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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00738179




Registration number
NCT00738179
Ethics application status
Date submitted
19/08/2008
Date registered
20/08/2008
Date last updated
6/02/2015

Titles & IDs
Public title
Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease
Scientific title
Sleep Apnea cardioVascular Endpoints Study - Investigating the Effectiveness of Treatment With CPAP vs Standard Care in Reducing CV Morbidity and Mortality in Patients With Co-existing CV Disease and Moderate-severe Obstructive Sleep Apnea.
Secondary ID [1] 0 0
ANZCTR 12608000409370
Secondary ID [2] 0 0
SAVE001
Universal Trial Number (UTN)
Trial acronym
SAVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Apnea 0 0
Cardiovascular Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Continuous Positive Airway Pressure (CPAP)
Other interventions - Standard care

Experimental: 1 - CPAP plus standard care of cardiovascular risk factors

Active Comparator: 2 - Standard care alone


Treatment: Devices: Continuous Positive Airway Pressure (CPAP)
CPAP worn nightly

Other interventions: Standard care
Standard care of cardiovascular risk factors

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
A composite of the CV endpoints of CV death, non-fatal acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisation for unstable angina or transient ischaemic attack.
Timepoint [1] 0 0
Reviewed 6-monthly; average patient follow up, 4.5 years
Secondary outcome [1] 0 0
Composite of CV death, MI & ischaemic stroke; components of primary composite endpoint; re-vascularisation procedures; all-cause death; new onset atrial fibrillation; new onset diabetes; OSA symptom scores; mood; health-related quality of life.
Timepoint [1] 0 0
Reviewed 6-monthly; average patient follow up, 4.5 years.
Secondary outcome [2] 0 0
In a sub-sample of 600 subjects pathophysiological mechanisms of CPAP-induced CV event reduction will be explored by assessing various intermediate markers of CV risk
Timepoint [2] 0 0
baseline and at 6-months, 2 and 4 years following randomisation
Secondary outcome [3] 0 0
Cardiac MRI to assess effects of CPAP on cardiac structure and function. - In a sub-sample of 150 participants (75 from the CPAP plus standard treatment and 75 from the standard treatment arms) the effect of CPAP on cardiac and vascular function using cardiac MRI will be investigated. The sub-study will evaluate left and right ventricular mass, volume and systolic/diastolic function and compliance of the aorta.
Timepoint [3] 0 0
Randomisation and at 6 months follow-up

Eligibility
Key inclusion criteria
1. Males and females, any race, and aged between 45 and 75 years

2. Evidence of established coronary or cerebrovascular disease as evident by:

- Coronary artery disease

- Previous MI (equal to or greater than 90 days prior to ApneaLinkTM
assessment)

- Stable angina or unstable angina (Clinical event equal to or greater than 30
days and confirmatory test equal to or greater than 7 days prior to
ApneaLinkTM assessment) defined as either =70% diameter stenosis of at least
one major epicardial artery segment, or =50% diameter stenosis of the left
main coronary artery, or >50% stenosis in at least two major epicardial
arteries.; or positive stress test (ST depression equal to or greater than 2
mm or a positive nuclear perfusion scintigram)

- Multi-vessel percutaneous angioplasty (PTCA) and/or stent equal to or
greater than 90 days prior to ApneaLinkTM assessment

- Multi-vessel coronary artery bypass surgery (CABG) >1 year prior to
ApneaLinkTM assessment

- Cerebrovascular disease

- Previous stroke (includes definite or presumed cerebral ischaemia/infarction
and intracerebral but not subarachnoid haemorrhage) equal to or greater than
90 days prior to ApneaLinkTM assessment or minor disabling stroke with
minimal residual neurological disability (modified Rankin Score of '0 = no
symptoms' or '1 = No significant disability despite symptoms, able to carry
out all usual duties and activities' within 7 days of stroke onset) =7 days
prior to ApneaLinkTM assessment.

- Previous transient ischaemic event (TIA) of the brain or retina (symptoms
<24 hours) but not of presumed vertebrobasilar system ischemia. The TIA
diagnosis must be confirmed by a suitably qualified clinician (=7 days but
<1year prior to ApneaLinkTM assessment)

3. Patients have moderate-severe OSA (equivalent to apnea plus hypopneas index [AHI] >30
per hour of sleep) as determined by a = 4% oxygen dip rate > 12/ h on overnight
testing using the ApneaLinkTM device and confirmed by the SAVE core lab in Adelaide
upon receipt of the ApneaLinkTM data

4. Patients are able and willing to give appropriate informed consent
Minimum age
45 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from entry if ANY of the criteria listed below are met:

1. Any condition that in the opinion of the responsible physician or investigator makes
the potential participant unsuitable for the study. For example,

- co-morbid disease with severe disability or likelihood of death

- significant memory, perceptual, or behavioural disorder

- neurological deficit (e.g. limb paresis) preventing self administration of the
CPAP mask

- contraindication to CPAP use e.g. pneumothorax

- residence sufficiently remote from the clinic to preclude follow-up clinic visits

2. Any planned coronary or carotid revascularisation procedure in the next 6 months

3. Severe respiratory disease defined as

- severe chronic obstructive pulmonary disease (FEV1/FVC < 70% and FEV1 < 50%
predicted), or

- resting, awake SaO2 < 90% by ApneaLinkTM device

4. New York Heart Association (NYHA) categories III-IV of heart failure

5. Other household member enrolled in SAVE trial or using CPAP

6. Prior use of CPAP treatment for OSA

7. Increased risk of a sleep-related accident and/or excessive daytime sleepiness,
defined by any one of the following:

- driver occupation (eg truck, taxi)

- 'fall-asleep' accident or 'near miss' accident in previous 12 months

- high (> 15) score on the Epworth Sleepiness Scale

8. Severe nocturnal desaturation documented on the ApneaLinkTM device as > 10% overnight
recording time with arterial oxygen saturation of < 80%

9. Cheyne-Stokes Respiration (CSResp)

- CSResp identified on ApneaLinkTM nasal pressure recording by typical
crescendo-decrescendo pattern of respiration with associated apneas and/or
hypopneas in the absence of inspiratory flow limitation.

- patients excluded if > 50% of nasal pressure - defined apneas and hypopneas
judged to be due to CSResp.

Study design
Purpose of the study
Prevention
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
SA
Recruitment hospital [1] 0 0
Adelaide Institute for Sleep Health, Repatriation General Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5041 - Adelaide
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
São Paulo
Country [2] 0 0
China
State/province [2] 0 0
Beijing
Country [3] 0 0
India
State/province [3] 0 0
Andhra Pradesh
Country [4] 0 0
Spain
State/province [4] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Other
Name
Adelaide Institute for Sleep Health
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Philips Respironics
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Health and Medical Research Council, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
ResMed
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Fisher and Paykel Healthcare
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
The George Institute
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Health Research Council, New Zealand
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Obstructive Sleep Apnea (OSA) is a condition in which a person stops breathing for several
seconds at a time due to relaxation of the throat muscles. This can occur many times during
sleep. It is known to cause sleepiness and poor concentration during the day. Research
indicates that OSA may be a modifiable risk factor for cardiovascular disease due to its
association with hypertension, stroke, heart attack and sudden death. The standard therapy
for symptomatic OSA is continuous positive airway pressure (CPAP). CPAP has been shown to
effectively reduce snoring, obstructive episodes and daytime sleepiness and to modestly
reduce blood pressure and other risk factors for cardiovascular disease. The overall aim of
SAVE is to determine if CPAP can reduce the risk of heart attack, stroke or heart failure for
people with OSA.
Trial website
https://clinicaltrials.gov/show/NCT00738179
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
R D McEvoy
Address 0 0
Adelaide Institute for Sleep Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00738179