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© 2025 Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Introduction

Acute lower respiratory infections (ALRIs) remain the leading causes of repeated hospitalisations among young disadvantaged Australian and New Zealand First Nations and Timorese children. Severe (hospitalised) and recurrent ALRIs in the first years of life are associated with future chronic lung diseases (eg, bronchiectasis) and impaired lung function. Despite the high burden and long-term consequences of severe ALRIs, clinical, evidence-based and feasible interventions (other than vaccine programmes) that reduce ALRI hospitalisations in children are limited. This randomised controlled trial (RCT) will address this unmet need by trialling a commonly prescribed macrolide antibiotic (azithromycin) for 6–12 months. Long-term azithromycin was chosen as it reduces ALRI rates by 50% in Australian and New Zealand First Nations children with chronic suppurative lung disease or bronchiectasis. The aim of this multicentre, international, double-blind, placebo-containing RCT is to determine whether 6–12 months of weekly azithromycin administered to Australian and New Zealand First Nations and Timorese children after their hospitalisation with an ALRI reduces subsequent ALRIs compared with placebo. Our primary hypothesis is that children receiving long-term azithromycin will have fewer medically attended ALRIs over the intervention period than those receiving placebo.

Methods and analysis

We will recruit 160 Australian and New Zealand First Nations and Timorese children aged <2 years to a parallel, superiority RCT across four hospitals from three countries (Australia, New Zealand and Timor-Leste). The primary outcome is the rate of medically attended ALRIs during the intervention period. The secondary outcomes are the rates and proportions of children with ALRI-related hospitalisation, chronic symptoms/signs suggestive of underlying chronic suppurative lung disease or bronchiectasis, serious adverse events, and antimicrobial resistance in the upper airways, and cost-effectiveness analyses.

Ethics and dissemination

The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Health Research (Australia), Health and Disability Ethics Committee (New Zealand) and the Institute National of Health-Research Technical Committee (Timor-Leste) approved this study. The study outcomes will be disseminated to academic and medical communities via international peer-reviewed journals and conference presentations, and findings reported to health departments and consumer-based health organisations.

Clinical trial registration

Australia New Zealand Clinical Trial Registry ACTRN12619000456156.

Details

Title
Azithromycin to prevent acute lower respiratory infections among Australian and New Zealand First Nations and Timorese children (PETAL trial): study protocol for a multicentre, international, double-blind, randomised controlled trial
Author
McCallum, Gabrielle B 1   VIAFID ORCID Logo  ; Byrnes, Catherine A 2 ; Morris, Peter S 1 ; Grimwood, Keith 3 ; Marsh, Robyn L 4 ; Chatfield, Mark D 5 ; Bowden, Emily R 1 ; Schutz, Kobi L 1 ; Sarmento, Nevio 6 ; Fancourt, Nicholas 7 ; Francis, Joshua 6 ; Zhao, Yuejen 8   VIAFID ORCID Logo  ; Vieira, Adriano 1 ; Hare, Kim M 1 ; Bonney, Dennis 9 ; Trenholme, Adrian 10 ; Lawrence, Shirley 10 ; Marwick, Felicity 11 ; Karvonen, Bronwyn 12 ; Maclennan, Carolyn 1 ; Connors, Christine 13 ; Smith-Vaughan, Heidi 1 ; Milena Santos Lay 14 ; Endang Soares da Silva 15 ; Chang, Anne B 16 

 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia 
 Department of Pediatrics, Starship Children's Health, Auckland, Auckland, New Zealand; The University of Auckland Department of Paediatrics Child and Youth Health, Auckland, Auckland, New Zealand 
 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; School of Medicine and Dentistry, Griffith University, Southport, Queensland, Australia 
 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; University of Tasmania School of Health Sciences, Launceston, Tasmania, Australia 
 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; Faculty of Health, Medicine and Behavioural Sciences, University of Queensland, Kedron, Queensland, Australia 
 Global and Tropical Health, Menzies School of Health Research, Casuarina, Northern Territory, Australia 
 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia 
 Health Statistics and Informatics, Northern Territory Department of Health, Casuarina, Northern Territory, Australia 
 Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; Department of Paediatrics, Royal Darwin Hospital Department of Maternal and Child Health, Darwin, Northern Territory, Australia 
10  Department of Paediatrics, Middlemore Hospital, Auckland, Auckland, New Zealand 
11  Northern Territory Department of Health, Casuarina, Northern Territory, Australia 
12  School Nurse, St Francis of the Fields Primary School, Strathfieldsaye, Victoria, Australia 
13  Top End Health Services, Northern Territory Department of Health, Casuarina, Northern Territory, Australia 
14  Department of Paediatrics, Guido Valadares National Hospital, Dili, Timor-Leste 
15  Partnership for Human Development, Dili, Timor-Leste 
16  Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia; The Australian Centre for Health Services Innovations, Queensland University of Technology, Brisbane, Queensland, Australia 
First page
e097455
Section
Paediatrics
Publication year
2025
Publication date
2025
Publisher
BMJ Publishing Group LTD
e-ISSN
20446055
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3163362153
Copyright
© 2025 Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.