Interaction between human immunodeficiency virus (HIV) drugs (non-nucleoside reverse transcriptase inhibitors [NNRTIs]) and anti-platelet agents
| ISRCTN | ISRCTN68035289 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68035289 |
| Clinical Trials Information System (CTIS) | 2008-006371-67 |
| Protocol serial number | RLBUHT 3729 |
| Sponsor | Royal Liverpool University Hospital and the University of Liverpools Biomedical Research Centre (UK) |
| Funder | National Institute for Health Research (NIHR) (UK) - through the Royal Liverpool University Hospital and the University of Liverpools Biomedical Research Centre (ref: UoL000399. R&D 3729) |
- Submission date
- 28/10/2009
- Registration date
- 17/12/2009
- Last edited
- 19/05/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Not provided at time of registration
Contact information
Scientific
Professor and Hon Consultant Infectious Diseases
University of Liverpool
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom
| Phone | +44 (0)151 794 5560 |
|---|---|
| khoo@liv.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open-label sequential randomised single phase multi-dose proof-of-concept study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Effect of thienopyridine derivative (clopidogrel) on the disposition of efavirenz and neviparine in human immunodeficiency virus (HIV) positive patients: a randomised single-phase multi-dose proof-of-concept study |
| Study objectives | The plasma concentration of non-nucleoside reverse transcriptase inhibitors (NNRTIs) (nevirapine and efavirenz) may be pharmacologically enhanced in-vivo through inhibition of CYP2B6 with clopidogrel. |
| Ethics approval(s) | National Research Ethics Service (Northwest Research Ethics Committee) (UK) approved on the 28th August 2009 (ref: 09/H1010/6) |
| Health condition(s) or problem(s) studied | Human immunodeficiency virus (HIV) |
| Intervention | Study patients on nevirapine should be receiving 200 mg 12-hourly. Study patients on efavirenz who are taking 600 mg at night would be converted to 600 mg in the morning as follows: 400 mg mane, 200 mg nocte for 1 day, then 600 mg for 1 day followed by the study day. Study Day 1: Patients are fasted from midnight and attend at 08:00 hours without taking their pills. After breakfast and blood sampling for pharmacokinetic profiles patients would then be administered initial dose of clopidogrel (Plavix®, 75 mg once daily; Sanofi Synthelabo, Guildford, United Kingdom) and would self-administer the remaining dose at home for the remaining 6 days. Joint sponsor details: The University of Liverpool (UK) Pembroke Place Liverpool L69 3GF United Kingdom http://www.liv.ac.uk/ |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Efavirenz, nevirapine, clopidogrel |
| Primary outcome measure(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 hours. |
| Key secondary outcome measure(s) |
1. Change in Cmax, Cmin, and weight-corrected apparent oral clearance (CL/F)/kg of efavirenz/nevirapine |
| Completion date | 15/12/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 37 |
| Key inclusion criteria | 1. Aged greater than 18 years, either sex 2. On efavirenz (EFV) or nevirapine (NVP) containing regimen for greater than or equal to 6 months 3. Viral load less than or equal to 40 copies/ml and any CD4 count 4. No laboratory evidence of NNRTI toxicity: 4.1. Alanine aminotransferase (ALT) less than or equal to upper limit of normal (ULN) 4.2. Bilirubin less than or equal to ULN 4.3. Albumin greater than or equal to 30 g 4.4. Creatinine less than or equal to ULN 5. Not pregnant (for contraception, patients would be advised to use non-oestrogen based contraceptive devices) 6. No inter-current acute illness 7. No past medical history of coronary heart disease 8. No history of bleeding diathesis 9. No history of allergy to thienopyridines |
| Key exclusion criteria | 1. Unable to provide informed consent 2. Known or suspected poor adherence to anti-retroviral therapy (ART) 3. Continuing intravenous (IV) drug user 4. On a HIV protease inhibitor or any known P450 inhibitors or inducers 5. Platelets less than or equal to 100 x 10^9/l 6. Neutrophils less than or equal to 1.0 x 10^9/ml |
| Date of first enrolment | 15/11/2009 |
| Date of final enrolment | 15/12/2009 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
L69 3GF
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 08/09/2021 | 19/05/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
19/05/2022: EU Clinical Trials Register results added.
03/01/2020: Added EudraCT number. No publications found, verifying study status with principal investigator.
20/05/2016: No publications found, verifying study status with principal investigator.
