Treatment Strategy for Rifampin-Susceptible Tuberculosis

N Engl J Med. 2023 Mar 9;388(10):873-887. doi: 10.1056/NEJMoa2212537. Epub 2023 Feb 20.


Background: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.

Methods: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points.

Results: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups.

Conclusions: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB number, NCT03474198.).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antitubercular Agents* / adverse effects
  • Antitubercular Agents* / therapeutic use
  • Diarylquinolines* / adverse effects
  • Diarylquinolines* / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Ethambutol / adverse effects
  • Ethambutol / therapeutic use
  • Humans
  • Isoniazid / adverse effects
  • Isoniazid / therapeutic use
  • Linezolid* / adverse effects
  • Linezolid* / therapeutic use
  • Pyrazinamide / adverse effects
  • Pyrazinamide / therapeutic use
  • Rifampin* / adverse effects
  • Rifampin* / therapeutic use
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Pulmonary* / complications
  • Tuberculosis, Pulmonary* / drug therapy


  • Antitubercular Agents
  • Ethambutol
  • Isoniazid
  • Linezolid
  • Pyrazinamide
  • Rifampin
  • bedaquiline
  • Diarylquinolines

Associated data