Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial
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...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-018-2608-5 |
| _version_ | 1819265872972218368 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chishala Chabala |
| collection | DOAJ |
| description | 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: PACTR201505001141379, 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017. |
| first_indexed | 2024-12-23T20:52:17Z |
| format | Article |
| id | doaj.art-c7b492728303475aa269ac5a2bc5f4ce |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-23T20:52:17Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-c7b492728303475aa269ac5a2bc5f4ce2022-12-21T17:31:38ZengBMCTrials1745-62152018-04-0119111210.1186/s13063-018-2608-5Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trialChishala Chabala0Anna Turkova1Margaret J. Thomason2Eric Wobudeya3Syed Hissar4Vidya Mave5Marieke van der Zalm6Megan Palmer7Monica Kapasa8Perumal K. Bhavani9Sarath Balaji10Priyanka A. Raichur11Anne-Marie Demers12Graeme Hoddinott13Ellen Owen-Powell14Aarti Kinikar15Philippa Musoke16Veronica Mulenga17Rob Aarnoutse18Helen McIlleron19Anneke Hesseling20Angela M. Crook21Mark Cotton22Diana M. Gibb23on behalf of the SHINE trial teamUniversity Teaching Hospital, Children’s HospitalMedical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and MethodologyMedical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and MethodologyMakerere University-John Hopkins University Care LtdIndia Council of Medical Research, National Institute for Research in TuberculosisByramjee Jeejeebhoy Government Medical CollegeDesmond Tutu TB Centre, Stellenbosch UniversityDesmond Tutu TB Centre, Stellenbosch UniversityUniversity Teaching Hospital, Children’s HospitalIndia Council of Medical Research, National Institute for Research in TuberculosisIndia Institute of Child Health and Hospital for ChildrenByramjee Jeejeebhoy Government Medical CollegeDesmond Tutu TB Centre, Stellenbosch UniversityDesmond Tutu TB Centre, Stellenbosch UniversityMedical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and MethodologyByramjee Jeejeebhoy Government Medical CollegeMakerere University-John Hopkins University Care LtdUniversity Teaching Hospital, Children’s HospitalRadbound University Medical CenterUniversity of Cape TownDesmond Tutu TB Centre, Stellenbosch UniversityMedical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and MethodologyFamily Infectious Diseases Clinical Research Unit, Stellensbosch UniversityMedical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and MethodologyAbstract 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.http://link.springer.com/article/10.1186/s13063-018-2608-5TuberculosisEfficacyHIVShorter courseChild |
| spellingShingle | 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 Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial Trials Tuberculosis Efficacy HIV Shorter course Child |
| 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 | Tuberculosis Efficacy HIV Shorter course Child |
| url | http://link.springer.com/article/10.1186/s13063-018-2608-5 |
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