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Trial registered on ANZCTR


Registration number
ACTRN12616001153404
Ethics application status
Approved
Date submitted
17/08/2016
Date registered
24/08/2016
Date last updated
21/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised clinical trial to evaluate the effects of continuous positive airway pressure (CPAP) on nocturnal beat to beat blood pressure and vascular function
Scientific title
A randomised clinical trial to evaluate the effects of continuous positive airway pressure (CPAP) on nocturnal beat to beat blood pressure and vascular function in patients with obstructive sleep apnoea.
Secondary ID [1] 289279 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 298864 0
Condition category
Condition code
Respiratory 298932 298932 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be subjected to both active continuous positive airway pressure (CPAP) (their usual settings) and sham CPAP while undergoing polysomnography on two separate nights in a randomised order. Each night will be separated by at least one week, but no more than 6 weeks between visits. Participants will use their own clinically fitted mask (i.e. nasal mask, full face mask etc). Each sleep study will be for a duration of ~8h. The sleep study will be conducted at The Centre for Sleep Science at The University of Western Australia.
Intervention code [1] 295534 0
Treatment: Devices
Comparator / control treatment
The control treatment will be 'sham CPAP' which provides non effective pressure during sleep. The sham CPAP has a flow-restricting segment in a connector proximal to the mask. It also has extra air holes in the connector which are not visible. These increase the exhalation flow as they are distal to the flow restricting segment and allow adequate escape of carbon dioxide from the patient while producing sub-therapeutic CPAP pressure..
Control group
Placebo

Outcomes
Primary outcome [1] 299173 0
Nocturnal beat to beat blood pressure measured by a Finapress device throughout the night.
(Finometer Pro).
Timepoint [1] 299173 0
Measured continuously throughout each (active CPAP and sham CPAP) night. The Finometer will start measuring just prior to "lights out" and will continue measuring until after the three standard morning blood pressures (measured via dinamap) after "lights on" in the morning.
Primary outcome [2] 299177 0
Conduit artery function: Brachial and femoral artery flow mediated dilation (FMD) will be assessed according to best practice guidelines. A cuff is inflated (220mmHg) around the forearm and upper thigh for 5min to induce ischaemic conditions whilst high resolution ultrasound of the brachial and femoral artery are obtained pre-post- artery occlusion. The FMD% increase in artery dilation is an indicator of artery function and independently predicts CV events.
Timepoint [2] 299177 0
Flow mediated dilation will be performed prior to and after sleep in both conditions. This will be conducted approximately 30min after arrival into the sleep centre (~3h prior to sleep) and 30 min after wake in the morning.
Primary outcome [3] 299375 0
Intracranial cerebral blood velocity: Cerebral blood flow velocity (CBFv) is assessed by combining bilateral measures of middle (MCA) and posterior cerebral artery (PCA) flow velocities using non-invasive transcranial Doppler (TCD) ultrasound. Blood flow to the brain will also be simultaneously collected using non-invasive duplex ultrasound of the internal carotid artery and vertebral artery (VA). Cerebral vascular reactivity to carbon dioxide is assessed using breathing mixtures. Participants are asked to breathe the gas mixtures through a non-re-breathing three-way breathing apparatus (i.e., mouthpiece, disposable spirometry filter, spirometer, hans rudolph three way valve) connected to each douglas bag through a sterilised respiratory bore tubing.
Timepoint [3] 299375 0
CBFv will be performed prior to and after sleep in both conditions. This will be conducted approximately 1h after arrival into the sleep centre (~2h prior to sleep) and 1h after wake in the morning.
Secondary outcome [1] 326508 0
Urinary catecholamines
Timepoint [1] 326508 0
Urine will be collected in both conditions (active and sham CPAP) over ~12 hours from when participants first arrive at The Centre for Sleep Science (after first voiding their bladder) until their first void the following morning.

Eligibility
Key inclusion criteria
Participants will be individuals with obstructive sleep apnoea and who have been established on Continuous positive airway pressure (CPAP) therapy within the last three years. They will also need to be compliant with CPAP therapy (average nightly use > 4 hours per night at the last review). Only participants whose CPAP therapy has been shown to be effective (i.e., residual AHI <10/hr on CPAP machine download or polysomnographic assessment of control of OSA while using CPAP) will be included.
Minimum age
25 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current smoker
2. Alcohol consumption more than 21 standard units per week
3. Significant cardiovascular disease including unstable angina, cardiac failure (NYHA > level 2), important arrhythmia (e.g. atrial fibrillation (AF), 2nd, 3rd degree heart block), history of myocardial infarction (MI) within last 3 months and previous history of stroke.
4. Severely and inadequately controlled hypertension (i.e. BP >180/110 mmHg).
5. Severe respiratory disease but excluding those with more than moderate obstructive lung disease i.e. reduced ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC ratio) and FEV1 < 50% or moderate restrictive lung disease i.e. FVC or total lung capacity (TLC < 50%). However stable lung disease with less severe disease can be recruited.
6. Severe nocturnal desaturation documented on polysomnography (PSG) > 2% night sleep-time with arterial oxygen saturation of <85%.
7. Central (non-obstructive) sleep apnoea (central events > 50% AHI or > 15 events/hour).
8. Predominant Cheyne-Stokes respiration.
9. Other serious medical disorders (disabling neurological disorders, life threatening malignancy, renal failure requiring dialysis, peripheral artery diseases and etc.)
10. Change of medication in the last 3 months
11. Morbid obesity (BMI> 40kg/m2).
12. OSA not primary sleep disorder, i.e. exclude if primary insomnia diagnosis, narcolepsy or primary restless legs/ periodic limb movement syndrome (PLMS).
13. Professional drivers.
14. Raynaud's phenomenon.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study is powered on the primary outcome of overnight blood pressure difference between the active and sham CPAP (as determined by Finapress, beat to beat blood pressure).
The standardised difference (i.e., SD of the difference between mean night time blood pressure, based on the Davies et al. study - i.e. between OSA and normal subjects) is 11 mm Hg,
Assume power (1- beta) = 80% and alpha = 0.05.
We consider the minimum clinically significant difference in overnight blood pressure between active CPAP and sham CPAP is 9mm Hg overnight (i.e. equivalent to 3 mmHg over 24 hours). Based on these assumptions for a cross over design we need 16 completed subjects.

Statistical analysis will be performed with the use of statistical software package (IBM 'Registered Trademark' SPSS 'Registered Trademark' Statistics 21). Paired t -tests will be used for the comparison of the mean blood pressure changes.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/09/2016
Actual
8/09/2016
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
30/03/2019
Actual
Sample size
Target
16
Accrual to date
14
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 5849 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 13287 0
6009 - Nedlands
Recruitment postcode(s) [2] 13288 0
6009 - Crawley

Funding & Sponsors
Funding source category [1] 294231 0
University
Name [1] 294231 0
The University of Western Australia
Country [1] 294231 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Highway, Nedlands, Western Australia, 6009
Country
Australia
Secondary sponsor category [1] 293168 0
None
Name [1] 293168 0
Address [1] 293168 0
Country [1] 293168 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295116 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 295116 0
Ethics committee country [1] 295116 0
Australia
Date submitted for ethics approval [1] 295116 0
Approval date [1] 295116 0
Ethics approval number [1] 295116 0
2014-027
Ethics committee name [2] 295694 0
The University of Western Australia
Ethics committee address [2] 295694 0
Ethics committee country [2] 295694 0
Australia
Date submitted for ethics approval [2] 295694 0
Approval date [2] 295694 0
06/05/2016
Ethics approval number [2] 295694 0
RA/4/1/8291

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65518 0
Prof Peter Eastwood
Address 65518 0
School of Anatomy, Physiology and Human Biology
The University of Western Australia (M309)
35 Stirling Highway
CRAWLEY WA 6009
Country 65518 0
Australia
Phone 65518 0
+61 8 93461706
Fax 65518 0
Email 65518 0
[email protected]
Contact person for public queries
Name 65519 0
Nigel McArdle
Address 65519 0
WA sleep disorders Research Institute (WASDRI)
Hospital Avenue,
Nedlands, 6009
Western Australia
Country 65519 0
Australia
Phone 65519 0
+61 8 93462422
Fax 65519 0
Email 65519 0
[email protected]
Contact person for scientific queries
Name 65520 0
Peter Eastwood
Address 65520 0
School of Anatomy, Physiology and Human Biology
The University of Western Australia (M309)
35 Stirling Highway
CRAWLEY WA 6009
Country 65520 0
Australia
Phone 65520 0
+61 8 93461706
Fax 65520 0
Email 65520 0
[email protected]

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