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Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
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 effectiv...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909210/ https://www.ncbi.nlm.nih.gov/pubmed/29673395 http://dx.doi.org/10.1186/s13063-018-2608-5 |
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author | Chabala, Chishala Turkova, Anna Thomason, Margaret J. Wobudeya, Eric Hissar, Syed Mave, Vidya van der Zalm, Marieke Palmer, Megan Kapasa, Monica Bhavani, Perumal K. Balaji, Sarath Raichur, Priyanka A. Demers, Anne-Marie Hoddinott, Graeme Owen-Powell, Ellen Kinikar, Aarti Musoke, Philippa Mulenga, Veronica Aarnoutse, Rob McIlleron, Helen Hesseling, Anneke Crook, Angela M. Cotton, Mark Gibb, Diana M. |
author_facet | Chabala, Chishala Turkova, Anna Thomason, Margaret J. Wobudeya, Eric Hissar, Syed Mave, Vidya van der Zalm, Marieke Palmer, Megan Kapasa, Monica Bhavani, Perumal K. Balaji, Sarath Raichur, Priyanka A. Demers, Anne-Marie Hoddinott, Graeme Owen-Powell, Ellen Kinikar, Aarti Musoke, Philippa Mulenga, Veronica Aarnoutse, Rob McIlleron, Helen Hesseling, Anneke Crook, Angela M. Cotton, Mark Gibb, Diana M. |
author_sort | Chabala, Chishala |
collection | PubMed |
description | 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: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-018-2608-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5909210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59092102018-04-30 Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial Chabala, Chishala Turkova, Anna Thomason, Margaret J. Wobudeya, Eric Hissar, Syed Mave, Vidya van der Zalm, Marieke Palmer, Megan Kapasa, Monica Bhavani, Perumal K. Balaji, Sarath Raichur, Priyanka A. Demers, Anne-Marie Hoddinott, Graeme Owen-Powell, Ellen Kinikar, Aarti Musoke, Philippa Mulenga, Veronica Aarnoutse, Rob McIlleron, Helen Hesseling, Anneke Crook, Angela M. Cotton, Mark Gibb, Diana M. Trials Study Protocol 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: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-018-2608-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-19 /pmc/articles/PMC5909210/ /pubmed/29673395 http://dx.doi.org/10.1186/s13063-018-2608-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Chabala, Chishala Turkova, Anna Thomason, Margaret J. Wobudeya, Eric Hissar, Syed Mave, Vidya van der Zalm, Marieke Palmer, Megan Kapasa, Monica Bhavani, Perumal K. Balaji, Sarath Raichur, Priyanka A. Demers, Anne-Marie Hoddinott, Graeme Owen-Powell, Ellen Kinikar, Aarti Musoke, Philippa Mulenga, Veronica Aarnoutse, Rob McIlleron, Helen Hesseling, Anneke Crook, Angela M. Cotton, Mark Gibb, Diana M. Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title | Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title_full | Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title_fullStr | Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title_full_unstemmed | Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title_short | Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial |
title_sort | shorter treatment for minimal tuberculosis (tb) in children (shine): a study protocol for a randomised controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909210/ https://www.ncbi.nlm.nih.gov/pubmed/29673395 http://dx.doi.org/10.1186/s13063-018-2608-5 |
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