The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children

Claire S Waddington, Charlie McLeod, Peter Morris, Asha Bowen, Mark Naunton, Jonathan Carapetis, Keith Grimwood, Roy Robins-Browne, Carl D Kirkwood, Robert Baird, David Green, Ross Andrews, Deborah Fearon, Joshua Francis, Julie A Marsh, Thomas Snelling, Claire S Waddington, Charlie McLeod, Peter Morris, Asha Bowen, Mark Naunton, Jonathan Carapetis, Keith Grimwood, Roy Robins-Browne, Carl D Kirkwood, Robert Baird, David Green, Ross Andrews, Deborah Fearon, Joshua Francis, Julie A Marsh, Thomas Snelling

Abstract

Introduction: Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease. Randomised trials in other populations suggest nitazoxanide accelerates recovery for children with Giardia, amoebiasis, Cryptosporidium, Rotavirus and Norovirus gastroenteritis, as well as in cases where no enteropathogens are found.

Methods and analysis: This double blind, 1:1 randomised, placebo controlled trial is investigating the impact of oral nitazoxanide on acute gastroenteritis in hospitalised Australian Aboriginal children aged 3 months to <5 years. Dosing is based on age-based dosing. The primary endpoint is the time to resolution of 'significant illness' defined as the time from randomisation to the time of clinical assessment as medically ready for discharge, or to the time of actual discharge from hospital, whichever occurs first. Secondary endpoints include duration of hospitalisation, symptom severity during the period of significant illness and following treatment, duration of rehydration and drug safety. Patients will be followed for medically significant events for 60 days. Analysis is based on Bayesian inference. Subgroup analysis will occur by pathogen type (bacteria, virus or parasite), rotavirus vaccination status, age and illness severity.

Ethics and dissemination: Ethics approval has been granted by the Central Australian Human Research Ethics Committee (HREC-14-221) and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC2014-2172). Study investigators will ensure that the trial is conducted in accordance with the principles of the Declaration of Helsinki. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication.

Trial registration number: ACTRN12614000381684.

Keywords: Bayesian inference; cryptosporidium; diarrhoea; gastrointestinal infections; nitazoxanide.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Trial flow chart. SAE, serious adverse events.

References

    1. World Health Organisation and UNICEF. The Integrated Global action plan for Pneumonia and Diarrhoea (GAPPD). 2013. (accessed 13 Aug 2017).
    1. Kotloff KL, Nataro JP, Blackwelder WC, et al. . Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013;382:209–22. 10.1016/S0140-6736(13)60844-2
    1. Li SQ, Guthridge S, Tursan d’Espaignet E, et al. . From infancy to young adulthood: health status in the Northern Territory. Darwin: Department of Health and Community Services, 2006. (accessed 13 Aug 2017).
    1. Dey A, Wang H, Menzies R, et al. . Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program. Med J Aust 2012;197:453–7. 10.5694/mja12.10062
    1. Armstrong P. Rotaviral gastroenteritis in the NT: a description of the epidemiology 1995-2001 and future directions for research. Northern Territory Disease Control Bulletin 2001;8:1–5.
    1. Gelbart B, Hansen-Knarhoi M, Binns P, et al. . Rotavirus outbreak in a remote Aboriginal community: the burden of disease. J Paediatr Child Health 2006;42:775–80. 10.1111/j.1440-1754.2006.00976.x
    1. Niehaus MD, Moore SR, Patrick PD, et al. . Early childhood diarrhea is associated with diminished cognitive function 4 to 7 years later in children in a northeast Brazilian shantytown. Am J Trop Med Hyg 2002;66:590–3. 10.4269/ajtmh.2002.66.590
    1. Guerrant DI, Moore SR, Lima AA, et al. . Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil. Am J Trop Med Hyg 1999;61:707–13. 10.4269/ajtmh.1999.61.707
    1. Rossignol J-F, Lopez-Chegne N, Julcamoro LM, et al. . Nitazoxanide for the empiric treatment of pediatric infectious diarrhea. Trans R Soc Trop Med Hyg 2012;106:167–73. 10.1016/j.trstmh.2011.11.007
    1. Rossignol JF. Nitazoxanide in the treatment of acquired immune deficiency syndrome-related cryptosporidiosis: results of the United States compassionate use program in 365 patients. Aliment Pharmacol Ther 2006;24:887–94. 10.1111/j.1365-2036.2006.03033.x
    1. Rossignol JF, Abu-Zekry M, Hussein A, et al. . Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial. Lancet 2006;368:124–9. 10.1016/S0140-6736(06)68852-1
    1. Rossignol J–F, Kabil SM, El–Gohary Y, et al. . Effect of nitazoxanide in diarrhea and enteritis caused by cryptosporidium species. Clin Gastroenterol Hapatol 2006;4:320–4. 10.1016/j.cgh.2005.12.020
    1. Rossignol JF, Kabil SM, El-Gohary Y, et al. . Nitazoxanide in the treatment of amoebiasis. Trans R Soc Trop Med Hyg 2007;101:1025–31. 10.1016/j.trstmh.2007.04.001
    1. Rossignol JF, Lopez-Chegne N, Julcamoro LM, et al. . Nitazoxanide for the empiric treatment of pediatric infectious diarrhea. Trans R Soc Trop Med Hyg 2012;106:167–73. 10.1016/j.trstmh.2011.11.007
    1. Rossignol JF, El-Gohary YM. Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial. Aliment Pharmacol Ther 2006;24:1423–30. 10.1111/j.1365-2036.2006.03128.x
    1. Department of Health. Northern Territory resident population estimates by age, sex, indigenous status and health districts (1971-2016)’, prepared by health gains planning, file updated on 27 February 2017: ABS Estimated Resident Population, 2017.
    1. World Health Organization. The treatment of diarrhoea. 2005.
    1. McLeod C, Morris PS, Snelling TL, et al. . Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012. Rural Remote Health 2014;14:2759.
    1. Teran CG, Teran-Escalera CN, Villarroel P. Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind, controlled trial in Bolivian children. Int J Infect Dis 2009;13:518–23. 10.1016/j.ijid.2008.09.014
    1. Escobedo AA, Alvarez G, González ME, et al. . The treatment of giardiasis in children: single-dose tinidazole compared with 3 days of nitazoxanide. Ann Trop Med Parasitol 2008;102:199–207. 10.1179/136485908X267894
    1. Juan JO, Lopez Chegne N, Gargala G, et al. . Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru. Trans R Soc Trop Med Hyg 2002;96:193–6.
    1. World Medical Association. World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310:219104 10.1001/jama.2013.281053
    1. International Council for Harmonisation. Guidelines for good clinical practice, 2016. (accessed 4 Sep 2017).

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