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
EudraCT/CTIS number	2008-006371-67
Secondary identifying numbers	RLBUHT 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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Saye Khoo
Scientific

Professor and Hon Consultant Infectious Diseases
University of Liverpool
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom

Phone	+44 (0)151 794 5560
Email	khoo@liv.ac.uk

Study information

Study design	Open-label sequential randomised single phase multi-dose proof-of-concept study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient 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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Efavirenz, nevirapine, clopidogrel
Primary outcome measure	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. All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month).
Secondary outcome measures	1. Change in Cmax, Cmin, and weight-corrected apparent oral clearance (CL/F)/kg of efavirenz/nevirapine 2. Safety and tolerability of co-administration of clopidogrel and efavirenz/nevirapine All measures determined at the end of the study duration and data analysis (entire study duration is 8 days and data analysis approximately 3 weeks to a month).
Overall study start date	15/11/2009
Completion date	15/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	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

England
United Kingdom

Study participating centre

Professor and Hon Consultant Infectious Diseases

Liverpool
L69 3GF
United Kingdom

Sponsor information

Royal Liverpool University Hospital and the University of Liverpools Biomedical Research Centre (UK)
Government

Royal Liverpool & Broadgreen University NHS Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom

Phone	+44(0)151 794 5560
Email	mdanjuma@liv.ac.uk
"ROR"	https://ror.org/01ycr6b80

Funders

Funder type

Government

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)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	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

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.