Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection

• Status: Completed
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centers for Disease Control and Prevention
• Collaborator: VA Office of Research and Development
• Treatments: Isoniazid; Rifampin; Rifapentine

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