• Bern-Thomas Nyang'wa, Catherine Berry, Emil Kazounis, Ilaria Motta, Nargiza Parpieva, Zinaida Tigay, Varvara Solodovnikova, Irina Liverko, Ronelle Moodliar, Matthew Dodd, Nosipho Ngubane, Mohammed Rassool, Timothy D McHugh, Melvin Spigelman, MooreDavid A JDAJFrom the Public Health Department, Operational Center Amsterdam (OCA), Médecins sans Frontières, Amsterdam (B.-T.N., K.R.); the Public Health Department, OCA, Médecins sans Frontières (C.B., E.K., I.M.), the London School of Hygiene and T, Koert Ritmeijer, Philipp du Cros, Katherine Fielding, and TB-PRACTECAL Study Collaborators.
• From the Public Health Department, Operational Center Amsterdam (OCA), Médecins sans Frontières, Amsterdam (B.-T.N., K.R.); the Public Health Department, OCA, Médecins sans Frontières (C.B., E.K., I.M.), the London School of Hygiene and Tropical Medicine (B.-T.N., M.D., D.A.J.M., K.F.), and University College London (T.D.M.) - all in London; the Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent (N.P., I.L.), and the Republican Phthisiological Hospital No. 2, Nukus (Z.T.) - both in Uzbekistan; the Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus (V.S.); THINK TB and HIV Investigative Network, Durban (R.M.), and Wits Health Consortium, Johannesburg (N.N., M.R.) - both in South Africa; the Global Alliance for TB Drug Development, New York (M.S.); and the Burnet Institute, Melbourne, VIC, Australia (P.C.).
• N. Engl. J. Med. 2022 Dec 22; 387 (25): 233123432331-2343.

BackgroundIn 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.MethodsWe 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.ResultsRecruitment 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%).ConclusionsIn 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.).Copyright © 2022 Massachusetts Medical Society.

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