Overview

This trial is active, not recruiting.

Condition tuberculosis
Treatments rpt + inh once weekly for 3 months given by dot, isoniazid (inh) daily for 9 months
Phase phase 3
Sponsor Centers for Disease Control and Prevention
Collaborator Department of Veterans Affairs
Start date June 2001
End date October 2010
Trial size 8595 participants
Trial identifier NCT00023452, CDC TBTC Study 26, CDC-NCHSTP-3041

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose prevention
Arm
(Active Comparator)
Isoniazid (INH) daily for 9 months (240 to 270 total doses).
isoniazid (inh) daily for 9 months Isoniazid
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.
(Experimental)
Isoniazid / Rifapentine (RPT/INH) weekly for 3 months (11 to 12 total doses) given by Directly Observed Therapy (DOT)
rpt + inh once weekly for 3 months given by dot INH
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).

Primary Outcomes

Measure
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
time frame: Baseline up to Month 33

Secondary Outcomes

Measure
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy
time frame: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment
time frame: Baseline up to 33 Months
Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH
time frame: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
time frame: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])
Percentage of Participants With Death Due to Any Cause
time frame: Baseline up to Month 35
Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone
time frame: Baseline to Month 33
Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH
time frame: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Percentage of Participants Who Completed the Treatment Regimen
time frame: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment
time frame: Baseline up to Month 33
Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
time frame: Baseline up to Month 33
Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment
time frame: Baseline to Month 33
Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy
time frame: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)
Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
time frame: Baseline up to Month 33
Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
time frame: Baseline up to Month 33

Eligibility Criteria

Male or female participants at least 2 years old.

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

Additional Information

Official title TBTC Study 26: Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for 3 Months Versus Daily Isoniazid for 9 Months for the Treatment of Latent Tuberculosis Infection
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2012.
Information provided to ClinicalTrials.gov by Centers for Disease Control and Prevention.