Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in HIV
This study is not yet open for participant recruitment.
Verified December 2012 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: December 4, 2012
Last verified: December 2012
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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: | March 2013 |
| Estimated Study Completion Date: | August 2015 |
| Estimated Primary Completion Date: | March 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 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: | December 4, 2012 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Tuberculosis 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 Anti-Infective Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013