PMID- 33737410 OWN - NLM STAT- MEDLINE DCOM- 20211027 LR - 20211027 IS - 1399-3003 (Electronic) IS - 0903-1936 (Linking) VI - 58 IP - 4 DP - 2021 Oct TI - The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial. LID - 2002819 [pii] LID - 10.1183/13993003.02819-2020 [doi] AB - INTRODUCTION: The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces reconsultation due to clinical deterioration in "at risk" children presenting with influenza-like illness (ILI) in primary or ambulatory care. METHODS: "At risk" children aged from 6 months to 12 years presenting within 5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or a 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 reconsulting 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 reconsultation 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 out of 265 children (23.0%) reconsulted due to clinical deterioration. No evidence of a treatment effect was observed for reconsultation due to clinical deterioration (33 out of 133 for co-amoxiclav (24.8%) and 28 out of 132 (21.2%) for placebo; adjusted risk ratio (RR) 1.16, 95% confidence interval (CI) 0.75-1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events (AEs) were reported (32 out of 136 (23.5%) for co-amoxiclav and 22 out of 135 (16.3%) for placebo; adjusted RR 1.45, 95% CI 0.90-2.34). In total, 66 AEs were reported (co-amoxiclav, n=37; placebo, n=29). Nine serious AEs were reported per group, although none were considered related to study medication. CONCLUSION: Our trial did not find evidence that treatment with co-amoxiclav reduces risk of reconsultation 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. CI - Copyright (c)The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org. FAU - Wang, Kay AU - Wang K AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK kay.wang@phc.ox.ac.uk. FAU - Semple, Malcolm G AU - Semple MG AUID- ORCID: 0000-0001-9700-0418 AD - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. AD - Dept of Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK. FAU - Moore, Michael AU - Moore M AD - Academic Unit, Primary Care and Population Sciences, University of Southampton, Aldermoor Health Centre, Southampton, UK. FAU - Hay, Alastair D AU - Hay AD AD - Centre for Academic Primary Care, Population Health Sciences, Bristol Medical School, Bristol, UK. FAU - Tonner, Sharon AU - Tonner S AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Galal, Ushma AU - Galal U AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Grabey, Jenna AU - Grabey J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Carver, Tricia AU - Carver T AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Perera, Rafael AU - Perera R AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Yu, Ly-Mee AU - Yu LM AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Mollison, Jill AU - Mollison J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Little, Paul AU - Little P AD - Dept of Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK. FAU - Farmer, Andrew AU - Farmer A AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Butler, Christopher C AU - Butler CC AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. FAU - Harnden, Anthony AU - Harnden A AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Primary Care, Oxford, UK. LA - eng SI - ISRCTN/ISRCTN70714783 SI - EudraCT/2013-002822-21 GR - RP-PG-1210-12012/Department of Health/United Kingdom PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20211007 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 RN - 0 (Anti-Bacterial Agents) SB - IM MH - Ambulatory Care MH - Anti-Bacterial Agents/therapeutic use MH - Child MH - Double-Blind Method MH - Humans MH - *Influenza, Human/drug therapy MH - Pandemics MH - Treatment Outcome COIS- Conflict of interest: K. Wang held a National Institute for Health Research (NIHR) Academic Clinical Lectureship during the conduct of the study and currently holds a NIHR Postdoctoral Fellowship. Conflict of interest: M.G. Semple reports grants from the UK NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool and the Wellcome Trust Enhancing Research Activity in Epidemic Situations (ERAES) Programme during the conduct of the study, and grants from the Wellcome Trust and the Bill & Melinda Gates Foundation, as well as grants from UK NIHR Efficacy and Mechanism Evaluation, outside the submitted work; and is a minority owner of Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work. Conflict of interest: M. Moore has nothing to disclose. Conflict of interest: A.D. Hay has nothing to disclose. Conflict of interest: S. Tonner has nothing to disclose. Conflict of interest: U. Galal has nothing to disclose. Conflict of interest: J. Grabey has nothing to disclose. Conflict of interest: T. Carver has nothing to disclose. Conflict of interest: R. Perera receives funding from the NIHR Oxford Biomedical Research Centre (BRC), the NIHR Oxford Medtech and In-Vitro Diagnostics Cooperative (MIC), the NIHR Applied Research Collaboration (ARC) Oxford and Thames Valley, and the Oxford Martin School. Conflict of interest: L-M. Yu has nothing to disclose. Conflict of interest: J. Mollison has nothing to disclose. Conflict of interest: P. Little has nothing to disclose. Conflict of interest: A. Farmer receives funding from the NIHR Oxford BRC and is a NIHR Senior Investigator. Conflict of interest: C.C. Butler reports grants from the NIHR as an NIHR Senior Investigator and the NIHR Health Technology Assessment Programme to support the study, as well as grants from the NIHR Health Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance and grants from NIHR Health for the MIC for innovative diagnostics and monitoring technology to enhance community healthcare, during the conduct of the study; personal fees for advisory board work from Roche Molecular Systems and Pfizer, and grants from Roche Molecular Diagnostics, outside the submitted work. Afinion CRP devices and associated training to participating general practices were provided at no cost to the study by Alere and was part of a publicly funded research consortia that include industrial partners. Conflict of interest: A. Harnden has nothing to disclose. EDAT- 2021/03/20 06:00 MHDA- 2021/10/28 06:00 CRDT- 2021/03/19 06:36 PHST- 2020/07/17 00:00 [received] PHST- 2021/02/18 00:00 [accepted] PHST- 2021/03/20 06:00 [pubmed] PHST- 2021/10/28 06:00 [medline] PHST- 2021/03/19 06:36 [entrez] AID - 13993003.02819-2020 [pii] AID - 10.1183/13993003.02819-2020 [doi] PST - epublish SO - Eur Respir J. 2021 Oct 7;58(4):2002819. doi: 10.1183/13993003.02819-2020. Print 2021 Oct.