McCallum, Gabrielle B

Byrnes, Catherine A

Morris, Peter S

Grimwood, Keith

Marsh, Robyn L

Chatfield, Mark D

Bowden, Emily R

Schutz, Kobi L

Sarmento, Nevio

Fancourt, Nicholas

Francis, Joshua

Zhao, Yuejen

Vieira, Adriano

Hare, Kim M

Bonney, Dennis

Trenholme, Adrian

Lawrence, Shirley

Marwick, Felicity

Karvonen, Bronwyn

Maclennan, Carolyn

Connors, Christine

Smith-Vaughan, Heidi

Santos Lay, Milena

Soares da Silva, Endang

Chang, Anne B

2025-02-05

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.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.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.Australia New Zealand Clinical Trial Registry ACTRN12619000456156.

Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia gabrielle.mccallum@menzies.edu.au.

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.

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.

Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.

Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, 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.

Global and Tropical Health, Menzies School of Health Research, Casuarina, Northern Territory, 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.

Child and Maternal Health, Menzies School of Health Research, Darwin, 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.

Department of Paediatrics, Middlemore Hospital, Auckland, Auckland, New Zealand.

Department of Paediatrics, Middlemore Hospital, Auckland, Auckland, New Zealand.

Northern Territory Department of Health, Casuarina, Northern Territory, Australia.

School Nurse, St Francis of the Fields Primary School, Strathfieldsaye, Victoria, Australia.

Child and Maternal Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.

Top End Health Services, 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, Guido Valadares National Hospital, Dili, Timor-Leste.

Partnership for Human Development, Dili, Timor-Leste.

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.

BMJ Open . 2025 Feb 5;15(2):e097455. doi: 10.1136/bmjopen-2024-097455.

2044-6055

0000-0002-0210-1468

0000-0002-5775-4503

https://pubmed.ncbi.nlm.nih.gov/39909513/?otool=iaurydwlib

https://hdl.handle.net/10137/14009

Antibiotics

Child

Paediatric thoracic medicine

Randomized Controlled Trial

Respiratory infections

Humans

Azithromycin

Anti-Bacterial Agents

Respiratory Tract Infections

Australia

New Zealand

Double-Blind Method

Randomized Controlled Trials as Topic

Multicenter Studies as Topic

Hospitalization

Child

Infant

Child, Preschool

Acute Disease

Bronchiectasis

Male

Female

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.

Journal Article

Publication