search
Back to results

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
McMaster Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Appendicitis Perforated focused on measuring Child, Piperacillin, Ceftriaxone, Metronidazole

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    June 26, 2023
    Last Updated
    July 4, 2023
    Sponsor
    McMaster Children's Hospital
    search

    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

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs