Multi-institutional Trial of Non-operative Management of Appendicitis

Active, not recruiting

• Conditions: Appendicitis
• Interventions: Other: Non-operative

• Registration Number: NCT02271932
• Lead Sponsor: Nationwide Children's Hospital

Brief Summary

A successful non-operative management strategy for early appendicitis will decrease the number of children requiring surgery and may improve the quality of care related to the treatment of appendicitis. To account for the child-family perspective and treatment preferences, the investigators will perform a study in which patients and their families choose between antibiotics alone (Non-operative group) or appendectomy (Surgery group) at ten U.S. hospitals. This study will determine the effectiveness of non-operative management of early appendicitis with antibiotics alone in children and compare differences in morbidity, disability, quality of life, satisfaction, and cost between families choosing surgery or non-operative management.

Detailed Description

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.

Study Timeline

• Study Start: 2014-10-01
• Study First Submitted: 2014-10-20
• Study First Submitted QC: 2014-10-21
• Study First Posted: 2014-10-22
• Primary Completion: 2019-11-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-09
• Study Completion: 2023-11-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 1076

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-operative	Non-operative	Non-operative management consists of hospital admission for observation with a minimum of 24 hours of intravenous antibiotics and a minimum of 12 hours nil per os (NPO). With clinical improvement, patients are switched to oral antibiotics and discharged home with a prescription for oral antibiotics to complete a total antibiotic course of 7 days (including the duration of intravenous antibiotics).

Primary Outcome Measures

Name	Time	Method
Disability Days	1 year	Number of days without normal schedule
Success rate	1 year	success rate at 1 year is percent of patients choosing non-operative management who have not undergone an appendectomy

Secondary Outcome Measures

Name	Time	Method
Perforated appendicitis	1 year	percent of patients with perforated appendicitis at operation

Trial Locations

Locations (1)

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States