2R2: Higher Dose Rifampin for 2 Months vs Standard Dose Rifampin for Latent TB.

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Rationale:

Shorter regimens of high dose daily rifampin may be safe, and as effective as the standard rifampin regimen when taken for 4 months to treat latent TB (LTBI). However, there is insufficient evidence on the optimal dose of rifampin that has similar efficacy as the standard 4-month rifampin regimen without jeopardizing safety or affecting completion rates.

Objectives:

The general purpose of this study is to determine if rifampin at double or triple the standard dose for 2 months is as safe and effective as the standard dose of rifampin when taken for 4 months to treat latent tuberculosis (TB).

Treatment:

Persons who need treatment for latent TB, will be given rifampin, either at the standard dose (10mg/kg/day) for 4 months (control arm); or at double dose (20mg/kg/day) for 2 months (intervention arm 1); or at triple dose (30mg/kg/day) for 2 months (intervention arm 2).

Design:

This is 1:1:1 randomized, phase 2b, partially blind, controlled trial. The two higher doses (intervention arms) will be administered double-blind: participants and providers will be aware of the duration of their regimen, but they will both remain blinded to the specific dose (i.e. 20 or 30 mg/kg/day) for those randomized to 2-months regimens. All members of the same household of a patient with newly diagnosed active pulmonary TB will be randomized together (i.e. cluster randomized).

Population and setting:

Adults and children aged 10 years and above, who have latent TB infection and are recommended by their doctor to take treatment for latent TB can participate in the study.

The planned number of persons with latent TB to recruit is about 1359 in total (or about 453 for each of the three arms).

The study will take place in 6 sites: four in Canada (Calgary, Edmonton, Montreal and Vancouver), one in Indonesia (Bandung) and one in Viet Nam (1 clinic in Ho Chi Min City and 3 clinics in Ha Noi).

Outcomes:

Primary outcomes are: 1) Treatment completion and 2) Safety (i.e. grade 3-5 adverse events).

Secondary outcomes are: 1) Safety (i.e. grade 1-2 adverse events) and 2) Efficacy (i.e. rates of active TB in the 26 months post-randomization). More information on how outcomes are defined is provided in the detailed description below.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McGill University; McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Treatments: Rifampin

Criteria

Inclusion Criteria:

• Adults, and children aged 10 and older who weigh at least 25kg.

• Evidence of latent TB infection: positive tuberculin skin test (5mm or greater or 10mm or greater, based on National guidelines) or positive interferon gamma release assay.

• Eligible to take latent TB treatment according to Canadian guidelines in the Canadian sites, and according to World Health Organization (WHO) guidelines in the international sites (this includes household contacts, other contacts, HIV infected, other causes of immune suppression, fibronodular disease on chest-x ray (CXR), or other indication).

Exclusion Criteria:

• Children aged 0-9 and children aged 10 or older who weigh less than 25kg

• Pregnancy

• Baseline AST or ALT that is at least 3 times higher than upper limit of normal

• Baseline Grade 3-4 abnormalities of hematological tests (WBC, platelets or hemoglobin).

• Prior treatment for latent or active TB.

• Rifampin contra-indicated - due to potential drug interactions that are considered too important, or difficult to manage, by health care provider; or due to history of allergy/ hypersensitivity to rifampin, rifabutin or rifapentine.

• Household contacts of index TB patients with confirmed, or suspected rifampin resistant TB.