Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease - Full Text View

Sponsor:	Adelaide Institute for Sleep Health
Collaborators:	Respironics ResMed Fisher and Paykel Healthcare The George Institute
Information provided by:	Adelaide Institute for Sleep Health
ClinicalTrials.gov Identifier:	NCT00738179

Purpose

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.

Condition	Intervention	Phase
Sleep Apnea Cardiovascular Disease	Device: Continuous Positive Airway Pressure (CPAP) Other: Standard care	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official 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.

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Heart Failure Sleep Apnea

U.S. FDA Resources

Further study details as provided by Adelaide Institute for Sleep Health:

Primary Outcome Measures:

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. [ Time Frame: Reviewed 6-monthly; average patient follow up, 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Reviewed 6-monthly; average patient follow up, 4 years. ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and at 6-months, 2 and 4 years following randomisation ] [ Designated as safety issue: No ]

Estimated Enrollment:	5000
Study Start Date:	September 2008
Estimated Study Completion Date:	September 2015
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental CPAP plus standard care of cardiovascular risk factors	Device: Continuous Positive Airway Pressure (CPAP) CPAP worn nightly
2: Active Comparator Standard care alone	Other: Standard care Standard care of cardiovascular risk factors

Detailed Description:

There is increasing evidence to indicate that OSA is an important modifiable risk factor for CV disease including stroke, MI, and heart failure. Increased nocturnal arterial blood pressure (BP), hypercoagulability, oxidative stress, inflammation, insulin resistance and cardiac arrhythmias are all associated with OSA. These effects are presumed to accelerate the progression of atheromatous disease, particularly within the coronary or cerebral vasculature. Moreover, OSA also appears to increase the risk of sudden death during sleep, which is different from the circadian pattern of sudden death in those without OSA, suggesting that episodes of apnea may have a direct triggering effect for cardiac arrhythmias or MI.

CPAP is now standard therapy for symptomatic OSA, with adherence to treatment comparable to that of other therapies for common chronic diseases. CPAP can eliminate apneas and improve daytime sleepiness, mood and quality of life. Furthermore, short term (1-3 months) randomised controlled trials of CPAP have shown modest reductions in blood pressure (BP) and other markers of CV disease, including C-reactive protein (CRP) and coagulation. However, the epidemiological data is complicated by potential residual confounding factors and the randomised evidence is limited. Thus, a direct causal link between OSA and CV disease remains inconclusive. The management of OSA, therefore, remains principally directed towards symptom control rather than CV risk modification.

The present trial aims to test whether long-term use of CPAP can reduce the incidence of CV events. If the trial shows that CPAP treatment of OSA reduces the incidence of CV events it will influence clinical practice toward the early detection and management of OSA, and add CPAP to the range of strategies available for the prevention of CV disease.

Eligibility

Ages Eligible for Study:	45 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females, any race, and aged between 45 and 75 years
Evidence of established coronary or cerebrovascular disease as evident by:
- Coronary artery disease
  - Previous MI (equal to or greater than 90 days prior to informed consent)
  - Stable angina or unstable angina (equal to or greater than 30 days prior to informed consent) each with documented multi-vessel coronary artery disease or 50% or more stenosis in at least two major coronary arteries on coronary angiography, 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 informed consent
  - Multi-vessel coronary artery bypass surgery (CABG) >1 year prior to informed consent
- Cerebrovascular disease
  - Previous stroke (includes definite or presumed cerebral ischaemia/infarction and intracerebral haemorrhage) equal to or greater than 90 days prior to informed consent
  - Previous transient ischaemic event (TIA) of the brain or retina (symptoms <24 hours) with the diagnosis confirmed by a neurologist 30 days to I year prior to informed consent
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 ApneaLink data
Patients are able and willing to give appropriate informed consent

Exclusion Criteria:

Patients will be excluded from entry if ANY of the criteria listed below are met:

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 within the next 2 years
- significant memory, perceptual, or behavioural disorder
- neurological deficit (eg. limb paresis) preventing self administration of the CPAP mask
- residence sufficiently remote from the clinic to preclude follow-up clinic visits
Any planned coronary or carotid revascularisation procedure in the next 6 months
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
New York Heart Association (NYHA) categories III-IV of heart failure
Stroke due to subarachnoid haemorrhage
Other household member enrolled in SAVE trial or using CPAP
Prior use of CPAP treatment for OSA
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
Severe nocturnal desaturation documented on the ApneaLinkTM device as > 10% overnight recording time with arterial oxygen saturation of < 80%
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738179

Contacts

Contact: R D McEvoy	+61 8 8275 1359	doug.mcevoy@rgh.sa.gov.au
Contact: S Mead	+61 8 8275 2879	samantha.mead@rgh.sa.gov.au

Locations

Australia, South Australia
Repatriation General Hospital	Recruiting
Adelaide, South Australia, Australia, 5052
Contact: R D McEvoy

Sponsors and Collaborators

Adelaide Institute for Sleep Health

Respironics

ResMed

Fisher and Paykel Healthcare

The George Institute

Investigators

Principal Investigator:

R D McEvoy

Adelaide Institute for Sleep Health

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Adelaide Institute for Sleep Health ( Professor Doug McEvoy )
Study ID Numbers:	SAVE001, ANZCTR 12608000409370
Study First Received:	August 19, 2008
Last Updated:	May 26, 2009
ClinicalTrials.gov Identifier:	NCT00738179 History of Changes
Health Authority:	Australia: Human Research Ethics Committee

Keywords provided by Adelaide Institute for Sleep Health:

Continuous Positive Airway Pressure (CPAP)
Obstructive Sleep Apnea (OSA)
Cardiovascular (CV)
Cardiovascular Disease
Clinical Trial

Additional relevant MeSH terms:

Signs and Symptoms
Sleep Apnea Syndromes
Respiratory Tract Diseases
Apnea
Nervous System Diseases
Respiration Disorders

Sleep Apnea, Obstructive
Sleep Disorders
Dyssomnias
Signs and Symptoms, Respiratory
Cardiovascular Diseases
Sleep Disorders, Intrinsic

ClinicalTrials.gov processed this record on November 30, 2009