Sleep ApneaPhase 3SAVENCT00738179
Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease
A Phase 3 study testing Continuous Positive Airway Pressure (CPAP) in people with Sleep Apnea and Cardiovascular Disease, run by Adelaide Institute for Sleep Health at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Sleep Apnea, Cardiovascular Disease
- What is being tested?
- Continuous Positive Airway Pressure (CPAP)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,500 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Sep 2008to Dec 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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
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- 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)
- 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
- Patients are able and willing to give appropriate informed consent
Who cannot join
- 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
- 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
Show all 22Show fewer
- 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
- 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.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Australia1 site
Adelaide Institute for Sleep Health, Repatriation General Hospital
Adelaide, South Australia, 5041
Brazil1 site
Brazil Principal Investigator: Geraldo Lorenzi Filho, Heart Institute, University of São Paulo
São Paulo
China1 site
Regional Coordinating Centre China: The George Institute China Beijing
Beijing, Beijing Municipality, 100088
India1 site
Regional Coordinating Centre India: The George Institute India 839C, Road No. 44A Jubilee Hills
Hyderabad, Andhra Pradesh, 500 033
Spain1 site
Regional Coordinating Centre Spain: Spanish Respiratory Society (Sociedad Española de Neumología y Cirugía Torácica) (SEPAR)
Barcelona, 08029
About this 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.
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.
Read the 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.
- Conditions
- Sleep Apnea, Cardiovascular Disease
- Being tested
- Continuous Positive Airway Pressure (CPAP), Standard care
- Keywords
- Continuous Positive Airway Pressure (CPAP), Obstructive Sleep Apnea (OSA), Cardiovascular (CV), Cardiovascular Disease, Clinical Trial
- Medical subject headings
- Sleep Apnea Syndromes, Cardiovascular Diseases, Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Positive Airway Pressure (CPAP)Device
CPAP worn nightly
Standard careOther
Standard care of cardiovascular risk factors
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | CPAP plus standard care of cardiovascular risk factors Receives: Device: Continuous Positive Airway Pressure (CPAP) |
| 2 | Active comparator | Standard care alone Receives: Other: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Reviewed 6-monthly; average patient follow up, 4.5 years
Secondary outcomes (3)
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.
Measured: Reviewed 6-monthly; average patient follow up, 4.5 years.
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
Measured: baseline and at 6-months, 2 and 4 years following randomisation
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.
Measured: Randomisation and at 6 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Sleep ApneaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adelaide Institute for Sleep Health
- Sponsor type
- University, hospital or other
- Collaborators
- Philips Respironics, National Health and Medical Research Council, Australia, ResMed, Fisher and Paykel Healthcare, The George Institute, Health Research Council, New Zealand
- Responsible party
- Principal investigator, Professor R. Doug McEvoy, Adelaide Institute for Sleep Health
- Investigators
- R D McEvoy, Principal investigator, Adelaide Institute for Sleep Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00738179
- Sponsor's protocol ID
- SAVE001
- Other IDs
- ANZCTR 12608000409370
- Acronym
- SAVE
- Status last verified
- Feb 2015
- First submitted
- 19 Aug 2008
- Last updated
- 6 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
You S, Zheng D, Loffler KA, McEvoy RD, Li Q, Han Q, Barbe F, Liu CF, Cao Y, Wang X, Lorenzi-Filho G, Tripathi M, Anderson C; as the SAVE Investigators. Central Obesity and Recurrent Cardiovascular Events in Patients With Obstructive Sleep Apnea: The SAVE Study. Neurology. 2026 Aug 11;107(3):e218334. doi: 10.1212/WNL.0000000000218334. Epub 2026 Jul 21.
PubMed 42479992You S, Zheng D, Harris K, Loffler KA, McEvoy RD, Peters R, Li Q, Barbe F, Chen L, Chen X, Cao Y, Liu CF, Lorenzi-Filho G, Woodward M, Chalmers J, Anderson CS; SAVE Investigators. Frailty and Recurrent Cardiovascular Events in Patients With Obstructive Sleep Apnoea: The SAVE Study. J Cachexia Sarcopenia Muscle. 2026 Apr;17(2):e70252. doi: 10.1002/jcsm.70252.
PubMed 41852085Cheng Y, Ou Q, Chen B, Loffler KA, Doug McEvoy R, Xu Y, Wang Q, Lao M. The changes of AHI after long-term CPAP in patients with comorbid OSA and cardiovascular disease. Sleep Breath. 2023 May;27(2):511-518. doi: 10.1007/s11325-022-02633-y. Epub 2022 May 14.
PubMed 35562555Lao M, Cheng Y, Gao X, Ou Q. The interaction among OSA, CPAP, and medications in patients with comorbid OSA and cardiovascular/cerebrovascular disease: a randomized controlled trial. BMC Pulm Med. 2022 Mar 21;22(1):99. doi: 10.1186/s12890-022-01879-2.
PubMed 35313858Stevens D, Loffler KA, Buman MP, Dunstan DW, Luo Y, Lorenzi-Filho G, Barbe FE, Anderson CS, McEvoy RD; SAVE investigators. CPAP increases physical activity in obstructive sleep apnea with cardiovascular disease. J Clin Sleep Med. 2021 Feb 1;17(2):141-148. doi: 10.5664/jcsm.8792.
PubMed 32951632Li J, McEvoy RD, Zheng D, Loffler KA, Wang X, Redline S, Woodman RJ, Anderson CS. Self-reported Snoring Patterns Predict Stroke Events in High-Risk Patients With OSA: Post Hoc Analyses of the SAVE Study. Chest. 2020 Nov;158(5):2146-2154. doi: 10.1016/j.chest.2020.05.615. Epub 2020 Jul 15.
PubMed 32679238Loffler KA, Heeley E, Freed R, Meng R, Bittencourt LR, Gonzaga Carvalho CC, Chen R, Hlavac M, Liu Z, Lorenzi-Filho G, Luo Y, McArdle N, Mukherjee S, Yap HS, Zhang X, Palmer LJ, Anderson CS, McEvoy RD, Drager LF; SAVE Substudy Investigators. Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease. Diabetes Care. 2020 Aug;43(8):1859-1867. doi: 10.2337/dc19-2006. Epub 2020 Apr 14.
PubMed 32291275Li J, Zheng D, Loffler KA, Wang X, McEvoy RD, Woodman RJ, Luo Y, Lorenzi-Filho G, Barbe F, Tripathi M, Anderson CS; SAVE Investigators. Sleep duration and risk of cardiovascular events: The SAVE study. Int J Stroke. 2020 Oct;15(8):858-865. doi: 10.1177/1747493020904913. Epub 2020 Feb 3.
PubMed 32013799Van Ryswyk E, Anderson CS, Antic NA, Barbe F, Bittencourt L, Freed R, Heeley E, Liu Z, Loffler KA, Lorenzi-Filho G, Luo Y, Margalef MJM, McEvoy RD, Mediano O, Mukherjee S, Ou Q, Woodman R, Zhang X, Chai-Coetzer CL. Predictors of long-term adherence to continuous positive airway pressure in patients with obstructive sleep apnea and cardiovascular disease. Sleep. 2019 Oct 9;42(10):zsz152. doi: 10.1093/sleep/zsz152.
PubMed 31587046Ou Q, Chen B, Loffler KA, Luo Y, Zhang X, Chen R, Wang Q, Drager LF, Lorenzi-Filho G, Hlavac M, McArdle N, Mukherjee S, Mediano O, Barbe F, Anderson CS, McEvoy RD, Woodman RJ; SAVE investigators. The Effects of Long-term CPAP on Weight Change in Patients With Comorbid OSA and Cardiovascular Disease: Data From the SAVE Trial. Chest. 2019 Apr;155(4):720-729. doi: 10.1016/j.chest.2018.08.1082. Epub 2018 Sep 27.
PubMed 30268694Loffler KA, Heeley E, Freed R, Anderson CS, Brockway B, Corbett A, Chang CL, Douglas JA, Ferrier K, Graham N, Hamilton GS, Hlavac M, McArdle N, McLachlan J, Mukherjee S, Naughton MT, Thien F, Young A, Grunstein RR, Palmer LJ, Woodman RJ, Hanly PJ, McEvoy RD; SAVE (Sleep Apnea Cardiovascular Endpoints) Investigators. Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1456-1462. doi: 10.1164/rccm.201703-0603OC.
PubMed 28743190McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE Investigators and Coordinators. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28.
PubMed 27571048Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress. Sleep. 2015 Aug 1;38(8):1247-57. doi: 10.5665/sleep.4902.
PubMed 25669180Chai-Coetzer CL, Luo YM, Antic NA, Zhang XL, Chen BY, He QY, Heeley E, Huang SG, Anderson C, Zhong NS, McEvoy RD. Predictors of long-term adherence to continuous positive airway pressure therapy in patients with obstructive sleep apnea and cardiovascular disease in the SAVE study. Sleep. 2013 Dec 1;36(12):1929-37. doi: 10.5665/sleep.3232.
PubMed 24293768
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00738179
- Acronym / sponsor ID
- SAVE / SAVE001
- Conditions
- Sleep Apnea, Cardiovascular Disease
- Keywords
- Continuous Positive Airway Pressure (CPAP), Obstructive Sleep Apnea (OSA), Cardiovascular (CV), Cardiovascular Disease, Clinical Trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,500 participants (estimated)
- Lead sponsor
- Adelaide Institute for Sleep HealthUniversity, hospital or other
- Collaborators
- Philips Respironics, National Health and Medical Research Council, Australia, ResMed, Fisher and Paykel Healthcare, The George Institute, Health Research Council, New Zealand
- Study start
- Sep 2008
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 20 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Device: Continuous Positive Airway Pressure (CPAP)CPAP plus standard care of cardiovascular risk factors |
| 2 | Active comparator | Other: Standard careStandard care alone |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Males and females, any race, and aged between 45 and 75 years
- Evidence of established coronary or cerebrovascular disease as evident by:
- 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
- Patients are able and willing to give appropriate informed consent
Key exclusion criteria (22 listed)
- Any condition that in the opinion of the responsible physician or investigator makes the potential participant unsuitable for the study. For example,
- Any planned coronary or carotid revascularisation procedure in the next 6 months
- Severe respiratory disease defined as
- New York Heart Association (NYHA) categories III-IV of heart failure
- Other household member enrolled in SAVE trial or using CPAP
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous Positive Airway Pressure (CPAP)CPAP worn nightly | Device | 1 |
| Standard careStandard care of cardiovascular risk factors | Other | 2 |
Primary outcome
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, 4.5 years
3 secondary outcomes
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, 4.5 years.
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
Cardiac MRI to assess effects of CPAP on cardiac structure and function.
Time frame: Randomisation and at 6 months follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2015.
- Derived from this study: PubMed 42479992You S, Zheng D, Loffler KA, McEvoy RD, Li Q, Han Q, Barbe F, Liu CF, Cao Y, Wang X, Lorenzi-Filho G, Tripathi M, Anderson C; as the SAVE Investigators. Central Obesity and Recurrent Cardiovascular Events in Patients With Obstructive Sleep Apnea: The SAVE Study. Neurology. 2026 Aug 11;107(3):e218334. doi: 10.1212/WNL.0000000000218334. Epub 2026 Jul 21.
- Derived from this study: PubMed 41852085You S, Zheng D, Harris K, Loffler KA, McEvoy RD, Peters R, Li Q, Barbe F, Chen L, Chen X, Cao Y, Liu CF, Lorenzi-Filho G, Woodward M, Chalmers J, Anderson CS; SAVE Investigators. Frailty and Recurrent Cardiovascular Events in Patients With Obstructive Sleep Apnoea: The SAVE Study. J Cachexia Sarcopenia Muscle. 2026 Apr;17(2):e70252. doi: 10.1002/jcsm.70252.
- Derived from this study: PubMed 35562555Cheng Y, Ou Q, Chen B, Loffler KA, Doug McEvoy R, Xu Y, Wang Q, Lao M. The changes of AHI after long-term CPAP in patients with comorbid OSA and cardiovascular disease. Sleep Breath. 2023 May;27(2):511-518. doi: 10.1007/s11325-022-02633-y. Epub 2022 May 14.
- Derived from this study: PubMed 35313858Lao M, Cheng Y, Gao X, Ou Q. The interaction among OSA, CPAP, and medications in patients with comorbid OSA and cardiovascular/cerebrovascular disease: a randomized controlled trial. BMC Pulm Med. 2022 Mar 21;22(1):99. doi: 10.1186/s12890-022-01879-2.
- Derived from this study: PubMed 32951632Stevens D, Loffler KA, Buman MP, Dunstan DW, Luo Y, Lorenzi-Filho G, Barbe FE, Anderson CS, McEvoy RD; SAVE investigators. CPAP increases physical activity in obstructive sleep apnea with cardiovascular disease. J Clin Sleep Med. 2021 Feb 1;17(2):141-148. doi: 10.5664/jcsm.8792.
- Derived from this study: PubMed 32679238Li J, McEvoy RD, Zheng D, Loffler KA, Wang X, Redline S, Woodman RJ, Anderson CS. Self-reported Snoring Patterns Predict Stroke Events in High-Risk Patients With OSA: Post Hoc Analyses of the SAVE Study. Chest. 2020 Nov;158(5):2146-2154. doi: 10.1016/j.chest.2020.05.615. Epub 2020 Jul 15.
- Derived from this study: PubMed 32291275Loffler KA, Heeley E, Freed R, Meng R, Bittencourt LR, Gonzaga Carvalho CC, Chen R, Hlavac M, Liu Z, Lorenzi-Filho G, Luo Y, McArdle N, Mukherjee S, Yap HS, Zhang X, Palmer LJ, Anderson CS, McEvoy RD, Drager LF; SAVE Substudy Investigators. Continuous Positive Airway Pressure Treatment, Glycemia, and Diabetes Risk in Obstructive Sleep Apnea and Comorbid Cardiovascular Disease. Diabetes Care. 2020 Aug;43(8):1859-1867. doi: 10.2337/dc19-2006. Epub 2020 Apr 14.
- Derived from this study: PubMed 32013799Li J, Zheng D, Loffler KA, Wang X, McEvoy RD, Woodman RJ, Luo Y, Lorenzi-Filho G, Barbe F, Tripathi M, Anderson CS; SAVE Investigators. Sleep duration and risk of cardiovascular events: The SAVE study. Int J Stroke. 2020 Oct;15(8):858-865. doi: 10.1177/1747493020904913. Epub 2020 Feb 3.
- Derived from this study: PubMed 31587046Van Ryswyk E, Anderson CS, Antic NA, Barbe F, Bittencourt L, Freed R, Heeley E, Liu Z, Loffler KA, Lorenzi-Filho G, Luo Y, Margalef MJM, McEvoy RD, Mediano O, Mukherjee S, Ou Q, Woodman R, Zhang X, Chai-Coetzer CL. Predictors of long-term adherence to continuous positive airway pressure in patients with obstructive sleep apnea and cardiovascular disease. Sleep. 2019 Oct 9;42(10):zsz152. doi: 10.1093/sleep/zsz152.
- Derived from this study: PubMed 30268694Ou Q, Chen B, Loffler KA, Luo Y, Zhang X, Chen R, Wang Q, Drager LF, Lorenzi-Filho G, Hlavac M, McArdle N, Mukherjee S, Mediano O, Barbe F, Anderson CS, McEvoy RD, Woodman RJ; SAVE investigators. The Effects of Long-term CPAP on Weight Change in Patients With Comorbid OSA and Cardiovascular Disease: Data From the SAVE Trial. Chest. 2019 Apr;155(4):720-729. doi: 10.1016/j.chest.2018.08.1082. Epub 2018 Sep 27.
- Derived from this study: PubMed 28743190Loffler KA, Heeley E, Freed R, Anderson CS, Brockway B, Corbett A, Chang CL, Douglas JA, Ferrier K, Graham N, Hamilton GS, Hlavac M, McArdle N, McLachlan J, Mukherjee S, Naughton MT, Thien F, Young A, Grunstein RR, Palmer LJ, Woodman RJ, Hanly PJ, McEvoy RD; SAVE (Sleep Apnea Cardiovascular Endpoints) Investigators. Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1456-1462. doi: 10.1164/rccm.201703-0603OC.
- Derived from this study: PubMed 27571048McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE Investigators and Coordinators. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R D McEvoy principal investigator
Adelaide Institute for Sleep Health
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Continuous Positive Airway Pressure (CPAP) in people with Sleep Apnea and Cardiovascular Disease, run by Adelaide Institute for Sleep Health at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia, Brazil, China, India, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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, 4.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00738179, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2015.