Appendectomy vs. Symptomatic Treatment in Uncomplicated Acute Appendicitis Among Pediatric Patients

Appendicitis Clinical Trial

— APPSYPP  

Official title:

A Randomized, Controlled Multicenter Feasibility Pilot Trial on Imaging Confirmed Uncomplicated Acute Appendicitis: Appendectomy vs. Symptomatic Treatment in Pediatric Patients (the APPSYPP) Trial Study Protocol

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05289713
• Other study ID #: APPSYPP
• Status: Recruiting
• Phase: N/A
• Start date: March 10, 2023
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Helsinki University Central Hospital
• Contact: Janne Suominen, MD, PhD
• Phone: +358504272977
• Email: janne.suominen[@]hus.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The APPSYPP trial is a randomized national multicenter feasibility superiority pilot study comparing appendectomy with symptomatic treatment in children with imaging-confirmed uncomplicated acute appendicitis. Patients are recruited from all five Finnish university hospitals. Inclusion criteria are: 1) age 7-15 years, 2) imaging-confirmed uncomplicated acute appendicitis (no appendicolith, perforation, abscess, or tumor suspicion), and 3) CRP ≤ 65 mg/l. Patients are randomized to receive emergency appendectomy or symptomatic treatment. In the surgery group, patients undergo laparoscopic appendectomy within 18 hours after randomization. In order to ensure patient safety, symptomatically treated patients are hospitalized for at least 24 hours, and receive intravenous fluids and analgesics according to standard clinical practice. Primary outcome is treatment success at 30 days defined by not fulfilling any of the treatment failure criteria. In the surgery group, treatment failure is defined as normal appendiceal histopathology or any postintervention complication requiring general anesthesia. In the symptomatic treatment group, treatment failure is defined as inability to discharge from hospital without appendectomy within 48 hours after randomization with a finding of histopathologically inflamed appendix, appendectomy during the initial hospital stay due to clinical progression of appendicitis with histopathologically and surgically confirmed complicated acute appendicitis, appendectomy with a histopathological finding of acute appendicitis after hospital discharge, or any complication of appendicitis requiring general anesthesia. Predefined secondary outcomes include later appendectomies, recurrence of histopathologically confirmed appendicitis and associated symptoms, postintervention complications, return to normal daily activities, quality of, resolution of appendicitis in US imagining after 1 month of symptomatic treatment, comparison of US and MRI findings at presentation, and differences in serum biomarkers and fecal microbiota composition.

Description:

While antibiotic treatment is an effective and safe treatment for most adults and children with imaging-confirmed uncomplicated acute appendicitis, emerging evidence further indicates that antibiotics and symptomatic treatment strategies may have similar efficacy and safety in uncomplicated acute appendicitis among adults. There are no randomized studies comparing appendectomy to symptomatic treatment in children.

The APPSYPP trial is a randomized national multicenter feasibility superiority pilot study comparing appendectomy with symptomatic treatment in children with imaging-confirmed uncomplicated acute appendicitis. Patients are recruited from all five Finnish university hospitals. Inclusion criteria are: 1) age 7-15 years, 2) imaging-confirmed uncomplicated acute appendicitis (no appendicolith, perforation, abscess, or tumor suspicion), and 3) CRP ≤ 65 mg/l. Patients are randomized to receive emergency appendectomy or symptomatic treatment. In the surgery group, patients undergo laparoscopic appendectomy within 18 hours after randomization. In order to ensure patient safety, symptomatically treated patients are hospitalized for at least 24 hours, and receive intravenous fluids and analgesics according to standard clinical practice. Primary outcome is treatment success at 30 days defined by not fulfilling any of the treatment failure criteria. In the surgery group, treatment failure is defined as normal appendiceal histopathology or any postintervention complication requiring general anesthesia. In the symptomatic treatment group, treatment failure is defined as inability to discharge from hospital without appendectomy within 48 hours after randomization with a finding of histopathologically inflamed appendix, appendectomy during the initial hospital stay due to clinical progression of appendicitis with histopathologically and surgically confirmed complicated acute appendicitis, appendectomy with a histopathological finding of acute appendicitis after hospital discharge, or any complication of appendicitis requiring general anesthesia.

The APPSYPP feasibility trial aims to assess the symptomatic treatment in children with imaging-confirmed uncomplicated acute appendicitis and whether this can safely be studied in a larger patient cohort in the future.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: December 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 15 Years

Eligibility

Inclusion Criteria:

• age 7-15 years

• clinical diagnosis of uncomplicated acute appendicitis confirmed by US and/or MRI:

adequately visualized appendix with a diameter of 6.1-11.0 mm without evidence of perforation, abscess, appendicolith or tumor suspicion

• CRP = 65 mg/l

Exclusion Criteria:

• inability to give informed consent

• age under 7 or over 15 years

• antibiotic administration within 14 days prior to enrolment

• any previous treatment for acute appendicitis

• severe nausea and/or vomiting preventing oral fluid intake

• systemic disease potentially compromising the safety of symptomatic treatment of acute appendicitis (e.g. type 2 diabetes, malignancy, immune deficiency, or a medical condition requiring immunosuppressant medication)

• diffuse peritonitis or complicated acute appendicitis at imaging (perforation, abscess, appendicolith or tumor suspicion)

• inadequately visualized appendix

• age and sex adjusted BMI over 27 kg/m2 and no MRI performed

• CRP > 65 mg/l.

Related Conditions & MeSH terms

• Appendicitis

Intervention

Procedure:
• appendectomy
Laparoscopic appendectomy is performed within 18 hours after randomization in the surgery group. Patients in the symptomatic treatment group are carefully monitored and the same intervention (laparoscopic appendectomy) is performed in case of treatment failure.

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki

Sponsors (5)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Kuopio University Hospital, Oulu University Hospital, Tampere University Hospital, Turku University Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum biomarkers and fecal microbiota	Differences in serum biomarkers and fecal microbiota composition between treatment arms as an exploratory endpoint for future research. Serum biomarkers are investigated using proteomics and fecal microbiota composition is analyzed using a phylogenetic microarray. The microarray consists of oligonucleotide probes for the V1 and V6 regions on the 16S ribosomal RNA gene and summarized as abundancies of species-level, genus-level, and phylum-level groups.	1 month
Primary	Treatment success at 30d follow-up.	Treatment success is defined by not fulfilling any of the following treatment failure criteria.; Treatment failure in the surgery group: Normal histopathology of the removed appendix.; Any complication of acute appendicitis or surgery requiring general anesthesia (GA) within 30 d.; Treatment failure in the symptomatic treatment group: Inability to discharge from hospital within 48 h after randomization without appendectomy due to persisting symptoms and unmet discharge criteria with a finding of histopathologically inflamed appendix.; Appendectomy due to clinical suspicion of progressive appendicitis including increasing pain not responding to the defined non-opioid analgesics during the initial hospital stay with a finding of histopathologically and surgically confirmed complicated acute appendicitis.; Appendectomy with a histopathologically confirmed acute appendicitis after hospital discharge within 30 d.; Any complication of AA reiring GA within 30 d.	30 days
Secondary	Postintervention complications	Categorized according to Clavien-Dindo classification (Grades I-V).	1 year
Secondary	Recurrent appendicitis	Recurrence of appendicitis (Histopathological diagnosis).	1 year
Secondary	Recurrent symptoms	The number of emergency department visits or hospitalizations due to symptoms related to appendicitis.	1 year
Secondary	Recovery of normal daily activities	Recovery to normal daily activities, school and sports. Reported in days.	1 year
Secondary	QoL	Quality of life evaluated by PedsQL, a validated questionnaire	1 year
Secondary	Resolution of acute appendicitis	Resolution of acute appendicitis, verified by US imaging.	1 month
Secondary	Comparison of US and MRI in diagnostics	Comparison of US and MRI findings (appendix visibility/normal/uncomplicated/complicated appendicitis) at presentation in the same patient. Percentage (%) of patients with either normal appendix, uncomplicated appendicitis, complicated appendicitis or not visible appendix. Imaging modalities are compared to each other and with histopathological analysis. Whether MRI imaging can improve diagnostics.	1 month