title: The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress.
abstract: The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed.
  
  
  BACKGROUND
  NCT00738179.
  ACTRN12608000409370.
authors: The Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, SA, Australia.|School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.
authors: Nick A
authors: NA
authors: Antic
authors: School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.|The George Institute for Global Health, The University of Sydney, New South Wales, Australia.
authors: Emma
authors: E
authors: Heeley
authors: School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.|The George Institute for Global Health, The University of Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors: Craig S
authors: CS
authors: Anderson
authors: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Yuanming
authors: Y
authors: Luo
authors: Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai, China.
authors: Jiguang
authors: J
authors: Wang
authors: School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.|The George Institute for Global Health, The University of Sydney, New South Wales, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.|Imperial College, London, United Kingdom.
authors: Bruce
authors: B
authors: Neal
authors: Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.|Centre for Integrated Research and Understanding of Sleep Woolcock Institute of Medical Research, University of Sydney, New South Wales, Australia.
authors: Ron
authors: R
authors: Grunstein
authors: School of Medicine at the University of Lleida Barcelona, Spain.
authors: Ferran
authors: F
authors: Barbe
authors: Pulmonary Division - Heart Institute (InCor) University of São Paulo, Brazil.
authors: Geraldo
authors: G
authors: Lorenzi-Filho
authors: Shanghai Rui Jin Hospital, Shanghai, China.
authors: Shaoguang
authors: S
authors: Huang
authors: Department of Medicine and Division of Sleep, Brigham and Women's Hospital and Beth Israel Medical Center, Boston, MA.
authors: Susan
authors: S
authors: Redline
authors: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Nanshan
authors: N
authors: Zhong
authors: The Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, SA, Australia.|School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, SA, Australia.
authors: R Doug
authors: RD
authors: McEvoy
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications* / Q000517:prevention & control* / Q000628:therapy; D045422:Continuous Positive Airway Pressure; D003299:Cooperative Behavior; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000941:ethics* / Q000379:methods*; D018401:Sample Size; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000628:therapy*; D057212:Therapeutic Equipoise; D013997:Time Factors
keywords: OSA; cardiovascular; clinical trial; outcomes