Phase 3
Completed N=3,000
Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
Source: ClinicalTrials.gov NCT01404312 ↗Enrolled (actual)
3,000
Serious AEs
3.6%
Results posted
Dec 2018
Primary outcomePrimary: Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause — 0.6506; 0.6736 Events per 100 person-years
◆ Published Evidence
Highly cited
371citations · ~53 / year
One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis.
Summary
HIV-infected people have an increased risk of developing active tuberculosis (TB). At the time the study was designed, the standard course of treatment for TB was 6 to 9 months of isoniazid (INH).This study compared the safety and effectiveness of a 4-week regimen of rifapentine (RPT) plus INH versus a standard 9-month regimen of INH in HIV-infected people who are at risk of developing active TB.
Linked Publications (5)
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One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis.
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Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention.
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Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine.
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Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials.
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Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause |
0.6506; 0.6736 | — |
| SECONDARY Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs |
1405; 1390; 83; 108 | 0.073 |
| SECONDARY Number of Participants With a Targeted Adverse Event |
1445; 1446; 43; 52 | 0.405 |
| SECONDARY 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 |
16; 25; 11; 31; 1461; 1442 | — |
| SECONDARY Cumulative Incidence of Death From Any Cause |
0.35; 0.63; 0.49; 1.15; 1.05; 1.62 | 0.3078 |
| SECONDARY Cumulative Incidence of Death Due to a Non-TB Event |
0.3; 0.5; 0.4; 1.0; 0.9; 1.5 | 0.2802 |
| SECONDARY Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis |
1; 1; 14; 11; 2; 1 | — |
| SECONDARY Efavirenz (EFV) Plasma Concentrations in Arm A |
3787; 3870; 4082 | — |
| SECONDARY Nevirapine (NVP) Plasma Concentrations in Arm A |
7573; 6234; 5797 | — |
| SECONDARY EFV Plasma Concentrations in Arm B |
— | — |
Eligibility 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:
- Absolute neutrophil count (ANC) greater than 750 cells/mm^3
- Hemoglobin greater than or equal to 7.4 g/dL
- Platelet count greater than or equal to 50,000/mm^3
- AST (SGOT) and ALT (SGPT) less than or equal to three times the upper limit of normal (ULN)
- 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
Data sourced from ClinicalTrials.gov (NCT01404312) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.