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

Nyang'wa, BT; Berry, C; Kazounis, E; Motta, I; Parpieva, N; Tigay, Z; Solodovnikova, V; ... Fielding, K; + view all (2022) A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. New England Journal of Medicine , 387 (25) pp. 2331-2343. 10.1056/NEJMoa2117166. Green open access

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Abstract

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.)

Type: Article
Title: A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1056/NEJMoa2117166
Publisher version: https://doi.org/10.1056/NEJMoa2117166
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Humans, Antitubercular Agents, Drug Therapy, Combination, Moxifloxacin, Rifampin, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Adolescent, Young Adult, Adult, Linezolid, Administration, Oral
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10164236
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