Clinical Trials

MainTitle

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

This study has been completed
Sponsor
AIDS Clinical Trials Group

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier
NCT01601626

First received: May 16, 2012
Last updated: December 11, 2017
Last Verified: December 2017
History of Changes
Purpose

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
Intervention Model: Parallel Assignment
Masking: None (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

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 ]
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 ]
  • 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 ]
  • Percent of participants who experienced TB relapse/recurrence (Arm B vs Arm A and Arm B vs Arm C) [ Time Frame: Through 72 weeks ]
  • 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 ]
  • Percent of participants whose HIV viral load was less than 400 copies/mL (Arm A vs Arm C) [ Time Frame: 48 weeks ]
  • Percent of participants whose HIV viral load was less than 50 copies/mL (Arm A vs Arm C) [ Time Frame: 48 weeks ]
  • Percent of participants reporting a grade 3 or 4 adverse event or laboratory abnormality [ Time Frame: Through 72 weeks ]
  • Percent of participants who interrupted or discontinued at least one HIV drug due to toxicity [ Time Frame: Through week 72 ]
  • Percent of participants who interrupted or discontinued at least one TB drug due to toxicity [ Time Frame: Through week 72 ]
  • Percent of participants who experienced HIV virologic failure [ Time Frame: Through week 72 ]
  • Percent of participants who experienced TB IRIS [ Time Frame: Through week 72 ]
  • CD4 count change from randomization [ Time Frame: Through week 72 ]
  • Percent of participants who experienced a new AIDS-defining illness [ Time Frame: Through week 72 ]
  • Percent of participants who experienced death [ Time Frame: Through week 72 ]
  • Percent of participants who experienced a new AIDS-defining illness or death [ Time Frame: Through week 72 ]
  • Time to HIV virologic failure [ Time Frame: Through week 72 ]

Enrollment: 71
Study Start Date: April 2013
Study Completion Date: June 28, 2017
Primary Completion Date: January 19, 2017 (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 Name:
  • 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 Name:
  • 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 Name:
  • LPV/RTV
  • Aluvia
  • Kaletra

Drug: Raltegravir

400 mg orally twice daily from entry to Week 72.

Other Name:
  • 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

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
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

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
Hospital Nossa Senhora da Conceicao CRS (12201)
Porto Alegre, RS, Brazil, 9043010
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, Brazil, 21045
Haiti
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS (31730)
Port Au Prince, Haiti
Les Centres GHESKIO CRS (30022)
Port-au-Prince, Haiti, HT-6110
Kenya
Moi University Clinical Research Center CRS (12601)
Eldoret, Kenya, 30100
Peru
Investigaciones Medicas en Salud (INMENSA) (11302)
San Isidro, Lima, Peru
Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301)
Lima, Peru, 18 PE
South Africa
Wits HIV CRS (11101)
Johannesburg, Gauteng, South Africa
Durban Adult HIV CRS (11201)
Durban, South Africa, 4013 SF

Sponsors and Collaborators

AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)

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

More Information


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 11, 2017  

Additional relevant MeSH terms:
HIV Infections
Tuberculosis
Ritonavir
Lopinavir
Raltegravir Potassium
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Rifabutin
Pyridoxine

ClinicalTrials.gov processed this data on December 18, 2017
This information is provided by ClinicalTrials.gov.