To determine whether anti-platelet agent clopidigrel influences the disposition of NNRTIs (efavirenz and nevirapine)
Conditions
Interventions
Trade Name: Plavix (Sanofi Synthelabo, Guildford, United Kingdom)
Product Name: plavix
Product Code: B01AC04
Pharmaceutical Form: Tablet
Trade Name: viramune
Product Name: Nevirapine
Pharmaceutical
stocrin
Product Name: Efavirenz
Product Code: J05AG03
Pharmaceutical Form: Tablet
Sponsors
Royal Liverpool and Broadgreen University Hospital
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria HIV positive •Age 18 years and above •On EFV or NVP containing regimen for greater or equal to 6 months •Viral load less than or equal to 40 copies/ml and any CD4 count •No Laboratory evidence of NNRTI toxicity : ALT =ULN; Bilirubin =ULN;Albumin =30g;Creatinine =ULN •Not pregnant (for contraception, patients would be advised to use non-estrogen based contraceptive devices) •No inter-current acute illness. •No past medical history of coronary heart disease. •No history of bleeding diathesis •No history of allergy to thienopyridines Exclusion Criteria •Unable to provide informed consent •Known or suspected poor adherence to ART •Continuing IV drug user •On HIV protease inhibitor or any known P450 inhibitors or inducers •Neutrophils= 3.0 x 109/ml; HB 11.0g/dl •Platelets = 100 x 109/l Are the trial subjects under 18? Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: .Unable to provide informed consent .Known or suspected poor adherence to ART .Continuing IV drug user .On a PI or any other known P450 inhibitors or inducers .Platelets <100x109 L-1 .Neutrophils = 1.0 x 109/ml
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We wish to determine whether the cardiac drug clopidogrel inhibit the metabolism of the HIV drugs Efavirenz and Nevirapine and therefore increase the concentration of these drugs (efavirenz and nevirapine) in the body. The implication of this is both to minimise the risk of toxicity, but also the potential to exploit these interactions with the view to influence new formulations of these agents (efavirenz and nevirapine) which would potentially be less toxic.;Secondary Objective: We wish to determine the safety of taking both efavirenz, nevirapine and cardiac drug clopidogrel in HIV patients, a scenario that is likely to become common with increasing survival of HIV patients. ;Primary end point(s): Absolute change (demonstrated by significant difference) in plasma AUC of Efavirenz alone or Nevirapine alone if the respective (90% classical Confidence Interval for geometric mean ratio lies within 0.80-1.25 of the reference AUC 0-24 h. | — |
Countries
United Kingdom
Outcome results
None listed