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

Information source: Centers for Disease Control and Prevention
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Tuberculosis

Intervention: RPT + INH once weekly for 3 months given by DOT (Drug); Isoniazid (INH) daily for 9 months (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Centers for Disease Control and Prevention

Official(s) and/or principal investigator(s):
Elsa M Villarino, MD, MPH, Study Director, Affiliation: Centers for Disease Control and Prevention
Timothy Sterling, MD, Study Chair, Affiliation: Vanderbilt University

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).

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: 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

Secondary outcome:

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

Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment

Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH

Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH

Percentage of Participants With Death Due to Any Cause

Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone

Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH

Percentage of Participants Who Completed the Treatment Regimen

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

Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment

Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment

Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy

Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment

Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment

Detailed 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.

Eligibility

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Universidade Federal do Rio de Janeiro, Rio de Janeiro cep: 21941.590, Brazil

Agencia de Salut Publica, Barcelona 08023, Spain

Central Arkansas Veterans Health System, Little Rock, Arkansas 72205, United States

University of British Columbia, Vancouver, British Columbia Canada V5Z 4R4, Canada

LA County/USC Medical Center, Los Angeles, California 90033, United States

UCSD Medical Center, San Diego, California 92103, United States

University of California, San Francisco, San Francisco, California 94110, United States

Denver Department of Public Health and Hospitals, Denver, Colorado 80204, United States

Washington, D.C. VAMC, Washington, District of Columbia 20422, United States

Emory University, Department of Medicine, Atlanta, Georgia 30303, United States

Chicago VA Medical Center (Lakeside), Chicago, Illinois 60611, United States

Hines VA Medical Center, Hines, Illinois 60141, United States

University of Manitoba, Winnipeg, Manitoba CANADA R3A 1R8, Canada

Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0003, United States

Boston Medical Center, Boston, Massachusetts 02118, United States

New Jersey Medical School, Newark, New Jersey 07107-3001, United States

Columbia University/Presbyterian Medical Center, New York, New York 10032, United States

Harlem Hospital Center, New York, New York 10037, United States

Carolinas Medical Center, Charlotte, North Carolina 28203, United States

Duke University Medical Center, Durham, North Carolina 34222, United States

Montreal Chest Institute McGill University, Montreal, Quebec H2X 2P4Pq Canada, Canada

Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States

University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, United States

Michael Debakey Veterans Affairs Medical Center, Houston, Texas 77009, United States

Audi L. Murphy VA Hospital, San Antonio, Texas 78284, United States

Seattle King County Health Department, Seattle, Washington 98104, United States

Additional Information

(Click here for more information about the Tuberculosis Trials Consortium(TBTC)

Starting date: June 2001
Last updated: July 30, 2015

Page last updated: August 23, 2015

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