title: Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury.
abstract: BACKGROUND
  Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Prophylactic hypothermia is effective in laboratory models, but clinical studies to date have been inconclusive, partly because of methodological limitations. Our Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR) randomised controlled trial is currently underway comparing early, sustained hypothermia versus standard care in patients with severe TBI. We describe our study protocol and the challenges in conducting prophylactic hypothermia research in TBI.
  
  
  METHODS
  We aim to randomise 500 patients to either prophylactic 33°C hypothermia initiated within 3 hours of injury and continued for at least 72 hours, or standard normothermic management. Patients will be enrolled by paramedic services in the prehospital setting, or by emergency department staff at participating sites in Australia, New Zealand and Europe. The primary outcome will be the eight-level extended Glasgow outcome scale (GOSE), dichotomised to favourable and unfavourable outcomes at 6 months after injury. Secondary outcomes will include mortality at hospital discharge and at 6 months, ordinal analyses of 6-month GOSE outcomes, quality of life with health economic evaluations and the differential proportion of adverse events. We will predefine subgroup and interaction analyses.
  
  
  CONCLUSIONS
  After a run-in phase, recruitment for our main study began in December 2010. When the study is completed, we aim to provide evidence on the efficacy of prophylactic hypothermia in TBI to guide clinicians in their management of this devastating condition.
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia. Jamie.cooper@monash.edu.
authors.forename: Alistair
authors.initials: A
authors.lastname: Nichol
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Dashiell
authors.initials: D
authors.lastname: Gantner
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Presneill
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Lynnette
authors.initials: L
authors.lastname: Murray
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Trapani
authors.affiliation: Department of Intensive Care, The Alfred Hospital, Melbourne, VIC, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bernard
authors.affiliation: Centre of Excellence in Traumatic Brain Injury Research, The Alfred Hospital, Monash University, Melbourne, VIC, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Cameron
authors.affiliation: Réanimation médicale CHRU, H^pital Jean Minjoz, Besançon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Capellier
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Forbes
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Colin
authors.initials: C
authors.lastname: McArthur
authors.affiliation: Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Lynette
authors.initials: L
authors.lastname: Newby
authors.affiliation: Queensland Ambulance Service, Brisbane, QLD, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rashford
authors.affiliation: Department of Surgery, Monash University, Melbourne, VIC, Australia.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Rosenfeld
authors.affiliation: Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Tony
authors.initials: T
authors.lastname: Smith
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Stephenson
authors.affiliation: Department of Surgery, Monash University, Melbourne, VIC, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Varma
authors.affiliation: Department of Intensive Care, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Walker
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Webb
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: D James
authors.initials: DJ
authors.lastname: Cooper
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000628:therapy*; D003422:Critical Care; D004632:Emergency Medical Services; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D015337:Multicenter Studies as Topic; D017063:Outcome Assessment, Health Care; D012107:Research Design