@article{adbdb916e3af4d598c22037b876e2b87,
title = "Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): A protocol for a randomised controlled trial",
abstract = "Introduction Treatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB. Methods and analysis A double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression. Ethics Ethical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT). Dissemination Findings of the study will be published in peer-reviewed publications and conference presentations. Trial registration number ACTRN12616000215426.",
keywords = "latent tuberculosis tuberculosis, multidrug-resistant mycobacterium tuberculosis fluoroquinolones, therapeutic use humans clinical trial protocol, therapeutic use levofloxacin",
author = "Fox, {Greg J.} and Nguyen, {Cam Binh} and Nguyen, {Thu Anh} and Tran, {Phuong Thuy} and Marais, {Ben J.} and Graham, {Steve M.} and Nguyen, {Binh Hoa} and Kavi Velen and Dowdy, {David W.} and Paul Mason and Britton, {Warwick J.} and Behr, {Marcel A.} and Andrea Benedetti and Dick Menzies and Nguyen, {Viet Nhung} and Marks, {Guy B.}",
note = "Funding Information: 1Central Clinical School, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia 2Woolcock Institute of Medical Research, Glebe, New South Wales, Australia 3The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia 4The University of Sydney Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, New South Wales, Australia 5Murdoch Childrens Research Institute, Parkville, Victoria, Australia 6Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia 7The National Lung Hospital, Hanoi, Vietnam 8Department of Epidemiology, John Hopkins Bloomberg, Baltimore, Maryland, USA 9Taronga Institute of Science and Learning, Taronga Conservation Society, Sydney, New South Wales, Australia 10Tuberculosis Research Program, The Centenary Institute of Cancer Medicine and Cell Biology, Sydney, New South Wales, Australia 11Department of Medicine, McGill University, Montreal, Quebec, Canada 12McGill International Tuberculosis Centre, McGill University, Montreal, Quebec, Canada 13Departments of Medicine and of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Quebec, Canada 14South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia Contributors GJF wrote the proposal for this study that was awarded funding. GJF, CBN, TAN, BM, SG, BHN, DWD, WJB, MB, AB, DM, VNN and GBM made important intellectual contributions to the study protocol. GJF, CBN, TAN, BM, SG, BHN, DWD, WJB, MB, AB, DM, VNN and GBM contributed to the multiple revisions of this study protocol. GJF and AB performed statistical calculations for sample size and power. GJF wrote the first draft of the manuscript. CBN, TAN, BM, SG, BHN, PTT, KV, DWD, WJB, MB, AB, PM, DM, VNN and GBM contributed substantially to manuscript versions. All authors revised and approved the final manuscript. The funding agency played no part in any aspect of the study, nor the decision to submit this manuscript for publication. Funding Information: funding This work is supported by the Australian National Health and Medical Research Council (NHMRC) grant application number 1081443. GJF was supported by a NHMRC CJ Martin Fellowship (APP 1054107) and NHMRC Career Development Fellowship (APP 1148372). The trial sponsor is the Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW Australia, 2037. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2020",
month = jan,
day = "2",
doi = "10.1136/bmjopen-2019-033945",
language = "English (US)",
volume = "10",
journal = "BMJ open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "1",
}