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Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial

Authors: Chishala Chabala, Anna Turkova, Margaret J. Thomason, Eric Wobudeya, Syed Hissar, Vidya Mave, Marieke van der Zalm, Megan Palmer, Monica Kapasa, Perumal K. Bhavani, Sarath Balaji, Priyanka A. Raichur, Anne-Marie Demers, Graeme Hoddinott, Ellen Owen-Powell, Aarti Kinikar, Philippa Musoke, Veronica Mulenga, Rob Aarnoutse, Helen McIlleron, Anneke Hesseling, Angela M. Crook, Mark Cotton, Diana M. Gibb, on behalf of the SHINE trial team

Published in: Trials | Issue 1/2018

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Abstract

Background

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.

Methods/design

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.

Discussion

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.

Trial registration

International Standard Randomised Controlled Trials Number: ISRCTN63579542, 14 October 2014.
Pan African Clinical Trials Registry Number: PACTR20150500114​1379, 14 May 2015.
Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.
Appendix
Available only for authorised users
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Metadata
Title
Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
Authors
Chishala Chabala
Anna Turkova
Margaret J. Thomason
Eric Wobudeya
Syed Hissar
Vidya Mave
Marieke van der Zalm
Megan Palmer
Monica Kapasa
Perumal K. Bhavani
Sarath Balaji
Priyanka A. Raichur
Anne-Marie Demers
Graeme Hoddinott
Ellen Owen-Powell
Aarti Kinikar
Philippa Musoke
Veronica Mulenga
Rob Aarnoutse
Helen McIlleron
Anneke Hesseling
Angela M. Crook
Mark Cotton
Diana M. Gibb
on behalf of the SHINE trial team
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2608-5

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