Treatment Strategy for Rifampin-Susceptible Tuberculosis.

Nicholas I Paton ORCID logo ; Christopher Cousins ; Celina Suresh ; Erlina Burhan ; Ka Lip Chew ; Victoria B Dalay ; Qingshu Lu ; Tutik Kusmiati ; Vincent M Balanag ; Shu Ling Lee ; +12 more... Rovina Ruslami ; Yogesh Pokharkar ; Irawaty Djaharuddin ; Jani JR Sugiri ; Rholine S Veto ; Christine Sekaggya-Wiltshire ; Anchalee Avihingsanon ; Rohit Sarin ; Padmasayee Papineni ORCID logo ; Andrew J Nunn ; Angela M Crook ; TRUNCATE-TB Trial Team ; (2023) Treatment Strategy for Rifampin-Susceptible Tuberculosis. The New England journal of medicine, 388 (10). pp. 873-887. ISSN 0028-4793 DOI: 10.1056/NEJMoa2212537
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BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In 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. RESULTS: Of 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. CONCLUSIONS: A 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.).


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