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

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dc.contributor.authorChabala, Chishala
dc.contributor.authorTurkova, Anna
dc.contributor.authorThomason, Margaret J
dc.contributor.authorWobudeya, Eric
dc.contributor.authorHissar, Syed
dc.contributor.authorMave, Vidya
dc.contributor.authorvan der Zalm, Marieke
dc.contributor.authorPalmer, Megan
dc.contributor.authorKapasa, Monica
dc.contributor.authorBhavani, Perumal K
dc.contributor.authorBalaji, Sarath
dc.contributor.authorRaichur, Priyanka A
dc.contributor.authorDemers, Anne-Marie
dc.contributor.authorHoddinott, Graeme
dc.contributor.authorOwen-Powell, Ellen
dc.contributor.authorKinikar, Aarti
dc.contributor.authorMusoke, Philippa
dc.contributor.authorMulenga, Veronica
dc.contributor.authorAarnoutse, Rob
dc.contributor.authorMcIlleron, Helen
dc.contributor.authorHesseling, Anneke
dc.contributor.authorCrook, Angela M
dc.contributor.authorCotton, Mark
dc.contributor.authorGibb, Diana M
dc.date.accessioned2018-05-03T11:08:26Z
dc.date.available2018-05-03T11:08:26Z
dc.date.issued2018-04-19
dc.date.updated2018-04-22T03:25:08Z
dc.description.abstractBackground: 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 smearnegative 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.
dc.identifier.apacitationChabala, C., Turkova, A., Thomason, M. J., Wobudeya, E., Hissar, S., Mave, V., ... Gibb, D. M. (2018). Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial. <i>Trials</i>, http://hdl.handle.net/11427/27863en_ZA
dc.identifier.chicagocitationChabala, Chishala, Anna Turkova, Margaret J Thomason, Eric Wobudeya, Syed Hissar, Vidya Mave, Marieke van der Zalm, et al "Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial." <i>Trials</i> (2018) http://hdl.handle.net/11427/27863en_ZA
dc.identifier.citationChabala, C., Turkova, A., Thomason, M. J., Wobudeya, E., Hissar, S., Mave, V., ... & Balaji, S. (2018). Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial. Trials, 19(1), 237.
dc.identifier.ris TY - Journal Article AU - Chabala, Chishala AU - Turkova, Anna AU - Thomason, Margaret J AU - Wobudeya, Eric AU - Hissar, Syed AU - Mave, Vidya AU - van der Zalm, Marieke AU - Palmer, Megan AU - Kapasa, Monica AU - Bhavani, Perumal K AU - Balaji, Sarath AU - Raichur, Priyanka A AU - Demers, Anne-Marie AU - Hoddinott, Graeme AU - Owen-Powell, Ellen AU - Kinikar, Aarti AU - Musoke, Philippa AU - Mulenga, Veronica AU - Aarnoutse, Rob AU - McIlleron, Helen AU - Hesseling, Anneke AU - Crook, Angela M AU - Cotton, Mark AU - Gibb, Diana M AB - 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 smearnegative 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. DA - 2018-04-19 DB - OpenUCT DP - University of Cape Town J1 - Trials LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial TI - Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial UR - http://hdl.handle.net/11427/27863 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s13063-018-2608-5
dc.identifier.urihttp://hdl.handle.net/11427/27863
dc.identifier.vancouvercitationChabala C, Turkova A, Thomason MJ, Wobudeya E, Hissar S, Mave V, et al. Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial. Trials. 2018; http://hdl.handle.net/11427/27863.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceTrials
dc.source.urihttps://trialsjournal.biomedcentral.com/
dc.subject.otherTuberculosis
dc.subject.otherEfficacy
dc.subject.otherHIV
dc.subject.otherShorter course
dc.subject.otherChild
dc.titleShorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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