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Trial registered on ANZCTR


Registration number
ACTRN12616001078448p
Ethics application status
Not yet submitted
Date submitted
26/07/2016
Date registered
10/08/2016
Date last updated
10/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial to compare the quality of induction using two different premedication combinations in children with Autism Spectrum Disorder (ASD) undergoing surgery.
Scientific title
Premedication and preparation for children with Autism Spectrum Disorder:
A multi-centre randomised, blinded trial to determine the quality of induction using combination of low dose clonidine and midazolam versus placebo plus high dose of midazolam as premedication.
Secondary ID [1] 289761 0
Nil Known
Universal Trial Number (UTN)
U1111-1185-7439
Trial acronym
Pre-ASD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Children with Autism Spectrum Disorder 299623 0
Having an operation 299624 0
Needing premedication 299625 0
Condition category
Condition code
Mental Health 299584 299584 0 0
Autistic spectrum disorders
Anaesthesiology 299638 299638 0 0
Anaesthetics
Surgery 299639 299639 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Children with ASD who require premedication for operation and have received the preparation package, will be randomised to either placebo (water) plus standard dose of midazolam or low doses of clonidine plus midazolam. The intervention group will be given clonidine 3mcg/kg, 60 minutes before the operation and midazolam 0.3 mg/kg, 30 minutes before the operation. The maximum dose of clonidine is 250 mcg and maximal dose of midazolam is 12 mg. The standard of care group will receive water (placebo) 60 minutes before the operation and 0.5 mg of midazolam 30 minutes before the operation. the maximum dose of midazolam is 20 mg. All medication will be given orally.
The preparation package includes a face mask to practice, information re trial and how to prepare and distract the child, baseline information about the child and 3 booklets to choose from in order to prepare children for operation. these booklets are social stories that are for children with different level of understanding and the standard hospital booklet. The social stories are prepared by chief investigator (Dr Taghizadeh). The hospital booklet is written by Marieke Mitchell and is called "Going to hospital, what will it be like?". Social story are very commonly used in the educational setting and multiple studies support their use. The concept of social story was developed by Carol Gray (Gray and Garand, 1993) in order to explain social situations to children with ASD and to teach them the appropriate responses that are expected of them. Gary suggested a specific combination of directive, perspective and descriptive sentences. Parents may choose any booklet that they find helpful to their child. The preparation package is sent 7-10 days before the operation.
Intervention code [1] 295412 0
Prevention
Intervention code [2] 295469 0
Treatment: Drugs
Comparator / control treatment
Placebo (water) plus midazolam at standard dose of 0.5 mg/kg up to maximum of 20 mg at 30 minutes before the operation. All premedication are given orally.
Control group
Active

Outcomes
Primary outcome [1] 299057 0
Smooth or steal induction as per Almanrader Scale of 3-5. Almanrader scale is used in multiple studies before. There is no gold standard scale for induction and most studies use a 4 or 5 point scale.
Timepoint [1] 299057 0
Induction of anaesthesia
Secondary outcome [1] 326042 0
Emergence delirium (agitation) in recovery room as measured by Watcha scale (>2)
Timepoint [1] 326042 0
From the time of admission to stage 1 recovery, every 30 minutes until discharge from stage 2 recovery.
Secondary outcome [2] 326043 0
Satisfaction of parents with preparation program as measured by a likert scale
Timepoint [2] 326043 0
The parents receive the preparation package. as part of this package there is a questionnaire to be filled up before coming to hospital. one of the questions is their satisfaction with preparation program.
Secondary outcome [3] 326044 0
Describing the characteristics of children that do not accept premedication or spit it up. The outcome is assessed by report from the nurses that administer the premedication in the medical record.
Timepoint [3] 326044 0
After taking the premedication i.e. 60 minutes and 30 minutes before operation.
Secondary outcome [4] 326198 0
Whether the child has a steal induction. steal induction means to give the child inhalation anaesthetic without waking the child up. that means the child comes to operating room asleep. Every effort is made not to wake him/her up. N2o/ O2 is introduced without touching the face for 1-2 minutes. Slowly increasing sevoflurane.
Timepoint [4] 326198 0
At the time of induction of anaesthesia
Secondary outcome [5] 326199 0
Post operative vomiting
Timepoint [5] 326199 0
Recovery room. The investigator will follow the patient up in recovery room, so the episodes of vomiting can be recorded directly. If not possible then medical records will be consulted.
Secondary outcome [6] 326200 0
Post operative pain score using r-FLACC scale.
Timepoint [6] 326200 0
Recovery room including stage 1 and 2. The rFLACC is assessed every 15 minutes for 60 minutes.
Secondary outcome [7] 326201 0
Post operative behavioural changes, using PBRHB
Timepoint [7] 326201 0
At one week follow up
Secondary outcome [8] 326202 0
Length of stay in stage 1 and 2 recovery rooms
Timepoint [8] 326202 0
Recovery room. Either directly measured as investigator is expected to follow the patient in recover room or by consulting the medical records.
Secondary outcome [9] 326203 0
Cost of preparation package
Timepoint [9] 326203 0
Before operation, from the cost involved when we prepare and send the preparation package.
Secondary outcome [10] 326204 0
Satisfaction of parents and anaesthetists with premedication using a likert type scale
Timepoint [10] 326204 0
Parents at the end of operation before discharge and anaesthetists while the patient is having the operation
Secondary outcome [11] 326205 0
Adverse events including hypoxia, hypotension, bradycardia, excessive sedation. This outcome is provided either directly or by reviewing the medical records. The anaesthetist provide the information in the case report form about the complications during the operation.
Timepoint [11] 326205 0
From the premedication until discharge
Secondary outcome [12] 326206 0
Anxiety of parents and children having operation at the time of induction and discharge, using Visual Analogue Scale for anxiety.
Timepoint [12] 326206 0
At the time of induction of anaesthesia and at the time of discharge.
Secondary outcome [13] 326207 0
Comparison of premedication booklets. the parents will be asked which premedication booklet was most useful and why. There are 3 choices. Two social stories and 1 usual hospital booklet.
Timepoint [13] 326207 0
On admission to hospital
Secondary outcome [14] 326289 0
Describe the characteristic of children that require significant restraint or ketamine despite premedication assessed by direct observation or by review of medical records. Their individual characteristics is determined from the baseline medical questionnaire including the premedication group, intellectual abilities, use of psychotropic medications and behavioural challenges.
Timepoint [14] 326289 0
This outcome is assessed either before induction as the child maybe agitated and anaesthetist may give extra doses of ketamine or at the time of induction, the child may require significant restraint or intramuscular ketamine

Eligibility
Key inclusion criteria
Diagnosed with ASD , between the ages of 4-16 years, ASA 1 or 2, No contraindication to premedication. Any type of operation is permitted. They are scheduled to undergo surgery.
Minimum age
4 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
ASA 3 or 4, cardiac/ respiratory conditions that exclude the use of sedation, obesity with weight more than 95% for age or BMI >30 (whatever is lower), previous intolerance or allergy to either medication or formulation component, Gastrointestinal disorders that affect absorption.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study pharmacist will prepare study packs based on the randomisation schedule using variable block sizes, stratified for site and age that are provided by our study statistician.
After the consent, the investigator will choose the lowest number study pack .
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The statistician will provide the randomisation schedule using variable block sizes, stratified by age : less than 12 or more than or equal 12 years and the site : Royal Children Hospital of Melbourne (RCH) or Royal Dental Hospital of Victoria (RDH).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on assumption that midazolam provides smooth or steal induction in 60% of participants and adding clonidine will improve this outcome by 25%, , 57 participants in each group is required with beta error of 20% and alpha error of 5%. based on 2 sided chi-squared test.
The primary outcome of smooth or steal induction will be presented as proportion in each group with the comparison between the groups presented as a difference in proportion and as odds ratio from a logistic regression model adjusted for site and age with 95% CI and p-value. The results will be presented as number needed to treat and 95% CI. Multiple imputation is used to handle the missing data. All data will be analysed as intention to treat basis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/09/2016
Actual
Date of last participant enrolment
Anticipated
20/11/2017
Actual
Date of last data collection
Anticipated
27/11/2017
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6266 0
The Royal Dental Hospital of Melbourne - Carlton
Recruitment hospital [2] 6267 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 13702 0
3052 - Parkville
Recruitment postcode(s) [2] 13703 0
3053 - Carlton

Funding & Sponsors
Funding source category [1] 294146 0
Charities/Societies/Foundations
Name [1] 294146 0
Australian and New Zealand College of Anaesthetists (ANZCA)
Country [1] 294146 0
Australia
Primary sponsor type
Hospital
Name
Murdoch Children Research Institute (MCRI)
Address
Flemington Rd, Parville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 292972 0
None
Name [1] 292972 0
NONE
Address [1] 292972 0
NONE
Country [1] 292972 0
Other collaborator category [1] 279118 0
Individual
Name [1] 279118 0
Prof. Andrew Davidson
Address [1] 279118 0
MCRI, Flemington Rd, Parkville, VIC 3052
Country [1] 279118 0
Australia
Other collaborator category [2] 279119 0
Individual
Name [2] 279119 0
Dr Poranee Wongprsartsuk
Address [2] 279119 0
Royal Children's Hospital (RCH), Flemington Rd, Parkville, Vic 3052
Country [2] 279119 0
Australia
Other collaborator category [3] 279120 0
Individual
Name [3] 279120 0
Prof. Katrina Williams
Address [3] 279120 0
MCRI, Flemington Rd, Parkville 3052, VIC
Country [3] 279120 0
Australia
Other collaborator category [4] 279121 0
Individual
Name [4] 279121 0
Dr Amandeep Nanuan
Address [4] 279121 0
Royal Dental Hospital (RDH), 720 Swanston st, Carlton 3053, vic
Country [4] 279121 0
Australia
Other collaborator category [5] 279122 0
Individual
Name [5] 279122 0
Mrs Jill Budge
Address [5] 279122 0
RDH, 720 Swanston st,Carlton 3053, Vic
Country [5] 279122 0
Australia
Other collaborator category [6] 279123 0
Individual
Name [6] 279123 0
Prof. David Story
Address [6] 279123 0
Melbourne University, Parkville, Vic 3052
Country [6] 279123 0
Australia
Other collaborator category [7] 279124 0
Individual
Name [7] 279124 0
Dr Balvindar Kaur
Address [7] 279124 0
RCH, Flemington rd, Parkville 3052, Vic
Country [7] 279124 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 295557 0
RCH HREC
Ethics committee address [1] 295557 0
Ethics committee country [1] 295557 0
Australia
Date submitted for ethics approval [1] 295557 0
18/08/2016
Approval date [1] 295557 0
Ethics approval number [1] 295557 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67726 0
Dr Neda Taghizadeh
Address 67726 0
MCRI, Anaesthetic Trial Group, Level 4, Flemington Rd, Parkville 3052, VIC
Country 67726 0
Australia
Phone 67726 0
+61422722173
Fax 67726 0
Email 67726 0
neda.taghizadeh@mcri.edu.au
Contact person for public queries
Name 67727 0
Neda Taghizadeh
Address 67727 0
MCRI, Flemington rd, Parkville, 3052, VIC
Country 67727 0
Australia
Phone 67727 0
1300766439
Fax 67727 0
Email 67727 0
neda.taghizadeh@mcri.edu.au
Contact person for scientific queries
Name 67728 0
Neda Taghizadeh
Address 67728 0
MCRI, Flemington rd, Parkville, Vic 3052
Country 67728 0
Australia
Phone 67728 0
1300766439
Fax 67728 0
Email 67728 0
neda.taghizadeh@mcri.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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