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

NCT02687464 | Completed DMC

• 1 other identifier: 15100493
• Study Type: interventional
• Target: 978
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Pediatric Surgery; Pediatrics; Randomized controlled trial,; Antibiotics; Cost effectiveness

Outcome Measures

Primary Outcomes (1)

• treatment failure

  The primary outcome is treatment failure. Treatment failure is defined as: (i) additional intervention related to appendicitis requiring general anesthesia within 1 year of randomization (this includes the recurrence of appendicitis after non-operative treatment, which will be treated with appendectomy) or (ii) negative appendectomy. This definition of the primary outcome will capture all important parameters in both treatment groups including specifically: failure of antibiotic treatment requiring appendectomy, significant complication (defined as requiring general anaesthesia) in either treatment group, recurrence of acute appendicitis (treated by appendectomy) and negative appendectomy.

  within 1 year of randomization

Secondary Outcomes (4)

• treatment efficacy

  within 1 year of randomization

• complications

  within 1 year of randomization

• time to discharge

  1 year from randomization

• number and duration of hospital admissions

  within 1 year of randomization

Study Arms (2)

Non-operative treatment group

EXPERIMENTAL

IV fluids, minimum 12 hrs IV antibiotics, minimum 12 hrs clear PO fluids only, regular clinical review. Discharge within 24 hrs after randomization, if study criteria met. If stable but not adequate improvement for discharge, non-operative management continues. If not improved by 48 hrs, appendectomy will be done. Discharge home once vital signs are within normal limits, light oral diet tolerated, adequate oral pain relief and mobile. Total 10 days of antibiotics (IV and oral) following randomization will be given. Antibiotics used vary between centers and will be current standard of care in that center; improving study feasibility and increased generalization of results.

Other: Non-operative treatment

Appendectomy group

ACTIVE COMPARATOR

Laproscopic appendectomy within 18 hrs of randomization. IV antibiotics given from time of randomization and continued post-operatively per the standardized treatment regimen: children with visibly normal appendix or non-perforated acute appendicitis will receive no further antibiotics; children with perforated appendicitis will continue IV 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.

Procedure: Appendectomy

Interventions

Non-operative treatment OTHER

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.

Non-operative treatment group

Appendectomy PROCEDURE

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.

Also known as: Laparoscopic appendectomy

Appendectomy group

Eligibility Criteria

• Age: 5 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• children (age 5-16 years)
• clinical and /or radiological diagnosis (ultrasound \[US\] and/or CT scan) of acute non-perforated appendicitis
• written informed parental/legal guardian permission in accordance with local regulations and institutional policy
• written informed child assent or waiver in accordance with local regulations and institutional policy

You may not qualify if:

• suspicion of perforated appendicitis
• presentation with an appendix mass or phlegmon (on physical examination and/or imaging)
• non-operative management (2 or more rounds of intravenous antibiotics) initiated at an outside institution
• previous episode of appendicitis or appendix mass/phlegmon treated non-operatively
• current treatment for malignancy
• positive pregnancy test (if part of a clinical routine)
• diagnosis of Cystic Fibrosis (CF)

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• Provincial Health Services Authority British Columbia: collaborator
• Alberta Children's Hospital: collaborator
• Children's Hospital of Western Ontario: collaborator
• St. Justine's Hospital: collaborator
• Children's Hospital of Winnipeg: collaborator
• Le Bonheur Children's Hospital: collaborator
• Karolinska University Hospital: collaborator
• Hospital for Children and Adolescents, Finland: collaborator
• University of Southampton: collaborator
• UCL Institute of Child Health: collaborator
• KK Women's and Children's Hospital: collaborator
• Uppsala University Children's Hospital: collaborator

Study Sites (1)

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

Related Publications (2)

• St Peter SD, Noel-MacDonnell JR, Hall NJ, Eaton S, Suominen JS, Wester T, Svensson JF, Almstrom M, Muenks EP, Beaudin M, Piche N, Brindle M, MacRobie A, Keijzer R, Engstrand Lilja H, Kassa AM, Jancelewicz T, Butter A, Davidson J, Skarsgard E, Te-Lu Y, Nah S, Willan AR, Pierro A. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial. Lancet. 2025 Jan 18;405(10474):233-240. doi: 10.1016/S0140-6736(24)02420-6.

  PMID: 39826968 DERIVED

• Hall NJ, Eaton S, Abbo O, Arnaud AP, Beaudin M, Brindle M, Butter A, Davies D, Jancelewicz T, Johnson K, Keijzer R, Lapidus-Krol E, Offringa M, Piche N, Rintala R, Skarsgard E, Svensson JF, Ungar WJ, Wester T, Willan AR, Zani A, St Peter SD, Pierro A. Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial. BMJ Paediatr Open. 2017 May 18;1(1):bmjpo-2017-000028. doi: 10.1136/bmjpo-2017-000028. eCollection 2017.

  PMID: 29637088 DERIVED

MeSH Terms

Conditions

Appendicitis

Interventions

Appendectomy

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Shawn D St. Peter, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shawn St. Peter, MD, Director of Research, Department of Surgery

Study Record Dates

• First Submitted: January 13, 2016
• First Posted: February 22, 2016
• Study Start: January 20, 2016
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)