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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

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

Conditions
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Patient-Controlled Analgesia

Intervention / Treatment
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* Drug: Morphine
* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single site randomised embedded trial comparing the side effects of two standard intravenous opioid PCAs, namely morphine and oxycodone. There are two treatment arms, namely morphine and oxycodone, with patients randomised to each arm. Apart from the consent and randomisation process there will be no change to current pre-existing practices for PCAs and patient care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous (IV) Morphine Patient controlled analgesia (PCA)<br>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<br>* Intravenous (IV) delivery via Patient Controlled Analgesia device (PCA) 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout<br>|
| Active Comparator: IV Oxycodone PCA<br>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<br>* Intravenous (IV) delivery via Patient Controlled Analgesia device (PCA) 20mcg/kg bolus to a maximum of 1mg with a 5-minute lockout<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paediatric, Post-operative Pain, Patient-controlled analgesia, Paediatric analgesia, Post-operative, Embedded clinical trials