Pavlinac Patricia B, Singa Benson O, John-Stewart Grace C, Richardson Barbra A, Brander Rebecca L, McGrath Christine J, Tickell Kirkby D, Amondi Mary, Rwigi Doreen, Babigumira Joseph B, Kariuki Sam, Nduati Ruth, Walson Judd L
Department of Global Health, University of Washington, Seattle, Washington, USA.
Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
BMJ Open. 2017 Dec 29;7(12):e019170. doi: 10.1136/bmjopen-2017-019170.
Child mortality due to infectious diseases remains unacceptably high in much of sub-Saharan Africa. Children who are hospitalised represent an accessible population at particularly high risk of death, both during and following hospitalisation. Hospital discharge may be a critical time point at which targeted use of antibiotics could reduce morbidity and mortality in high-risk children.
In this randomised, double-blind, placebo-controlled trial (Toto Bora Trial), 1400 children aged 1-59 months discharged from hospitals in Western Kenya, in Kisii and Homa Bay, will be randomised to either a 5-day course of azithromycin or placebo to determine whether a short course of azithromycin reduces rates of rehospitalisation and/or death in the subsequent 6-month period. The primary analysis will be modified intention-to-treat and will compare the rates of rehospitalisation or death in children treated with azithromycin or placebo using Cox proportional hazard regression. The trial will also evaluate the effect of a short course of azithromycin on enteric and nasopharyngeal infections and cause-specific morbidities. We will also identify risk factors for postdischarge morbidity and mortality and subpopulations most likely to benefit from postdischarge antibiotic use. Antibiotic resistance in and among enrolled children and their primary caregivers will also be assessed, and cost-effectiveness analyses will be performed to inform policy decisions.
Study procedures were reviewed and approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington and the Kenyan Pharmacy and Poisons Board. The study is being externally monitored, and a data safety and monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders.
NCT02414399.
在撒哈拉以南非洲的大部分地区，因传染病导致的儿童死亡率仍然高得令人无法接受。住院儿童是一个可接触到的群体，在住院期间及出院后死亡风险特别高。出院可能是一个关键时间点，在此阶段针对性地使用抗生素可以降低高危儿童的发病率和死亡率。
在这项随机、双盲、安慰剂对照试验（托托博拉试验）中，1400名年龄在1至59个月、从肯尼亚西部基苏木和霍马湾的医院出院的儿童将被随机分为接受为期5天的阿奇霉素疗程或安慰剂，以确定短期阿奇霉素疗程是否能降低随后6个月内的再次住院率和/或死亡率。主要分析将采用改良意向性分析，并使用Cox比例风险回归比较接受阿奇霉素或安慰剂治疗的儿童的再次住院率或死亡率。该试验还将评估短期阿奇霉素疗程对肠道和鼻咽感染以及特定病因发病率的影响。我们还将确定出院后发病和死亡的风险因素以及最有可能从出院后使用抗生素中获益的亚人群。还将评估入选儿童及其主要照顾者体内及之间的抗生素耐药性，并进行成本效益分析以为政策决策提供依据。
研究程序已由肯尼亚医学研究所、华盛顿大学和肯尼亚药房与毒药委员会的机构审查委员会审查并批准。该研究正在接受外部监测，并且已组建了一个数据安全与监测委员会来监测患者安全并评估干预措施的疗效。该试验的结果将发表在同行评审的科学期刊上，并在相关学术会议上以及向主要利益相关者进行展示。
NCT02414399。
