A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis

N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166.


Background: In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed.

Methods: We conducted an open-label, phase 2-3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points.

Results: Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%).

Conclusions: In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782.).

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antitubercular Agents* / administration & dosage
  • Antitubercular Agents* / adverse effects
  • Antitubercular Agents* / pharmacology
  • Antitubercular Agents* / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Linezolid / administration & dosage
  • Linezolid / adverse effects
  • Linezolid / therapeutic use
  • Moxifloxacin / administration & dosage
  • Moxifloxacin / adverse effects
  • Moxifloxacin / therapeutic use
  • Rifampin / adverse effects
  • Rifampin / pharmacology
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Pulmonary* / drug therapy
  • Young Adult


  • Antitubercular Agents
  • Moxifloxacin
  • Rifampin
  • bedaquiline
  • pretomanid
  • Linezolid

Associated data

  • ClinicalTrials.gov/NCT02589782