Appendectomy Versus Non-Operative Treatment For Acute Non-Perforated Appendicitis in Children

Summary

Rationale and Aim: The standard treatment for acute appendicitis in children is appendectomy. An increasing body of evidence from the adult literature suggests that acute appendicitis may be treated effectively with antibiotics alone, avoiding the need for surgery. The aim of this study is to investigate the effectiveness of non-operative treatment of acute appendicitis in children.

Study design: Pragmatic, parallel-group, unmasked, non-inferiority multicentre randomized controlled trial (RCT).

Patient allocation: Children will be randomly allocated (age 5-16 years) with a diagnosis of acute appendicitis to either laparoscopic appendectomy or treatment with antibiotics. Randomization will be performed using stratification to ensure equal distribution between groups of presenting clinical and demographic features that may influence outcome including gender, duration of symptoms and center.

Interventions: One group of children will undergo laparoscopic appendectomy that is the current standard treatment for children with acute appendicitis. The other group will be treated with intravenous antibiotics. A treatment pathway specifically designed for this study will be used.

Primary Outcome: To be meaningful to parents of, and clinicians treating, children with acute appendicitis, the primary outcome is treatment failure defined as: (i) any additional intervention related to appendicitis requiring general anesthesia within 1 year of randomization (including recurrence of appendicitis after non-operative treatment, which we will treat with appendectomy) or (ii) negative appendectomy. Secondary outcomes are: (i) complications; (ii) time to discharge following randomization; (iii) number and duration of hospital admissions.

Sample size and data analysis: The proposed RCT has a 20% non-inferiority margin to test the null hypothesis that treatment with antibiotics is inferior to appendectomy. Based on data from collaborating centers and a pilot study that we have performed, we expect recruitment of 978 children in total (90% power) over 19 months allowing for drop out. Follow-up will be for 12 months.

Conditions

• Appendicitis

Interventions

OTHER

Non-operative treatment

will receive a minimum of 12 hours intravenous antibiotics and then receive oral antibiotics once they have shown clinical improvement (a total course of 10 days of antibiotics (intravenous and oral). They will be discharged home once they meet a standardized set of criteria to be used in all centers. The choice of antibiotics will vary between centers and will be the antibiotic regimen that is current standard of care in that center allowing each center to maintain current protocols will improve study feasibility and increase generalization of the results.

PROCEDURE

Appendectomy

will undergo laparoscopic appendectomy within 18 hours of randomization and will receive intravenous antibiotics per each site's standard care, from the time of randomization and post-operatively according to a defined and standardized treatment regimen based on consensus for this trial. Children with a visibly normal appendix or non-perforated acute appendicitis will receive no further antibiotics; children with perforated appendicitis will continue to receive intravenous antibiotics for a minimum of 3 days, and then per local practice. The type of antibiotics used in each center will be identical to those used in the non-operative treatment group and are not specified by the study.

Sponsors & Collaborators

• Provincial Health Services Authority

  collaborator OTHER

• Alberta Children's Hospital

  collaborator OTHER

• Children's Hospital of Western Ontario

  collaborator OTHER

• St. Justine's Hospital

  collaborator OTHER

• Children's Hospital of Winnipeg

  collaborator UNKNOWN

• Le Bonheur Children's Hospital

  collaborator OTHER

• Karolinska University Hospital

  collaborator OTHER

• Hospital for Children and Adolescents, Finland

  collaborator OTHER

• University of Southampton

  collaborator OTHER

• UCL Institute of Child Health

  collaborator UNKNOWN

• KK Women's and Children's Hospital

  collaborator OTHER_GOV

• Uppsala University Children's Hospital

  collaborator UNKNOWN

• Children's Mercy Hospital Kansas City

  lead OTHER

Principal Investigators

• Shawn D St. Peter, MD · Children's Mercy Hospital Kansas City

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-01-20

Primary Completion

2023-03-02

Completion

2023-03-02

Countries

• United States

Study Locations