NCT03988933: 2R2

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

Completed Phase 2 Last updated 13 April 2026

What this trial tests

Phase 2 trial testing Rifampin double dose in Latent Tuberculosis in 1,368 participants. Completed in 31 December 2024.

Timeline

20 September 2019

Primary endpoint
31 January 2023

31 December 2024

Quick facts

Lead sponsor	McGill University Health Centre/Research Institute of the McGill University Health Centre
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	1,368
Start date	20 September 2019
Primary completion	31 January 2023
Estimated completion	31 December 2024
Sites	9 locations across Canada, Indonesia, Vietnam

Drugs / interventions tested

• Rifampin double dose — full drug profile →
• Rifampin triple dose — full drug profile →
• Rifampin standard dose — full drug profile →

Conditions studied

• Latent Tuberculosis — all drugs for Latent Tuberculosis →

Sponsor

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

Who can join

10 and older, any sex, with Latent Tuberculosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical standards for the diagnosis, treatment and prevention of TB infection.
   Migliori GB, Wu SJ, Matteelli A, Zenner D, et al · · 2022 · cited 55× · PMID 35197159 · DOI 10.5588/ijtld.21.0753
2. Management of Tuberculosis Infection: Current Situation, Recent Developments and Operational Challenges.
   Agbota G, Bonnet M, Lienhardt C. · · 2023 · cited 16× · PMID 36986284 · DOI 10.3390/pathogens12030362
3. High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.
   Ruslami R, Fregonese F, Apriani L, Barss L, et al · · 2024 · cited 11× · PMID 38552659 · DOI 10.1016/s2213-2600(24)00076-6
4. High dose rifampin for 2 months vs standard dose rifampin for 4 months, to treat TB infection: Protocol of a 3-arm randomized trial (2R2).
   Fregonese F, Apriani L, Barss L, Benedetti A, et al · · 2023 · cited 4× · PMID 36730240 · DOI 10.1371/journal.pone.0278087
5. Population Pharmacokinetic Modeling of Standard- and High-Dose Rifampicin for Tuberculosis Preventive Therapy in the 2R2 Randomized Controlled Trial.
   Gafar F, Svensson EM, Yunivita V, Fregonese F, et al · · 2026 · PMID 41589392 · DOI 10.1093/infdis/jiag052
6. Costs of 4 Months of Rifampin Versus 2 Months of Double-dose Rifampin for Tuberculosis Infection: Post-Hoc Analysis of a Phase 2b Randomized Trial.
   Romanowski K, Pham Ngoc Y, Barss L, Jabbour E, et al · · 2025 · PMID 40980570 · DOI 10.1093/ofid/ofaf563