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
  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:


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: 471
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:
  • LPV/RTV
  • Aluvia
  • Kaletra
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:
  • LPV/RTV
  • Aluvia
  • Kaletra
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:
  • 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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: June 5, 2014
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 July 28, 2014