Nausea and Vomiting in Postoperative Paediatric Patients With Patient-Controlled Analgesia (PCA): Morphine vs Oxycodone (POPCORN)

A Comparison of Nausea and Vomiting in Postoperative Paediatric Patients With Patient-controlled Analgesia (PCA): Morphine vs Oxycodone (POPCORN)

POPCORN trial will compare the side effects and effectiveness of Morphine versus Oxycodone medication when prescribed for use as patient controlled analgesia (PCA) for pain relief for paediatric patients after-surgery. This trial is embedded into routine patient care using the hospital electronic medical record (EMR). Participants will be randomly assigned to either medication after they enrol in the study.

The main questions the POPCORN trial aims to answer are:

• 1. Is there a difference in the usage of medication to treat nausea and vomiting for those who received oxycodone PCA versus morphine PCA for post-surgery pain relief?
• 2. Is there a difference in side effects or pain relief needed between the two groups?

Study activities are as follows:

• Participants enrolled to study during their pre-operative consultation
• Participants are randomly assigned to morphine or oxycodone
• No further study-specific activities expected from participant after enrolment and randomisation
• Participant receives routine medical care as planned
• Clinicians record assessments as per routine care in electronic medical record (EMR)
• EMR data are extracted as trial data

Study Overview

• Status: Recruiting
• Conditions: Patient-Controlled Analgesia
• Intervention / Treatment: Drug: Morphine; Drug: Oxycodone

Detailed Description

Morphine and oxycodone are commonly used intravenous (IV) opioids in adult and paediatric post-operative patients. Traditionally, morphine has been preferentially prescribed with PCA. However, IV oxycodone is rapidly becoming more popular. Despite systematic reviews describing their use within the adult population, very little is known about the comparative side-effect profiles of morphine versus oxycodone within the paediatric post-operative population. Both options are currently in use and considered standard of care at The Royal Children's Hospital (RCH), Melbourne, Australia. However, there is limited literature to support a clinician's choice between IV oxycodone PCA versus IV morphine PCA.

The aim of this embedded randomized controlled trial is to compare the side-effect profile of IV oxycodone PCA to IV morphine PCA in post-operative paediatric patients.

This is a single site, randomised, embedded trial with two intervention arms, namely IV morphine PCA and IV oxycodone PCA. The study will not be blinded due to the need for opioid syringes to be readily identifiable on the ward. Apart from the consent and randomisation process, there will be no change to current pre-existing practices around PCA use and patient care. Adopting a health informatics approach; patient identification, consent, randomization and reporting of outcomes will be embedded within the EMR.

The primary objective is to compare antiemetic use between the two intervention arms. The secondary objectives will be a comparison of PCA side effects, efficacy and opioid use between the two arms. Outcome data must be what is already recorded as part of usual clinical care within the EMR including: antiemetic administration, respiratory depression (new oxygen and/or high dose naloxone use), urinary retention (need for in-dwelling catheter insertion), constipation (medication laxative administration), itch (RCH Itch Score (0-4 Likert scale)), nausea and vomiting, sedation (0-4 University of Michigan Scoring System), pain (Wong-Baker FACES Pain Rating Scale/Visual Analogue Scale (VAS 0-10) and total opioid consumption (mg/kg/day).

• Study Type: Interventional
• Enrollment (Estimated): 690
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Justine Adams; Phone Number: 03 8341 6200; Email: justine.adams@mcri.edu.au
• Study Contact Backup: Name: Suzette Sheppard; Phone Number: 03 9345 4901; Email: Suzette.sheppard@mcri.edu.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Recruiting
      • The Royal Children's Hospital
      • Contact: Justine Adams; Phone Number: 03 8341 6200; Email: justine.adams@mcri.edu.au
      • Contact: Su May Koh; Phone Number: 03 9345 5233; Email: Su.Koh@rch.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postoperative patients who are appropriate for a PCA including those aged 6 and above and up to age 18 years.
• Those deemed appropriate for either morphine or oxycodone by their treating anaesthetist.
• American Society of Anaesthesiologists (ASA) score 1-3 inclusive
• Those whose parents or legal guardians have provided informed consent on the patient's behalf.

Exclusion Criteria:

• Any patients with an allergy, hypersensitivity, or contraindication to morphine or oxycodone.
• Patients in the age group with significant intellectual disability or physical incapacity rendering them incapable of using the PCA device
• ASA score 4 or above
• Inability or unwillingness of parent or legal guardian to provide informed consent for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous (IV) Morphine Patient controlled analgesia (PCA); Morphine PCA IV 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout- as per current RCH Children's Pain Management Service (CPMS) dosing and use.	Drug: Morphine; Intravenous (IV) delivery via Patient Controlled Analgesia device (PCA) 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout
Active Comparator: IV Oxycodone PCA; Oxycodone PCA IV 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout- as per current RCH Children's Pain Management Service (CPMS) dosing and use.	Drug: Oxycodone; Intravenous (IV) delivery via Patient Controlled Analgesia device (PCA) 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout; Other Names: Oxycodone Juno; Oxycodone HCI Medsurge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiemetic use	Prescription incidence and administration of any of the following to participant: Granisetron, Ondansetron, Droperidol, Metoclopramide, Cyclizine, Dexamethasone, and Promethazine	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Respiratory Depression	Measured as any new oxygen and/or high dose naloxone use (10mcg/kg to max of 400mcg). This will exclude administration of low dose naloxone when used to manage incidence of itch.	The time at which the PCA is first attached to the child and either up to 72 hours or 4 hours after ceasing PCA, whichever is first.
Incidence of Urinary Retention	Indicated by need for an in-dwelling catheter (IDC) insertion	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Reports of Itch	Measured using RCH Itch Score (0-4 Likert scale) where a higher score indicates worse pruritus/itch. 0=comfortable, no itch, 1=itches a little, doesn't interfere with activity, 2= itches more, sometimes interferes with activity, 3= itches a lot, difficult to be still/concentrate, 4= itches most terribly, impossible to sit still/concentrate	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Reports of Nausea	Measured via 0-10 visual analogue scale (VAS) scale Nausea will be measured using the nausea scale (0-10 Baxter Retching Faces scale / VAS)	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Sedation levels	Measured via University of Michigan Scoring System (0-4 scale) where a higher score indicates higher sedation level. 0= awake and alert, 1= minimally sedated, 2=moderately sedated, 3=deep sedation, 4=unrousable	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Incidence of Constipation	Recorded laxative administered is indicative. Medication laxatives only, no food laxatives.	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Reported pain levels	Measured via Wong-Baker FACES Pain Rating Scale or Visual Analogue Scale (0-10) higher is more pain. If both a pain scale and a rating are reported but don't align the higher of the two will be used.	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Total opioid consumption	All opioids administered, including any background infusions are accurately documented in the EMR. Total opioid administered will be calculated from the EMR. The total morphine equivalent dose will be calculated.	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.
Incidence of Vomiting	Incidence of vomiting will be measured using the documentation of number of vomiting episodes. This will be reported for each day over the study period.	From PCA attachment to 72 hours or 4 hours after ceasing PCA, whichever is first.

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Investigators: Principal Investigator: Sue May Koh, Murdoch Children's Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2024
• Primary Completion (Estimated): March 19, 2026
• Study Completion (Estimated): March 19, 2027

Study Registration Dates

• First Submitted: December 16, 2023
• First Submitted That Met QC Criteria: December 16, 2023
• First Posted (Actual): December 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Post-operative; Paediatric; Patient-controlled analgesia; Post-operative Pain; Paediatric analgesia; Embedded clinical trials
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Signs and Symptoms, Digestive; Perceptual Disorders; Vomiting; Agnosia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine; Oxycodone
• Other Study ID Numbers: 91523

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Beginning 12 months following analysis and article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by the Murdoch Children's Research Institute's (MCRI's) independent data use review committee (not including trial sponsor-investigator) and who accept MCRI's conditions, under a collaborator agreement, for accessing participant data after de-identification (text, tables, figures, and appendices) that underlies reported results, along with trial protocol, Statistical Analysis Plan (SAP) and Participant Information and Consent Forms (PICF).
• IPD Sharing Time Frame: 12 months following analysis and publication of the primary outcome
• IPD Sharing Access Criteria: Requests for access to previously published anonymised datasets by the scientific community will be reviewed and determined by an independent committee within the MCRI and in accordance with institute policy.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No