Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania

Background Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting wi...

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Main Authors: Per Ashorn, Sarah S Somji, Pratibha Dhingra, Usha Dhingra, Arup Dutta, Prabhabati Devi, Jitendra Kumar, Saikat Deb, Om Prakash Semwal, Sunil Sazawal, Karim Manji, Rodrick Kisenge, Mohamed Bakari, Enju Liu, Christopher Sudfeld, Christopher P Duggan, Rajiv Bahl, Jonathon L Simon
Format: Article
Language:English
Published: BMJ Publishing Group 2019-09-01
Series:BMJ Paediatrics Open
Online Access:https://bmjpaedsopen.bmj.com/content/3/1/e000460.full
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author Per Ashorn
Sarah S Somji
Pratibha Dhingra
Usha Dhingra
Arup Dutta
Prabhabati Devi
Jitendra Kumar
Saikat Deb
Om Prakash Semwal
Sunil Sazawal
Karim Manji
Rodrick Kisenge
Mohamed Bakari
Enju Liu
Christopher Sudfeld
Christopher P Duggan
Rajiv Bahl
Jonathon L Simon
author_facet Per Ashorn
Sarah S Somji
Pratibha Dhingra
Usha Dhingra
Arup Dutta
Prabhabati Devi
Jitendra Kumar
Saikat Deb
Om Prakash Semwal
Sunil Sazawal
Karim Manji
Rodrick Kisenge
Mohamed Bakari
Enju Liu
Christopher Sudfeld
Christopher P Duggan
Rajiv Bahl
Jonathon L Simon
author_sort Per Ashorn
collection DOAJ
description Background Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed.Methods/design The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6–59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration.Discussion The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6–59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea.Trial registration number NCT03078842.Trial status Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.
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spelling doaj-art-b2e92873bc7a45af9b1b710a2c72fa9e2024-12-01T15:55:08ZengBMJ Publishing GroupBMJ Paediatrics Open2399-97722019-09-013110.1136/bmjpo-2019-000460Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and TanzaniaPer Ashorn0Sarah S Somji1Pratibha Dhingra2Usha Dhingra3Arup Dutta4Prabhabati Devi5Jitendra Kumar6Saikat Deb7Om Prakash Semwal8Sunil Sazawal9Karim Manji10Rodrick Kisenge11Mohamed Bakari12Enju Liu13Christopher Sudfeld14Christopher P Duggan15Rajiv Bahl16Jonathon L Simon17Department of Pediatrics, Tampere University Hospital, Tampere, Finland1 Department of Pediatrics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania2 Centre for Public Health Kinetics (CPHK), New Delhi, Delhi, IndiaCenter for Public Health Kinetics, New Delhi, IndiaCenter for Public Health Kinetics, New Delhi, India2 Centre for Public Health Kinetics (CPHK), New Delhi, Delhi, India2 Centre for Public Health Kinetics (CPHK), New Delhi, Delhi, IndiaCenter for Public Health Kinetics, New Delhi, India2 Centre for Public Health Kinetics (CPHK), New Delhi, Delhi, IndiaCenter for Public Health Kinetics, New Delhi, IndiaDepartment of Pediatrics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, United Republic ofDepartment of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania1 Department of Pediatrics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of TanzaniaDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children`s Hospital, Boston, Massachusetts, USA4 Harvard University T H Chan School of Public Health, Boston, Massachusetts, USADepartments of Nutrition and Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Maternal, Newborn, Child and Adolescent Health and Ageing, World Health Organization, Geneva, Switzerland8 Organisation mondiale de la Sante, Geneva, SwitzerlandBackground Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed.Methods/design The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6–59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration.Discussion The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6–59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea.Trial registration number NCT03078842.Trial status Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.https://bmjpaedsopen.bmj.com/content/3/1/e000460.full
spellingShingle Per Ashorn
Sarah S Somji
Pratibha Dhingra
Usha Dhingra
Arup Dutta
Prabhabati Devi
Jitendra Kumar
Saikat Deb
Om Prakash Semwal
Sunil Sazawal
Karim Manji
Rodrick Kisenge
Mohamed Bakari
Enju Liu
Christopher Sudfeld
Christopher P Duggan
Rajiv Bahl
Jonathon L Simon
Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
BMJ Paediatrics Open
title Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
title_full Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
title_fullStr Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
title_full_unstemmed Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
title_short Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania
title_sort effect of dose reduction of supplemental zinc for childhood diarrhoea study protocol for a double masked randomised controlled trial in india and tanzania
url https://bmjpaedsopen.bmj.com/content/3/1/e000460.full
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