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Trial registered on ANZCTR


Registration number
ACTRN12618000448246
Ethics application status
Approved
Date submitted
9/03/2018
Date registered
28/03/2018
Date last updated
18/09/2019
Date data sharing statement initially provided
18/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Steroid Nasal Spray for Sleep Disordered Breathing in Children
Scientific title
Efficacy of intranasal steroid for Sleep Disordered Breathing in children: a randomised, double-blind placebo-controlled trial - The MIST trial
Secondary ID [1] 293880 0
Nil
Universal Trial Number (UTN)
Trial acronym
The MIST Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Disordered Breathing 306346 0
Condition category
Condition code
Respiratory 305434 305434 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
mometasone furoate 50 micrograms / spray; 1 spray each nostril daily for 6 weeks

Adherence will be assessed by weight of medication bottles prior to dispensing and on return after the 6 week intervention period.
Intervention code [1] 300144 0
Treatment: Drugs
Comparator / control treatment
0.1mL Normal Saline spray; one spray each nostril daily for 6 weeks.

Adherence will be measured by weight of medication bottles prior to dispensing and on return after the 6 week intervention period.
Control group
Placebo

Outcomes
Primary outcome [1] 304564 0
Proportion of participants with resolution of symptoms of sleep disordered breathing as defined by Brouillette score <-1
Timepoint [1] 304564 0
6 weeks post randomisation
Secondary outcome [1] 344408 0
Proportion of participants with resolution of symptoms of sleep disordered breathing, as defined by Brouillette Score <-1
Timepoint [1] 344408 0
6, 12, 18 and 24 months post randomisation
Secondary outcome [2] 344409 0
SDB symptoms of participants, as measured by score of parent-completed questionnaire:
Pediatric Sleep Questionnaire - Sleep Disordered Breathing subscale
Timepoint [2] 344409 0
6 weeks and 6, 12, 18 and 24 months post randomisation
Secondary outcome [3] 344410 0
Quality of life of participants, as measured by score of parent-completed questionnaire:
Pediactric Quality of Life Inventory
Timepoint [3] 344410 0
6 weeks post randomisation
Secondary outcome [4] 344411 0
Behavioural and emotional status of child, as measured by score of parent-completed questionnaire:
Strengths and Difficulties Questionnaire
Timepoint [4] 344411 0
6 weeks post randomisation
Secondary outcome [5] 344412 0
Proportion of responders, based on parent assessment of post intervention health-related benefit, as measured by score of parent-completed questionnaire:
Glasgow Children's Benefit Inventory
Timepoint [5] 344412 0
6 weeks post randomisation
Secondary outcome [6] 344413 0
Proportion of responders to intervention, based on parent assessment of need for surgery, measured by response to parent question:
"Do you feel you child needs surgery now, to treat their snoring and difficulty breathing?"
Timepoint [6] 344413 0
6 weeks and 6, 12, 18 and 24 months post randomisation
Secondary outcome [7] 344414 0
Proportion of responders to intervention, based on parent assessment of need for specialist care, measured by composite score of parent questions:
Do you think your child’s snoring and breathing difficulty needs review now by a hospital specialist?
If no to above would you be happy to have your child taken off the hospital clinic waiting list?
Timepoint [7] 344414 0
6 weeks and 6, 12, 18 and 24 months post randomisation
Secondary outcome [8] 344415 0
Parent Satisfaction with medical therapy, as measured by score of parent-completed 5 point Likert Scale
Timepoint [8] 344415 0
6 weeks post intervention
Secondary outcome [9] 344416 0
ENT assessment of need for surgery (yes or no) based on review of findings from a combination of:
Brouillette Score, PSQ-SDB subscale and the Sleep Clinical Record (a structured examination of nose, jaw and throat)
Timepoint [9] 344416 0
6 weeks post randomisation
Secondary outcome [10] 344417 0
Number of participants who have undergone Tonsillectomy and/or adenoidectomy (T&A), or are on waitlist for T&A surgery as determined at follow up telephone calls
Timepoint [10] 344417 0
6, 12, 18 and 24 months post randomisation
Secondary outcome [11] 344418 0
Number of adverse events (AEs) throughout the 6 week treatment period as well as number of solicited AEs within the first week after commencing treatment, taken from diary entries where the solicited AE’s are prompted. Adverse events may include nasal irritation, nose bleed, sneezing, headache, sore throat and cough.
Timepoint [11] 344418 0
6 weeks post intervention
Secondary outcome [12] 344419 0
Compliance to treatment during the course of the treatment period as assessed by weight of returned treatment/placebo bottles
Timepoint [12] 344419 0
6 weeks post randomisation
Secondary outcome [13] 344420 0
Treatment for SDB during follow up period, including specialty of Doctor seen and number of appointments

Timepoint [13] 344420 0
6, 12, 18 and 24 months post randomisation
Secondary outcome [14] 344421 0
Treatment for SDB during follow up period, including medication used, and duration of treatment
Timepoint [14] 344421 0
6, 12, 18 and 24 months post randomisation
Secondary outcome [15] 344440 0
Proportion of responders to intervention, based on parent willingness to proceed to surgery based on response to parent question:
"If surgery were recommended to treat your child’s snoring and difficulty breathing now, would you be happy to proceed?"
Timepoint [15] 344440 0
6 weeks and 6, 12, 18 and 24 months post randomisation

Eligibility
Key inclusion criteria
Patients aged 3 to 12 years of age, referred to Upper Airways, Sleep, Respiratory and Ear Nose Throat (ENT) clinics at the Royal Children’s Hospital (RCH) and Sleep and ENT clinic at Monash Medical Centre (MMC) will be screened by telephone for symptoms of SDB
• Children with a Brouillette score =/> -1 will be eligible
Minimum age
3 Years
Maximum age
12 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children will be excluded if:
• BMI > 97th centile
• Stertor while awake and at rest
• Past Tonsillectomy and/or Adenoidectomy
• Craniofacial, neuromuscular, syndromic or defined genetic disorders
• Haemorrhagic diathesis or recurrent nosebleeds
• Use of intranasal or systemic corticosteroid within the past 6 weeks
• Active nasal infection or nasal trauma not fully healed
• Active tonsillitis

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)
The allocation schedule will be held by the Clinical Trials Pharmacist at each site and will remain blinded to all other study staff. Upon randomisation, the study doctor will call the clinical trials pharmacist at the respective site, who will provide the randomisation code for that participant. This code will be used for prescription of the treatment medication.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence will be generated by an independent statistician, by permuted random block randomisation
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 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The sample size has been calculated at 276 children, with 138 per treatment
arm. This was calculated by estimating that 30% of the saline group and 50%
of the INS group will respond with a resolution of symptoms captured by the
primary outcome of the Brouillette Score <-1. This estimation is based on the
results of a previous audit of patients in the Upper Airway Clinic at RCH (currently
not published). Using a two group chi-square test with a 0.05 two-sided significance
level will have 90% power to detect this difference between the INS and saline
group (odds ratio of 2.333) with a sample size in each group of 124. We have
allowed for a loss to follow up of up to 10%, increasing the sample size to 138
per arm, or 276 total.

Participants will be included in the Intention to treat population (ITT) if they
were randomised into the study, regardless of whether they received study
medication. The ITT population will be the primary population to assess
efficacy. The safety population will include any participant randomised into
the study that received at least one dose of study medication. The per-protocol
population (PP) will include any participant who was randomised and received
at least 80% of the protocol-required doses of study medication and fulfilled all
protocol-required assessments.

Primary outcome
The proportion of participants in each treatment arm with resolution of symptoms
at 6 weeks (Brouillette score <-1) will be calculated with 95% confidence intervals
(CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Secondary Outcomes
This same method will be used to analyse the numbers of participants who progress
to surgery at 6, 12, 18 and 24 months.

SDB symptom scores at 6 weeks (for sleep, quality of life and emotional and
behavioural function, all measured by questionnaire) will be presented as mean scores
95% CIs in the two treatment arms, and the treatment arms will be compared using
a linear regression adjusted for centre. Parent satisfaction with medical treatment
will be analysed using the same methodology.

Data on any further treatment given for SDB following the 6-week intervention period
Will be described by treatment arm, and any imbalance by treatment arm will be
investigated.

Logistic regression models will be fitted to determine whether clinical factors at
baseline or severity of SDB symptoms at baseline were associated with response
to the intervention.

Recruitment
Recruitment status
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)
VIC
Recruitment hospital [1] 9872 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 9873 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 9874 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 18666 0
3052 - Parkville
Recruitment postcode(s) [2] 18667 0
3168 - Clayton
Recruitment postcode(s) [3] 18668 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 298504 0
Charities/Societies/Foundations
Name [1] 298504 0
Royal Children's Hospital Foundation
Address [1] 298504 0
Level 2, 48 Flemington Road
Parkville
VIC 3052
Country [1] 298504 0
Australia
Funding source category [2] 298507 0
Other
Name [2] 298507 0
Murdoch Children's Research Institute
Address [2] 298507 0
50 Flemington Rd
Parkville
VIC 3052
Country [2] 298507 0
Australia
Funding source category [3] 303859 0
Charities/Societies/Foundations
Name [3] 303859 0
Monash Health Foundation
Address [3] 303859 0
Monash Medical Centre
246 Clayton Rd
Clayton
Victoria 3168
Country [3] 303859 0
Australia
Primary sponsor type
Other
Name
Murdoch Children's Research Institute
Address
50 Flemington Rd
Parkville
VIC 3052
Country
Australia
Secondary sponsor category [1] 297642 0
Charities/Societies/Foundations
Name [1] 297642 0
Royal Children's Hospital Foundation
Address [1] 297642 0
Level 2, 48 Flemington Road
Parkville
VIC 3052
Country [1] 297642 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299484 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 299484 0
50 Flemington Rd
Parkville
VIC 3052
Ethics committee country [1] 299484 0
Australia
Date submitted for ethics approval [1] 299484 0
10/01/2018
Approval date [1] 299484 0
21/03/2018
Ethics approval number [1] 299484 0
38005A

Summary
Brief summary
Breathing problems in sleep (known as sleep disordered breathing - SDB) is a common problem in childhood (seen in up to 10%). SDB can affect children along a spectrum from snoring without sleep disruption, to obstructive sleep apnoea (OSA) with severely disrupted sleep and pauses in breathing. SDB symptoms are now the most common reason for tonsillectomy surgery in children. However, some of these children may benefit from less invasive medical treatment. This study is trying to find out if a nasal steroid spray (INS) (mometasone furoate) can help reduce SDB symptoms. We will ask children 3-12years old to be part of the study. We will do an examination and ask parents to complete questionnaires on their child’s SDB symptoms, and other things related to good sleep such as their child’s emotions and behaviour, and quality of life. We will give them either INS or saline spray (salty water) for 6 weeks, and then repeat the assessments to see the effect of the INS versus saline. We will also monitor who has surgery over the next two years. We expect that INS will reduce the symptoms of SDB, and ultimately reduce the need for surgery, thereby improving the health and quality of life of children with SDB, and also reducing health care costs.
Trial website
https://www.mcri.edu.au/research/projects/mist-trial
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80566 0
Dr Kirsten Perrett
Address 80566 0
Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052
Country 80566 0
Australia
Phone 80566 0
+613 9936 6278
Fax 80566 0
Email 80566 0
kirsten.perett@rch.org.au
Contact person for public queries
Name 80567 0
Dr Alice Baker
Address 80567 0
Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052
Country 80567 0
Australia
Phone 80567 0
+613 9345 5522
Fax 80567 0
Email 80567 0
alice.baker@rch.org.au
Contact person for scientific queries
Name 80568 0
Dr Kirsten Perrett
Address 80568 0
Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052
Country 80568 0
Australia
Phone 80568 0
+613 9936 6278
Fax 80568 0
Email 80568 0
kirsten.perrett@rch.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data underlying published results only
When will data be available (start and end dates)?
From 6 months after publication; no end date determined
Available to whom?
To those who have been approved by the Investigator Team, and have signed a Data Access Agreement, with approved plan of analysis, appropriate acknowledgements and any additional costs covered.
Available for what types of analyses?
Only analysis pre-approved by the Investigator Team
How or where can data be obtained?
Subject to approvals by the Investigator Team - enquiries to kirsten.perrett@rch.org.au
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
How or where can supporting documents be obtained?
Type [1] 4391 0
Study protocol
Citation [1] 4391 0
Link [1] 4391 0
Email [1] 4391 0
kirsten.perrett@rch.org.au
Other [1] 4391 0
Attachment [1] 4391 0
Type [2] 4392 0
Statistical analysis plan
Citation [2] 4392 0
Link [2] 4392 0
Email [2] 4392 0
kirsten.perrett@rch.org.au
Other [2] 4392 0
Attachment [2] 4392 0
Type [3] 4393 0
Informed consent form
Citation [3] 4393 0
Link [3] 4393 0
Email [3] 4393 0
kirsten.perrett@rch.org.au
Other [3] 4393 0
Attachment [3] 4393 0
Summary results
No Results