Piperacillin/Tazobactam Versus Ceftriaxone and Metronidazole for Children With Perforated Appendicitis

NCT07869095 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: HHS-582929
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

The ALPACA-MC trial is a blinded, multicentre randomized controlled trial comparing two postoperative antibiotic treatments for children undergoing laparoscopic appendectomy for perforated appendicitis. Perforated appendicitis occurs when the appendix has developed a hole or has burst. The study will include 180 children from several pediatric hospitals. After surgery, participants will be randomly assigned to receive either piperacillin/tazobactam (PT) or ceftriaxone plus metronidazole (CM). The child, family, healthcare team, and researchers assessing the outcomes will not know which treatment was received. The main purpose of the study is to determine whether PT reduces hospital length of stay compared with CM. The study will also compare other important outcomes, including surgical site infections, the need for additional imaging or procedures, emergency department visits, and hospital readmissions. Children will be followed for 30 days after surgery. At 30 days, families will be contacted to ask about any additional complications and how well the child has recovered. This will include questions about returning to school, sports or other physical activities, and the child's overall health and quality of life. The results of this study will help determine which antibiotic treatment is most appropriate for children with perforated appendicitis and may help guide future clinical practice and antibiotic stewardship.

Conditions

Appendicitis Perforated; Appendectomy, Laparoscopic; Antibiotic; Pediatric; Randomized Controlled Trial

Keywords

Piperacillin; Tazobactam; Ceftriaxone; Metronidazole

Outcome Measures

Primary Outcomes (1)

• Length of hospital stay

  Length of stay in hospital during index admission.

  Measured as the number of days from index hospital admission to hospital discharge, assessed up to 30 days.

Secondary Outcomes (8)

• Number of participants with deep or organ-space surgical site infection

  Within 30 days of surgery.

• Number of participants requiring post-operative ultrasound

  Within 30 days of surgery.

• Number of participants undergoing percutaneous drain insertion

  Within 30 days of surgery.

• Number of participants undergoing peripherally inserted central catheter (PICC) insertion

  Within 30 days of surgery.

• Number of participants receiving parenteral nutrition

  Within 30 days of surgery.

Other Outcomes (2)

• Health-related quality of life: disease-specific

  30 days after surgery.

• Health-related quality of life: generic

  30 days after surgery.

Study Arms (2)

Piperacillin/tazobactam

EXPERIMENTAL

Drug: Piperacillin/Tazobactam

Ceftriaxone + Metronidazole

ACTIVE COMPARATOR

Drug: Ceftriaxone + Metronidazole

Interventions

Piperacillin/Tazobactam DRUG

Piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h) and normal saline once daily.

Piperacillin/tazobactam

Ceftriaxone + Metronidazole DRUG

Ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV daily) and metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h).

Ceftriaxone + Metronidazole

Eligibility Criteria

• Age: 0 Weeks - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster Children's Hospital: lead
• Alberta Children's Hospital: collaborator
• Children's Hospital, London Health Sciences Center: collaborator
• Montreal Children's Hospital of the MUHC: collaborator
• The Hospital for Sick Children: collaborator

Related Publications (8)

• Briatico D, Safa N, Flageole H, Khan S, Pernica J, Eltorki M, Cohen E, Livingston MH. Assessing the Longitudinal outcomes of Piperacillin/tazobactam versus ceftriAxone and metronidazole for Children with perforated Appendicitis (ALPACA): A protocol for a pilot randomized controlled trial. PLoS One. 2025 Nov 7;20(11):e0335991. doi: 10.1371/journal.pone.0335991. eCollection 2025.

  PMID: 41202087 BACKGROUND

• Armstrong J, Sriranjan J, Briatico D, Khan S, Eltorki M, Livingston MH. Piperacillin/tazobactam versus ceftriaxone/metronidazole for children with perforated appendicitis: a systematic review and meta-analysis. Pediatr Surg Int. 2025 Nov 4;42(1):3. doi: 10.1007/s00383-025-06227-z.

  PMID: 41186640 BACKGROUND

• Zeineddin S, Pitt JB, Linton S, De Boer C, Hu A, Carter M, Alayleh A, Abdullah F, Raval M, Goldstein SD. Postoperative Antibiotics for Complicated Appendicitis in Children: Piperacillin/Tazobactam Versus Ceftriaxone with Metronidazole. J Pediatr Surg. 2023 Jun;58(6):1128-1132. doi: 10.1016/j.jpedsurg.2023.02.027. Epub 2023 Feb 17.

  PMID: 36931937 BACKGROUND

• Cramm SL, Graham DA, Feng C, Allukian M, Blakely ML, Chandler NM, Cowles RA, Kunisaki SM, Lipskar AM, Russell RT, Santore MT, Campbell BT, Commander SJ, DeFazio JR, Dukleska K, Echols JC, Esparaz JR, Gerall C, Griggs CL, Hanna DN, He K, Keane OA, McLean SE, Pace E, Scholz S, Sferra SR, Tracy ET, Zhang L, Rangel SJ; Eastern Pediatric Surgery Network. Use of Antipseudomonal Antibiotics is Not Associated With Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children With Complicated Appendicitis: Results From a Multicenter Regional Research Consortium. Ann Surg. 2024 Jun 1;279(6):1070-1076. doi: 10.1097/SLA.0000000000006152. Epub 2023 Nov 16.

  PMID: 37970676 BACKGROUND

• 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.

  PMID: 34876294 BACKGROUND

• 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.

  PMID: 34132703 BACKGROUND

• 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.

  PMID: 27989365 BACKGROUND

• 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.

  PMID: 27521710 BACKGROUND

MeSH Terms

Conditions

Appendicitis

Interventions

Piperacillin, Tazobactam Drug Combination; Ceftriaxone; Metronidazole

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Cefotaxime; Cephacetrile; Cephalosporins; Thiazines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Michael Livingston, MD, MSc, FRCSC

CONTACT

905-521-2100; livingm@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): April 1, 2027
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share