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

Launched by CENTERS FOR DISEASE CONTROL AND PREVENTION · Mar 15, 2018

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for people with latent tuberculosis infection (LTBI), which is when someone has the bacteria that causes tuberculosis (TB) in their body but does not have active TB disease. The trial compares a shorter, 6-week daily treatment using a drug called rifapentine to the standard treatment that lasts 12 to 16 weeks. The goal is to see if the shorter treatment is just as safe and effective as the longer one. The study will involve about 3,400 participants who are at higher risk of developing active TB, such as those who have been in close contact with someone with TB or have certain health conditions.

To be eligible for the trial, participants must be at least 12 years old, have a positive test for LTBI, and not have active TB. They should also not be pregnant or breastfeeding. Participants will be randomly assigned to receive either the experimental treatment (6 weeks of rifapentine) or the standard treatment for a set period. Throughout the trial, participants will be monitored for any side effects and to see if they develop active TB. This trial is an important step in finding potentially shorter and easier treatments for those at risk of TB.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Males or non-pregnant, non-breastfeeding females \> 12 years old. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment.
• * Persons with LTBI who do not have evidence of TB disease and are at increased risk of progression to TB. M. tuberculosis infection may be demonstrated by either a positive 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 of progression 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 A positive nucleic acid amplification test (NAAT)/GeneXpert in the source case may be used for enrollment prior to culture confirmation
• • 2. Recent M. tuberculosis infection, defined as converting from a documented negative to positive TST or IGRA within 2 years prior to enrollment. Persons without known close contact to someone with active pulmonary TB who have a conversion by IGRA may require additional evaluation to rule out a false conversion.
• • 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 history of treatment for TB or LTBI.
• • 5. Recent (within 3 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, with abnormal chest X-ray, and no evidence of active TB.
• • 6. Recent (within 2 years prior to enrollment) immigration to the United States or other country with low to moderate TB incidence, from a country with an estimated incidence rate of TB \> 150 per 100,000
• • 7. An increased risk of TB due to medical conditions such as end-stage renal disease, or due to use of immunosuppressive medications such as chronic steroids or TNF-alpha inhibitors.
• • Willing to provide signed informed consent, or parental permission and participant assent.
• Exclusion Criteria:
• • Current confirmed culture-positive or clinical TB.
• • Suspected current TB. Includes cases in which active TB cannot be eliminated as a possibility (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 consecutive days with INH within 2 years prior to enrollment.
• • A documented history of completing an adequate course of treatment for TB disease or LTBI 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 is determined+.
• • HIV-seropositive and on antiretroviral therapy that cannot be given with rifampin or rifapentine due to drug-drug interactions.
• • Receiving concomitant medications that are known to be contraindicated with any study drug.
• • Females who are currently pregnant, breastfeeding, or intend to become pregnant within 120 days of enrollment.
• • Weight \< 25 kg.