Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in HIV
Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infection; Tuberculosis
Intervention: Lopinavir/Ritonavir (Drug); Lopinavir/Ritonavir (Drug); Raltegravir (Drug); Isoniazid (Drug); Pyridoxine (Drug); Pyrazinamide (Drug); Ethambutol (Drug); Rifabutin (Drug); Rifampin (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: AIDS Clinical Trials Group Official(s) and/or principal investigator(s): Constance A Benson, MD, Study Chair, Affiliation: University of California, San Diego Umesh Lalloo, MD, FRCP, Study Chair, Affiliation: Nelson R. Mandela School of Medicine
Summary
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percent of participants whose HIV viral load was less than 400 copies/mL (Arm B vs Arm A and Arm B vs Arm C)
Secondary outcome: Percent of participants who experienced mycobacterial culture conversion (Arm B vs Arm A and Arm B vs Arm C)Percent of participants who experienced TB treatment failure (Arm B vs Arm A and Arm B vs Arm C) Percent of participants who experienced TB relapse/recurrence (Arm B vs Arm A and Arm B vs Arm C) Percent of participants whose HIV viral load was less than 50 copies/mL (Arm B vs Arm A and Arm B vs Arm C) Percent of participants whose HIV viral load was less than 400 copies/mL (Arm A vs Arm C) Percent of participants whose HIV viral load was less than 50 copies/mL (Arm A vs Arm C) Percent of participants reporting a grade 3 or 4 adverse event or laboratory abnormality recurrence Percent of participants who interrupted or discontinued at least one HIV drug due to toxicity Percent of participants who interrupted or discontinued at least one TB drug due to toxicity Percent of participants who experienced HIV virologic failure Percent of participants who experienced TB IRIS CD4 count change from randomization Percent of participants who experienced a new AIDS-defining illness Percent of participants who experienced death Percent of participants who experienced a new AIDS-defining illness or death Time to HIV virologic failure
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Instituto de Pesquisa Clinica Evandro Chagas (12101), Rio de Janeiro 21045, Brazil; Recruiting Sandra W. Cardoso, Phone: 552-125-644933, Email: sandra.wagner@bol.com.br Beatriz Grinsztejn, MD, PhD, Principal Investigator
Wits HIV CRS (11101), Johannesburg, Gauteng, South Africa; Recruiting Paulina Vunandlala, Phone: 27-11-2768800, Email: pvunandlala@witshealth.co.za Prudence Ive, FCP, Principal Investigator
Additional Information
Starting date: April 2013
Last updated: August 5, 2015
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