Initial Antibiotics and Delayed Appendectomy for Acute Appendicitis

Study Overview
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Brief Summary
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Several recent studies have examined the feasibility and benefits of nonoperative treatment of perforated appendicitis in children. One such study showed a trend toward longer operative times for patients randomized to immediate appendectomy, but no overall advantage. In another larger study, the costs of delayed appendectomy for perforated appendicitis were higher - in part related to readmissions in the interval (6-8 weeks). Nevertheless, these and other studies have demonstrated the safety of delaying appendectomy for perforated appendicitis. Emergency appendectomy is a well-established approach, and postoperative recovery in children is fast. Nevertheless, from the onset of symptoms through the hospital stay and the postoperative recovery, appendicitis causes a disruption of a family's normal routine (absence from school and work) of up to 1-2 weeks. Because this is an unplanned operation, patients have to wait until an operating room becomes available, or elective operations have to be placed on hold to accommodate the emergency operation. Each year, more than 250 children undergo an appendectomy at HCH. This represents 250 episodes of emergency surgery, or about one emergency add-on operation per working day. If an initial trial of antibiotics is safe for the treatment of appendicitis, converting an emergency operation into an elective, scheduled outpatient procedure may reduce stress and disruption of routine for patients and their families - and may allow better operating room planning for health care professionals and hospitals. The investigators hypothesize that initial antibiotic treatment of acute (non-perforated) appendicitis, followed by scheduled outpatient appendectomy, reduces the overall cost of treating the disease and results in greater patient and family satisfaction. This pilot study aims to establish the safety and feasibility of treating acute appendicitis with intravenous antibiotics, followed by outpatient oral antibiotics. Patients and their families will be offered the possibility of initial nonoperative treatment and subsequent outpatient elective appendectomy in a nonrandomized, single arm study.

Official Title
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Initial Antibiotics and Delayed Appendectomy for Acute Appendicitis

Conditions
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Acute Appendicitis

Intervention / Treatment
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* Drug: Piperacillin + Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maximum 48-hour-history of abdominal pain Diagnosis of acute appendicitis based on clinical, laboratory and/or radiologic criteria Exclusion Criteria: Duration of symptoms > 48 hours Presence of an appendiceal abscess on imaging Clinical or laboratory suspicion of advanced appendicitis, peritonitis or perforation Significant comorbidities Inability or unwillingness to complete a 1-week course of oral antibiotics Allergy to penicillin

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Piperacillin + Amoxicillin<br>Piperacillin/Tazobactam (Zosyn®) 100 mg/kg, up to adult dose of 3 g, i.v. q 6 hours x 2 doses, followed by Ampicillin/Clavulanate (Augmentin®) 50 mg/kg/d p.o. in 3 divided doses for 1 week. | Drug: Piperacillin + Amoxicillin<br> <br> * Other names: Augmentin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment failures | If after a period of at least 8 hours (and 2 doses of intravenous antibiotics), the patient's symptoms worsen, or fail to subside within 18 hours, the patient will undergo an emergent/urgent appendectomy, and treatment will proceed as per standard-of-care (1 intraoperative dose of antibiotics, with or without postoperative antibiotics, progressive postoperative diet and discharge home once tolerating a regular diet). The patient will then be considered having failed nonoperative treatment. | Worsening of symptoms at 8 hours or failure of improvement at 18 hours of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-saving of initial nonoperative treatment for early appendicitis | Cost of nonoperative treatment will be calculated as follows: Hospitalization charges (# hospital days - observation) + costs of antibiotics (actual number of doses/days) + outpatient surgery hospital fee (operating room and PACU time) + additional costs associated with unanticipated events (e.g., Emergency room visits after initial discharge). Control costs (contemporary data) will consider the following: Hospitalization charges (# hospital days) + intravenous antibiotics (price/dose x number of doses). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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appendicitis