Phase 3
N=8,053
Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection
Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT00023452 ↗Enrolled (actual)
8,053
Serious AEs
2.1%
Results posted
Sep 2012
Primary outcome: Primary: 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 — 0.43; 0.19 TB cases per 100 participants w/followup
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- RPT + INH once weekly for 3 months given by DOT (Drug); Isoniazid (INH) daily for 9 months (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Centers for Disease Control and Prevention
- Primary completion
- Oct 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0.43; 0.19 | — |
| SECONDARY 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 |
0.37; 0.16 | — |
| SECONDARY Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment |
0.49; 0.24 | — |
| SECONDARY Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH |
3.8; 4.9 | 0.02 sig |
| SECONDARY Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH |
2.2; 2.7; 0.4; 0.4 | 0.24 |
| SECONDARY Percentage of Participants With Death Due to Any Cause |
1.0; 0.8 | 0.22 |
| SECONDARY Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone |
14; 15 | — |
| SECONDARY Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH |
31.0; 17.9 | <0.001 sig |
| SECONDARY Percentage of Participants Who Completed the Treatment Regimen |
69.0; 82.1 | <0.0001 sig |
| SECONDARY 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 |
0.11; 0.05 | — |
| SECONDARY Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment |
15; 0; 0; 14 | — |
| SECONDARY Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment |
3.5; 1.01 | — |
| SECONDARY Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy |
3.12; 1.07 | — |
| SECONDARY Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment |
0.74; 0.00 | — |
| SECONDARY Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment |
1.35; 0.00 | — |
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:
- 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.
- 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.
- HIV-seropositive, TST positive (> 5 mm induration) persons.
- 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
Data sourced from ClinicalTrials.gov (NCT00023452). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.