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

Last updated: July 31, 2024
Sponsor: Centers for Disease Control and Prevention
Overall Status: Completed

Phase

3

Condition

Lung Disease

Hiv

Treatment

RPT + INH once weekly for 3 months given by DOT

Isoniazid (INH) daily for 9 months

Clinical Study ID

NCT00023452
CDC-NCHSTP-3041
CDC TBTC Study 26
  • Ages > 2
  • All Genders

Study 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

INCLUSION criteria:

  • Males or nonpregnant, non-nursing females > 2 years old.

  • Tuberculin (PPD) skin test reactors at high risk for developing TB but withoutevidence of active TB. High-risk reactors are defined as:

  1. Household and other close contacts of persons with culture-confirmed TB who areTST-positive as part of a contact investigation conducted within two years ofthe date of enrollment. Close contact is defined as > 4 hours in a sharedairspace during a one-week period. Among close contacts, a positive TST isdefined as > 5 mm induration after 5 TU of PPD placed intradermally using theMantoux technique.

  2. TST converters--converting from a documented negative to positive TST within atwo-year period. This is defined as persons with a tuberculin skin test of > 10mm within two years of a nonreactive test or persons with an increase of > 10mm 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 priorhistory of TB treatment, > 5 mm induration on TST, and 3 sputum culturesnegative for M. tuberculosis on final report.

  • HIV-seropositive close contacts of persons with culture-confirmed TB, regardless ofTST status. In addition, HIV-seropositive close contacts of persons withculture-confirmed TB who have a documented history of completing an adequate courseof treatment for active TB or latent TB infection, are also eligible.

  • Willing to provide signed informed consent, or parental consent and participantassent.

Exclusion

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 > 30consecutive days with INH during the previous 2 years.

  • A documented history of a completing an adequate course of treatment for active TBor 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 amongpersons in whom AST is determined

  • Pregnant or nursing females

  • Persons currently receiving or planning to receive HIV-1 protease inhibitors ornonnucleoside reverse transcriptase inhibitors in the first 90 days afterenrollment.

  • Weight < 10.0 kg

Study Design

Total Participants: 8053
Treatment Group(s): 2
Primary Treatment: RPT + INH once weekly for 3 months given by DOT
Phase: 3
Study Start date:
June 01, 2001
Estimated Completion Date:
September 30, 2013

Study 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.

Connect with a study center

  • Universidade Federal do Rio de Janeiro

    Rio de Janeiro, cep: 21941.590
    Brazil

    Site Not Available

  • University of British Columbia

    Vancouver, British Columbia Canada V5Z 4R4
    Canada

    Site Not Available

  • University of Manitoba

    Winnipeg, Manitoba CANADA R3A 1R8
    Canada

    Site Not Available

  • Montreal Chest Institute McGill University

    Montreal, Quebec H2X 2P4Pq Canada
    Canada

    Site Not Available

  • Agencia de Salut Publica

    Barcelona, 08023
    Spain

    Site Not Available

  • Central Arkansas Veterans Health System

    Little Rock, Arkansas 72205
    United States

    Site Not Available

  • LA County/USC Medical Center

    Los Angeles, California 90033
    United States

    Site Not Available

  • UCSD Medical Center

    San Diego, California 92103
    United States

    Site Not Available

  • University of California, San Francisco

    San Francisco, California 94110
    United States

    Site Not Available

  • Denver Department of Public Health and Hospitals

    Denver, Colorado 80204
    United States

    Site Not Available

  • Washington, D.C. VAMC

    Washington, District of Columbia 20422
    United States

    Site Not Available

  • Emory University, Department of Medicine

    Atlanta, Georgia 30303
    United States

    Site Not Available

  • Chicago VA Medical Center (Lakeside)

    Chicago, Illinois 60611
    United States

    Site Not Available

  • Hines VA Medical Center

    Hines, Illinois 60141
    United States

    Site Not Available

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland 21287-0003
    United States

    Site Not Available

  • Boston Medical Center

    Boston, Massachusetts 02118
    United States

    Site Not Available

  • New Jersey Medical School

    Newark, New Jersey 07107-3001
    United States

    Site Not Available

  • Columbia University/Presbyterian Medical Center

    New York, New York 10032
    United States

    Site Not Available

  • Harlem Hospital Center

    New York, New York 10037
    United States

    Site Not Available

  • Carolinas Medical Center

    Charlotte, North Carolina 28203
    United States

    Site Not Available

  • Duke University Medical Center

    Durham, North Carolina 34222
    United States

    Site Not Available

  • Vanderbilt University Medical Center

    Nashville, Tennessee 37232
    United States

    Site Not Available

  • University of North Texas Health Science Center

    Fort Worth, Texas 76107-2699
    United States

    Site Not Available

  • Michael Debakey Veterans Affairs Medical Center

    Houston, Texas 77009
    United States

    Site Not Available

  • Audi L. Murphy VA Hospital

    San Antonio, Texas 78284
    United States

    Site Not Available

  • Seattle King County Health Department

    Seattle, Washington 98104
    United States

    Site Not Available

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