Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA)

Appendicitis Perforated Clinical Trial

— ALPACA  

Official title:

Assessing the Longitudinal Outcomes of Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA): a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05943223
• Other study ID #: McmasterCH
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 2024
• Est. completion date: December 2024

Study information

• Verified date: July 2023
• Source: McMaster Children's Hospital
• Contact: Daniel Briatico, MSc
• Phone: 9055212100
• Email: briaticd[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Appendicitis
• Appendicitis Perforated

Intervention

Drug:
• Piperacillin/tazobactam
Post-operative piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h)
• Normal saline
Post-operative normal saline 50 mL once daily
• CefTRIAXone Injection
Post-operative ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV once daily)
• Metronidazole Injection
Post-operative metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
McMaster Children's Hospital

References & Publications (6)

Gerber JS, Jackson MA, Tamma PD, Zaoutis TE; COMMITTEE ON INFECTIOUS DISEASES, PEDIATRIC INFECTIOUS DISEASES SOCIETY. Antibiotic Stewardship in Pediatrics. Pediatrics. 2021 Jan;147(1):e2020040295. doi: 10.1542/peds.2020-040295. — View Citation

Kashtan MA, Graham DA, Melvin P, Hills-Dunlap JL, Anandalwar SP, Rangel SJ. Ceftriaxone with Metronidazole versus Piperacillin/Tazobactam in the management of complicated appendicitis in children: Results from a multicenter pediatric NSQIP analysis. J Pediatr Surg. 2022 Oct;57(10):365-372. doi: 10.1016/j.jpedsurg.2021.11.009. Epub 2021 Nov 20. — View Citation

Lee J, Garvey EM, Bundrant N, Hargis-Villanueva A, Kang P, Osuchukwu O, Dekonenko C, Svetanoff WJ, St Peter SD, Padilla B, Ostlie D. IMPPACT (Intravenous Monotherapy for Postoperative Perforated Appendicitis in Children Trial): Randomized Clinical Trial of Monotherapy Versus Multi-drug Antibiotic Therapy. Ann Surg. 2021 Sep 1;274(3):406-410. doi: 10.1097/SLA.0000000000005006. — View Citation

Linnaus ME, Ostlie DJ. Complications in common general pediatric surgery procedures. Semin Pediatr Surg. 2016 Dec;25(6):404-411. doi: 10.1053/j.sempedsurg.2016.10.002. Epub 2016 Oct 29. — View Citation

St Peter SD, Snyder CL. Operative management of appendicitis. Semin Pediatr Surg. 2016 Aug;25(4):208-11. doi: 10.1053/j.sempedsurg.2016.05.003. Epub 2016 May 10. — View Citation

St Peter SD, Tsao K, Spilde TL, Holcomb GW 3rd, Sharp SW, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Ostlie DJ. Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial. J Pediatr Surg. 2008 Jun;43(6):981-5. doi: 10.1016/j.jpedsurg.2008.02.018. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recruitment rate	Number of participants randomized per month	Through study completion (average of 1 year)
Other	Consent rate	Number of participants who consent to participate divided by those who are approached for consent	Through study completion (average of 1 year)
Other	Rate of protocol violations	Number of participants who do not receive study treatments within 8 hours of surgery, miss a scheduled study treatment, and/or experience treatment crossover divided by those randomized	Through study completion (average of 1 year)
Other	Rate of loss to follow-up	Number of participants who cannot be contacted by phone 3 months after discharge from hospital divided by those randomized	Through study completion (average of 1 year)
Other	Cost of trial	Total cost of internal pilot study in Canadian dollars divided by the number of participants randomized	Through study completion (average of 1 year)
Primary	Length of stay	Length of stay in hospital during index admission	Index admission
Secondary	Percutaneous drain insertion	Percutaneous drain insertion by Interventional Radiology	Within 30 days of surgery
Secondary	Deep or organ-space surgical site infection	Deep or organ-space surgical site infection	Within 30 days of surgery
Secondary	Insertion of Peripherally Inserted Central Catheter (PICC)	Insertion of Peripherally Inserted Central Catheter (PICC)	Within 30 days of surgery
Secondary	Parenteral nutrition	Need for parenteral nutrition	Within 30 days of surgery
Secondary	Post-operative ultrasound	Need for post-operative ultrasound	Within 30 days of surgery
Secondary	Clostridium difficile infection	Clostridium difficile infection (confirmed with stool sample and requiring treatment)	Within 30 days of surgery
Secondary	Return to the emergency department	Return to the emergency department within 30 days of surgery	Within 30 days of surgery
Secondary	Readmission to hospital	Readmission to hospital within 30 days of surgery	Within 30 days of surgery
Secondary	Late complications	Telephone confirmation of no additional complications related to perforated appendicitis requiring assessment in clinic, emergency department visit, or admission to hospital	Telephone call 3 months after surgery
Secondary	Exit survey	Parents will complete a descriptive questionnaire about the study by telephone	Telephone call 3 months after surgery