title: Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Traumatic brain injury is a leading cause of death and disability worldwide. Laboratory and clinical studies demonstrate a possible beneficial effect of erythropoietin in improving outcomes in the traumatic brain injury cohort. However, there are concerns regarding the association of erythropoietin and thrombosis in the critically ill. A large-scale, multi-centre, blinded, parallel-group, placebo-controlled, randomised trial is currently underway to address this hypothesis.
  
  
  METHODS
  The erythropoietin in traumatic brain injury trial is a stratified prospective, multi-centre, randomised, blinded, parallel-group, placebo-controlled phase III trial. It aims to determine whether the administration of erythropoietin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at six months after injury. The trial is designed to recruit 606 patients between 15 and 65 years of age with severe (Glasgow Coma Score: 3 to 8) or moderate (Glasgow Coma Score: 9 to 12) traumatic brain injury in Australia, New Zealand, Kingdom of Saudi Arabia, France, Finland, Germany and Ireland. Trial patients will receive either subcutaneous erythropoietin or placebo within 24 hours of injury, and weekly thereafter for up to three doses during the intensive care unit admission. The primary outcome will be the combined proportion of unfavourable neurological outcomes at six months: severe disability or death. Secondary outcomes will include the rate of proximal deep venous thrombosis detected by compression Doppler ultrasound, six-month mortality, the proportion of patients with composite vascular events (deep venous thrombosis, pulmonary embolism, myocardial infarction, cardiac arrest and cerebrovascular events) at six months and quality of life with health economic evaluations.
  
  
  CONCLUSIONS
  When completed, the trial aims to provide evidence on the efficacy and safety of erythropoietin in traumatic brain injury patients, and to provide clear guidance for clinicians in their management of this devastating condition.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials registry: ACTRN12609000827235 (registered on 22 September 2009). Clinicaltrials.gov: NCT00987454 (registered on 29 September 2009). European Drug Regulatory Authorities Clinical Trials: 2011-005235-22 (registered on 18 January 2012).
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. alistair.nichol@monash.edu.|Department of Intensive Care Medicine, The Alfred, Commercial Road, Melbourne, 3004, Australia. alistair.nichol@monash.edu.|Department of Anaesthesia and Intensive Care Medicine, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. alistair.nichol@monash.edu.|School of Medicine and Medical Sciences, University College Dublin, Elm Park, Dublin 4, Ireland. alistair.nichol@monash.edu.
authors.forename: Alistair
authors.initials: A
authors.lastname: Nichol
authors.affiliation: Department of Intensive Care, Western Health, Gordon Street, Footscray, 3011, Australia. craig.french@wh.org.au.|Department of Medicine North West Academic Centre, The University of Melbourne, Grattan Street, Parkville, 3052, Australia. craig.french@wh.org.au.
authors.forename: Craig
authors.initials: C
authors.lastname: French
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. lorraine.little@monash.edu.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Little
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. intensive@fastmail.com.au.|Department of Intensive Care, Mater Health Services, Raymond Terrace, South Brisbane, 4101, Australia. intensive@fastmail.com.au.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Presneill
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. jamie.cooper@monash.edu.|Department of Intensive Care Medicine, The Alfred, Commercial Road, Melbourne, 3004, Australia. jamie.cooper@monash.edu.
authors.forename: D James
authors.initials: DJ
authors.lastname: Cooper
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. haddads55@yahoo.com.|Department of Intensive Care, King Abdulaziz Medical City, PO Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia. haddads55@yahoo.com.
authors.forename: Samir
authors.initials: S
authors.lastname: Haddad
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. jacques.duranteau@bct.aphp.fr.|Service d'Anesthésie-Réanimation, Hôpitaux universitaires Paris Sud, Assistance Publique des Hôpitaux de Paris, Hôpital de Bicêtre, 78, rue du Général Leclerc, 94275, Le Kremlin Bicêtre, France. jacques.duranteau@bct.aphp.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Duranteau
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Centre Hospitalier Universitaire La Cavale Blanche Université de Bretagne Ouest, 29609, Brest Cedex, France. olivier.huet@chu-brest.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huet
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, PO Box 266, FIN-00029, Helsinki, Finland. Markus.Skrifvars@hus.fi.
authors.forename: Markus
authors.initials: M
authors.lastname: Skrifvars
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. Arabi@NGHA.MED.SA.|Intensive Care Department, College of Medicine King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, PO Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia. Arabi@NGHA.MED.SA.
authors.forename: Yaseen
authors.initials: Y
authors.lastname: Arabi
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, 3004, Australia. rinaldo.bellomo@austin.org.au.|Department of Medicine North West Academic Centre, The University of Melbourne, Grattan Street, Parkville, 3052, Australia. rinaldo.bellomo@austin.org.au.|Department of Intensive Care, Austin Health, Studley Road, Heidelberg, 3084, Australia. rinaldo.bellomo@austin.org.au.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000188:drug therapy*; D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018401:Sample Size; D013923:Thromboembolism / Q000517:prevention & control; D018608:Ultrasonography, Doppler
chemical_list: D004921:Erythropoietin