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Abstract
Introduction Early childhood pneumonia is a common problem globally with long-term complications that include bronchiectasis and chronic obstructive pulmonary disease. It is biologically plausible that these long-term effects may be minimised in young children at increased risk of such sequelae if any residual lower airway infection and inflammation in their developing lungs can be treated successfully by longer antibiotic courses. In contrast, shortened antibiotic treatments are being promoted because of concerns over inducing antimicrobial resistance. Nevertheless, the optimal treatment duration remains unknown. Outcomes from randomised controlled trials (RCTs) on paediatric pneumonia have focused on short-term (usually <2 weeks) results. Indeed, no long-term RCT-generated outcome data are available currently. We hypothesise that a longer antibiotic course, compared with the standard treatment course, reduces the risk of chronic respiratory symptoms/signs or bronchiectasis 24 months after the original pneumonia episode.
Methods and analysis This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are ‘clinical cure’ at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.
Ethics and dissemination The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children’s and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.
Trial registration ACTRN12616000046404.
- pneumonia
- children
- clinical trials
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Footnotes
Contributors ABC conceived and designed the study, drafted the manuscript and was primarily responsible for obtaining the grant. KG co-conceived and designed the study, had a major input into the grant submission and edited the manuscript. RSW led the statistical components for grant submission. JWU, SMF, TWY, MHO, AMN, JdB, PSM, BL, PT contributed to study design, grant submission and manuscript. CAB is the lead investigator at the Auckland site and obtained a 2-year grant for recruiting the children in New Zealand. SMF is the lead investigator in Kota Kinabalu, MHO is the lead investigator in Kuching, AMN is the lead investigator in Kuala Lumpur and obtained a Malaysian grant that supported the study in Kuala Lumpur. NN and NS are the lead investigators at the Klang site. GBM initiated the project, prepared the SOPs, submitted the ethics application and is currently coordinating all aspects of the project. HSV leads the laboratory component of assessing nasopharyngeal bacteria and its resistance to antibiotics. All authors read and approved the final manuscript.
Funding The study is funded by a 5-year Australian National Health and Medical Research Council (NHMRC) project grant (number 1098443) and supported by a NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (grant number 1040830). The New Zealand site is supported by a 2-year grant from CureKids, New Zealand (grant 3571). The Kuala Lumpur site is partially funded by a University Malaya Research Grant RP026-14HTM. AC is supported by a NHMRC practitioner fellowship (grant 1058213). GM is supported by a NHMRC early career fellowship (grant 1111705). The views expressed in this publication are those of the authors and do not reflect the views of the NHMRC. The primary grant is held by the Menzies School of Health Research (Darwin), which also acts as the trial sponsor.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data sharing among institutions is in accordance to the Australian NHMRC multi-institutional agreement.
Patient consent for publication Not required.