Non-operative treatment strategy versus surgery for children with simple appendicitis: non-inferiority randomised controlled trial.

Objective: To compare a non-operative treatment strategy with appendectomy for children with simple appendicitis, in terms of complications, avoidance of appendectomy, health related quality of life, and costs, after one year of follow-up. Design: Non-inferiority randomised controlled trial. Setting: 15 academic or general teaching hospitals, Netherlands, 1 January 2017 to 19 October 2023. Participants: 302 children, aged 7-17 years with imaging confirmed simple appendicitis, excluding those with a faecolith. Interventions: Participants were randomised to the non-operative treatment strategy group (n=151) or the appendectomy group (n=151). The non-operative treatment strategy group received 48 hours of intravenous amoxicillin-clavulanic acid and gentamicin, followed by five days of oral amoxicillin-clavulanic acid. Main outcome measures: The primary outcome was the proportion of participants with a complication within one year (non-inferiority margin of 5%). Secondary outcomes were the number of participants not requiring appendectomy, health related quality of life, and costs. Results: In the intention-to-treat population, 14/151 (9.3%) participants in the non-operative treatment strategy group versus 13/151 (8.6%) in the appendectomy group had a complication during the one year follow-up period (absolute risk difference 0.7%, upper limit of 95% confidence interval (CI) 7.1%). Appendectomy was avoided in 105/151 (69.5%) participants in the non-operative treatment strategy group. No difference was found in health related quality of life between the treatment groups. Costs (both direct and societal) were lower in the non-operative treatment strategy group (mean difference €767 (£668; US$902), 95% CI 320 to 1214 for direct costs and €874, 118 to 1631 for societal costs). In the non-operative treatment strategy group, length of hospital stay was significantly longer (3.3±2.4 Conclusions: Non-inferiority of a non-operative treatment strategy for acute simple appendicitis in children could not be proven significantly. Most of the 95% CI was within the 5% non-inferiority margin, however, with a probability of 90.7% that a non-operative treatment strategy resulted in an increase in complications of ≤5%. Absolute risk difference in the proportion of participants with complications was marginal. Surgery was avoided in about 70% of participants in the non-operative treatment strategy group. Health related quality of life was comparable between the treatment strategies. A non-operative treatment strategy was associated with lower costs, but longer time in hospital, more unscheduled healthcare visits, and lower patient satisfaction at the one year follow-up, measured by the Net Promoter Score. Trial registration: NCT02848820; NTR5977.