Appendicitis Perforated
Conditions
Keywords
Child, Piperacillin, Ceftriaxone, Metronidazole
Brief summary
This study is an internal pilot for a multicenter, blinded randomized controlled trial. The purpose of the multicenter trial is to determine whether post-operative piperacillin/tazobactam is more effective than ceftriaxone and metronidazole for children treated with laparoscopic appendectomy for perforated appendicitis. We plan to conduct an internal pilot study to determine whether a blinded multicenter randomized controlled trial is feasible.
Detailed description
Acute appendicitis is the most common indication for emergency surgery in children. The management of this condition is typically an urgent laparoscopic appendectomy under general anesthesia. If the appendix is found to be perforated at the time of surgery, then patients need to stay in hospital for intravenous antibiotics. Patients who do not respond to antibiotic therapy experience prolonged length of stay, need for additional procedures (such as percutaneous drain insertion), or other complications. This represents significant morbidity for patients and their families. Children with perforated appendicitis were previously treated with post-operative ampicillin, gentamicin, and metronidazole (also known as "triple therapy"). In 2008, a randomized controlled trial showed that triple therapy is non-inferior to ceftriaxone and metronidazole (CM) in terms of intra-abdominal abscess formation and wound infection. CM is also less expensive and has a simplified dosing regimen. As such, post-operative CM became the standard of care for perforated appendicitis at most children's hospitals. In 2021, an open-label RCT suggested that piperacillin/tazobactam (PT) is more effective than CM for children with perforated appendicitis. Patients randomized to PT had a reduced rate of intra-abdominal abscess formation compared to those treated with CM (odds ratio (OR) 4.80, p=0.002). This trial was not blinded and there was no allocation concealment. In contrast, a multicenter, observational study reported no difference in the rate of intra-abdominal abscess formation among patients treated with PT compared to CM. The conflicting results of these two studies add further uncertainty regarding the choice of antibiotics for these patients. Another factor that should be considered regarding the use of PT versus CM in children with perforated appendicitis is antibiotic stewardship. PT is a broad-spectrum antibiotic with increased effectiveness against Pseudomonas aeruginosa and resistant Escherichia coli. As a result, this medication is often reserved for patients with confirmed Pseudomonas infection, oncology patients with febrile neutropenia, or those who are critically ill and admitted to the intensive care unit. The current study is an internal pilot for a multicenter, blinded randomized controlled trial. The purpose of the multicenter trial is to determine whether post-operative piperacillin/tazobactam is more effective than ceftriaxone and metronidazole for children treated with laparoscopic appendectomy for perforated appendicitis. We plan to conduct an internal pilot study to determine whether a blinded multicenter randomized controlled trial is feasible.
Interventions
DRUGPiperacillin/tazobactam
Post-operative piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h)
DRUGNormal saline
Post-operative normal saline 50 mL once daily
DRUGCefTRIAXone Injection
Post-operative ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV once daily)
DRUGMetronidazole Injection
Post-operative metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h)
Sponsors
McMaster Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Internal pilot study
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Laparoscopic appendectomy * Perforated appendicitis confirmed intra-operatively (i.e., visible hole in appendix, fecalith found in peritoneal cavity, intra-abdominal abscess, and/or purulent fluid in peritoneal cavity)
Exclusion criteria
* Non-operative treatment (e.g., due to abscess) * Interval laparoscopic appendectomy * Conversion to open procedure * Non-perforated appendicitis * Confirmed or suspected allergy to penicillins or cephalosporins * Renal impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of stay | Index admission | Length of stay in hospital during index admission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percutaneous drain insertion | Within 30 days of surgery | Percutaneous drain insertion by Interventional Radiology |
| Deep or organ-space surgical site infection | Within 30 days of surgery | Deep or organ-space surgical site infection |
| Insertion of Peripherally Inserted Central Catheter (PICC) | Within 30 days of surgery | Insertion of Peripherally Inserted Central Catheter (PICC) |
| Parenteral nutrition | Within 30 days of surgery | Need for parenteral nutrition |
| Post-operative ultrasound | Within 30 days of surgery | Need for post-operative ultrasound |
| Clostridium difficile infection | Within 30 days of surgery | Clostridium difficile infection (confirmed with stool sample and requiring treatment) |
| Return to the emergency department | Within 30 days of surgery | Return to the emergency department within 30 days of surgery |
| Readmission to hospital | Within 30 days of surgery | Readmission to hospital within 30 days of surgery |
| Late complications | Telephone call 3 months after surgery | Telephone confirmation of no additional complications related to perforated appendicitis requiring assessment in clinic, emergency department visit, or admission to hospital |
| Exit survey | Telephone call 3 months after surgery | Parents will complete a descriptive questionnaire about the study by telephone |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORMichael H Livingston, MD, MSc
McMaster Children's Hospital
Outcome results
None listed