Clinical trial NCT05289713: Appendectomy vs. Symptomatic Treatment in Uncomplicated Acute Appendicitis Among Pediatric Patients
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Appendicitis
Keywords: uncomplicated acute appendicitis
symptomatic treatment
spontaneous resolution
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Turku University Hospital
name: Tampere University Hospital
name: Kuopio University Hospital
name: Oulu University Hospital
First posted: 2022-03-21
Enrollment: 64
Sex: ALL
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment success at 30d follow-up.
timeFrame: 30 days
Secondary outcomes:
measure: Postintervention complications
timeFrame: 1 year
measure: Recurrent appendicitis
timeFrame: 1 year
measure: Recurrent symptoms
timeFrame: 1 year
measure: Recovery of normal daily activities
timeFrame: 1 year
measure: QoL
timeFrame: 1 year
measure: Resolution of acute appendicitis
timeFrame: 1 month
measure: Comparison of US and MRI in diagnostics
timeFrame: 1 month
Other outcomes:
measure: Serum biomarkers and fecal microbiota
timeFrame: 1 month
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Janne Suominen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puputti J, Suominen JS, Luoto T, Hiltunen P, Ripatti L, Nikoskelainen M, Nuutinen S, Sinikumpu JJ, Tahkola E, Porela-Tiihonen S, Hurme S, Salminen P, Pakarinen MP. 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. Contemp Clin Trials. 2022 Dec;123:106970. doi: 10.1016/j.cct.2022.106970. Epub 2022 Oct 22.