@article{71d4e17d0745476db287be9e604d8f5c,
title = "A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB",
abstract = "B A C K G R O U N D: Treatment for TB is lengthy and toxic, and new regimens are needed. M E T H O D S: 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. R E S U LT S: 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 6Pa2 0 0MZ, 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{\th} 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 and 2/68 (2.9%) controls died. C O N C L U S I O N: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.",
keywords = "Drug resistance, K E Y W O R D S: tuberculosis, TB treatment, TB-HIV",
author = "Tweed, {C. D.} and Wills, {G. H.} and Crook, {A. M.} and E. Amukoye and V. Balanag and Ban, {A. Y.L.} and Bateson, {A. L.C.} and Betteridge, {M. C.} and W. Brumskine and J. Caoili and Chaisson, {R. E.} and M. Cevik and F. Conradie and R. Dawson and {del Parigi}, A. and A. Diacon and Everitt, {D. E.} and Fabiane, {S. M.} and R. Hunt and Ismail, {A. I.} and U. Lalloo and L. Lombard and C. Louw and M. Malahleha and McHugh, {T. D.} and Mendel, {C. M.} and F. Mhimbira and Moodliar, {R. N.} and V. Nduba and Nunn, {A. J.} and I. Sabi and Sebe, {M. A.} and Selepe, {R. A.P.} and S. Staples and S. Swindells and {van Niekerk}, {C. H.} and E. Variava and M. Spigelman and Gillespie, {S. H.}",
note = "Funding Information: The authors thank all the participants for their participation in the study; the nursing and laboratory staff; all those who advised, volunteered, or otherwise supported community engagement around the STAND clinical trial sites; and the members of the DSMC for their oversight of the safety of the trial. 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 f{\"u}r 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. AMC and AJN are supported by Medical Research Council Grant: MC_UU_12023/27 Tuberculosis Treatment Trials. Publisher Copyright: {\textcopyright} 2021 International Union against Tubercul. and Lung Dis.. All rights reserved.",
year = "2021",
month = apr,
day = "1",
doi = "10.5588/IJTLD.20.0513",
language = "English (US)",
volume = "25",
pages = "305--314",
journal = "International Journal of Tuberculosis and Lung Disease",
issn = "1027-3719",
publisher = "International Union against Tubercul. and Lung Dis.",
number = "4",
}