Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA) (ALPACA)
Primary Purpose
Appendicitis Perforated
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Piperacillin/tazobactam
Normal saline
CefTRIAXone Injection
Metronidazole Injection
Sponsored by
About this trial
This is an interventional treatment trial for Appendicitis Perforated focused on measuring Child, Piperacillin, Ceftriaxone, Metronidazole
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Piperacillin/tazobactam
Ceftriaxone and metronidazole
Arm Description
Outcomes
Primary Outcome Measures
Length of stay
Length of stay in hospital during index admission
Secondary Outcome Measures
Percutaneous drain insertion
Percutaneous drain insertion by Interventional Radiology
Deep or organ-space surgical site infection
Deep or organ-space surgical site infection
Insertion of Peripherally Inserted Central Catheter (PICC)
Insertion of Peripherally Inserted Central Catheter (PICC)
Parenteral nutrition
Need for parenteral nutrition
Post-operative ultrasound
Need for post-operative ultrasound
Clostridium difficile infection
Clostridium difficile infection (confirmed with stool sample and requiring treatment)
Return to the emergency department
Return to the emergency department within 30 days of surgery
Readmission to hospital
Readmission to hospital 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
Exit survey
Parents will complete a descriptive questionnaire about the study by telephone
Full Information
NCT ID
NCT05943223
First Posted
June 26, 2023
Last Updated
July 4, 2023
Sponsor
McMaster Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05943223
Brief Title
Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA)
Acronym
ALPACA
Official Title
Assessing the Longitudinal Outcomes of Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA): a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2024 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster Children's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Appendicitis Perforated
Keywords
Child, Piperacillin, Ceftriaxone, Metronidazole
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Internal pilot study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Piperacillin/tazobactam
Arm Type
Experimental
Arm Title
Ceftriaxone and metronidazole
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Piperacillin/tazobactam
Intervention Description
Post-operative piperacillin/tazobactam 100 mg/kg IV q8h (to a maximum of 4.5 g IV q8h)
Intervention Type
Drug
Intervention Name(s)
Normal saline
Intervention Description
Post-operative normal saline 50 mL once daily
Intervention Type
Drug
Intervention Name(s)
CefTRIAXone Injection
Intervention Description
Post-operative ceftriaxone 50 mg/kg IV once daily (to a maximum of 2 g IV once daily)
Intervention Type
Drug
Intervention Name(s)
Metronidazole Injection
Intervention Description
Post-operative metronidazole 10 mg/kg IV q8h (to a maximum of 500 mg IV q8h)
Primary Outcome Measure Information:
Title
Length of stay
Description
Length of stay in hospital during index admission
Time Frame
Index admission
Secondary Outcome Measure Information:
Title
Percutaneous drain insertion
Description
Percutaneous drain insertion by Interventional Radiology
Time Frame
Within 30 days of surgery
Title
Deep or organ-space surgical site infection
Description
Deep or organ-space surgical site infection
Time Frame
Within 30 days of surgery
Title
Insertion of Peripherally Inserted Central Catheter (PICC)
Description
Insertion of Peripherally Inserted Central Catheter (PICC)
Time Frame
Within 30 days of surgery
Title
Parenteral nutrition
Description
Need for parenteral nutrition
Time Frame
Within 30 days of surgery
Title
Post-operative ultrasound
Description
Need for post-operative ultrasound
Time Frame
Within 30 days of surgery
Title
Clostridium difficile infection
Description
Clostridium difficile infection (confirmed with stool sample and requiring treatment)
Time Frame
Within 30 days of surgery
Title
Return to the emergency department
Description
Return to the emergency department within 30 days of surgery
Time Frame
Within 30 days of surgery
Title
Readmission to hospital
Description
Readmission to hospital within 30 days of surgery
Time Frame
Within 30 days of surgery
Title
Late complications
Description
Telephone confirmation of no additional complications related to perforated appendicitis requiring assessment in clinic, emergency department visit, or admission to hospital
Time Frame
Telephone call 3 months after surgery
Title
Exit survey
Description
Parents will complete a descriptive questionnaire about the study by telephone
Time Frame
Telephone call 3 months after surgery
Other Pre-specified Outcome Measures:
Title
Recruitment rate
Description
Number of participants randomized per month
Time Frame
Through study completion (average of 1 year)
Title
Consent rate
Description
Number of participants who consent to participate divided by those who are approached for consent
Time Frame
Through study completion (average of 1 year)
Title
Rate of protocol violations
Description
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
Time Frame
Through study completion (average of 1 year)
Title
Rate of loss to follow-up
Description
Number of participants who cannot be contacted by phone 3 months after discharge from hospital divided by those randomized
Time Frame
Through study completion (average of 1 year)
Title
Cost of trial
Description
Total cost of internal pilot study in Canadian dollars divided by the number of participants randomized
Time Frame
Through study completion (average of 1 year)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Briatico, MSc
Phone
9055212100
Ext
75231
Email
briaticd@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Michael H Livingston, MD, MSc
Phone
9055212100
Ext
75231
Email
livingm@mcmaster.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael H Livingston, MD, MSc
Organizational Affiliation
McMaster Children's Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27521710
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.
Results Reference
background
PubMed Identifier
27989365
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.
Results Reference
background
PubMed Identifier
18558169
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.
Results Reference
background
PubMed Identifier
34132703
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.
Results Reference
background
PubMed Identifier
34876294
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.
Results Reference
background
PubMed Identifier
33372120
Citation
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.
Results Reference
background
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Piperacillin/Tazobactam Versus ceftriAxone and Metronidazole for Children With Perforated Appendicitis (ALPACA)
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