Prophylactic Antibiotics to prevent chest infections in children with neurological impairment (PARROT): A randomised controlled trial.

Abstract

Background: Advances care have improved survival in children with non-progressive neurological impairment (NI). Respiratory disease is frequent, with lower respiratory tract infections (LRTI) causing hospitalisations, bronchiectasis, and premature death. Prophylactic antibiotics are increasingly used, but their effectiveness, safety, and impact on quality of life remain unclear due to a lack of robust evidence. Aim(s): To determine if 52 weeks of azithromycin prophylaxis reduces hospital admissions for LRTI in children with NI. Method(s): PARROT was a parallel-group, blinded RCT across 19 UK and 3 Australian paediatric centres. Participants (aged 3-17) had neurological impairment, persistent respiratory symptoms (assessed via LRSQ-Neuro), and a history of recurrent LRTI or prior prophylactic antibiotic use. Those previously on prophylactic antibiotics underwent an 8-week washout period before randomisation. Result(s): Ninety participants were randomised to azithromycin (n=47) or placebo (n=43); 62 (69%) from Australia and 28 (31%) from the UK. Due to COVID-19 challenges, recruitment ended early. Sixty-five (72%) completed treatment (azithromycin n=30, placebo n=35). Hospitalisation rates for LRTI were 36.7% (azithromycin) vs. 25.7% (placebo) (ARR 95% CI 0.11 [-0.12 to 0.33], RR 1.43 [0.68-2.97]). Conclusion(s): This is the first RCT assessing prophylactic antibiotics in children with NI. Due to early trial closure, there is insufficient evidence to confirm azithromycin's effectiveness. However, this study demonstrates the feasibility of clinical trials in this often-overlooked population, highlighting the need for further research.