Appendicitis PerforatedPhase 2ALPACANCT05943223
Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA)
A Phase 2 study testing Piperacillin/tazobactam, Normal saline and CefTRIAXone Injection in people with Appendicitis Perforated, run by McMaster Children's Hospital at 1 site in Canada.
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… Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Appendicitis Perforated
- What is being tested?
- Piperacillin/tazobactam, Normal saline and CefTRIAXone Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- 9 Sep 2024to 20 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessing the Longitudinal Outcomes of Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA): a Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Appendicitis Perforated
- Being tested
- Piperacillin/tazobactam, Normal saline, CefTRIAXone Injection, Metronidazole Injection
- Keywords
- Child, Piperacillin, Ceftriaxone, Metronidazole
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin/tazobactamDrug
Post-operative piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h)
Normal salineDrug
Post-operative normal saline 50 mL once daily
CefTRIAXone InjectionDrug
Post-operative ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV once daily)
Metronidazole InjectionDrug
Post-operative metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h)
| Study group | Role | What they receive |
|---|---|---|
| Piperacillin/tazobactam | Experimental | Not described Receives: Drug: Piperacillin/tazobactam; Drug: Normal saline |
| Ceftriaxone and metronidazole | Active comparator | Not described Receives: Drug: CefTRIAXone Injection; Drug: Metronidazole Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of stay
Length of stay in hospital during index admission
Measured: Index admission
Secondary outcomes (10)
Percutaneous drain insertion
Percutaneous drain insertion by Interventional Radiology
Measured: Within 30 days of surgery
Deep or organ-space surgical site infection
Deep or organ-space surgical site infection
Measured: Within 30 days of surgery
Insertion of Peripherally Inserted Central Catheter (PICC)
Insertion of Peripherally Inserted Central Catheter (PICC)
Measured: Within 30 days of surgery
Parenteral nutrition
Need for parenteral nutrition
Measured: Within 30 days of surgery
Post-operative ultrasound
Need for post-operative ultrasound
Measured: Within 30 days of surgery
Clostridium difficile infection
Clostridium difficile infection (confirmed with stool sample and requiring treatment)
Measured: Within 30 days of surgery
Return to the emergency department
Return to the emergency department within 30 days of surgery
Measured: Within 30 days of surgery
Readmission to hospital
Readmission to hospital within 30 days of surgery
Measured: Within 30 days of surgery
Late complications
Telephone confirmation of no additional complications related to perforated appendicitis requiring assessment in clinic, emergency department visit, or admission to hospital
Measured: Telephone call 3 months after surgery
Exit survey
Parents will complete a descriptive questionnaire about the study by telephone
Measured: Telephone call 3 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2023
- Study start9 Sep 2024
- Primary completion16 Jul 2025
- Study completion20 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Appendicitis PerforatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Internal pilot study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Livingston, McMaster Children's Hospital
- Investigators
- Michael H Livingston, MD, MSc, Principal investigator, McMaster Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05943223
- Sponsor's protocol ID
- McmasterCH
- Acronym
- ALPACA
- Status last verified
- Jul 2026
- First submitted
- 26 Jun 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27521710Linnaus 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.
PubMed 27989365St 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.
PubMed 18558169Lee 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.
PubMed 34132703Kashtan 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.
PubMed 34876294Gerber 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.
PubMed 33372120Briatico 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.
PubMed 41202087
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Longitudinal Outcomes of Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA): a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05943223
- Acronym / sponsor ID
- ALPACA / McmasterCH
- Conditions
- Appendicitis Perforated
- Keywords
- Child, Piperacillin, Ceftriaxone, Metronidazole
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- McMaster Children's HospitalUniversity, hospital or other
- Study start
- 9 Sep 2024 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 20 Oct 2025 (actual)
- First posted
- 13 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Internal pilot study
| Arm | Type | Receives |
|---|---|---|
| Piperacillin/tazobactam | Experimental | Drug: Piperacillin/tazobactam, Drug: Normal saline |
| Ceftriaxone and metronidazole | Active comparator | Drug: CefTRIAXone Injection, Drug: Metronidazole Injection |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin/tazobactamPost-operative piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h) | Drug | Piperacillin/tazobactam |
| Normal salinePost-operative normal saline 50 mL once daily | Drug | Piperacillin/tazobactam |
| CefTRIAXone InjectionPost-operative ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV once daily) | Drug | Ceftriaxone and metronidazole |
| Metronidazole InjectionPost-operative metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h) | Drug | Ceftriaxone and metronidazole |
Primary outcome
Length of stay
Time frame: Index admission
Length of stay in hospital during index admission
10 secondary outcomes
Percutaneous drain insertion
Time frame: Within 30 days of surgery
Deep or organ-space surgical site infection
Time frame: Within 30 days of surgery
Insertion of Peripherally Inserted Central Catheter (PICC)
Time frame: Within 30 days of surgery
Parenteral nutrition
Time frame: Within 30 days of surgery
Post-operative ultrasound
Time frame: Within 30 days of surgery
Clostridium difficile infection
Time frame: Within 30 days of surgery
Return to the emergency department
Time frame: Within 30 days of surgery
Readmission to hospital
Time frame: Within 30 days of surgery
Late complications
Time frame: Telephone call 3 months after surgery
Exit survey
Time frame: Telephone call 3 months after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Background: PubMed 27521710St 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.
- Background: PubMed 27989365Linnaus 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.
- Background: PubMed 18558169St 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.
- Background: PubMed 34132703Lee 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.
- Background: PubMed 34876294Kashtan 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.
- Background: PubMed 33372120Gerber 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.
- Derived from this study: PubMed 41202087Briatico 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael H Livingston, MD, MSc principal investigator
McMaster Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Piperacillin/tazobactam, Normal saline and CefTRIAXone Injection in people with Appendicitis Perforated, run by McMaster Children's Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of stay (time frame: Index admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05943223, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.