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Trial registered on ANZCTR


Registration number
ACTRN12619001211156p
Ethics application status
Submitted, not yet approved
Date submitted
30/07/2019
Date registered
30/08/2019
Date last updated
30/08/2019
Date data sharing statement initially provided
30/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical Utility of Obstructive Sleep Apnoea Physiology in Predicting Response to Treatment
Scientific title
An Observational Study of the Clinical Utility of Obstructive Sleep Apnoea Physiology in Predicting Response to Treatment
Secondary ID [1] 297337 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
obstructive sleep apnoea 311453 0
Condition category
Condition code
Respiratory 310091 310091 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This intervention study will investigate the effect that making additional physiological information available to clinicians and patients at the time of obstructive sleep apnoea diagnosis has on treatment referral patterns and patient outcomes.

Over the last 5yrs there has been an accumulating body of evidence that understanding an individual patient's physiology can help predict response to treatment for obstructive sleep apnoea. In particular understanding the contribution of loop gain, arousal threshold, upper airway dilator muscle activity and upper airway anatomy. These experimental parameters are not available for clinical use. Our group has developed tools that allow for this information to be made readily available to clinicians at the time of OSA diagnosis.

The aim of this study will be to make measurements of an individual's loop gain, arousal threshold, upper airway dilator muscle activity and upper airway anatomy at the time of obstructive sleep apnoea diagnosis. Our tool allows for these measurements to be made from routinely collected clinical data (sleep study) and thus does not require any additional testing above and beyond standard clinical practice.

The tool that we will employ for the purpose of this study is a bespoke Matlab code that models the respiratory system. We have currently employed this methodology in ober a dozen clinical studies in Australia and the USA. The tool is experimental and not commercially available. We take regular clinical physiological data (sleep study) and feed that data into our MATLAB code which analyzes the signals and outputs the variables mentioned above. This is then output in a report that clinicians can read. The MATLAB code and analysis is made on data collected using standard sleep study setup. No additional instrumentation or equipment is required.


The additional physiological information will be made available at the time of diagnosis and will be kept with the patient's sleep study results (medical records) so that it can be referred back to at any time. The additional physiological information will be kept with the patient's medical record in accordance with usual practice for keeping and maintaining medical records see https://www2.health.vic.gov.au/about/legislation/health-records-act

The first year of the study (observational arm) will be comppared to the second year of the study (interventional arm) to understand how clinicians treatment patterns have changed with the access to additional physiological parameters (treatment modality recommended, number of treatment trials for a given patient, patient ouutcomes including sleepp study results and QOL measures).
Intervention code [1] 313587 0
Diagnosis / Prognosis
Comparator / control treatment
The first year of the study will be the comparator/control with the additional diagnostic information to be introduced in the second year of the study.
Control group
Active

Outcomes
Primary outcome [1] 318983 0
The proportion of patients receiving treatment with each of: continuous positive airways pressure, mandibular advancement splint, upper airway surgery and positional therapy.
This outcome will be assessed based on a combination of patient reporting and device metrics (for CPAP users). This outcome is a composite primary outcome.
Timepoint [1] 318983 0
12 months from treatment initiation
Primary outcome [2] 320977 0
apnoea and hypopnoea index as assessed with a diagnostic sleep study with treatment in situ.
Timepoint [2] 320977 0
Post treatment initiation, timepoint will very from treatment to treatment but it is anticipated that the treatment assessment sleep study will be performed within 3 months of treatment initiation.
Primary outcome [3] 320978 0
Symptoms of sleepiness as measured by Functional Outcomes of Sleep Questionnaire.
Timepoint [3] 320978 0
6 and 12 months from the time of treatment initiation.
Secondary outcome [1] 366623 0
Time to definitive treatment as assessed by the period of time from the diagnosis of sleep apnoea to successful treatment (i.e. treatment is efficacious in terms of AHI measurement and patient is compliant with treatment). This outcome will be assessed by calculating the time from diagnosis of sleep apnoea to the measurement of treatment efficacy on a treatment AHI obtained through a sleep study with the treatment in situ and confirmation of patient compliance with treatment.
Timepoint [1] 366623 0
2 years from study commencement
Secondary outcome [2] 373762 0
Epworth Sleepiness Score
Timepoint [2] 373762 0
2 years from study commencement

Eligibility
Key inclusion criteria
Patients who are being investigated for suspected obstructive sleep apnoea through the Monash University Healthy Sleep Clinic
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Receiving medication that could affect ventilation (i.e. morphine derivatives, benzodiazepines, theophylline) or muscle control.
• Previous surgical treatment for OSA and/or obesity
• Women who are pregnant or breastfeeding

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
None
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
None
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
The clinic will run for one year as an observational arm and the second year as an interventional arm. In this way the study design could be considered stepped or sequential.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
No current data exists on the treatment referral patterns and treatment responses for patients seeking treatment for OSA, mainly because the two most efficacious treatments for OSA (CPAP and mandibular advancement splints [MAS]) are not medicare supported treatments. Additionally, there is no current data to inform a sample size calculation of the effect that OSA physiology will have on treatment patterns.
This highlights the urgent need for our observational study which will provide two crucial insights. Firstly, we will understand the usual treatment patterns of best practice treatment of OSA in the Australian context. Secondly, we will be able to determine the impact on these treatment patterns of understanding OSA physiology. These data will inform a future randomised controlled trial in this area by providing data for future sample size calculations.

Primary Outcome: Independent samples t-test (or non-parametric equivalent) will be used to determine if there is a significant difference in the number of patients being referred for each OSA treatment (CPAP, MAS, surgery, positional therapy) between the observational period and the period when physiological information is made available at the time of diagnosis.

Secondary Outcomes: Independent samples t-test (or non-parametric or categorical equivalent) will be used to determine if there is a significant difference in patient outcomes (AHI, ESS, QOL measures) between the observational period and the period when physiological information is made available at the time of diagnosis.

Additional analyses:
We will determine if any of the physiological traits predict worse outcome to treatment overall. This will be done by regressing the physiological parameters on to the treatment outcome variables using multiple regression analysis.
We will determine if the addition of OSA physiology at the time of diagnosis reduces the time to definitive treatment by performing an independent samples t-test on the time to definitive treatment between the observational period and the period when physiological information is made available at the time of diagnosis.
We will determine if any of the physiological traits predict longer time to definitive treatment outcome. This will be done by regressing the physiological parameters on to the time to definitive treatment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13069 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 25576 0
3168 - Clayton
Recruitment postcode(s) [2] 25577 0
3168 - Notting Hill

Funding & Sponsors
Funding source category [1] 301900 0
Government body
Name [1] 301900 0
National Health and Medical Resarch Council
Country [1] 301900 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Rd
Clayton
Victoria
3168
Country
Australia
Secondary sponsor category [1] 301653 0
None
Name [1] 301653 0
Address [1] 301653 0
Country [1] 301653 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302590 0
Monash Health HREC
Ethics committee address [1] 302590 0
246 Clayton Rd
Clayton
Victoria
3168
Ethics committee country [1] 302590 0
Australia
Date submitted for ethics approval [1] 302590 0
27/02/2019
Approval date [1] 302590 0
Ethics approval number [1] 302590 0

Summary
Brief summary
Continuous positive airway pressure (CPAP) is the current gold standard treatment for OSA. While efficacious, CPAP is poorly tolerated. Nightly use may be inadequately brief and 50% of patients do not continue CPAP therapy beyond 3 months. Although alternative treatments such as mouth guard devices and surgery exist for CPAP-intolerant patients, individual responses to these treatments are difficult to predict and as such many clinicians and patients are stuck in a trial and error paradigm for these treatments.

Traditionally OSA has been thought to be a disorder of aberrant upper airway anatomy. Recently, it has become clear though that OSA can be caused by both anatomical and non-anatomical pathophysiology. Much of this paradigm change can be attributed to recent developments to the ability to measure this physiology – work that has been carried out by our research team at Monash Health and Monash University. We have developed readily applicable clinical tool that can predict the patient’s response to upper airway surgery and mandibular advancement splint treatments. The tools we have developed are now ready for direct translation to the clinical setting.

In this exciting research project we will run an observation study to assess the impact of making physiological information available to clinicians at the time of OSA diagnosis on the treatment referral patterns and treatment outcomes of OSA patients. We hope that this extra physiological data will be able to predict patient response to CPAP-alternative treatments and give clinicians and patients extra treatment options that are tailored to patients personal physiology.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90742 0
Dr Simon Joosten
Address 90742 0
Monash Health, Monash Lung and Sleep Department
246 Clayton Rd
Clayton
Victoria
3168
Country 90742 0
Australia
Phone 90742 0
+61 3 95942900
Fax 90742 0
Email 90742 0
[email protected]
Contact person for public queries
Name 90743 0
Dr Simon Joosten
Address 90743 0
Monash Health
246 Clayton Rd
Clayton
Victoria
3168
Country 90743 0
Australia
Phone 90743 0
+61 3 95942900
Fax 90743 0
Email 90743 0
[email protected]
Contact person for scientific queries
Name 90744 0
Dr Simon Joosten
Address 90744 0
Monash Health
246 Clayton Rd
Clayton
Victoria
3168
Country 90744 0
Australia
Phone 90744 0
+61 3 95942900
Fax 90744 0
Email 90744 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Unidentifiable patient data will be stored for analysis for primary and secondary endpoints.All patient data will be made available to patients and treating clinicians in the intervention phase of the study.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.