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

Bern-Thomas Nyang’waUniversity College LondonCatherine BerryPublic Health Department, OCA, Médecins sans FrontièresEmil KazounisFrom 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.)Ilaria MottaPublic Health Department, OCA, Médecins sans FrontièresNargiza ParpievaUniversity College LondonZinaida TigayFrom 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.)Varvara SolodovnikovaMédecins Sans FrontièresIrina LiverkoFrom 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.)Ronelle MoodliarUniversity College LondonMatthew DoddUniversity College LondonNosipho NgubaneFrom 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.)Mohammed RassoolWits Health Consortium, JohannesburgTimothy D. McHughFrom 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.)Melvin SpigelmanFrom 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.)David MooreMédecins Sans FrontièresKoert RitmeijerUniversity College LondonPhilipp du CrosBurnet Institute, Melbourne, VIC, AustraliaKatherine FieldingUniversity College London

New England Journal of Medicinejournal2022en

Ochiq kirishBronza

ABI

Annotatsiya

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.).

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Tuberculosis Research and Epidemiology Misinformation and Its Impacts Clinical Reasoning and Diagnostic Skills

Identifikatorlar

DOI: 10.1056/nejmoa2117166

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