Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in HIV
This study is currently recruiting participants.
Verified May 2013 by AIDS Clinical Trials Group
Sponsor:
AIDS Clinical Trials Group
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01601626
First received: May 16, 2012
Last updated: May 29, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
There is a rapidly-growing need to identify evidence-based, safe, and effective co-treatment regimens for HIV-related tuberculosis (TB) among patients who require protease inhibitor-based antiretroviral therapy. This study will compare three alternative co-treatment options among participants in high TB endemic resource-constrained settings, in which one co-treatment option explores if an additional anti-HIV drug needs to be used when patients are being treated with a protease inhibitor together with rifabutin-based anti-TB treatment.
Accrual will take place in two accrual periods. Accrual period 1 will enroll 60 participants who will undergo an initial dose-finding period before continuing regular study follow-up. Once the review of the dose-finding pharmacokinetic and safety data from accrual period 1 participants is completed, accrual period 2 will begin.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infection Tuberculosis |
Drug: Lopinavir/Ritonavir Drug: Raltegravir Drug: Isoniazid Drug: Pyridoxine Drug: Pyrazinamide Drug: Ethambutol Drug: Rifabutin Drug: Rifampin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized, Phase 2b Study of a Double-Dose Lopinavir/Ritonavir-Based Antiretroviral Regimen With Rifampin-Based Tuberculosis Treatment Versus a Standard-Dose Lopinavir/Ritonavir-Based Antiretroviral Regimen With Rifabutin-Based Tuberculosis Treatment With or Without Raltegravir in HIV-1-Infected Persons Requiring Treatment for Active TB and HIV |
Resource links provided by NLM:
Genetics Home Reference related topics:
complement factor I deficiency
Drug Information available for:
Isoniazid
Pyridoxine hydrochloride
Pyridoxine
Ethambutol
Pyrazinamide
Ethambutol hydrochloride
Rifampin
Rifabutin
Ritonavir
Lopinavir
Raltegravir
Raltegravir potassium
U.S. FDA Resources
Further study details as provided by AIDS Clinical Trials Group:
Primary Outcome Measures:
- Percent of participants whose HIV viral load was less than 400 copies/mL (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Percent of participants who experienced mycobacterial culture conversion (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
- Percent of participants who experienced TB treatment failure (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: At or after 24 weeks ] [ Designated as safety issue: No ]
- Percent of participants who experienced TB relapse/recurrence (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: Through 72 weeks ] [ Designated as safety issue: No ]
- Percent of participants whose HIV viral load was less than 50 copies/mL (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Percent of participants whose HIV viral load was less than 400 copies/mL (Arm A vs Arm C) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Percent of participants whose HIV viral load was less than 50 copies/mL (Arm A vs Arm C) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- Percent of participants reporting a grade 3 or 4 adverse event or laboratory abnormality recurrence [ Time Frame: Through 72 weeks ] [ Designated as safety issue: Yes ]
- Percent of participants who interrupted or discontinued at least one HIV drug due to toxicity [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- Percent of participants who interrupted or discontinued at least one TB drug due to toxicity [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- Percent of participants who experienced HIV virologic failure [ Time Frame: Through week 72 ] [ Designated as safety issue: No ]
- Percent of participants who experienced TB IRIS [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- CD4 count change from randomization [ Time Frame: Through week 72 ] [ Designated as safety issue: No ]
- Percent of participants who experienced a new AIDS-defining illness [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- Percent of participants who experienced death [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- Percent of participants who experienced a new AIDS-defining illness or death [ Time Frame: Through week 72 ] [ Designated as safety issue: Yes ]
- Time to HIV virologic failure [ Time Frame: Through week 72 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 426 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | October 2015 |
| Estimated Primary Completion Date: | October 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: A: Standard-dose LPV/r-based+2 NRTIs w/RBT-based TB Treatment |
Drug: Lopinavir/Ritonavir
Two LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry to Week 72.
Other Names:
Drug: Isoniazid
300 mg orally once daily from entry through Week 24.
Other Name: INH
Drug: Pyrazinamide
20 to 30 mg/kg orally once daily (not to exceed 2 g per day) from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: PZA
Drug: Ethambutol
15 to 20 mg/kg orally once daily from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: EMB
Drug: Rifabutin
300 mg of rifabutin orally once until LPV/RTV is started; then the dose will be reduced to 150 mg daily from the start of LPV/RTV through Week 24.
Other Name: RBT
|
| Active Comparator: B: Double-dose LPV/r + 2 NRTIs with RIF-based TB treatment |
Drug: Lopinavir/Ritonavir
Four LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry through Week 72.
Other Names:
Drug: Isoniazid
300 mg orally once daily from entry through Week 24.
Other Name: INH
Drug: Pyridoxine
25 mg orally once daily from entry to Week 24.
Drug: Pyrazinamide
20 to 30 mg/kg orally once daily (not to exceed 2 g per day) from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: PZA
Drug: Ethambutol
15 to 20 mg/kg orally once daily from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: EMB
Drug: Rifampin
Weight-based dose; for weight < 45 kg: 450 mg orally once daily; for weight > 45 kg: 600 mg orally once daily, from entry to week 24.
Other Name: RIF
|
| Experimental: C: Standard-Dose LPV/r+ 2NRTIs+RAL w/RBT-based TB treatment |
Drug: Lopinavir/Ritonavir
Two LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry to Week 72.
Other Names:
Drug: Raltegravir
400 mg orally twice daily from entry to Week 72.
Other Names:
Drug: Isoniazid
300 mg orally once daily from entry through Week 24.
Other Name: INH
Drug: Pyridoxine
25 mg orally once daily from entry to Week 24.
Drug: Pyrazinamide
20 to 30 mg/kg orally once daily (not to exceed 2 g per day) from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: PZA
Drug: Ethambutol
15 to 20 mg/kg orally once daily from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).
Other Name: EMB
Drug: Rifabutin
300 mg of rifabutin orally once until LPV/RTV is started; then the dose will be reduced to 150 mg daily from the start of LPV/RTV through Week 24.
Other Name: RBT
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- HIV-1 infection
- CD4+/CD8+ T-cell count obtained within 30 days prior to study entry
- Confirmed or probable pulmonary or extrapulmonary TB (more information on the criterion can be found in the protocol)
- Chest x-ray within 30 days prior to study entry.
- A PI-based antiretroviral (ART) regimen is required, as determined by the participant's primary clinician/clinical facility.
- Certain laboratory values obtained within 14 days prior to study entry (more information on the criterion can be found in the protocol)
- For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry and 72 hours of starting study medications.
- Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs.
- Karnofsky performance score > 40 within 14 days prior to study entry, and likelihood of survival, in the opinion of the site investigator, for at least 6 months.
- Ability to swallow oral medications.
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
Exclusion Criteria:
- History of completed TB treatment and resolution of TB symptoms less than 1 year prior to the current TB episode at study entry, or incomplete treatment for a prior episode of TB (i.e., defaulted past TB treatment) at any time prior to the current TB episode.
- Documented multidrug-resistant tuberculosis (MDR TB) or extensively drug-resistant (XDR) TB.
- Participants infected with a rifamycin resistant strain of TB (more information on the criterion can be found in the protocol).
- Receipt of more than 28 cumulative days of anti-TB treatment for the current TB episode prior to study entry.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Active illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry, or that in the opinion of the site investigator, might otherwise interfere with adherence to study requirements.
- Pregnant or breastfeeding.
- Anticipated receipt of prohibited medications (more information on the criterion can be found in the protocol).
- Known intolerance/allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations.
- History of close contact with known MDR or XDR TB patients at any time prior to study entry.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01601626
Locations
| Brazil | |
| Instituto de Pesquisa Clinica Evandro Chagas (12101) | Recruiting |
| Rio de Janeiro, Brazil, 21045 | |
| Contact: Sandra W. Cardoso 552-125-644933 sandra.wagner@bol.com.br | |
| Principal Investigator: Beatriz Grinsztejn, MD, PhD | |
| South Africa | |
| Wits HIV CRS (11101) | Recruiting |
| Johannesburg, Gauteng, South Africa | |
| Contact: Paulina Vunandlala 27-11-2768800 pvunandlala@witshealth.co.za | |
| Principal Investigator: Prudence Ive, FCP | |
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
| Study Chair: | Constance A Benson, MD | University of California, San Diego |
| Study Chair: | Umesh Lalloo, MD, FRCP | Nelson R. Mandela School of Medicine |
More Information
No publications provided
| Responsible Party: | AIDS Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT01601626 History of Changes |
| Other Study ID Numbers: | ACTG A5290, 1U01AI068636 |
| Study First Received: | May 16, 2012 |
| Last Updated: | May 29, 2013 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis HIV Protease Inhibitors Anti-HIV Agents Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Mycobacterium Infections |
Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Ethambutol Isoniazid Pyrazinamide Rifampin Rifabutin Lopinavir Ritonavir Pyridoxine Vitamin B 6 Pyridoxal Antitubercular Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on June 17, 2013