Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease

NCT00738179 | Unknown Phase 3 DMC

• 2 other identifiers: SAVE001ANZCTR 12608000409370
• Study Type: interventional
• Target: 2,500
• Locations: 5 countries
• Sites: 5

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.

Conditions

Sleep Apnea; Cardiovascular Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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

  baseline and at 6-months, 2 and 4 years following randomisation

• Cardiac MRI to assess effects of CPAP on cardiac structure and function.

  Randomisation and at 6 months follow-up

Study Arms (2)

1

EXPERIMENTAL

CPAP plus standard care of cardiovascular risk factors

Device: Continuous Positive Airway Pressure (CPAP)

2

ACTIVE COMPARATOR

Standard care alone

Other: Standard care

Interventions

Continuous Positive Airway Pressure (CPAP) DEVICE

CPAP worn nightly

1

Standard care OTHER

Standard care of cardiovascular risk factors

2

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Adelaide Institute for Sleep Health: lead
• Philips Respironics: collaborator
• National Health and Medical Research Council, Australia: collaborator
• ResMed: collaborator
• Fisher and Paykel Healthcare: collaborator
• The George Institute: collaborator
• Health Research Council, New Zealand: collaborator

Study Sites (5)

Adelaide Institute for Sleep Health, Repatriation General Hospital

Adelaide, South Australia, 5041, Australia

Location

Brazil Principal Investigator: Geraldo Lorenzi Filho, Heart Institute, University of São Paulo

São Paulo, Brazil

Location

Regional Coordinating Centre China: The George Institute China Beijing

Beijing, Beijing Municipality, 100088, China

Location

Regional Coordinating Centre India: The George Institute India 839C, Road No. 44A Jubilee Hills

Hyderabad, Andhra Pradesh, 500 033, India

Location

Regional Coordinating Centre Spain: Spanish Respiratory Society (Sociedad Española de Neumología y Cirugía Torácica) (SEPAR)

Barcelona, 08029, Spain

Location

Related Publications (12)

• Cheng 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.

  PMID: 35562555 DERIVED

• Lao 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.

  PMID: 35313858 DERIVED

• Stevens 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.

  PMID: 32951632 DERIVED

• Li 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.

  PMID: 32679238 DERIVED

• Loffler 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.

  PMID: 32291275 DERIVED

• Li 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.

  PMID: 32013799 DERIVED

• Van 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.

  PMID: 31587046 DERIVED

• Ou 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.

  PMID: 30268694 DERIVED

• Loffler 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.

  PMID: 28743190 DERIVED

• McEvoy 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.

  PMID: 27571048 DERIVED

• Antic 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.

  PMID: 25669180 DERIVED

• Chai-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.

  PMID: 24293768 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Sleep Apnea Syndromes; Cardiovascular Diseases; Sleep Apnea, Obstructive

Interventions

Continuous Positive Airway Pressure; Standard of Care

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• R D McEvoy

  Adelaide Institute for Sleep Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Director

Study Record Dates

• First Submitted: August 19, 2008
• First Posted: August 20, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 6, 2015

Record last verified: 2015-02

Locations

BR (1); AU (1); IN (1); CN (1); ES (1)