Recipient organisationAlder Hey Children's NHS Foundation Trust
Funding£1.5M
PeriodMar 2019 — Jun 2024
In plain English
AI plain-English summary
A 12-month course of the antibiotic azithromycin will be tested against a placebo in 500 children with neurological impairment who are prone to severe chest infections. These children have non-progressive brain injuries that leave them with persistent respiratory symptoms and a high risk of hospitalisation for lower respiratory tract infections. Currently, there is no standard care pathway for them. Doctors prescribe prophylactic antibiotics on an ad hoc basis because almost no evidence exists to guide treatment or guidelines. If the trial shows that azithromycin reduces hospitalisations, it would give clinicians a proven, low-cost tool to prevent a major cause of illness and hospital stays in a vulnerable group. Fewer hospitalisations would mean less disruption to family life, better school attendance, and reduced strain on paediatric wards. The trial also tracks antibiotic resistance in nasal swabs, so any benefit can be weighed against the risk of driving resistance. For parents and carers, the difference could be a child who spends more time at home and less time acutely ill.
View original technical description
Design Joint UK/Australian multicentre, randomised, double blind, placebo controlled trial comparing 12-month azithromycin to placebo in children with NI at risk of LRTI Setting 37 secondary and tertiary paediatric centres in UK and 3 large centres in Australia with associated networks Target Population Children and young persons with non-progressive NI with persistent respiratory symptoms at risk of hospitalisation for LRTI Exclusion criteria Children with progressive causes of NI, neuromuscular disorders or with pre-existing non-neurological conditions such as CF, immunodeficiency, hypersensitivity or contra-indications to taking macrolides etc. Health technologies being assessed Liquid formulation of Azithromycin vs matched placebo Measurements of costs and outcomes Primary outcome is the proportion of children hospitalised for LRTI. Other outcomes will include: • Need for healthcare utilization (GP visits/A&E attendances), rescue antibiotics, changes in concomitant medications, etc. • Nasal swab microbiology and bacteria AMR profiling; bacterial & viral microbiology during hospitalisations for presumed LRTI • HR-QoL of both child and parent/carer • Respiratory symptom questionnaire responses • Actigraphy/sleep questionnaire assessment of parent and child sleep quality/amount[28] • School attendance • Resource use by questionnaire and linked routine data from NHS Digital to for HES and GP attendance • CHU9D utility measure for estimation of QALYs Data management/analysis Data will be centrally managed on a GCP compliant database (Infermed MACRO). A complete statistical analysis plan will be written before any comparative analysis is done. The primary analysis will use principle of intention to treat on all randomized participants. Binary outcomes will be reported as relative risk and 95% CIs. Continuous outcomes will be reported as change from baseline and analysed using analysis of covariance. Time to event outcomes will be summarised by Kaplan-Meier curves and compared overall using logrank tests and survival regression methods. Missing data will be monitored and strategies developed to minimise its occurrence. Sample size To detect a 30% reduction in hospitalisation rate in children with NI and respiratory symptoms at risk of LRTI, with 90% power (alpha 0.05), we would require 225 patients per group, increasing to 250 allowing for 10% loss to follow-up/attrition, i.e. 500 children in total. Difference between current and planned pathways There is no current standard care pathway for these children, hence the need for this study. Currently, there is little evidence to guide practice or the development of guidelines and prophylactic antibiotics are prescribed on an ad hoc basis. Project timetable -6–0 mths: REC/HRA 0–6 mths: Set-up 6–12 mths: Internal pilot 13–54 mths: Trial recruitment proper 6-54 mths: HES/GP & school attendance data collection and analysis in select centres 54-60 mths: Data analysis & monograph preparation Expertise in team PMc/JG/JP/RL/AC/LT/PG/DR/KW/CS-clinical expertise; MP-leverage of CRN resources; HJS-PPI rep.; CM-PPI expertise; PMc/JG/AC/MP-expertise in leading multicenter RCTs; JP/RL/CM/DR/KW-expertise in running definitive RCTs in children with NI; RL/DR-experience in use of GP/HES data for research; HH/PRW/AJ-biostat/trial methodology expertise; PG-sleep/NI expertise; DE-microbiological/genomic expertise; MW-drug/formulations expertise; DH-HEA expertise.
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