The clinical and cost effectiveness of a conservative treatment pathway compared to appendicectomy in children with uncomplicated acute appendicitis: study protocol for a randomised controlled multi-centre open-label parallel-group non-inferiority trial (CONTRACT 2 trial) in the United Kingdom (UK).

backgroundCurrently, the most frequently used treatment for acute appendicitis in children in the United Kingdom (UK) is an appendicectomy. However, there is increasing scientific and patient interest and research into non-operative treatment of appendicitis. Despite a number of non-randomised studies in children and randomised studies in adults, comparative outcomes of non-operative treatment and appendicectomy in comparable groups of children remain unknown. Following the successful completion of a feasibility study, we now aim to perform a UK-based multi-centre open-label randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of non-operative treatment pathway of acute uncomplicated appendicitis in children compared with appendicectomy.

methodsNon-inferiority RCT with internal pilot, health economic evaluation and qualitative communication sub-study. The study is conducted in England, Northern Ireland, Scotland and Wales at both specialist children's hospitals and district general hospitals. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Sample size is 376 participants, recruited by surgeons and supported by research staff and randomised with a 1:1 allocation ratio to either non-operative treatment pathway (intervention) or appendicectomy (control). Participants in the intervention arm are treated with antibiotics, analgesia and regular clinical assessment to ensure clinical improvement. Participants in the control arm receive appendicectomy. Randomisation is minimised by age, sex, duration of symptoms and centre. The primary end-point is a composite outcome of treatment success at 1 year following randomisation. Secondary outcomes include: duration of hospital stay, measures of recovery from acute appendicitis, complications, need for further treatment, persistent symptoms, health care resource use, quality of life and costs. Adverse events, serious adverse events and suspected unexpected serious adverse events are collected directly on the database and by paper form up to 12-month visit. Primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin to test the hypothesis that non-operative treatment pathway is non-inferior to appendicectomy. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative sub-study. This will include recording of recruitment consultations, which will inform future interventions to optimise recruitment. We have involved children, young people and parents in study design and delivery. DISCUSSION: This RCT will allow determination of the comparative clinical and cost-effectiveness of non-operative treatment pathway compared to appendicectomy for children with uncomplicated acute appendicitis in the UK. TRIAL STATUS: First planned enrolment-December 2022, first actual recruit-March 2022, current status of trial-open to recruitment.

trial registrationISRCTN16720026 . Registered on July 28, 2021.