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

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.

Conditions

• Latent Tuberculosis

Interventions

DRUG

Rifampin double dose

Double dose of rifampin for 2 months.

DRUG

Rifampin triple dose

Triple dose of rifampin for 2 months.

DRUG

Rifampin standard dose

Standard dose of rifampin for 4 months.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• McGill University Health Centre/Research Institute of the McGill University Health Centre

  lead OTHER

Principal Investigators

• Dick Menzies · RI-MUHC

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

10 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-09-20

Primary Completion

2023-01-31

Completion

2024-12-31

Countries

• Canada
• Indonesia
• Vietnam

Study Locations