Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of nonoperative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a costeffectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% noninferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials. gov: NCT02687464. Registered on Jan 13th 2016. BACKGROUND Acute appendicitis is the most common surgical emergency in children. The lifetime risk of developing appendicitis is 7%–8%, with a peak incidence in the teenage years. The associated financial burden of treating appendicitis is very large. For over 100 years, surgical removal of the appendix has been deemed necessary to effectively treat acute appendicitis. Appendectomy remains the cornerstone of treatment for acute appendicitis, with the What is already known on this topic? ► Appendectomy has been the mainstay of treatment of acute appendicitis for over 100 years. ► Recently the need for surgery for uncomplicated acute appendicitis has been challenged and current data suggest the majority of children can be treated with a non-operative treatment pathway instead of surgery. ► The comparative safety and efficacy of non-operative treatment compared with surgery have not yet been