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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]

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

Condition category

Condition code

Respiratory

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]

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]

Proportion of participants with resolution of symptoms of sleep disordered breathing as defined by Brouillette score <-1

Timepoint [1]

6 weeks post randomisation

Secondary outcome [1]

Proportion of participants with resolution of symptoms of sleep disordered breathing, as defined by Brouillette Score <-1

Timepoint [1]

6, 12, 18 and 24 months post randomisation

Secondary outcome [2]

SDB symptoms of participants, as measured by score of parent-completed questionnaire:
Pediatric Sleep Questionnaire - Sleep Disordered Breathing subscale

Timepoint [2]

6 weeks and 6, 12, 18 and 24 months post randomisation

Secondary outcome [3]

Quality of life of participants, as measured by score of parent-completed questionnaire:
Pediactric Quality of Life Inventory

Timepoint [3]

6 weeks post randomisation

Secondary outcome [4]

Behavioural and emotional status of child, as measured by score of parent-completed questionnaire:
Strengths and Difficulties Questionnaire

Timepoint [4]

6 weeks post randomisation

Secondary outcome [5]

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]

6 weeks post randomisation

Secondary outcome [6]

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]

6 weeks and 6, 12, 18 and 24 months post randomisation

Secondary outcome [7]

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]

6 weeks and 6, 12, 18 and 24 months post randomisation

Secondary outcome [8]

Parent Satisfaction with medical therapy, as measured by score of parent-completed 5 point Likert Scale

Timepoint [8]

6 weeks post intervention

Secondary outcome [9]

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]

6 weeks post randomisation

Secondary outcome [10]

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]

6, 12, 18 and 24 months post randomisation

Secondary outcome [11]

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]

6 weeks post intervention

Secondary outcome [12]

Compliance to treatment during the course of the treatment period as assessed by weight of returned treatment/placebo bottles

Timepoint [12]

6 weeks post randomisation

Secondary outcome [13]

Treatment for SDB during follow up period, including specialty of Doctor seen and number of appointments

Timepoint [13]

6, 12, 18 and 24 months post randomisation

Secondary outcome [14]

Treatment for SDB during follow up period, including medication used, and duration of treatment

Timepoint [14]

6, 12, 18 and 24 months post randomisation

Secondary outcome [15]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/04/2018

Actual

8/06/2018

Date of last participant enrolment

Anticipated

31/01/2020

Actual

Date of last data collection

Anticipated

31/01/2022

Actual

Sample size

Target

276

Accrual to date

170

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Childrens Hospital - Parkville

Recruitment hospital [2]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [3]

Casey Hospital - Berwick

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3168 - Clayton

Recruitment postcode(s) [3]

3806 - Berwick

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Royal Children's Hospital Foundation

Address [1]

Level 2, 48 Flemington Road
Parkville
VIC 3052

Country [1]

Australia

Funding source category [2]

Other

Name [2]

Murdoch Children's Research Institute

Address [2]

50 Flemington Rd
Parkville
VIC 3052

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

Monash Health Foundation

Address [3]

Monash Medical Centre
246 Clayton Rd
Clayton
Victoria 3168

Country [3]

Australia

Primary sponsor type

Other

Name

Murdoch Children's Research Institute

Address

50 Flemington Rd
Parkville
VIC 3052

Country

Australia

Secondary sponsor category [1]

Charities/Societies/Foundations

Name [1]

Royal Children's Hospital Foundation

Address [1]

Level 2, 48 Flemington Road
Parkville
VIC 3052

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Children's Hospital Human Research Ethics Committee

Ethics committee address [1]

50 Flemington Rd
Parkville
VIC 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/01/2018

Approval date [1]

21/03/2018

Ethics approval number [1]

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

Dr Kirsten Perrett

Address

Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052

Country

Australia

Phone

+613 9936 6278

Fax

[email protected]

Contact person for public queries

Name

Alice Baker

Address

Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052

Country

Australia

Phone

+613 9345 5522

Fax

[email protected]

Contact person for scientific queries

Name

Kirsten Perrett

Address

Royal Children's Hospital
50 Flemington Rd
Parkville
VIC 3052

Country

Australia

Phone

+613 9936 6278

Fax

[email protected]

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 [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Email
4391	Study protocol	[email protected]
4392	Statistical analysis plan	[email protected]
4393	Informed consent form	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Effectiveness of Intranasal Mometasone Furoate vs Saline for Sleep-Disordered Breathing in Children: A Randomized Clinical Trial.	2023	https://dx.doi.org/10.1001/jamapediatrics.2022.5258

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically