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Trial registered on ANZCTR


Registration number
ACTRN12617001652369
Ethics application status
Approved
Date submitted
2/11/2017
Date registered
22/12/2017
Date last updated
2/11/2018
Date data sharing statement initially provided
2/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Autoinflation for Aboriginal and Torres Strait Islander Children with OME (middle ear infection)
Scientific title
A multi-centre randomised controlled trial to compare nasal balloon autoinflation versus no nasal balloon autoinflation for otitis media with effusion in Aboriginal and Torres Strait Islander children
Secondary ID [1] 293227 0
None
Universal Trial Number (UTN)
Trial acronym
INFLATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Otitis Media with Effusion 305254 0
Health of Aboriginal Children 305255 0
Condition category
Condition code
Ear 304564 304564 0 0
Other ear disorders
Infection 304565 304565 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasal autoinflation using the Otovent device: Children with unilateral or bilateral otitis media with effusion will be randomised to nasal balloon autoinflation (Otovent) 3 times a day for a minimum of 1 to a maximum of 3 months (treatment will cease at month 1 where no type B tympanograms are detected in any ear at that time. Regardless of tympanometry findings at Month 3, Otovent treatment will cease at that time.)
An Otovent kit (1 x nose piece and 10 medical balloons) will be provided to those randomised to Otovent at the Day 0 clinic visit. Children will place a balloon over the end of the Otovent moulded plastic nose piece and place the nose piece at the opening of one nostril while occluding the other. The child will take a breath, close their mouth and blow through their nose in an attempt to inflate the balloon using their nose, then change the nose piece to the alternate nostril and again inflate the balloon.
Adherence to treatment will be supported by a phone call at Day 3 (and clinic visit if needed) and weekly phone calls from Day 0 - Month 3 where Otovent treatment is continuing at Month 1. Children will be provided with age and gender appropriate stickers to add to an Adherence Diary each time the Otovent is used.
Intervention code [1] 299484 0
Treatment: Devices
Comparator / control treatment
Standard care (observation only followed by referral for ENT assessment if bilateral OME or reduced hearing is detected at Month 3).
Control group
Active

Outcomes
Primary outcome [1] 303787 0
Proportion of children showing improvement of OME determined by change of at least one Type B tympanogram to a normal Type A or C1 tympanogram at Month 1 (OME improved by child).
Timepoint [1] 303787 0
Month 1
Secondary outcome [1] 340139 0
Proportion of children showing improvement of OME determined by change of at least one Type B tympanogram to a normal Type A or C1 tympanogram at Months 3 and 6 (OME improved by child)
Timepoint [1] 340139 0
Month 3 and 6
Secondary outcome [2] 340140 0
Proportion of ears showing change from a Type B tympanogram to a normal Type A or C1 tympanogram at Months 1, 3 and 6 (OME resolved by ear)
Timepoint [2] 340140 0
Months 1, 3 and 6
Secondary outcome [3] 340141 0
Proportion of children showing change from a unilateral Type B tympanogram to a normal Type A or C1 tympanogram at month 1, 3 and 6 (OME improved by child – unilateral subgroup)
Timepoint [3] 340141 0
Month 1, 3, and 6
Secondary outcome [4] 340142 0
Proportion of children showing change from bilateral Type B tympanograms to a normal Type A or C1 tympanogram in one or both ears at month 1, 3 and 6 (OME improved by child – bilateral subgroup)
Timepoint [4] 340142 0
Month 1, 3, and 6
Secondary outcome [5] 340143 0
Proportion of tympanometric deterioration from a Type A or C1 tympanogram to C2, C3 or B tympanogram in non-index ears at Months 1, 3 and 6 (new OME by ear – unilateral subgroup)
Timepoint [5] 340143 0
Month 1, 3, and 6
Secondary outcome [6] 353551 0
Average hearing levels (pure tone threshold audiometry) at Month 3 (hearing loss in worse hearing ear)
Timepoint [6] 353551 0
Month 3
Secondary outcome [7] 353552 0
Average hearing levels (pure tone threshold audiometry) at Month 3 (hearing loss in better hearing ear)
Timepoint [7] 353552 0
Month 3
Secondary outcome [8] 353553 0
Improvement in ear-related health and quality of life using the OMQ14 at Months 3, and 6
Timepoint [8] 353553 0
Months 3 and 6
Secondary outcome [9] 353554 0
Adverse events up to Months 1, 3 and 6 Known/possible adverse events include: *otalgia *allergy to latex *nose bleed *vertigo *respiratory tract infection Parent/Carers will complete a weekly symptom diary and a symptom/adverse event questionnaire during face to face clinic visits at Month 1, 3, and 6.
Timepoint [9] 353554 0
Month 1, 3 and 6
Secondary outcome [10] 353555 0
Adherence to autoinflation - Children will complete a daily Adherence Diary from Day 0 to Month 1
Timepoint [10] 353555 0
Weekly, Weeks 1-4
Secondary outcome [11] 353556 0
Medical and non-medical costs of OME and its treatment - Parent/Carers will complete a weekly questionnaire between Day 0 and Month 3 and at the Month 1, 3 and 6 clinics visits, regarding whether they spent any money on symptom relief medication, travel, Health Care Provider visits, or other expenses in relation to the Child's ear disease.
Timepoint [11] 353556 0
Month 1, 3 and 6
Secondary outcome [12] 353557 0
Qualitative exploration of parent/carer and health care provider, AMS research officer and AMS reference group perspectives of otitis media, research processes and the research experience including the experience of using nasal balloon autoinflation. Data will be collected primarily via individual semi-structured interviews and annual (AMS research officer) and end of study (AMS reference group) focus groups. A small amount of text data will be collected in limited open ended questions on the clinical trial questionnaires (CRF worksheets). This will relate to satisfaction with study processes and use of autoinflation and will be combined with interview data for analysis. Interviews will be undertaken by phone or in person, by trained interviewers in a private setting. The focus groups will be face to face.
Timepoint [12] 353557 0
Annually or end of study

Eligibility
Key inclusion criteria
1. Aboriginal and Torres Strait Islander
2. Aged 3 -16 years
3. Type B tympanogram in at least one ear
Minimum age
3 Years
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Child has current acute upper respiratory infection;
Current acute otitis media (defined as a Type B tympanogram plus either ear pain or a bulging ear drum on otoscopy);
Current perforated tympanic membrane or current grommet (ventilation tube);
Planned ENT surgery within next 3 months;
Children with a latex allergy;
A nosebleed in the last 3 weeks, or more than 1 nosebleed in the preceding 6 months;
A condition which increases the risk of complications (e.g. immunosuppression, genetic or chromosomal abnormality, cleft palate or mid-face abnormalities such as seen in Down Syndrome)
Inability to use the autoinflation device.
Previous participation in INFLATE

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)
Children will be randomised to Otovent treatment or standard care using the NHMRC Clinical Trial Centre (CTC) Interactive Voice Response System (IVRS). IVRS is a 24 hours per day, 7 days per week automated system which enables an immediate allocation to predetermined groups, subsequently confirmed by fax/email.
Neither the sponsor or sites will be blinded to allocation

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified using permuted blocks, using the three following characteristics
1. participating site
2. Child age (3 to 5 years versus 6 to 16 years)
3. unilateral or bilateral OME at presentation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome measure is the proportion of children showing change from a Type B tympanogram to Type A or C1 tympanograms in at least 1 ear at Month 1.

A sample size of 340 children (170 in each of Otovent® and standard care groups) will be sufficient to detect an absolute difference of 15% (relative difference RR=1.43 between groups in OME resolution rates at Month 1, with 80% power and a 5% significance level. The 15% difference represents a difference between 35% resolution in the control group and 50% resolution in the treatment group. This 15% absolute difference is clinically significant as it means the 65% non-resolution is reduced by a quarter. With 15% loss to follow up, 400 children will need to be randomised (or 534 for 90% power). This sample size will also detect an effect size of 0.3 (assuming a standardised SD=1) for a continuous secondary outcome.

The primary analysis will be on an intention-to-treat basis (ITT), including all children randomised. A secondary per protocol analysis, consisting of all randomised patients who have adhered to the treatment allocated and were not lost to follow up, will also be carried out. Missing data will be handled using multiple imputation in order to avoid underestimation of variance known to be present in single imputation approaches. The relative effect of autoinflation on the primary outcome at Month 1 will be estimated using a generalised linear model for binary data with log-link function, reporting relative risks (RR) and 95% CIs. Both unadjusted and adjusted RRs will be reported. Adjustment covariates will include age, sex, whether unilateral or bilateral OME, and randomisation site. The unit of analysis will be the child, rather than the ear, although a separate analysis will be carried out using each ear as the outcome, using generalised estimating equations to account for correlation and clustering. The same method will be used for the secondary outcomes of resolution at Month 1 and 6. Change in the ear-related quality of life (OMQ14) will be analysed using a linear mixed-effects model.

Cost effectiveness study and analysis
As a secondary outcome measure, we will assess the cost effectiveness of autoinflation compared to standard care, as measured through the incremental cost-effectiveness ratio (ICER). This is defined as: "ICER" = (C2 - C1)/(Q2 – Q1 ) where C2 and Q2 denote costs and ear related Quality of Life associated with the treatment received in the intervention group, and C1 and Q1 are the cost and ear related Quality of Life in the standard care group.
Medical and non-medical costs will be calculated from parent/carer data collected in the study data collection forms. Costs of treatment including medication cost, health service use (including planned ENT review and surgery) and non-medical costs will be computed for events related to OME and its treatment. We will estimate costs of health service use and complications by applying publicly available price factors to utilisation figures and applying longer term modelling to account for planned ENT review and surgery. Complications requiring hospital admission will be priced using the National Public Cost Weight Tables. Complications requiring a visit to a health service provider will be priced according to item numbers within the Australian universal health benefit scheme, Medicare. Missing cost effectiveness data will be managed through imputation, rather than deleting observations. Sensitivity analysis will be performed using both one-way and multi-way Monte Carlo simulations, and will allow us to estimate how much the uncertainty contributes to the overall results.

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)
ACT,NSW,QLD

Funding & Sponsors
Funding source category [1] 297801 0
Government body
Name [1] 297801 0
NHMRC Project Grant #1120317
Address [1] 297801 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 297801 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
Western Sydney University
School of Medicine
Campbelltown Campus
Narellan Road
Campbelltown, NSW, 2560, Australia
Country
Australia
Secondary sponsor category [1] 296842 0
None
Name [1] 296842 0
Address [1] 296842 0
Country [1] 296842 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298860 0
Aboriginal Health and Medical Research Council Ethics Committee
Ethics committee address [1] 298860 0
Aboriginal Health and Medical Research Council
of NSW. Level 3, 66 Wentworth Ave, Surry Hills, NSW 2010
Ethics committee country [1] 298860 0
Australia
Date submitted for ethics approval [1] 298860 0
13/06/2017
Approval date [1] 298860 0
22/06/2017
Ethics approval number [1] 298860 0
1286/17
Ethics committee name [2] 298907 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [2] 298907 0
Human Ethics Officer
Research Engagement, Development and Innovation (REDI)
Western Sydney University
Great Western Highway
Kingswood, NSW 2747
Ethics committee country [2] 298907 0
Australia
Date submitted for ethics approval [2] 298907 0
21/06/2017
Approval date [2] 298907 0
10/10/2017
Ethics approval number [2] 298907 0
1286/17
Ethics committee name [3] 298908 0
Human Research Ethics Committee for the NT Department of Health and Menzies School of Health (Menzies HREC)
Ethics committee address [3] 298908 0
Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research
Menzies School of Health Research
John Mathews Building (JMB)
Building 58, Royal Darwin Hospital Campus
Darwin, NT 0800
Ethics committee country [3] 298908 0
Australia
Date submitted for ethics approval [3] 298908 0
21/06/2017
Approval date [3] 298908 0
15/08/2017
Ethics approval number [3] 298908 0
2017-2895
Ethics committee name [4] 298909 0
Metro South Human Research Ethics Committee (Queensland Department of Health) (Metro South HREC)
Ethics committee address [4] 298909 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [4] 298909 0
Australia
Date submitted for ethics approval [4] 298909 0
21/06/2017
Approval date [4] 298909 0
29/08/2017
Ethics approval number [4] 298909 0
HREC/17/QPAH/461
Ethics committee name [5] 298910 0
The University of Queensland Medical Research Ethics Committee
Ethics committee address [5] 298910 0
Human Ethics, Research Management Office, UQ Research and Innovation
Cumbrae-Stewart Building (#72)
Brisbane QLD 4072
Ethics committee country [5] 298910 0
Australia
Date submitted for ethics approval [5] 298910 0
21/06/2017
Approval date [5] 298910 0
28/09/2017
Ethics approval number [5] 298910 0
2017000984

Summary
Brief summary
OME is the most common cause of hearing loss in childhood. When persistent, and particularly bilateral, the hearing loss resulting from OME has been associated with language delay, poor educational achievement and behavioural and developmental concerns. Aboriginal and Torres Strait Islander children have the highest rate of persistent, severe and complicated otitis media described in the literature. Persistent bilateral OME is the usual reason for surgical insertion of tympanostomy tubes (‘grommets’), the second most common cause of surgical admission to hospital for children in Australia. The net cost of otitis media in Australia in 2008 was estimated to be over one billion dollars.
Given the high health and cost burden of OME, a simple low cost management option is urgently needed. Standard care for OME is initial observation, followed by referral for hearing assessment if bilateral OME persists at 3 months, surgical management with tympanostomy tubes (‘grommets’) and treatment for hearing impairment are considered. Unfortunately, in addition to being costly, tympanostomy tubes have lower success rates in Aboriginal children and can be associated with chronic ear discharge in up to 50% of this group, resulting in more hearing loss than prior to surgery. Long term antibiotics are another treatment option for prolonged OME, but have low efficacy and carry the significant risk of promoting antibiotic resistance.

This study proposes the use of Otovent® nasal balloon autoinflation device, as a low cost, simple means of mechanically treating OME. High pressure exhaled air, forcibly opens the Eustachian tube (connecting the middle ear and the back of the nose), by blowing up a balloon through each nostril with the mouth closed. This re-introduces air into the middle ear space and allows the fluid to drain away. It has recently been recommended by the Royal Australian College of General Practitioners for use in OME, whilst results in non-Aboriginal children are inconclusive, the Otovent has never been tested in Aboriginal and Torres Strait Islander children.

The INFLATE Trial will use RCT evidence to determine whether nasal balloon autoinflation increases resolution of OME in Aboriginal and Torres Strait Islander children at 1 month.

The test group will use Otovent® 3 times daily as recommended by the product manufacturer. Duration of treatment in this study will be for a minimum of 1 to maximum of 3 months (if OME persists), in accordance with the current recommended treatment period, The comparator group will consist of standard care, that is, observation only, followed by referral for ENT assessment if reduced hearing or bilateral OME is detected at 3 Months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78466 0
Dr Penelope Abbott
Address 78466 0
Western Sydney University School of Medicine Campbelltown Campus
Building 30, Locked Bag 1797 Penrith, NSW, 2751
Country 78466 0
Australia
Phone 78466 0
+61 414645062
Fax 78466 0
Email 78466 0
P.Abbott@westernsydney.edu.au
Contact person for public queries
Name 78467 0
Dr Penelope Abbott
Address 78467 0
Western Sydney University School of Medicine Campbelltown Campus
Building 30, Locked Bag 1797 Penrith, NSW, 2751
Country 78467 0
Australia
Phone 78467 0
+61 414645062
Fax 78467 0
Email 78467 0
P.Abbott@westernsydney.edu.au
Contact person for scientific queries
Name 78468 0
Dr Penelope Abbott
Address 78468 0
Western Sydney University School of Medicine Campbelltown Campus
Building 30, Locked Bag 1797 Penrith, NSW, 2751
Country 78468 0
Australia
Phone 78468 0
+61 414645062
Fax 78468 0
Email 78468 0
P.Abbott@westernsydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Nil
What supporting documents are/will be available?
No other documents available
Summary results
Not applicable