• Nicholas I Paton, Christopher Cousins, Celina Suresh, Erlina Burhan, Ka Lip Chew, Victoria B Dalay, Qingshu Lu, Tutik Kusmiati, Vincent M Balanag, Shu Ling Lee, Rovina Ruslami, Yogesh Pokharkar, Irawaty Djaharuddin, Jani J R Sugiri, Rholine S Veto, Christine Sekaggya-Wiltshire, Anchalee Avihingsanon, Rohit Sarin, Padmasayee Papineni, Andrew J Nunn, Angela M Crook, and TRUNCATE-TB Trial Team.
• From the Infectious Diseases Translational Research Programme and Yong Loo Lin School of Medicine, National University of Singapore (N.I.P., C.C., C.S., P.P.), National University Hospital (K.L.C.), and Singapore Clinical Research Institute (Q.L., S.L.L., Y.P.) - all in Singapore; the Faculty of Medicine, Universitas Indonesia, and Persahabatan General Hospital, Jakarta (E.B.), Dr. Soetomo Hospital, Surabaya (T.K.), Universitas Padjadjaran, Bandung (R.R.), Dr. Wahidin Sudirohusodo Hospital, Makassar (I.D.), and Saiful Anwar Hospital, Malang (J.J.R.S.) - all in Indonesia; De La Salle Medical and Health Sciences Institute, Cavite (V.B.D.), the Lung Centre of the Philippines, Quezon City (V.M.B.), and the Tropical Disease Foundation, Makati (R.S.V.) - all in the Philippines; the Infectious Diseases Institute, Makerere University, Kampala, Uganda (C.S.-W.); HIV-NAT, Thai Red Cross AIDS Research Center and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (A.A.); the National Institute of TB and Respiratory Diseases, New Delhi, India (R.S.); and the London School of Hygiene and Tropical Medicine (N.I.P.) and the Medical Research Council Clinical Trials Unit at University College London (N.I.P., A.J.N., A.M.C.) - both in London.
• N. Engl. J. Med. 2023 Mar 9; 388 (10): 873887873-887.

BackgroundTuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.MethodsIn 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.ResultsOf 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.ConclusionsA 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 ClinicalTrials.gov number, NCT03474198.).Copyright © 2023 Massachusetts Medical Society.

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