Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Cissy Kityo Mutuluuza
ORCID ID
Contact details
Joint Clinical Research Centre (JCRC)
Plot 893 Ring Road
Butikiro house Mengo
Kampala
-
Uganda
+256 (0)414 201 148
ckityo@jcrc.co.ug
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01663168
Protocol/serial number
N/A
Study information
Scientific title
Toxicity 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)
Acronym
Study hypothesis
This 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
Joint Clinical Research Centre Institutional Review Board (IRB), Uganda, 14/10/2011
Study design
Parallel two-group open-label multi-centre randomised controlled pilot trial embedded within a larger randomised controlled trial (EARNEST)
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) / Tuberculosis (TB)
Intervention
Patients 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 type
Drug
Phase
Not Applicable
Drug names
Lopinavir/ritonavir, rifabutin
Primary outcome measure
Grade 3/4 adverse events over the course of the trial and time to first event
Secondary outcome measures
1. 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 trial start date
05/03/2012
Overall trial end date
31/01/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
140
Participant exclusion criteria
1. 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)
Recruitment start date
05/03/2012
Recruitment end date
31/01/2014
Locations
Countries of recruitment
Uganda
Trial participating centre
Joint Clinical Research Centre (JCRC)
Kampala
-
Uganda
Sponsor information
Organisation
MRC Clinical Trials Unit (UK)
Sponsor details
Aviation House
125 Kingsway
London
WC2B 6NH
United Kingdom
+44 (0)20 7670 4700
enquiries@ctu.mrc.ac.uk
Sponsor type
Research council
Website
Funders
Funder type
Industry
Funder name
Abbott
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
Basic results (scientific)
Publication list