Non-operative Management for Appendicitis in Children

A Prospective Randomised Controlled Non-inferiority Study to Evaluate the Effectiveness and Safety (APRES) of Non-operative Management in Children With Acute Uncomplicated Appendicitis

This study is designed to determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed acute uncomplicated appendicitis in children. Enrolled patients will be randomised and an allocation ratio of 1:1 will be made via weighted minimisation, where half of the patients will receive non-operative management with intravenous Piperacillin with Tazobactam, while the other half will have an appendicectomy.

Appendicectomy for acute appendicitis is one of the most commonly performed paediatric emergency operations in Australia. This standard treatment of acute uncomplicated appendicitis (AUA) has remained largely unchallenged since its introduction in the late nineteenth century, under the assumption that AUA progresses to perforation and thus complications should an operation be withheld. However, appendicectomy via laparoscopic or open approach is not without its risks.

Non-operative management (NOM) with antibiotics has been increasingly accepted as mainstay therapy for many intra-abdominal infections. In fact, children with appendicitis complicated by perforation, abscess or phlegmon formation are often preferentially treated non-operatively with antibiotic therapy, with or without percutaneous drainage. Systematic reviews and meta-analyses have demonstrated that antibiotics are a safe and effective treatment for AUA in adults and there is growing evidence that NOM is safe and effective in children.

Primary objectives:

To determine the safety and efficacy of non-operative antibiotic management of clinically diagnosed likely AUA in children.

Secondary objectives:

1. To compare the safety and efficacy of NOM of clinically diagnosed likely AUA with operative management (OM) in children.
2. To assess the cost-effectiveness of NOM of clinically diagnosed likely AUA against OM in children.
3. To assess the feasibility and acceptability of NOM of appendicitis in children.

This study will enrol 226 patients, age 5-16 years, with acute uncomplicated appendicitis at two tertiary children's hospitals. Allocation ratio of 1:1 will be made via weighted minimisation using the following criteria: age (5-8 years or 9-16 years), gender (male or female), and duration of symptoms (<48 or >48 hours).

Inclusion Criteria:

1. Age between 5 and 15 years;
2. Clinical diagnosis by at least one paediatric surgeon (or duty surgical registrar) of acute uncomplicated appendicitis based on with a combination of clinical, laboratory and/or imaging findings; that before the study would have led to the decision to recommend been subjected to an appendicectomy.

Exclusion Criteria: if one or more of the following is assessed to be present

1. Suspicion of perforated appendicitis on the basis of generalised peritonitis and/or imaging studyA diagnosis of perforated or complicated appendicitis (e.g. peritonitis, appendiceal mass) is made on the basis of clinical, laboratory and/or imaging findings;
2. Previous non-operative treatment of acute appendicitis;
3. Age younger than 5 years or older than 16 years;
4. Known intolerance or allergy to Piperacillin with Tazobactam;
5. Known history of inflammatory bowel disease, or other chronic abdominal pain syndrome;
6. Known concurrent significant illness;
7. Unable to obtain informed consent from parents or guardian;
8. Known to have a cognitive impairment, an intellectual disability or a mental illness that would impair participation.