INTRODUCTION: The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces re-consultation due to clinical deterioration in "at risk" children presenting with influenza-like illness (ILI) in primary or ambulatory care. METHODS: "At risk" children aged 6 months to 12 years presenting within f5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or placebo twice daily for 5 days (dosing based on age±weight). "At risk" groups included children with respiratory, cardiac, and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children, which would have allowed us to detect a reduction in the proportion of children re-consulting due to clinical deterioration from 40% to 26% with 90% power and 5% two-tailed alpha error, including allowance for 25% loss to follow-up and an inflation factor of 1.041. Participants, caregivers and investigators were blinded to treatment allocation. Intention-to-treat analysis included all randomised participants with primary outcome data on re-consultation due to clinical deterioration within 28 days. Safety analysis included all randomised participants. TRIAL REGISTRATION: ISRCTN 70714783. EudraCT 2013-002822-21. RESULTS: We recruited 271 children between February 11, 2015 and April 20, 2018. Primary outcome data were available for 265 children. Only 61/265 children (23.0%) re-consulted due to clinical deterioration. No evidence of a treatment effect was observed for re-consultation due to clinical deterioration (co-amoxiclav 33/133 (24.8%), placebo 28/132 (21.2%), adjusted risk ratio [RR] 1.16, 95% confidence interval [CI] 0.75 to 1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events were reported (co-amoxiclav 32/136 (23.5%), placebo 22/135 (16.3%), adjusted RR 1.45, 95% CI 0.90 to 2.34). Sixty-six adverse events were reported in total (co-amoxiclav n=37, placebo n=29). Nine serious adverse events were reported per group; none were considered related to study medication. CONCLUSION: Our trial did not find evidence that treatment with co-amoxiclav reduces risk of re-consultation due to clinical deterioration in "at risk" children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI.
Eur Respir J