Multi-institutional Trial of Non-operative Management of Appendicitis

Several randomized controlled trials comparing appendectomy to antibiotics alone in adults
with acute appendicitis have been reported from non-U.S. countries. These studies reveal that
non-operative management of appendicitis is a safe treatment for appendicitis and is
associated with a significantly lower risk of complications than appendectomy. We have
recently completed the first study in the U.S. examining the feasibility of non-operative
management of uncomplicated appendicitis in children. In our pilot study, patients and their
families chose between urgent appendectomy or antibiotics alone for treatment of
uncomplicated appendicitis. The success rate of non-operative management was 90% at 30 days
and 80% at a median follow-up of 8 months. In addition, patients in the non-operative group
demonstrated a significantly faster return to normal activity and reported higher quality of
life scores. The current proposal seeks to further investigate the effectiveness of
non-operative management with antibiotics alone as a treatment option for children with
uncomplicated appendicitis. When randomized trials are not feasible due to strong treatment
preferences or when only a small proportion of patients will accept randomization, a parallel
group non-randomized study where participants are allocated to their preferred treatment is a
valuable alternative. Based on feedback from a multi-disciplinary stakeholder group that was
convened to assess the potential impact of family preferences on study outcomes, recruitment,
and generalizability, we propose a multi-institutional trial in which patients and their
families choose between antibiotics alone (Non-operative group) or appendectomy (Surgery
group). We hypothesize that non-operative management will be successful in 75% of patients at
1 year follow-up and will be associated with fewer disability days, higher quality of life
scores, and lower costs than appendectomy. This study will enroll 795 patients, age 8-17
years, with uncomplicated appendicitis at 10 children's hospitals. The primary outcomes are:
1) differences in treatment-related disability between non-operative management and surgery
in children with uncomplicated appendicitis across 10 children's hospitals; and 2) the
success rate of non-operative management of uncomplicated appendicitis at 10 children's
hospitals, defined as the percent of patients treated non-operatively who do not undergo an
appendectomy. Secondary outcomes include differences between the groups in rates of
complicated appendicitis, post-treatment related complications, disability days of the
parent, quality of life and healthcare satisfaction measures, and total costs and the
incremental cost-effectiveness of non-operative management relative to appendectomy. The
proposed study will expand upon our previous pilot study by including patients from both
freestanding and non-freestanding children's hospitals with both urban and rural demographies
to determine the success rate and morbidity associated with non-operative management in a
population that better represents the overall population of children in the U.S. Successful
completion of this study may provide evidence for the effectiveness of non-operative
management of uncomplicated appendicitis as an alternative first line therapy in children.

Inclusion Criteria:

- English and non-English speaking patients

- Age : 8-17 years

- US or CT confirmed early appendicitis with US showing hyperemia, ≤ 1.1 cm in diameter,
compressible or non-compressible, no abscess, no fecalith, no phlegmon or CT showing
hyperemia, fat stranding, ≤ 1.1 cm in diameter, no abscess, no fecalith, no phlegmon

- White Blood Cell count > 5,000/µL and ≤ 18,000/µL

- Abdominal pain ≤ 48hours prior to receiving antibiotics

Exclusion Criteria:

- History of chronic intermittent abdominal pain

- Pain > 48 hours prior to first antibiotic dose

- Diffuse peritonitis

- Positive urine pregnancy test

- White Blood Cell ≤ 5,000/µL or ≥ 18,000/µL

- Presence of a fecalith on imaging

- Evidence on imaging studies concerning for evolving perforated appendicitis including
abscess or phlegmon

- Communication difficulties (e.g. severe developmental delay)