Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.
Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.
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DOI：
10.1186/s13063-018-2608-5
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发表时间：
2018-04-19
期刊：
影响因子：
2.5
通讯作者：
SHINE trial team
中科院分区：
文献类型：
--
作者：
Chabala C;Turkova A;Thomason MJ;Wobudeya E;Hissar S;Mave V;van der Zalm M;Palmer M;Kapasa M;Bhavani PK;Balaji S;Raichur PA;Demers AM;Hoddinott G;Owen-Powell E;Kinikar A;Musoke P;Mulenga V;Aarnoutse R;McIlleron H;Hesseling A;Crook AM;Cotton M;Gibb DM;SHINE trial team
儿童结核病（TB）通常是少杆菌型，非严重形式的肺结核很常见。儿童结核病治疗的证据主要来自成人研究。在涂阴肺结核成人患者中进行的试验表明，治疗时间可以有效地从6个月缩短到4个月。许多国家最近采用了新的儿科固定剂量复方抗结核治疗方法，使世界卫生组织（世卫组织）修订的剂量建议的实施变得可行。尚未在儿童大型研究中系统评估这些较高药物剂量的安全性和疗效，应确认代表体重和年龄范围的儿童的药代动力学。SHINE是一项多中心、开放标签、平行组、非劣效性、随机对照、双臂试验，使用修订的WHO儿科抗结核药物剂量，比较4个月方案与标准6个月方案。我们的目标是招募1200名16岁以下的非洲和印度儿童，他们患有非严重结核病，有或没有艾滋病毒感染。主要疗效和安全性终点是随机化后72周的TB无病生存期和3级或4级不良事件。巢式药代动力学研究将评估抗结核药物浓度，提供基于模型的最佳剂量预测，并测量抗逆转录病毒暴露，以描述艾滋病毒感染儿童亚组中的药物相互作用。社会经济分析将评估干预措施的成本效益，社会科学研究将进一步探讨这些新的儿科药物制剂的可接受性和适口性。虽然最近在结核病阳性成人中进行的结核病治疗缩短试验尚未成功，但这个问题从未在儿童中得到解决，他们主要患有少菌性，非严重的涂片阴性疾病。SHINE应告知儿童药物敏感性结核病的治疗缩短是否有效和安全，无论其HIV状态如何。该试验还将填补结核病高负担环境中新抗结核制剂和常用艾滋病毒药物的剂量和可接受性方面的现有知识空白。这项试验的积极结果可以简化和缩短治疗，提高依从性，并为许多结核病儿童节省费用。SHINE试验的招募工作于2016年7月开始;预计2020年将有结果。国际标准随机对照试验编号：ISRCTN 63579542，2014年10月14日。泛非临床试验注册编号：PACTR 201505001141379，2015年5月14日。临床试验注册中心-印度，注册编号：CTRI/2017/07/009119，2017年7月27日。本文的在线版本（10.1186/s13063-018-2608-5）包含补充材料，可供授权用户使用。
Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017. The online version of this article (10.1186/s13063-018-2608-5) contains supplementary material, which is available to authorized users.
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