Assessment of the Safety, Tolerability, and Effectiveness of Rifapentine Given Daily for LTBI

Last updated: September 25, 2024
Sponsor: Centers for Disease Control and Prevention
Overall Status: Active - Recruiting

Phase

2/3

Condition

Lung Disease

Hiv

Treatment

Rifapentine daily for 6 weeks

Rifampin and Isoniazid daily for 12 weeks

Rifampin daily for 16 weeks

Clinical Study ID

NCT03474029
CDC-NCHSTP-7024
  • Ages > 12
  • All Genders

Study Summary

This study is conducted to compare the safety and effectiveness of a novel short 6-week regimen of daily rifapentine (6wP, experimental arm) with a comparator arm of 12-16 weeks of rifamycin-based treatment (standard of care, control arm) of latent M. tuberculosis infection (LTBI).

This trial is conducted among persons who are at increased risk of progression to tuberculosis (TB) and require treatment of LTBI. The study will be conducted in low, medium and high TB incidence settings that have treatment of LTBI as their standard of care and offer 12-16 week rifamycin-based therapy as standard of care.

The hypothesis of this study is that the safety and effectiveness of the experimental treatment (6wP arm) is non-inferior to a comparator arm of 12-16 weeks of rifamycin-based treatment of LTBI (control arm).

Participants are enrolled and randomly assigned to one of the two study arms: experimental 6wP or control. The comparator (control) arm's treatment regimens include 12 weeks of once-weekly isoniazid (INH) and rifapentine (3HP), 12 weeks of daily INH and rifampin (3HR), and 16 weeks of daily rifampin (4R). A total of 560 participants per arm (1,120 total) for the evaluation of safety and 1,700 participants per arm (3,400 total) for the evaluation of effectiveness will be enrolled, given treatment as per randomization assignment, and followed for 24 months from the date of enrollment.

After completion of data collection, statistical analyses will be conducted to compare proportions of drug discontinuation due to adverse drug reaction (ADR) and proportions of newly diagnosed tuberculosis between 6wP and control arm.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females > 12 years old. Women ofchild-bearing potential who are not surgically sterilized must agree to practice anadequate method of contraception (barrier method or non-hormonal intrauterinedevice) or abstain from heterosexual intercourse during study drug treatment.

  • Persons with LTBI who do not have evidence of TB disease and are at increased riskof progression to TB. M. tuberculosis infection may be demonstrated by either apositive tuberculin skin test (TST) or a positive interferon gamma release assay (IGRA; e.g., QuantiFERON or T.SPOT.TB). Persons with LTBI at increased risk ofprogression to TB are those with one of the following:

  1. Household and other close contacts (> 4 hours of exposure in a one week period)within 2 years prior to enrollment, of persons with culture-confirmed TB Apositive nucleic acid amplification test (NAAT)/GeneXpert in the source casemay be used for enrollment prior to culture confirmation

  2. Recent M. tuberculosis infection, defined as converting from a documentednegative to positive TST or IGRA within 2 years prior to enrollment. Personswithout known close contact to someone with active pulmonary TB who have aconversion by IGRA may require additional evaluation to rule out a falseconversion.

  3. HIV co-infection (with CD4+ T-lymphocyte count > 100 cells/mm3).

  4. ≥ 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray and no prior historyof treatment for TB or LTBI.

  5. Recent (within 3 years prior to enrollment) immigration to the United States orother country with low to moderate TB incidence, with abnormal chest X-ray, andno evidence of active TB.

  6. Recent (within 2 years prior to enrollment) immigration to the United States orother country with low to moderate TB incidence, from a country with anestimated incidence rate of TB > 150 per 100,000

  7. An increased risk of TB due to medical conditions such as end-stage renaldisease, or due to use of immunosuppressive medications such as chronicsteroids or TNF-alpha inhibitors.

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

Exclusion

Exclusion Criteria:

  • Current confirmed culture-positive or clinical TB.

  • Suspected current TB. Includes cases in which active TB cannot be eliminated as apossibility (by the site investigator)

  • TB resistant to any rifamycin in the source case

  • A history of treatment for > 7 consecutive days with a rifamycin or > 30 consecutivedays with INH within 2 years prior to enrollment.

  • A documented history of completing an adequate course of treatment for TB disease orLTBI in a person who is HIV-seronegative.

  • History of allergy or intolerance to rifamycins.

  • Serum alanine aminotransferase (ALT; SGPT) or serum aspartate aminotransferase (AST;SGOT) > 5x upper limit of normal among persons in whom baseline ALT or AST isdetermined+.

  • HIV-seropositive and on antiretroviral therapy that cannot be given with rifampin orrifapentine due to drug-drug interactions.

  • Receiving concomitant medications that are known to be contraindicated with anystudy drug.

  • Females who are currently pregnant, breastfeeding, or intend to become pregnantwithin 120 days of enrollment.

  • Weight < 25 kg.

Study Design

Total Participants: 3400
Treatment Group(s): 4
Primary Treatment: Rifapentine daily for 6 weeks
Phase: 2/3
Study Start date:
August 01, 2019
Estimated Completion Date:
December 31, 2029

Connect with a study center

  • Liverpool Hospital

    Sydney,
    Australia

    Active - Recruiting

  • Paramatta Chest

    Sydney,
    Australia

    Active - Recruiting

  • Royal Prince Alfred Hospital

    Sydney,
    Australia

    Active - Recruiting

  • Calgary TB Clinic

    Calgary, Alberta T1Y 6H6
    Canada

    Active - Recruiting

  • Edmonton TB Clinic

    Edmonton, Alberta
    Canada

    Active - Recruiting

  • British Columbia Centre for Disease Control

    Vancouver, British Columbia
    Canada

    Active - Recruiting

  • Toronto Western Hospital

    Toronto, Ontario M5P 1N5
    Canada

    Active - Recruiting

  • McGill University Health Centre

    Montréal, Quebec H3A 0G4
    Canada

    Active - Recruiting

  • Desmond Tutu TB Center

    Stellenbosch,
    South Africa

    Site Not Available

  • California Department of Public Health

    San Francisco, California 94102
    United States

    Site Not Available

  • Denver Health and Hospital Authority

    Denver, Colorado 80204
    United States

    Active - Recruiting

  • George Washington University

    Washington, District of Columbia 20001
    United States

    Active - Recruiting

  • Washington DC VA Medical Center

    Washington, District of Columbia 20001
    United States

    Active - Recruiting

  • New York Harbor Healthcare System

    Manhattan, New York 10001
    United States

    Active - Recruiting

  • Columbia University

    New York, New York 10027
    United States

    Site Not Available

  • New York City Bureau of TB Control

    New York, New York 11201
    United States

    Active - Recruiting

  • Vanderbilt University

    Nashville, Tennessee 37235
    United States

    Site Not Available

  • Austin TB Clinic

    Austin, Texas 78702
    United States

    Site Not Available

  • University of North Texas Health Science Center

    Fort Worth, Texas 76107
    United States

    Site Not Available

  • San Antonio VA

    San Antonio, Texas 78201
    United States

    Active - Recruiting

  • Seattle King County Health Department

    Seattle, Washington 98101
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.