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Trial registered on ANZCTR


Registration number
ACTRN12621001236886
Ethics application status
Approved
Date submitted
1/07/2021
Date registered
13/09/2021
Date last updated
13/09/2021
Date data sharing statement initially provided
13/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
PEAChY-O
Pharmacological Emergency management of Agitation in Children and Young people: a randomised controlled trial of Oral medication
Scientific title
PEAChY-O
Pharmacological Emergency management of Agitation in Children and Young people: a randomised controlled trial of the effectiveness of Oral medication for the management of acute severe behavioural disturbance
Secondary ID [1] 304203 0
Nil known
Universal Trial Number (UTN)
U1111-1267-4036
Trial acronym
PEAChY-O
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
acute severe behavioural disturbance 321890 0
Condition category
Condition code
Emergency medicine 319621 319621 0 0
Other emergency care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PEAChY-O is a randomised controlled trial which will compare the effectiveness of oral olanzapine [arm one] to oral diazepam [arm two] for the management of paediatric acute severe behavioural disturbance occurring in the emergency department (ED).
ASBD will be determined by confirming the participant has a Sedation Assessment Tool (SAT) score of +1 or greater.
Dosing will be based on weight.
This is an open label study.
The trial medication will be provided by the clinical staff caring for the participant in the ED.
Only one dose will be provided as part of the PEAChY-O study.
No modifications to the doses or the medications provided will be allowed.
Ingestion in this trial is defined as the young person placing the medication in their mouth with the intent to consume it and the ED clinician deeming that they have ingested either the complete dose or enough to not require additional (or redosing of) medication.

Arm One:
Participants will receive 5mg olanzapine (sublingual wafer) if they weigh <40kg or 10mg if they weigh 40kg or greater.
Intervention code [1] 320538 0
Treatment: Drugs
Comparator / control treatment
Arm Two:
Participants will receive 5mg diazepam (tablet) if they weigh <40kg or 10mg if they weigh 40kg or greater.
Control group
Active

Outcomes
Primary outcome [1] 327482 0
The primary outcome will be successful sedation without the requirement for additional sedation 1 hour post randomisation.
Successful sedation will be assessed using the Sedation Assessment Tool.
Timepoint [1] 327482 0
1 hour post randomisation.
Secondary outcome [1] 395297 0
Medication related adverse events reported from randomisation until measurement of the primary outcome.

Medication related adverse events will be recorded on prospective case report forms by clinical staff and the participant's medical record will be reviewed retrospectively by research staff to determine if any adverse events were noted during the time period specified.
Timepoint [1] 395297 0
From randomisation until the primary outcome is measured (1 hour following randomisation).
Secondary outcome [2] 395298 0
Medication related adverse events reported from after the measurement of the primary outcome until the participant is discharged from hospital.

The participant's medical record will be reviewed retrospectively by research staff to determine if any adverse events were noted during the time period specified.
Timepoint [2] 395298 0
From 1 hour post randomisation (immediately after measurement of primary outcome) until the participant is discharged from hospital.
Secondary outcome [3] 395314 0
Further episodes of violent and acute behavioural disturbance in the ED after randomisation until discharge from the ED.

The participant's medical records will be reviewed retrospectively by research staff to determine if any further episodes of violence or behavioural disturbance were noted.
Timepoint [3] 395314 0
From randomisation until the participant leaves the ED.
Secondary outcome [4] 395315 0
Injuries to staff from randomisation until the participant's discharge from the ED.
For example: soft tissue injuries sustained from being punched or kicked.

The participant's medical records will be reviewed retrospectively by research staff to determine if any injuries to staff were documented. Research staff will also review the hospital's incident management recording system to identify if any injuries were reported during the participant's ED stay.
Timepoint [4] 395315 0
From time of randomisation until the participant leaves the ED.
Secondary outcome [5] 395318 0
Injuries to participants and/or their parents or guardians from randomisation until the participant's discharge from the ED.
For example: injuries related to physical or mechanical restraints inclusive of skin erythema or bruising.

The participant's medical records will be reviewed retrospectively by research staff to determine if any injuries to participants and/or their parents or guardians were documented.
Timepoint [5] 395318 0
From the time of randomisation until the participant leaves the ED.
Secondary outcome [6] 395321 0
Length of stay in the ED (from the time of randomisation).

The participant's medical record will be reviewed to determine the time at which the participant was discharged from the ED.
Timepoint [6] 395321 0
From the time of randomisation until the participant leaves the ED.
Secondary outcome [7] 395322 0
Length of stay in hospital (from the time of randomisation).

The participant's medical record will be reviewed to determine the time at which the participant was discharged from the hospital.
Note: this will only apply to participants who were admitted to the hospital.
Timepoint [7] 395322 0
From the time of randomisation until the participant leaves the hospital.
Secondary outcome [8] 395323 0
Disposition upon discharge from the ED.
For example: discharged home or admitted to a mental health unit.

The participant's medical record will be reviewed to determine their disposition upon discharge from the ED.
Timepoint [8] 395323 0
Measured at the time the participant is discharged from the ED.
Secondary outcome [9] 395324 0
Staff, participant and carer satisfaction with the management provided after 1 hour post randomisation but before the participant is discharged from the ED.

A satisfaction survey will be provided to each of the three groups outlined above. This survey will assess how satisfied the staff member, participant and/or carer was with how the medication provided helped them feel calm, how fast it worked and how well it was tolerated on a three point Likert Scale.
Timepoint [9] 395324 0
To be assessed as soon as practical after the primary outcome measurement is undertaken but must be measured before the participant is discharged from ED.
Secondary outcome [10] 395325 0
Healthcare resource use and costs incurred from time of randomisation until ED discharge.

The use and costs incurred will be determined through an audit of the participant's medical records reviewing to assist in determining the following factors:
number of ED staff members involved in the participant's care
the participant's length of stay in ED
cost of the participant's hospital stay
amount of time requiring high-dependency care in the ED
cost of medication provided
cost related to damage to property and/or ED equipment
cost of associated side effects or adverse events experienced
Timepoint [10] 395325 0
Measured from the time of randomisation until the participant is discharged from the ED.
Secondary outcome [11] 397644 0
Healthcare resource use and costs incurred from time of randomisation until hospital discharge.

The use and costs incurred will be determined through an audit of the participant's medical records reviewing to assist in determining the following factors:
number of ED staff members involved in the participant's care
amount of time requiring high-dependency care in the ED
cost related to damage to property and/or ED equipment
cost of medication provided
the participant's length of stay in the hospital
cost of the participant's hospital stay
cost of associated side effects or adverse events experienced whilst in the hospital
Timepoint [11] 397644 0
Measured from the time of randomisation until the participant is discharged from the hospital.
Secondary outcome [12] 397645 0
Clinician assessment of whether “successful sedation” was achieved.
This will be assessed at 1 hour post randomisation.
In addition to the objective primary outcome, this will provide the clinician caring for the participant the opportunity to provide a binary assessment of whether they believe successful sedation has been achieved using a yes/no scale.
Timepoint [12] 397645 0
Measured at the time of the primary outcome (1 hour post randomisation).
Secondary outcome [13] 397646 0
Whether a participant ingests their randomised medication or not.

This information will be documented on the prospective case report form by clinical staff.
Timepoint [13] 397646 0
Measured at 1 hour post randomisation.
Secondary outcome [14] 397647 0
Whether a participant ingests the prescribed weight-based dose or not.

This information will be documented on the prospective case report form by clinical staff. In addition, the participant's medical record will be reviewed to determine the dose provided.
Timepoint [14] 397647 0
Measured at 1 hour post randomisation.
Secondary outcome [15] 397649 0
Length of stay in the ED (from time of triage).

The participant's medical record will be reviewed to determine the time of triage for the participant as well as the time the participant is discharged from the ED.
Timepoint [15] 397649 0
Measured from the time the participant is triaged until they are discharged from the ED.
Secondary outcome [16] 397650 0
Length of stay in the hospital (from time of triage).

The participant's medical record will be reviewed to determine the time of triage for the participant as well as the time the participant is discharged from hospital. Note: this outcome will only be relevant to those participants who are admitted to hospital.
Timepoint [16] 397650 0
Measured from the time the participant is triaged until they are discharged from the hospital.

Eligibility
Key inclusion criteria
1. Age between 9 years and 17 years and 364 days.
2. SAT score of +1 or greater as determined by the ED clinician (i.e. patient deemed to be in a state of ASBD).
3. Concerted attempts at non-pharmacological management of the participant’s ASBD have failed.
4. ED clinician determines that medication is required to assist with management of the participant’s ASBD and oral medication is thought to be the most appropriate route of administration.
Minimum age
9 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known, documented or reported allergy or previous serious side effect to either olanzapine or diazepam.
2. Known, documented or reported non-response to either olanzapine or diazepam (e.g. in the medical record, a behavioural management plan [or similar] or by parent / guardian report).
3. Accompanying parent / guardian requests or refuses either olanzapine or diazepam
4. Obvious reversible aetiology for agitation that has been identified and not yet treated (e.g.: hypotension, hypoxia, hypoglycaemia).
5. Known pregnancy.
6. Known long QT syndrome.
7. Participants who have been enrolled in PEAChY-M during this ED admission (previous enrolment is not an exclusion criteria).
8. Participants who have been enrolled in PEAChY-O during a prior ED admission.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated block randomised lists will be created by an independent statistician stratified by site using variable block sizes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Assuming conservatively that 60% of participants reach successful sedation without the requirement for additional medication at 1 hour post randomisation (primary outcome) in the oral diazepam group, 165 participants would be required in each arm to provide 80% power to detect a 15% increase in the percentage with a positive outcome in the oral olanzapine group (to 75%), based on a two-sided test with alpha=0.05. Given the paucity of data, determining the expected difference from previous peer reviewed publications is challenging. However, a 15% increase in the number of participants successfully sedated at 1 hour would be considered clinically important.
In order to allow for a 5% loss to follow-up (which is a conservative estimate given the short time frame of the primary outcome), we aim to recruit a total of 348 participants to this trial (approximately 174 per group).
The main objectives of the trial – those relating to effectiveness – will be analysed using an intention to treat analysis. All participants, regardless of whether or not they ingest the medication they are randomised to, will be included in this analysis.
As part of this study there are also a number of objectives regarding the efficacy of the interventions. The efficacy objectives will be assessed using a per protocol analysis including only participants who ingest the medication to which they have been randomised within 30 minutes from randomisation.
Baseline and demographic characteristics will be summarised by randomised group in both the intention-to-treat and per protocol populations as means and standard deviations (SD) for continuous variables (or medians and interquartile rage for non-normal variables) and number and percentage for categorical variables.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 19432 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 19433 0
Monash Children’s Hospital - Clayton
Recruitment hospital [3] 19434 0
Perth Children's Hospital - Nedlands
Recruitment hospital [4] 19435 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [5] 19436 0
Gold Coast University Hospital - Southport
Recruitment hospital [6] 19437 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 19438 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 34014 0
3052 - Parkville
Recruitment postcode(s) [2] 34015 0
3168 - Clayton
Recruitment postcode(s) [3] 34016 0
6009 - Nedlands
Recruitment postcode(s) [4] 34017 0
5006 - North Adelaide
Recruitment postcode(s) [5] 34018 0
4215 - Southport
Recruitment postcode(s) [6] 34019 0
4101 - South Brisbane
Recruitment postcode(s) [7] 34020 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 308576 0
Government body
Name [1] 308576 0
Medical Research Futures Fund Million Minds Mission administered through the Department of Health
Address [1] 308576 0
Department of Health
GPO Box 9848
Canberra ACT 2601
Australia
Country [1] 308576 0
Australia
Funding source category [2] 308586 0
Government body
Name [2] 308586 0
Western Australia Child Research Fund
Address [2] 308586 0
PO Box 8172
Perth Business Centre
Perth WA 6849
Australia

Country [2] 308586 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Murdoch Children's Research Institute
Address
Royal Children's Hospital
50 Flemington Road, Parkville
Victoria 3052
Australia
Country
Australia
Secondary sponsor category [1] 309445 0
None
Name [1] 309445 0
Address [1] 309445 0
Country [1] 309445 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308518 0
Royal Children's Hospital Research Governance and Ethics Committee
Ethics committee address [1] 308518 0
Royal Children's Hospital
50 Flemington Road, Parkville
Victoria 3052
Ethics committee country [1] 308518 0
Australia
Date submitted for ethics approval [1] 308518 0
23/10/2020
Approval date [1] 308518 0
05/03/2021
Ethics approval number [1] 308518 0
HREC/66478/RCHM-2020

Summary
Brief summary
Acute severe behavioural disturbance (ASBD) is an emergency situation where a patient experiences severe agitation or aggression.
One of the common strategies used to manage those presenting to the emergency department (ED) with ASBD is the provision of medications. Medications assist in allowing the young person to gain control over their behaviour. In most instances, oral medications are used.
In individuals less than 18 years of age, there is no evidence available to guide doctors about which medications are the most efficacious, despite them being commonly used to manage ASBD. It is also not known how well these medications are tolerated by young people.
Therefore, the primary aim of this study is to determine whether, in children and adolescents with ASBD, oral olanzapine is more effective than oral diazepam at achieving successful sedation (i.e.: a state of calm) at 1 hour after randomisation. These medications were chosen as they are the two most commonly used medication in Australia.
This study will be a randomised, open label, multi-centre effectiveness trial which will enrol young people aged 9 to 17 and 364 days presenting to participating EDs with ASBD.
We hope to determine which medication is most effective and to assess the side effects of these medications.
We hypothesise that 15% more children will achieve successful sedation 1 hour after randomisation to olanzapine compared to those children who were randomised to diazepam.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110986 0
Prof Franz Babl
Address 110986 0
Emergency Research Group
Murdoch Children’s Research Institute
Royal Children's Hospital
50 Flemington Road, Parkville
Victoria 3052
Country 110986 0
Australia
Phone 110986 0
+61 3 9936 6635
Fax 110986 0
+61 3 9345 5938
Email 110986 0
franz.babl@rch.org.au
Contact person for public queries
Name 110987 0
Prof Franz Babl
Address 110987 0
Emergency Research Group
Murdoch Children’s Research Institute
Royal Children's Hospital
50 Flemington Road, Parkville
Victoria 3052
Country 110987 0
Australia
Phone 110987 0
+61 3 9936 6635
Fax 110987 0
+61 3 9345 5938
Email 110987 0
franz.babl@rch.org.au
Contact person for scientific queries
Name 110988 0
Prof Franz Babl
Address 110988 0
Emergency Research Group
Murdoch Children’s Research Institute
Royal Children's Hospital
50 Flemington Road, Parkville
Victoria 3052
Country 110988 0
Australia
Phone 110988 0
+61 3 9936 6635
Fax 110988 0
+61 3 9345 5938
Email 110988 0
franz.babl@rch.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results