Shorter Regimens for Latent Tuberculosis
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).
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications that prolong the QT interval and are not recommended with a fluoroquinolone.
What data supports the effectiveness of the drug regimen involving Levofloxacin, Rifapentine, Rifampin, and Rifampicin for latent tuberculosis?
Research suggests that using rifapentine instead of rifampin can shorten the treatment duration for latent tuberculosis, as seen in studies where rifapentine-based regimens reduced treatment time in mice. Additionally, regimens containing rifapentine have shown similar effectiveness to longer treatments, with higher completion rates, making them a promising option for shorter therapy.12345
Is the shorter regimen for latent tuberculosis using Levofloxacin and Rifapentine safe?
The shorter regimens using rifampin and rifapentine for latent tuberculosis are generally considered safe, with fewer liver-related side effects compared to longer treatments. Levofloxacin has also been shown to be safe in tuberculosis treatment, with adverse effects disappearing after stopping the drug.13678
How is the drug regimen for latent tuberculosis using Levofloxacin and Rifapentine, Rifampin different from other treatments?
Research Team
Dick Menzies, MD
Principal Investigator
RI-MUHC
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
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive one of the Tuberculosis Preventive Treatment (TPT) regimens: 4 months of Rifampin 10mg/kg, 2 months of Rifampin 20mg/kg, or 1 month of Levofloxacin and Rifapentine
Follow-up
Participants are monitored for safety and effectiveness after treatment, including detection of late adverse events and incident tuberculosis
Treatment Details
Interventions
- Levofloxacin and Rifapentine
- Rifampin
Find a Clinic Near You
Who Is Running the Clinical Trial?
McGill University Health Centre/Research Institute of the McGill University Health Centre
Lead Sponsor
Canadian Institutes of Health Research (CIHR)
Collaborator