopidogrel and Rifampicin
Clopidogrel: loading dose of 600 mg, then 75 mg o.d. for up to 28 days
Rifampicin: 300 mg b.d. for up to 28 days
Clopidogrel is an antithrombotic drug that is licensed for the treatment and prevention of arterial thrombosis, such as in people admitted to hospital with heart attacks. However, some people fail to achieve a substantial antithrombotic effect from the drug and one important reason for this is that their livers do not convert clopidogrel to its active form effectively. Current evidence suggests that these people are less protected by clopidogrel and have a higher risk of arterial thrombosis than those who respond well to clopidogrel. Rifampicin is an antibiotic that increases the activity of liver enzymes that convert clopidogrel to its active form and preliminary evidence indicates that it increases the effectiveness of clopidogrel. This raises the possibility that rifampicin might be used with clopidogrel to increase its clinical effectiveness. We wish to study this interaction further.
12 healthy volunteers will be recruited for this study after giving informed consent. Following Screening, the study will run over 28 days. Lab safety (clinical chemistry, haematology and urinalysis) will be undertaken on days 7, 22 and 28 in addition to screening. During the first visit, an intravenous cannula will be inserted into a forearm vein. Subjects will perform an erythromycin breath test. Subsequently, venous blood will be obtained via the intravenous cannula and platelet function studies will be performed and a plasma sample will be stored for baseline metabolite analysis. Subsequently the subjects will be administered a 600 mg loading dose of clopidogrel (Plavix, Sanofi Pharma Bristol−Myers Squibb) and further blood samples will be taken over 4 hours for clopidogrel metabolite analysis and platelet function studies. Subjects will then take clopidogrel 75 mg daily for a further 6 days and, 4 hours after the last dose, a further blood sample will be taken using venepuncture for platelet function studies and a plasma sample. After a washout period of 7 days, subjects will then start rifampicin 300 mg twice daily for 14 days (Rifadin, Aventis Pharma). On the 8th day of taking rifampicin, a further intravenous cannula will be inserted, the erythromycin breath test will be repeated, as above, and the same regimen of clopidogrel administration and blood testing will be repeated, this time with co−administration of rifampicin.
The data obtained will allow the following assessments: (i) comparison of the early effects of a 600 mg clopidogrel loading dose and late effects of clopidogrel after 7 days on platelet aggregation and receptor blockade; (ii) assessment of the effects of rifampicin on clopidogrel's action on platelet aggregation and receptor blockade following a loading dose and after prolonged administration of clopidogrel.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00696566
|Sheffield Clinical Research Facility, Royal Hallamshire Hospital|
|Sheffield, S. Yorkshire, United Kingdom, S10 2JF|
|Principal Investigator:||Robert F Storey||University of Sheffield|