Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in HIV

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01601626
First received: May 16, 2012
Last updated: June 5, 2014
Last verified: June 2014

May 16, 2012
June 5, 2014
April 2013
October 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01601626 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in HIV
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Tuberculosis
  • Drug: Lopinavir/Ritonavir
    Two LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry to Week 72.
    Other Names:
    • LPV/RTV
    • Aluvia
    • Kaletra
  • Drug: Lopinavir/Ritonavir
    Four LPV 200 mg/RTV 50 mg fixed-dose combination tablets orally twice daily from entry through Week 72.
    Other Names:
    • LPV/RTV
    • Aluvia
    • Kaletra
  • Drug: Raltegravir
    400 mg orally twice daily from entry to Week 72.
    Other Names:
    • RAL
    • Isentress
  • 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
  • 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: A: Standard-dose LPV/r-based+2 NRTIs w/RBT-based TB Treatment
    Interventions:
    • Drug: Lopinavir/Ritonavir
    • Drug: Isoniazid
    • Drug: Pyrazinamide
    • Drug: Ethambutol
    • Drug: Rifabutin
  • Active Comparator: B: Double-dose LPV/r + 2 NRTIs with RIF-based TB treatment
    Interventions:
    • Drug: Lopinavir/Ritonavir
    • Drug: Isoniazid
    • Drug: Pyridoxine
    • Drug: Pyrazinamide
    • Drug: Ethambutol
    • Drug: Rifampin
  • Experimental: C: Standard-Dose LPV/r+ 2NRTIs+RAL w/RBT-based TB treatment
    Interventions:
    • Drug: Lopinavir/Ritonavir
    • Drug: Raltegravir
    • Drug: Isoniazid
    • Drug: Pyridoxine
    • Drug: Pyrazinamide
    • Drug: Ethambutol
    • Drug: Rifabutin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
471
October 2015
October 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Brazil,   South Africa
 
NCT01601626
ACTG A5290, 1U01AI068636
Yes
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Constance A Benson, MD University of California, San Diego
Study Chair: Umesh Lalloo, MD, FRCP Nelson R. Mandela School of Medicine
AIDS Clinical Trials Group
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP