Europe - Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Rifabutin Pharmacokinetics (PK) substudy

ISRCTN ISRCTN13074752
DOI https://doi.org/10.1186/ISRCTN13074752
ClinicalTrials.gov number NCT01663168
Secondary identifying numbers N/A
Submission date
06/03/2012
Registration date
03/04/2012
Last edited
16/04/2019
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

Background and study aims
Some of the drugs used to treat HIV (anti-retrovirals) can affect the blood levels of other drugs used to treat tuberculosis (TB) – called a drug-drug interaction. The main drug used in second-line HIV treatment, Aluvia (lopinavir/ritonavir), is one of the drugs that has this effect. This is why people on second-line anti-retrovirals usually cannot use one of the main TB drugs, rifampicin, and instead will be prescribed a slightly different drug called rifabutin, which is less affected by these drug-drug interactions. Although blood levels of rifabutin are not as badly affected by Aluvia as blood levels of rifampicin, rifabutin blood levels are still increased a lot by taking Aluvia at the same time. This could lead to higher levels of side-effects because there is more of the drug in the body. Doctors have suggested that instead of taking rifabutin every day with Aluvia, it should only be taken three times a week, on Mondays, Wednesdays and Fridays. However, in the last 2 years, new studies have suggested that this three times a week regimen might not be enough and that it may not completely cure TB. So the purpose of this study is to find out whether taking rifabutin every day with Aluvia really does lead to more side-effects, and whether taking rifabutin three times a week with Aluvia really does lead to much lower levels of rifabutin in the blood.

Who can participate?
Adults/adolescents (aged 12 and older) with HIV and TB who are being treated with Aluvia and rifabutin.

What does the study involve?
Participants are randomly allocated to one of two groups. One group takes rifabutin three times a week (Monday/Wednesday/Friday). The other group takes rifabutin daily. Both groups also take Aluvia as part of their second-line anti-retroviral treatment.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
Joint Clinical Research Centre (Uganda).

When is the study starting and how long is it expected to run for?
March 2012 to January 2014.

Who is funding the study?
Abbott

Who is the main contact?
Dr Cissy Kityo Mutuluuza
ckityo@jcrc.co.ug

Study website

Contact information

Dr Cissy Kityo Mutuluuza
Scientific

Joint Clinical Research Centre (JCRC)
Plot 893 Ring Road
Butikiro house – Mengo
Kampala
-
Uganda

Phone +256 (0)414 201 148
Email ckityo@jcrc.co.ug

Study information

Study designParallel two-group open-label multi-centre randomised controlled pilot trial embedded within a larger randomised controlled trial (EARNEST)
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleToxicity and pharmacokinetics of different Rifabutin doses in HIV-infected adults and adolescents taking lopinavir / ritonavir as second-line anti-retroviral therapy (ART) (EARNEST Rifabutin PK substudy)
Study objectivesThis pilot randomised open-label pharmacokinetic substudy embedded within a larger randomised controlled trial (EARNEST) will compare 150 mg rifabutin daily versus thrice weekly, both in combination with lopinavir/ritonavir taken as part of second-line ART in the EARNEST trial of second-line antiretroviral therapy, in terms of
1. Toxicity
2. Pharmacokinetics of rifabutin, lopinavir/ritonavir, raltegravir (participants enrolled from arm B of main EARNEST trial only) and
3. PK/PD (pharmacokinetic/pharmacodynamic) relationships

EARNEST study registered under ISRCTN37737787
Ethics approval(s)Joint Clinical Research Centre Institutional Review Board (IRB), Uganda, 14/10/2011
Health condition(s) or problem(s) studiedHuman immunodeficiency virus (HIV) / Tuberculosis (TB)
InterventionPatients will be randomised in a ratio of 1:1 to the following two treatment groups:
Group 1: rifabutin (150 mg) three times a week (Monday/Wednesday/Friday)
Group 2: rifabutin (150 mg) daily

Total duration of intervention: at least 24 weeks
Patients in both groups will also be taking lopinavir/ritonavir as part of their second-line ART
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Lopinavir/ritonavir, rifabutin
Primary outcome measureGrade 3/4 adverse events over the course of the trial and time to first event
Secondary outcome measures1. Rifabutin and its 25-o-desacetyl metabolite pharmacokinetic parameters (from a population PK model)
2. Lopinavir/ritonavir pharmacokinetic parameters (from a population PK model)
3. Raltegravir pharmacokinetic parameters (from a population PK model)
4. Response to TB therapy (culture positive at 24 weeks or subsequent relapse/recurrence)
5. Rifamycin resistance
Overall study start date05/03/2012
Completion date31/01/2014

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants140
Key inclusion criteria1. HIV-1 infected adults/adolescents (12 years and older) receiving boosted protease inhibitor (almost exclusively lopinavir/ritonavir, Aluvia) containing second-line ART within the EARNEST trial
2. Enrolled with or developing tuberculosis (TB) during EARNEST trial follow-up
3. Currently receiving or planning to initiate rifabutin-containing anti-TB treatment (ie no contraindications to rifabutin)
4. Who provide written informed consent
Key exclusion criteria1. Patients who have already reached week 132 in the EARNEST trial at time of TB diagnosis will not be enrolled as practical considerations limit follow up to 12 weeks beyond the completion of the week 144 EARNEST visit.
2. Patients who have less than 10 weeks remaining in their course of TB treatment will not be enrolled as they will not contribute to the main PK evaluation at week 12 (window 10-14 weeks)
Date of first enrolment05/03/2012
Date of final enrolment31/01/2014

Locations

Countries of recruitment

  • Uganda

Study participating centre

Joint Clinical Research Centre (JCRC)
Kampala
-
Uganda

Sponsor information

MRC Clinical Trials Unit (UK)
Research council

Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom

Phone +44 (0)20 7670 4700
Email enquiries@ctu.mrc.ac.uk
Website http://www.ctu.mrc.ac.uk
ROR logo "ROR" https://ror.org/001mm6w73

Funders

Funder type

Industry

Abbott

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 17/07/2014 16/04/2019 Yes No

Editorial Notes

16/04/2019: No publications found, verifying study status with principal investigator.