Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection
Condition: Tuberculosis
MeSH terms: Infections; Tuberculosis; Latent Tuberculosis
Intervention: RPT + INH once weekly for 3 months given by DOT; Isoniazid (INH) daily for 9 months
Intervention description: Rifapentine (RPT) 900 mg once-weekly x 12 doses (3 months) for persons > 50.0 kg. For persons < 50.0 kg, the following doses will be given (Weight/Dose): 10.0-14.0 kg / 300 mg; 14.1-25.0 kg / 450 mg; 25.1-32.0 kg / 600 mg; 32.1-50.0 kg / 750 mg.
PLUS
Isoniazid (INH) 15 mg/kg (rounded up to nearest 50 or 100 mg; 900 mg max) once weekly x 12 doses if > 12 years old. INH 25 mg/kg (round up to nearest 50 or 100 mg; 900 mg max) if 2-11 years old.
Therapy will be given by Directly Observed Therapy (DOT).; Isoniazid (INH) 5 mg/kg (rounded up to nearest 50 or 100 mg; 300 mg max) daily x 270 doses (9 months) For children age 2 - 11, INH 10-15 mg/kg (round up to nearest 50 or 100 mg; 300 mg max) will be given.
Intervention MeSH terms: Isoniazid; Rifapentine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8053.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Latent TB infection

Summary:

      Open-label, multi-center, Phase III clinical trial to compare the effectiveness and
      tolerability of a three-month (12-dose) regimen of weekly rifapentine and isoniazid
      (3RPT/INH) to the effectiveness of a nine-month (270-dose)regimen of daily isoniazid (9INH)
      to prevent tuberculosis (TB) among high-risk tuberculin skin-test reactors, including
      children and HIV-infected persons, who require treatment of latent TB infection (LTBI).
    

Eligibility criteria:

        INCLUSION criteria:

          -  Males or nonpregnant, non-nursing females > 2 years old.

          -  Tuberculin (PPD) skin test reactors at high risk for developing TB but without
             evidence of active TB. High-risk reactors are defined as:

               1. Household and other close contacts of persons with culture-confirmed TB who are
                  TST-positive as part of a contact investigation conducted within two years of the
                  date of enrollment. Close contact is defined as > 4 hours in a shared airspace
                  during a one-week period. Among close contacts, a positive TST is defined as > 5
                  mm induration after 5 TU of PPD placed intradermally using the Mantoux technique.

               2. TST converters--converting from a documented negative to positive TST within a
                  two-year period. This is defined as persons with a tuberculin skin test of > 10
                  mm within two years of a nonreactive test or persons with an increase of > 10 mm
                  within a two-year period.

               3. HIV-seropositive, TST positive (> 5 mm induration) persons.

               4. Persons with > 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray, no prior
                  history of TB treatment, > 5 mm induration on TST, and 3 sputum cultures negative
                  for M. tuberculosis on final report.

          -  HIV-seropositive close contacts of persons with culture-confirmed TB, regardless of
             TST status. In addition, HIV-seropositive close contacts of persons with
             culture-confirmed TB who have a documented history of completing an adequate course of
             treatment for active TB or latent TB infection, are also eligible.

          -  Willing to provide signed informed consent, or parental consent and participant
             assent.

        EXCLUSION criteria:

          -  Current confirmed culture-positive or clinical TB

          -  Suspected TB (as defined by the site investigator)

          -  Tuberculosis resistant to isoniazid or rifampin in the source case

          -  A history of treatment for > 14 consecutive days with a rifamycin or > 30 consecutive
             days with INH during the previous 2 years.

          -  A documented history of a completing an adequate course of treatment for active TB or
             latent TB infection in a person who is HIV-seronegative.

          -  History of sensitivity/intolerance to isoniazid or rifamycins

          -  Serum aminotransferase aspartate (AST, SGOT) > 5x upper limit of normal among persons
             in whom AST is determined

          -  Pregnant or nursing females

          -  Persons currently receiving or planning to receive HIV-1 protease inhibitors or
             nonnucleoside reverse transcriptase inhibitors in the first 90 days after enrollment.

          -  Weight < 10.0 kg