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

Abstract

BackgroundAppendectomy 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 non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed.MethodsMulticentre, 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 cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children.DiscussionThe 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 numberclinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016.

Non-operative management of appendicitis in children

“…The main outcome of interest in individuals allocated to appendicectomy is likely complications of surgery. Many also believe that negative appendicectomy (ie, removal of an appendix in a child who did not actually have appendicitis) is equally important since this would represent surgery that had been performed unnecessarily 41. The negative appendicectomy rate in in the UK is approximately 10% for children treated in specialist paediatric surgical centres and 24% for children treated by adult general surgeons63 but in some centres in which all children have a radiological diagnosis (ultrasound with CT for equivocal findings) may be as low as 1%–2%.…”

Clinical recovery in children with uncomplicated appendicitis undergoing non-operative treatment: secondary analysis of a prospective cohort study

“…However, the results from the first large randomized trials are expected no sooner than 2020 [12, 16, 22, 33, 41]. Thus this is currently the best available evidence regarding clinical recovery.…”

Five lessons in uncomplicated appendicitis: Can we remove the surgery?

“…Children are considered eligible if they are aged 5–15 and have a diagnosis of acute uncomplicated appendicitis that would otherwise lead to a recommendation to operate . Other trials are also underway in the USA, Canada, Finland and the Netherlands . Findings from these studies will continue to inform us about the safety, efficacy and applicability of non‐operative management, and give a clearer picture of its place in the management of appendicitis in the new millennium.…”