The PRIMARY objective of this open-label Phase III clinical trial is to compare the effectiveness 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). The 3RPT/INH regimen will be given under direct observation and the 9INH regimen will be self-administered.~SECONDARY Objectives:~Compare the rates of drug discontinuation due to adverse drug reactions associated with 3RPT/INH and 9INH.~Compare the rates of drug discontinuation for any reason associated with 3RPT/INH and 9INH.~Compare the rates of any grade 3, 4, or 5 drug toxicity associated with 3RPT/INH and 9INH.~Compare treatment completion rates of 3RPT/INH and 9INH. Compare the efficacy (i.e., among persons who complete study-phase therapy) of 3RPT/INH and 9INH.~Compare the effectiveness and tolerability of 3RPT/INH and 9INH in HIV-infected persons.~Compare the effectiveness and tolerability of 3RPT/INH and 9INH in children < 18 years old.~Compare the rates of methadone withdrawal associated with 3RPT/INH and 9INH among persons concomitantly receiving methadone.~Describe patterns of antibiotic resistance among M. tuberculosis isolates in patients who develop TB despite treatment of latent infection.~Amendment of the study protocol to allow extension of enrollment to children < 12 years old and HIV-infected persons:~For assessment of the primary outcome, development of TB, a sample size of approximately 4,000 persons per arm will be required. To assess tolerability (one of the secondary outcomes) in sub-groups, children less than 12 years old and HIV-infected persons, a sample size of 644 per strata will be required. A sample size of 8,053 patients for the primary outcome was reached on February 15, 2008 (with expected follow-up completion time in 2010), leaving approximately 454 additional young children and 200 HIV-infected persons to be enrolled to achieve the targets of 644 for each group. The additional data on tolerability in those sub-groups will available for analysis in 2013.
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).