Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
Condition: Tuberculosis; HIV Infections
MeSH terms: Infections; Tuberculosis
Intervention: Rifapentine (RPT); Isoniazid (INH); Pyridoxine (Vitamin B6)
Intervention description: RPT dosing was be based on participants' weight:
Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets).
Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets).
Participants who weighed greater than 45 kg received 600 mg once daily (administered as four 150-mg tablets).; Participants received one 300-mg tablet or three 100-mg tablets of INH once daily.; Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines.
Participants who received 25 mg of pyridoxine took one 25-mg tablet once daily with INH.
Participants who received 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Intervention MeSH terms: Pyridoxine; Pyridoxal; Vitamin B 6; Isoniazid; Rifapentine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3000.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

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.
    

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:

               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