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Trial registered on ANZCTR


Registration number
ACTRN12619000699167
Ethics application status
Approved
Date submitted
17/12/2018
Date registered
9/05/2019
Date last updated
9/05/2019
Date data sharing statement initially provided
9/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
WAVES (West Australian cardioVascular Events in obstructive Sleep apnoea)
Scientific title
The interaction between obstructive sleep apnea and cardiovascular risk factors on cardiovascular disease
Secondary ID [1] 296196 0
Nil known
Universal Trial Number (UTN)
Trial acronym
WAVES
Linked study record
WASHS (Western Australian Sleep Health Study);
Please note: This trial was 10 years ago and not registered with ANZCTR. The data from this trial will be used as comparative historical data which will be used in the current study, ie. the same population will be followed up now 10 years on to look at the development of disease under various conditions during the intervening time period.

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 309835 0
Obstructive Sleep Apnea 309836 0
Condition category
Condition code
Cardiovascular 308624 308624 0 0
Coronary heart disease
Respiratory 308625 308625 0 0
Sleep apnoea

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The aim of this study is to explore the interaction between obstructive sleep apnoea (OSA) and other known cardiovascular disease (CVD) risk factors (e.g., diabetes) in the pathogenesis of CVD.
The study will utilise baseline data on a previously well characterised cohort of patients attending the SCGH sleep service between 2005 and 2010 – the Western Australian Sleep Health Study (WASHS). WASHS patients have previously provided clinical data (questionnaires and basic anthropometric information, eg body mass index) and blood samples (DNA and biochemical data including common measures of cardiovascular risk such as serum cholesterol) and laboratory sleep study data (full overnight polysomnography or PSG). The follow-up assessments included in WAVES will include a repeat questionnaire in all participants. The primary outcome will be incident cardiovascular disease (such as myocardial infarction).
We plan to study 500 who have not developed CVD in more detail, to determine the presence of early markers of cardiovascular disease (such as left ventricular hypertrophy on echocardiogram). We will select and invite 500 according to baseline matching factors (e.g., age, gender) that predict CVD. We will perform a matched comparison in these 500; comparing those on OSA treatment with CPAP to those that did not take up treatment (i.e., 250 in each group). This subset of 500 will be asked to have the following additional assessments: sleep study, anthropometric measurements, blood pressure, ECG (electrocardiogram), an echocardiogram, 24 hour blood pressure monitor, CT scan for coronary calcium, and a dual energy xray absorptiometry (DEXA) scan.
This study aims to determine whether OSA predisposes to the development of CVD, or early markers of CVD (n=500), independently of other known CVD risk factors. We will examine how OSA interacts with known CVD risk factors and determine what PSG metric of OSA severity best predicts CVD risk. We will also be able to determine the effect of standard OSA treatment i.e., CPAP on CVD risk.
The majority of participants will only complete an online questionnaire which will take approximately 30mins with no visits required and no further testing. Those on CPAP therapy will have a simple appointment which will require a single 1 hour visit to the sleep clinic and 1 week of wearing a activity tracking device which can then be returned by mail. Those 500 (250 on CPAP and 250 not on CPAP) chosen for further testing will require one overnight appointment (11 hrs) and additional appointments to complete the consent and testing procedure. Total of approximately 18hrs required with no further follow up.

Intervention code [1] 312526 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307586 0
Development of incident overt CVD over 10 years
- defined as a composite of the following: 1) coronary artery disease – hospitalization for unstable angina, AMI, intervention (angioplasty, stent, CABG), (2) cardiac failure, (3) AF or cardioversion for AF (4) insertion of permanent pacemaker, (5) sudden cardiac death, (6) ischaemic and haemorrhagic stroke or transient ischaemic attack, and (7) CVD mortality.
OUTCOME ASSESSMENT: This will be assessed based on self-reported questionnaires designed specifically for this study and verified with medical practices/hospitals.
Timepoint [1] 307586 0
10 years post original measurements (as part of WASHS study)
Secondary outcome [1] 352372 0
New onset hypertension, assessed with 24hr blood pressure readings and a self-reported questionnaire designed specifically for this study, with confirmation with GP as necessary
Timepoint [1] 352372 0
10 years post original data collection (WASHS)
Secondary outcome [2] 369481 0
Abnormal cardiac rhythm including abnormal heart rate variability, bradycardia, sinus pauses; assessed using ECG
Timepoint [2] 369481 0
10 years post WASHS
Secondary outcome [3] 369482 0
Arterial compliance assessed using Echo Doppler and OCT (Optical Coherence Tomography)
Timepoint [3] 369482 0
10 years post WASHS
Secondary outcome [4] 369488 0
Aortic calcification assessed using DEXA scans and CT scan for coronary artery calcium
Timepoint [4] 369488 0
10 years post WASHS
Secondary outcome [5] 369489 0
Cardiac pathology assessed using blood testing of CVD biomarkers (ie.., hsTn-I and NT-proBNP)
Timepoint [5] 369489 0
10 years post WASHS
Secondary outcome [6] 369490 0
Outcomes will be evaluated against a composite measure of both sleep quality and effective treatment of sleep disordered breathing assessed via polysomnography (PSG) and download of CPAP devices.
Timepoint [6] 369490 0
10 years post WASHS

Eligibility
Key inclusion criteria
Participated in the WASHS study between 2005-2010 at the West Australian Sleep Disorders Research Institute (WASDRI)
Minimum age
26 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Impaired capacity to consent, history of cardiovascular disease at baseline (i.e., taken during WASHs assessment between 2005-10)

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Both
Statistical methods / analysis
Power calculations
The derivation model is based on two-thirds of the sample (4,100*2/3 = 2,733). Given
that this is a study of moderate to high-risk population, a 20% to 30% absolute 10-year CVD risk is assumed. The power calculations are based on a conservative 20% 10-year CVD risk i.e. new CVD events in 546 participants. A Cox regression of the log hazard ratio on risk variables based on a sample of 2,733 observations achieves a 90% power at the 5% level of significance to detect a regression coefficient equal of 0.0974 (or Hazard Ratio of 1.10). (Hsieh FY, Lavori PW. Sample-­-size calculations for the Cox proportional hazards regression model with nonbinary covariates. Control Clin Trials 2000;21:552-­-60).This calculation takes into consideration the effect of any risk variable of interest being adjusted for other variables in the model, assuming a conservative R-squared of 10%.

Recruitment
Recruitment status
Not yet 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)
WA
Recruitment hospital [1] 12028 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 24185 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 300786 0
Government body
Name [1] 300786 0
National Health and Medical Research Council
Address [1] 300786 0
16 Marcus Clarke St, Canberra City ACT 2600
Country [1] 300786 0
Australia
Primary sponsor type
Other Collaborative groups
Name
West Australian Sleep Disorders Research Institute
Address
Department of Pulmonary Physiology and Sleep Medicine - Sir Charles Gairdner Hospital, Hospital Ave, Nedlands; Western Australia 6009
Country
Australia
Secondary sponsor category [1] 300508 0
None
Name [1] 300508 0
Address [1] 300508 0
Country [1] 300508 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301570 0
Sir Charles Gairdner Hospital Human Research Ethics Commitee
Ethics committee address [1] 301570 0
Human Research Ethics Office
Sir Charles Gairdner Hospital
Level 2, A Block, Hospital Avenue, NEDLANDS WA 6009
Ethics committee country [1] 301570 0
Australia
Date submitted for ethics approval [1] 301570 0
01/05/2018
Approval date [1] 301570 0
28/11/2018
Ethics approval number [1] 301570 0
RGS0000000823

Summary
Brief summary
The aim of this study is to explore the interaction between obstructive sleep apnoea (OSA) and other known cardiovascular disease (CVD) risk factors (e.g., diabetes) in the pathogenesis of CVD. Using baseline data collected between 2005 and 2010 we will describe and assess current cardiovascular status in approximately 2000 participants, 500 of which will be assessed in greater detail. With the primary aim of determining whether OSA predisposes to the development of CVD, or early markers of CVD (n=500), independently of other known CVD risk factors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87422 0
Prof David Hillman
Address 87422 0
West Australian Sleep Disorders Research Institute
Sir Charles Gairdner Hospital
Level 5, G Block, Hospital Avenue, NEDLANDS WA 6009
Country 87422 0
Australia
Phone 87422 0
+61 8 6457 2422
Fax 87422 0
Email 87422 0
David.Hillman@health.wa.gov.au
Contact person for public queries
Name 87423 0
Ms Clare Rea
Address 87423 0
West Australian Sleep Disorders Research Institute
Sir Charles Gairdner Hospital
Level 5, G Block, Hospital Avenue, NEDLANDS WA 6009
Country 87423 0
Australia
Phone 87423 0
+61 400 010 490
Fax 87423 0
Email 87423 0
Clare.Rea@health.wa.gov.au
Contact person for scientific queries
Name 87424 0
Ms Clare Rea
Address 87424 0
West Australian Sleep Disorders Research Institute
Sir Charles Gairdner Hospital
Level 5, G Block, Hospital Avenue, NEDLANDS WA 6009
Country 87424 0
Australia
Phone 87424 0
+61 400 010 490
Fax 87424 0
Email 87424 0
Clare.Rea@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices)
When will data be available (start and end dates)?
Beginning 9 months and ending 36 months following article publication.
Available to whom?
Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
Available for what types of analyses?
For individual participant data meta-analysis
How or where can data be obtained?
Proposals may be submitted up to 36 moths following article publication. After 36 moths the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at www.wasdri.org.au
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 1887 0
Study protocol
Citation [1] 1887 0
Link [1] 1887 0
Email [1] 1887 0
Other [1] 1887 0
Summary results
No Results