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A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Title: A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB
Authors: Tweed, C. D.; Wills, G. H.; Crook, A. M.; Amukoye, E.; Balanag, V.; Ban, A. Y.L.; Bateson, A. L.C.; Betteridge, M. C.; Brumskine, W.; Caoili, J.; Chaisson, R. E.; Cevik, M.; Conradie, F.; Dawson, R.; del Parigi, A.; Diacon, A.; Everitt, D. E.; Fabiane, S.M.; Hunt, R.; Ismail, A. I.; Lalloo, U.; Lombard, L.; Louw, C.; Malahleha, M.; McHugh, T. D.; Mendel, C. M.; Mhimbira, F.; Moodliar, R. N.; Nduba, V.; Nunn, A. J.; Sabi, I.; Sebe, M. A.; Selepe, R. A. P.; Staples, S.; Swindells, S.; van Niekerk, C. H.; Variava, E.; Spigelman, M.; Gillespie, S. H.
Contributors: European and Developing Countries; University of St Andrews.School of Medicine; University of St Andrews.Infection and Global Health Division; University of St Andrews.Sir James Mackenzie Institute for Early Diagnosis; University of St Andrews.Centre for Biophotonics; University of St Andrews.Biomedical Sciences Research Complex; University of St Andrews.Global Health Implementation Group; University of St Andrews.Gillespie Group
Publication Year: 2021
Collection: University of St Andrews: Digital Research Repository
Subject Terms: Pulmonary and Respiratory Medicine; Infectious Diseases; QR Microbiology; RM Therapeutics. Pharmacology; NDAS; SDG 3 - Good Health and Well-being; QR; RM
Description: STAND was sponsored by TB Alliance with support from the UK Department for International Development, UK Department of Health (London, UK), Bill and Melinda Gates Foundation (Seattle, WA, USA), US Agency for International Development (Washington DC, USA), Directorate General for International Cooperation of the Netherlands (Amsterdam, The Netherlands), Irish Aid (Dublin, Ireland), Australia Department of Foreign Affairs and Trade (Canberra ACT, Australia) and the Federal Ministry for Education and Research of Germany (Berlin, Germany) through KfW (Kreditanstalt fur Wiederaufbau) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH; Bethesda, MD, USA) under Award Numbers UM1 AI068634 and UM1 AI068636. AMC and AJN are supported by Medical Research Council Grant: MC_UU_12023/27 Tuberculosis Treatment Trials. ; BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed. METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed. RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI –2.2% to 15.4%) difference per protocol and 9.9% (95%CI –4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: International Journal of Tuberculosis and Lung Disease; 273672846; 85103500407; 000633227300007; Jisc: dce60838673f473f8a2e3b73eabd97c2; https://hdl.handle.net/10023/21773; https://www.scopus.com/pages/publications/85103500407
DOI: 10.5588/ijtld.20.0513
Availability: https://hdl.handle.net/10023/21773; https://doi.org/10.5588/ijtld.20.0513; https://www.scopus.com/pages/publications/85103500407
Rights: Copyright 2021 The Union. This article is Open Access under the terms of the Creative Commons CC BY licence.
Accession Number: edsbas.7D9A033C
Database: BASE