HIV InfectionsPhase 2NCT00640887
Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in Patients With TB/HIV Co-infection in South Africa
A Phase 2 study testing rifabutin in combination with efavirenz, rifabutin in combination with nevirapine and rifabutin in combination with lopinavir/ritonavir in people with HIV Infections and Tuberculosis, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in South Africa.
Trial summary
The overall aim of the project is to evaluate rifabutin (RBT) as a replacement for rifampicin (RMP), for the combined treatment of tuberculosis and HIV infection. RBT represents an alternative to RMP for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections, Tuberculosis
- What is being tested?
- rifabutin in combination with efavirenz, rifabutin in combination with nevirapine and rifabutin in combination with lopinavir/ritonavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSouth Africa
- Study dates
- Feb 2009to Oct 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pulmonary tuberculosis (proven by AFB positive sputum or culture)
- Having completed and adhered to 6 wks of intensive phase TB chemotherapy
- Positive HIV antibody and CD4 count >50 /mm3 and <=200
- Weight > 50 kg
- No ART in the preceding 3 months
- No more than 2 weeks or ART previously
Show all 10Show fewer
- No grade 3 or 4 clinical or laboratory findings
- Negative pregnancy test and appropriate contraceptive measures during the duration of the trial for female of childbearing age
- Having a firm home address that is readily accessible
- Karnofsky score>=80%
Who cannot join
- History of TB within the 3 years preceding the presenting episode of TB
- Previous treatment for MDR TB
- Concomitant OI requiring additional anti-infectious treatment
- Formal contraindication to any drug used in the trial
- Diabetes mellitus requiring drug treatment
- Recreational drug or alcohol abuse
Show all 15Show fewer
- History of drug hypersensitivity to TB or related medications
- Interrupted TB therapy for more than 1 week
- Less than 90% adherent to first 6 weeks of intensive phase chemotherapy
- Mental illness that could impair ability to give informed consent or result in poor adherence to trial protocol and therapy
- Neutropenia <1200 /L, anaemia <6.8 g/dL, liver function test > grade 2
- Requiring concomitant medications that may potentially interact with study drugs
- Pregnant or lactating women
- Karnofsky score >80%
- Any condition rendering the patient unable to understand the nature, scope, and possible consequences of thes study and to provide consent
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Unit for Clinical and Biomedical TB Research (Medical Research Council)
Durban, 4067
About this study
Official title: Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in South Africa: A Phase II Trial
The overall aim of the project is to evaluate rifabutin (RBT) as a replacement for rifampicin (RMP), for the combined treatment of tuberculosis and HIV infection. RBT represents an alternative to RMP for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated antiretroviral therapy (ART) drugs.
This phase II trial is to determine precisely the pharmacokinetics parameters of RBT in combination with different ART regimens in Vietnamese HIV infected patients with pulmonary tuberculosis, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of RBT and RMP regimens.
Read the detailed description
Patients will be offered to participated in the study after the first 6 weeks of the nationally recommended TB treatment. All the enrolled patients will be switched to rifabutin and randomized, two weeks later, to one of the three study ARV regimens. The RBT doses will be then adapted to the allocated ARV regimen according to a cross over scheme. Three full pharmacokinetics profile will be performed at different time point : before initiation of ARV, after one month of the first RFB dosage and one month after the second RFB dosage.
- Conditions
- HIV Infections, Tuberculosis
- Being tested
- rifabutin in combination with efavirenz, rifabutin in combination with nevirapine, rifabutin in combination with lopinavir/ritonavir
- Keywords
- HIV, Tuberculosis, Rifabutin, Pharmacokinetics, South Africa
- Medical subject headings
- HIV Infections, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rifabutin in combination with efavirenzDrug
Ia. arm 1a:
D4T/3TC/EFV(600mg)+INH/Rifabutin(450 mg OD 4 wks switch to 600 mg OD 4 wks);
Ib. arm 1b:
D4T/3TC/EFV(600mg)+INH/Rifabutin(600 mg OD 4 wks switch to 450 mg OD 4 wks);
rifabutin in combination with nevirapineDrug
IIa. arm 2a:
D4T/3TC/NVP(200mg)+INH/Rifabutin(300 mg OD 4 wks switch to 450 mg OD 4 wks);
IIb. arm 2b :
D4T/3TC/NVP(200mg)+INH/Rifabutin(450 mg OD 4 wks switch to 300 mg OD 4 wks);
rifabutin in combination with lopinavir/ritonavirDrug
IIIa. arm 3a :
D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg TPW 4 wks switch to 150 mg OD 4 wks);
IIIb. arm 3b:
D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg OD 4 wks switch to 150 mg TPW 4 wks).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | RBT associated with EFV based ART Receives: Drug: rifabutin in combination with efavirenz |
| 2 | Experimental | RBT associated with NVP based ART Receives: Drug: rifabutin in combination with nevirapine |
| 3 | Experimental | RBT associated with LPV/r based ART Receives: Drug: rifabutin in combination with lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve (AUC) of rifabutine measured (a)before introduction of ART;(b)after ART initiation (two different doses of RBT in combination with efavirenz, nevirapine or lopinavir/ritonavir)
Measured: 2, 6 and 10 weeks after randomisation
Secondary outcomes (2)
Area under the curve (AUC) of efavirenz, nevirapine and lopinavir/ritonavir in combination with two doses of rifabutine
Measured: 6 and 10 weeks after randomisation
Safety : proportion of patients with grade 3 and grade 4 adverse events
Measured: through out the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study startFeb 2009
- Primary completionOct 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Investigators
- Anthony D Harries, MD, PhD, Principal investigator, The international Union Against Tuberculosis and Lung Diseases (IUATLD), Paris, FranceAlexander PYM, MD, Principal investigator, Medical Research Council, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640887
- Sponsor's protocol ID
- ANRS12150a
- Status last verified
- Jun 2011
- First submitted
- 6 Feb 2008
- Last updated
- 20 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hennig S, Naiker S, Reddy T, Egan D, Kellerman T, Wiesner L, Owen A, McIlleron H, Pym A. Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis. Antimicrob Agents Chemother. 2015 Oct 19;60(1):617-20. doi: 10.1128/AAC.01195-15. Print 2016 Jan.
PubMed 26482301Naiker S, Connolly C, Wiesner L, Kellerman T, Reddy T, Harries A, McIlleron H, Lienhardt C, Pym A. Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy. BMC Pharmacol Toxicol. 2014 Nov 19;15:61. doi: 10.1186/2050-6511-15-61.
PubMed 25406657
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in South Africa: A Phase II Trial
- ClinicalTrials.gov ID
- NCT00640887
- Acronym / sponsor ID
- ANRS12150a
- Conditions
- HIV Infections, Tuberculosis
- Keywords
- HIV, Tuberculosis, Rifabutin, Pharmacokinetics, South Africa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Study start
- Feb 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 21 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall aim of the project is to evaluate rifabutin (RBT) as a replacement for rifampicin (RMP), for the combined treatment of tuberculosis and HIV infection. RBT represents an alternative to RMP for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated antiretroviral therapy (ART) drugs.
This phase II trial is to determine precisely the pharmacokinetics parameters of RBT in combination with different ART regimens in Vietnamese HIV infected patients with pulmonary tuberculosis, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of RBT and RMP regimens.
Detailed description
Patients will be offered to participated in the study after the first 6 weeks of the nationally recommended TB treatment. All the enrolled patients will be switched to rifabutin and randomized, two weeks later, to one of the three study ARV regimens. The RBT doses will be then adapted to the allocated ARV regimen according to a cross over scheme. Three full pharmacokinetics profile will be performed at different time point : before initiation of ARV, after one month of the first RFB dosage and one month after the second RFB dosage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rifabutin in combination with efavirenzRBT associated with EFV based ART |
| 2 | Experimental | Drug: rifabutin in combination with nevirapineRBT associated with NVP based ART |
| 3 | Experimental | Drug: rifabutin in combination with lopinavir/ritonavirRBT associated with LPV/r based ART |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Pulmonary tuberculosis (proven by AFB positive sputum or culture)
- Having completed and adhered to 6 wks of intensive phase TB chemotherapy
- Positive HIV antibody and CD4 count >50 /mm3 and <=200
- Weight > 50 kg
- No ART in the preceding 3 months
Key exclusion criteria (15 listed)
- History of TB within the 3 years preceding the presenting episode of TB
- Previous treatment for MDR TB
- Concomitant OI requiring additional anti-infectious treatment
- Formal contraindication to any drug used in the trial
- Diabetes mellitus requiring drug treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rifabutin in combination with efavirenzIa. arm 1a: D4T/3TC/EFV(600mg)+INH/Rifabutin(450 mg OD 4 wks switch to 600 mg OD 4 wks); Ib. arm 1b: D4T/3TC/EFV(600mg)+INH/Rifabutin(600 mg OD 4 wks switch to 450 mg OD 4 wks); | Drug | 1 |
| rifabutin in combination with nevirapineIIa. arm 2a: D4T/3TC/NVP(200mg)+INH/Rifabutin(300 mg OD 4 wks switch to 450 mg OD 4 wks); IIb. arm 2b : D4T/3TC/NVP(200mg)+INH/Rifabutin(450 mg OD 4 wks switch to 300 mg OD 4 wks); | Drug | 2 |
| rifabutin in combination with lopinavir/ritonavirIIIa. arm 3a : D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg TPW 4 wks switch to 150 mg OD 4 wks); IIIb. arm 3b: D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg OD 4 wks switch to 150 mg TPW 4 wks). | Drug | 3 |
Primary outcome
Area under the curve (AUC) of rifabutine measured (a)before introduction of ART;(b)after ART initiation (two different doses of RBT in combination with efavirenz, nevirapine or lopinavir/ritonavir)
Time frame: 2, 6 and 10 weeks after randomisation
2 secondary outcomes
Area under the curve (AUC) of efavirenz, nevirapine and lopinavir/ritonavir in combination with two doses of rifabutine
Time frame: 6 and 10 weeks after randomisation
Safety : proportion of patients with grade 3 and grade 4 adverse events
Time frame: through out the trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2011.
- Derived from this study: PubMed 26482301Hennig S, Naiker S, Reddy T, Egan D, Kellerman T, Wiesner L, Owen A, McIlleron H, Pym A. Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis. Antimicrob Agents Chemother. 2015 Oct 19;60(1):617-20. doi: 10.1128/AAC.01195-15. Print 2016 Jan.
- Derived from this study: PubMed 25406657Naiker S, Connolly C, Wiesner L, Kellerman T, Reddy T, Harries A, McIlleron H, Lienhardt C, Pym A. Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy. BMC Pharmacol Toxicol. 2014 Nov 19;15:61. doi: 10.1186/2050-6511-15-61.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony D Harries, MD, PhD principal investigator
The international Union Against Tuberculosis and Lung Diseases (IUATLD), Paris, France
Alexander PYM, MD principal investigator
Medical Research Council, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rifabutin in combination with efavirenz, rifabutin in combination with nevirapine and rifabutin in combination with lopinavir/ritonavir in people with HIV Infections and Tuberculosis, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve (AUC) of rifabutine measured (a)before introduction of ART;(b)after ART initiation (two different doses of RBT in combination with efavirenz, nevirapine or lopinavir/ritonavir) (time frame: 2, 6 and 10 weeks after randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00640887, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2011.