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Trial registered on ANZCTR


Registration number
ACTRN12616001514493
Ethics application status
Approved
Date submitted
31/10/2016
Date registered
3/11/2016
Date last updated
12/08/2019
Date data sharing statement initially provided
12/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of upper airway surgery on obstructive sleep apnoea
Scientific title
The effect of upper airway surgery on pathophysiological traits known to contribute to obstructive sleep apnoea
Secondary ID [1] 290006 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 300016 0
Upper airway surgery 300017 0
Condition category
Condition code
Respiratory 299911 299911 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention for this study is anatomically directed upper airway surgery with the aim of resolving obstructive sleep apnoea.
The specific set of operations performed will be tailored to each patient based on a comprehensive assessment of upper airway anatomy performed by staff specialist Ear Nose and Throat surgeons at Monash Health - a tertiary university teaching hospital.
The operations may include one or more of: turbinate surgery, septoplasty, modified uvulopalatopharyngeoplasty, adenoid surgery, palatine tonsil surgery, lingual tonsil surgery, tongue channelling.
Typically the combination of surgical procedures will be performed in one separation but in certain circumstances the combination of operations may be performed over 2 or more separations.
The duration of the operating procedure is contingent upon the combination of procedures performed but would typically occur over 1-2hrs.
Surgery will be conducted at Monash Health by staff of The Ear, Nose and Throat/Head and Neck Surgery Unit, Monash Health.
Follow-up to determine effect on obstructive sleep apnoea will occur 3 months post surgery.
Intervention code [1] 295715 0
Treatment: Surgery
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299395 0
Apnoea/hypopnoea index
Assessed by in laboratory polysomnography.
Timepoint [1] 299395 0
3 to 6 months following surgery
Secondary outcome [1] 327047 0
Steady state loop gain
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [1] 327047 0
3 to 6 months following surgery
Secondary outcome [2] 327048 0
Dynamic loop gain
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [2] 327048 0
3 to 6 months following surgery
Secondary outcome [3] 327049 0
Upper muscle responsiveness
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [3] 327049 0
3 to 6 months following surgery
Secondary outcome [4] 327050 0
Pharyngeal critical closing pressure
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [4] 327050 0
3 to 6 months following surgery
Secondary outcome [5] 327051 0
Arousal threshold
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [5] 327051 0
3 to 6 months following surgery
Secondary outcome [6] 327052 0
Body position specific apnoea/hypopnoea index
Assessed by in laboratory polysomnography.
Timepoint [6] 327052 0
3 to 6 months following surgery
Secondary outcome [7] 327053 0
Passive V0
Assessed during research polysomnography with continuous positive airways pressure.
Timepoint [7] 327053 0
3 to 6 months following surgery
Secondary outcome [8] 327054 0
Weight
Assessed with digital scales.
Timepoint [8] 327054 0
3 to 6 months following surgery
Secondary outcome [9] 327055 0
Body mass index
Timepoint [9] 327055 0
3 to 6 months following surgery
Secondary outcome [10] 327056 0
continuous positive airways pressure (CPAP) use
Assessed from CPAP device download and self report.
Timepoint [10] 327056 0
3 to 6 months following surgery
Secondary outcome [11] 327057 0
Friedman palate score
Timepoint [11] 327057 0
3 to 6 months following surgery
Secondary outcome [12] 327058 0
Friedman tonsil score
Timepoint [12] 327058 0
3 to 6 months following surgery
Secondary outcome [13] 327059 0
Mallampatti score assessed during physical examination.
Timepoint [13] 327059 0
3 to 6 months following surgery
Secondary outcome [14] 327060 0
Site of collapse at supine nasendoscopy
Timepoint [14] 327060 0
3 to 6 months following surgery
Secondary outcome [15] 327061 0
Epworth sleepiness score
Timepoint [15] 327061 0
3 to 6 months following surgery
Secondary outcome [16] 327062 0
Karolinska questionnaire to assess self reported sleepiness.
Timepoint [16] 327062 0
3 to 6 months following surgery
Secondary outcome [17] 327221 0
Functional Outcomes of Sleep Questionnaire
Timepoint [17] 327221 0
3 to 6 months following surgery
Secondary outcome [18] 327229 0
36 item short form health survey
Timepoint [18] 327229 0
3 to 6 months following surgery
Secondary outcome [19] 327352 0
Hospital Anxiety and Depression Scale
Timepoint [19] 327352 0
3 to 6 months following surgery
Secondary outcome [20] 328814 0
Snoring Apnoea Questionnaire
Timepoint [20] 328814 0
3 to 6 months following surgery
Secondary outcome [21] 329203 0
Magnetic Resonance Imaging characteristics of the upper airway
Timepoint [21] 329203 0
3 to 6 months post surgery
Secondary outcome [22] 330175 0
Nocturnal blood pressure measurement prior to and during sleep study
Timepoint [22] 330175 0
3 to 6 months following surgery

Eligibility
Key inclusion criteria
Confirmed diagnosis of obstructive sleep apnoea with an apnoea/hypopnoea index of greater than or equal to 15 events/hr. Diagnosis must be on level 1 or 2 sleep study and have occurred within at least 6 months enrolment into the trial.
Patients deemed appropriate and likely to respond to anatomically directed upper airway surgery as determined by staff specialists of the The Ear, Nose and Throat/Head and Neck Surgery Unit, Monash Health.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant co-morbid medical issues that would preclude surgery.
Administration of medications/drugs that interfere with ventilatory control.
Previous upper airway surgery for obstructive sleep apnoea. Patients cannot have any metallic implants/prostheses that would preclude magnetic resonance imaging (MRI) scanning.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A sample size of 24 OSA patients will give 80% power with an alpha=0.05 to detect a reduction of 15+/-25 (SD) in AHI (values calculated from the mean reduction in AHI during application of mandibular advancement devices - another anatomically based treatment, in a previous study by our group). Therefore, in order to allow for participant attrition (~30%), 30 patients will be enrolled.

Significant improvement in AHI and the OSA traits pre- and post-surgery will be assessed using paired Students t-test. If our data are non-parametric, the appropriate nonparametric tests (i.e. Mann-Whitney) will be used.

With regard to the secondary endpoint of 24hr blood pressure measurement, we have calculated that a sample size of 60 OSA patients will give 80% power with an alpha=0.05 to detect a reduction of -1.5±4.0mmHg in mean 24-hr blood pressure.

All patients who are enrolled for the purpose of measuring pre and post surgery traits will be invited to participate in the blood pressure project. With any further recruits only being required to complete the blood pressure project.

Data from the research polysomnogram (PSG) will provide baseline pathophysiological information for each patient. Multiple linear regression will be conducted to determine which baseline clinical and physiological variables are independently related to the greatest therapeutic reduction OSA severity (measured by apnoea-hypopnoea index, AHI). Furthermore we will conduct a 'responder' versus 'non-responder' analysis. Briefly, patients will be classified as a responder to surgery if they demonstrate a 50% reduction in their AHI & an AHI on therapy of less than 10 events per hour. Independent samples t-tests (or non-parametric equivalent) will then assess which baseline clinical and physiological variables separate 'responders' from 'non-responders'.
Changes in magnetic resonance imaging (MRI) characteristics pre- and post-surgery will be assessed using paired Student's t-test.

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] 6554 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 6555 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment postcode(s) [1] 14153 0
3165 - East Bentleigh
Recruitment postcode(s) [2] 14152 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 294409 0
University
Name [1] 294409 0
Monash University
Address [1] 294409 0
School of Clinical Sciences
Monash Medical Centre
246 Clayton Rd
Clayton 3168, Victoria.
Country [1] 294409 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Monash Health - Monash Medical Centre
246 Clayton Rd
Clayton 3168, Victoria.
Country
Australia
Secondary sponsor category [1] 293257 0
University
Name [1] 293257 0
Monash University
Address [1] 293257 0
Sleep and Circadian Laboratory
Ground Floor BASE Facility
246 Ferntreegully Rd
Notting Hill
Victoria 3168
Country [1] 293257 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295864 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 295864 0
Monash Health
246 Clayton Rd
Clayton 3168
Victoria, Australia
Ethics committee country [1] 295864 0
Australia
Date submitted for ethics approval [1] 295864 0
19/04/2016
Approval date [1] 295864 0
03/08/2016
Ethics approval number [1] 295864 0
16207A

Summary
Brief summary
Obstructive sleep apnoea (OSA) affects 1.5 million Australians and results in significant morbidity and mortality. However, half of patients cannot tolerate the leading treatment, continuous positive airways pressure (CPAP). For those intolerant of CPAP, a common treatment alternative involves upper airway surgery (UAS). Unfortunately, a significant number of patients referred for this treatment do not respond and suffer from residual OSA with its inherent cardiovascular and neurocognitive consequences. Furthermore, current clinical predictive tools are poor at identifying responders to UAS and there are no proven additional therapies to offer those patients failing UAS treatment.
The key to providing better predictors of OSA resolution with UAS is to understand how these interventions affect the physiology responsible for OSA. It is clear that UAS improves upper airway anatomy/collapsibility. However, poor upper airway anatomy is not the only factor contributing to OSA. Recent evidence suggests that several additional, non­anatomical, physiological traits contribute to the pathogenesis of OSA including: 1) an oversensitive ventilatory control system (i.e. high loop gain), 2) a low respiratory arousal threshold, and 3) poor pharyngeal dilator muscle effectiveness characterised by an inability of the pharyngeal muscles to hold open or stiffen the airway during sleep. However, it is not known how UAS alter these non­anatomical traits and whether abnormalities in these traits are the reason for the variability in the success of UAS treatments. Furthermore, it is also not known if targeting non­ anatomical traits with additional treatments (i.e. combination therapy) will improve outcomes for those patients who have had only a partial response to UAS. Our goal is to be able to accurately identify which OSA patients are good candidates for UAS therapy by identifying robust predictors of OSA resolution with these interventions. Furthermore, we aim to offer additional treatments to ‘salvage’ those patients who have failed to respond completely to UAS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68518 0
Dr Bradley Edwards
Address 68518 0
Sleep and Circadian Medicine Laboratory, Department of Physiology and
School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road
Notting Hill,
Victoria 3168
Country 68518 0
Australia
Phone 68518 0
+613 9905 0187
Fax 68518 0
+613 9905 3948
Email 68518 0
bradley.edwards@monash.edu
Contact person for public queries
Name 68519 0
Ms Elizabeth Skuza
Address 68519 0
Level 5,
Monash Medical Centre
246 Clayton Rd
Clayton
Victoria, 3168
Country 68519 0
Australia
Phone 68519 0
+613 9594 5398
Fax 68519 0
Email 68519 0
elizabeth.skuza@monash.edu
Contact person for scientific queries
Name 68520 0
Dr Bradley Edwards
Address 68520 0
Sleep and Circadian Medicine Laboratory , Department of Physiology and
School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences,Monash University
264 Ferntree Gully Road
Notting Hill,
Victoria 3168
Country 68520 0
Australia
Phone 68520 0
+613 9905 0187
Fax 68520 0
+613 9905 3948
Email 68520 0
bradley.edwards@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
No Results