Non-operative management of uncomplicated appendicitis in children: a randomised, controlled, non-inferiority study evaluating safety and efficacy

Background Appendicitis is the commonest paediatric surgical emergency. Adult studies suggest non-operative management (NOM) may have a place in care. There have been no adequately powered randomized controlled trials in children. Objective: to determine the safety and efficacy of NOM for paediatric simple appendicitis. Methods A non-inferiority randomized controlled trial was conducted comparing operative (OM) to NOM of SA in children aged five-15 years. Primary outcome was treatment success (no unplanned or unnecessary operation, or complication) at 30 days and 12 months, with a non-inferiority margin of 15%. (anzctr.org.au:ACTRN12616000788471). Results From 11 June 2016 to 30 November 2020, 222 children were randomized: 94 (42·34%) to OM and 128 (57·66%) to NOM. Non-inferiority of NOM was not demonstrated at either time point, with 45.67% of NOM patients subsequently undergoing operation. There was no significant difference in complications (p=0.399). Conclusions While noninferiority was not shown, NOM was safe, with no difference in adverse outcomes between the two groups. Further research to refine the place of NOM of simple appendicitis in children is required, including nuanced patient selection, longer term evaluation, the place of choice, and the acceptability of the treatment for children and their carers. Level of evidence Level 1 What is currently known There have been multiple studies examining the role of non-operative management (NOM) with antibiotics alone for appendicitis in adults, with inconclusive evidence regarding its non-inferiority to operative management. There have only been three pilot randomized control trial to date in children. What this study adds This is the first adequately powered randomized controlled trial in children. While non-inferiority was not shown, non-operative management was safe, and associated with significantly shorter time away from school and usual activities. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ACTRN12616000788471 ### Funding Statement There was no funding source for this study, including no research scholarship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics application status is approved by Ethics committee Sydney Children's Hospital Network HREC. Ethics approval number: HREC/15/SCHN/266 Parent or legal guardian consent was obtained for participation in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript and associated tables.