Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial

Abstract

Background: Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. We aimed to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the two treatments.

Methods: In this pragmatic, multicentre, parallel-group, unmasked, randomised, non-inferiority trial, children aged 5-16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were recruited from 11 children's hospitals in Canada, the USA, Finland, Sweden, and Singapore. Patients were randomly assigned (1:1) to the antibiotic or the appendicectomy group with an online stratified randomisation tool, with stratification by sex, institution, and duration of symptoms (≥48 h vs <48 h). The primary outcome was treatment failure within 1 year of random assignment. In the antibiotic group, failure was defined as removal of the appendix, and in the appendicectomy group, failure was defined as a normal appendix based on pathology. In both groups, failure was also defined as additional procedures related to appendicitis requiring general anaesthesia. Interim analysis was done to determine whether inferiority was to be declared at the halfway point. We used a non-inferiority design with a margin of 20%. All outcomes were assessed in participants with 12-month follow-up data. The trial was registered at ClinicalTrials.gov (NCT02687464).

Findings: Between Jan 20, 2016, and Dec 3, 2021, 936 patients were enrolled and randomly assigned to appendicectomy (n=459) or antibiotics (n=477). At 12-month follow-up, primary outcome data were available for 846 (90%) patients. Treatment failure occurred in 153 (34%) of 452 patients in the antibiotic group, compared with 28 (7%) of 394 in the appendicectomy group (difference 26·7%, 90% CI 22·4-30·9). All but one patient meeting the definition for treatment failure with appendicectomy were those with negative appendicectomies. Of those who underwent appendicectomy in the antibiotic group, 13 (8%) had normal pathology. There were no deaths or serious adverse events in either group. The relative risk of having a mild-to-moderate adverse event in the antibiotic group compared with the appendicectomy group was 4·3 (95% CI 2·1-8·7; p<0·0001).

Interpretation: Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy.

Funding: None.