Condition category
Infections and Infestations
Date applied
28/10/2009
Date assigned
17/12/2009
Last edited
20/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Saye Khoo

ORCID ID

Contact details

Professor and Hon Consultant Infectious Diseases
University of Liverpool
70 Pembroke Place
Liverpool
L69 3GF
United Kingdom
+44 (0)151 794 5560
khoo@liv.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RLBUHT 3729

Study information

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

Acronym

Study hypothesis

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

National Research Ethics Service (Northwest Research Ethics Committee) (UK) approved on the 28th August 2009 (ref: 09/H1010/6)

Study design

Open-label sequential randomised single phase multi-dose proof-of-concept study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Efavirenz, nevirapine, clopidogrel

Primary outcome measures

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 trial start date

15/11/2009

Overall trial end date

15/12/2009

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

37

Participant 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

Recruitment start date

15/11/2009

Recruitment end date

15/12/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Professor and Hon Consultant Infectious Diseases
Liverpool
L69 3GF
United Kingdom

Sponsor information

Organisation

Royal Liverpool University Hospital and the University of Liverpool’s Biomedical Research Centre (UK)

Sponsor details

Royal Liverpool & Broadgreen University NHS Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom
+44(0)151 794 5560
mdanjuma@liv.ac.uk

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research (NIHR) (UK) - through the Royal Liverpool University Hospital and the University of Liverpool’s Biomedical Research Centre (ref: UoL000399. R&D 3729)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

20/05/2016: No publications found, verifying study status with principal investigator.