Surgery Outperforms Antibiotics for Acute Uncomplicated Appendicitis in Children: Lancet

"Among nearly 850 children with primary outcome data, treatment failure at 12 months was observed in 34% of those treated with antibiotics, compared to 7% of those who underwent appendectomy. This resulted in a difference of 26.7%, surpassing the 20% non-inferiority margin," the researchers reported in The Lancet.

The growing support in the literature for the non-operative management of uncomplicated appendicitis has sparked interest in exploring alternatives to surgery. To contribute to this evolving discussion, Prof Shawn D St Peter, Department of Surgery, Children's Mercy, Kansas City, MO, USA, and colleagues aimed to determine whether treating uncomplicated appendicitis in children with antibiotics is inferior to appendicectomy by directly comparing the failure rates of the two approaches.

For this purpose, the researchers conducted a pragmatic, multicenter, parallel-group, unmasked, randomized non-inferiority trial involving children aged 5–16 with suspected non-perforated appendicitis. Participants were recruited from 11 hospitals across Canada, the USA, Finland, Sweden, and Singapore. They were identified based on clinical diagnosis with or without radiological confirmation.

Using an online stratified randomization tool, patients were allocated in a 1:1 ratio to either the antibiotic or appendicectomy group, with stratification by sex, institution, and symptom duration (≥48 hours vs. <48 hours). The primary outcome was treatment failure within one year of randomization. In the antibiotic group, failure was defined as the need for appendectomy, while in the appendicectomy group, it referred to a normal appendix on pathology. Additionally, failure in both groups included any appendicitis-related procedures requiring general anesthesia.

An interim analysis was performed at the study’s midpoint to assess whether inferiority could be declared. The trial employed a non-inferiority design with a 20% margin, and all outcomes were evaluated among participants with complete 12-month follow-up data.

The study revealed the following findings:

• Between January 20, 2016, and December 3, 2021, 936 patients were enrolled and randomized to either appendicectomy (n=459) or antibiotics (n=477).
• Primary outcome data at 12 months were available for 90% of the patients.
• Treatment failure occurred in 34% of the antibiotic group compared to 7% (28/394) of the appendicectomy group, with a difference of 26.7%.
• Nearly all treatment failures in the appendicectomy group were due to negative appendicectomies.
• Among patients in the antibiotic group who later underwent appendicectomy, 8% had normal pathology.
• There were no deaths or serious adverse events in either group.
• The relative risk of experiencing a mild-to-moderate adverse event was 4.3 times higher in the antibiotic group compared to the appendicectomy group.

The researchers concluded that antibiotic management for non-perforated appendicitis did not meet the 20% non-inferiority margin and was less effective than appendicectomy when considering cumulative failure rates.

Reference:

St Peter SD, Noel-MacDonnell JR, Hall NJ, Eaton S, Suominen JS, Wester T, Svensson JF, Almström M, Muenks EP, Beaudin M, Piché N, Brindle M, MacRobie A, Keijzer R, Engstrand Lilja H, Kassa AM, Jancelewicz T, Butter A, Davidson J, Skarsgard E, Te-Lu Y, Nah S, Willan AR, Pierro A. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial. Lancet. 2025 Jan 18;405(10474):233-240. doi: 10.1016/S0140-6736(24)02420-6. PMID: 39826968.