Shorter Regimens for Latent Tuberculosis

Recruiting in Palo Alto (17 mi)

+11 other locations

Overseen byDick Menzies, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Waitlist Available

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?Our study rationale is based on: 1. Tuberculosis Preventive Treatment (TPT) is given to healthy people and needs to be safe; 2. Tuberculosis Preventive Treatment (TPT) with shorter regimens are superior with respect to acceptance, completion, and costs; 3. 4 months of Rifampin 10mg/kg (4R10) is the safest regimen, but is completed by \<80% of patients; 4. The safety of 2 months of Rifampin 20mg/kg (2R20) is similar to that of 4 months of Rifampin 10mg/kg (4R10), but completion is a concern; 5. 1-month regimens have promising efficacy; 6. Safety and tolerability must be carefully assessed with comparisons to 4 months of Rifampin 10mg/kg (4R10), and head-to-head with each other. OBJECTIVES: The investigator will use a Bayesian adaptive Phase 2 randomized open-label trial design to test at least three experimental Tuberculosis Preventive Treatment (TPT) regimens to identify at least one regimen of ≤2 months duration that has non-inferior safety, completion, and tolerability in adults and children relative to the reference Tuberculosis Preventive Treatment (TPT) regimen. The shortest, safest, and best tolerated regimen identified in this Phase 2 trial will be tested for effectiveness and efficacy in a Phase 3 trial. Specific Tuberculosis Preventive Treatment (TPT) regimens (All are daily and self-administered) Reference: Rifampin at a dose of 10 mg/kg/day for 4 months (4R10); Experimental: 1) Rifampin at 20 mg/kg/day for 2 months (2R20); (2) one month Levofloxacin and Rifapentine (1LP). At a later stage a 3rd experimental regimen will be selected and added: one another novel 1-2-month regimen identified from pre-clinical and clinical studies. When selected, this will be explained fully including preliminary data on safety and efficacy in an amended protocol and consent - which will be submitted for ethics and regulatory approval at that time).

Eligibility Criteria

This trial is for individuals with latent TB or at risk of reactivating a TB infection. Participants should be healthy and able to take daily self-administered medication. The study excludes those who cannot follow the treatment plan, have conditions that might interfere with the drug's effectiveness, or are unable to provide informed consent.

Inclusion Criteria

I am at least 5 years old.

Positive test for TB infection: either Tuberculin test (>5mm, or >10mm, based on local guidelines) or interferon gamma release assay

I am recommended for TB preventive treatment as per Canadian or WHO guidelines.

Exclusion Criteria

I am allergic to or cannot take rifampin or rifapentine due to severe drug interactions.

My blood tests for liver function and blood cell counts are not showing severe problems.

Pregnancy

+5 more

Participant Groups

The trial is testing three different TB preventive treatments: a standard dose of rifampin for four months, a double dose of rifampin for two months, and one month of levofloxacin with rifapentine. It aims to find a regimen under two months long that's as safe and tolerable as the four-month reference treatment.

3Treatment groups

Experimental Treatment

Active Control

Group I: 2 months high dose rifampin (2R20)Experimental Treatment1 Intervention

60 doses daily self-administered rifampin at 20 mg/kg/day (max.1200 mg/day)

Group II: 1 month levofloxacin and rifapentine (1LP)Experimental Treatment1 Intervention

30 doses daily self-administered levofloxacin (15 mg/kg/day, max. 750 mg/day and rifapentine (10mg/kg/day, max. 600mg)

Group III: 4 months standard dose rifampin (4R10)Active Control1 Intervention

120 doses daily self-administered rifampin at 10 mg/kg/day (max. 600 mg/day)