Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)

• Register: ClinicalTrials.gov
• Last refreshed on: 15 November 2021
• Main ID: NCT01404312
• Date of registration: 26/07/2011
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
• Scientific title: Phase III Clinical Trial of Ultra-Short-Course Rifapentine/Isoniazid for the Prevention of Active Tuberculosis in HIV-Infected Individuals With Latent Tuberculosis Infection
• Date of first enrolment: May 23, 2012
• Target sample size: 3000
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01404312
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Botswana, Brazil, Haiti, India, Kenya, Malawi, Peru, Puerto Rico, South Africa, Tanzania, Thailand, Uganda, United States, Zambia, Zimbabwe

Contacts

• Name: Richard E. Chaisson, MD
• Affiliation: Johns Hopkins University

• Name: Susan Swindells, MBBS
• Affiliation: University of Nebraska

Key inclusion & exclusion criteria

Inclusion Criteria:

- HIV-1 infection

- Tuberculin skin test (TST) reactivity greater than or equal to 5 mm or a positive
interferon gamma release assay (IGRA) at any time prior to study entry, OR living in a
high TB burden area. More information on this criterion can be found in the protocol.

- Laboratory values obtained within 30 days prior to study entry:

1. Absolute neutrophil count (ANC) greater than 750 cells/mm^3

2. Hemoglobin greater than or equal to 7.4 g/dL

3. Platelet count greater than or equal to 50,000/mm^3

4. AST (SGOT) and ALT (SGPT) less than or equal to three times the upper limit of
normal (ULN)

5. Total bilirubin less than or equal to 2.5 times the ULN

- Chest radiograph or chest CT scan without evidence of active tuberculosis, unless one
has been performed within 30 days prior to entry

- Female participants of reproductive potential must have a negative serum or urine
pregnancy test performed within 7 days prior to study entry. More information on this
criterion can be found in the protocol.

- All participants must agree not to participate in a conception process (e.g., active
attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization)
while receiving RPT and for 6 weeks after stopping this drug

- Female participants who are participating in sexual activity that could lead to
pregnancy must agree to use one reliable non-hormonal form of contraceptive while
receiving RPT and for 6 weeks after stopping this drug. More information on this
criterion can be found in the protocol.

- Weight of greater than or equal to 30 kg

- Participant or legal guardian is able and willing to provide informed consent

Exclusion Criteria:

- Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior
to study entry or, at screening, presence of any confirmed or probable TB based on
criteria listed in the current ACTG Diagnosis Appendix

- History of multi-drug resistant (MDR) or extensively-drug resistant (XDR) TB at any
time prior to study entry

- Known exposure to MDR or XDR TB (e.g., household member of a person with MDR or XDR
TB) at any time prior to study entry

- Treatment for more than 14 consecutive days with a rifamycin or more than 30
consecutive days with INH at any time during the 2 years prior to enrollment

- For participants taking antiretroviral therapy (ART) at study entry, only approved
nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) or nevirapine
(NVP) for at least 4 weeks were permitted

- History of liver cirrhosis at any time prior to study entry.

- Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or
light stools within 90 days prior to study entry

- Diagnosis of porphyria at any time prior to study entry

- Peripheral neuropathy greater than or equal to Grade 2 according to the December 2004
(Clarification, August 2009) Division of AIDS (DAIDS) Toxicity Table, within 90 days
prior to study entry

- Known allergy/sensitivity or any hypersensitivity to components of study drugs or
their formulation

- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements

- Serious illness requiring systemic treatment and/or hospitalization within 30 days
prior to study entry

- Breastfeeding



Age minimum: 13 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Tuberculosis

Intervention(s)

Drug: Isoniazid (INH)

Dietary Supplement: Pyridoxine (Vitamin B6)

Drug: Rifapentine (RPT)

Primary Outcome(s)

Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause [Time Frame: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

Secondary Outcome(s)

Cumulative Incidence of Death Due to a Non-TB Event [Time Frame: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

EFV Plasma Concentrations in Arm B [Time Frame: Measured at weeks 0, 2 and 4]

Number of Participants in Each Category of Ordered Categorical Variable Indicating Most Stringent Level of Study Drug Management Due to Toxicity That Was Required Over the Treatment Period [Time Frame: From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)]

Number of Participants With a Targeted Adverse Event [Time Frame: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

Cumulative Incidence of Death From Any Cause [Time Frame: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

Nevirapine (NVP) Plasma Concentrations in Arm A [Time Frame: Measured at Weeks 0, 2, and 4]

Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs [Time Frame: From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

Efavirenz (EFV) Plasma Concentrations in Arm A [Time Frame: Measured at Weeks 0, 2, 4, and 16]

Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis [Time Frame: After TB diagnosis]

Secondary ID(s)

A5279

ACTG A5279

10848

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/12/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01404312