Early interventions to improve outcomes after
traumatic brain injury
Multi-centre randomised controlled trials of early acute interventions
(hypothermia, and erythropoietin) to improve outcomes after traumatic brain
injury
Chief Investigators: Professor Jamie Cooper, Professor Rinaldo Bellomo and
Associate Professor Stephen Bernard
Lead Organisation: Monash University
TAC Neurotrauma Funding: $2,086,100
Project Start Date: 1 January 2010
Project Summary:
Traumatic brain injury (TBI) is a major public health problem in Australia. The
Australian and New Zealand Intensive Care Society-Clinical Trials Group (ANZICSCTG) multi-centre Australasian Traumatic Brain Injury Study (ATBIS) reported a
35.1% mortality rate and a 51.5% unfavourable neurological outcomes (death and
severe disability) rate at 12 months in patients with severe TBI. In addition, the cohort
of patients with severe TBI included in our recent Saline versus Albumin resuscitation
(SAFE) randomised controlled trial (RCT) had an overall mortality of 32% and
unfavourable neurological outcome rate of 54% at 24 months. These results highlight
that the mortality and neurological morbidity associated with severe TBI in Australia
is exceptionally high. The medical lifetime cost of the 250+ Australian victims of TBI
who survive with significant disability each year is in excess of 750 million dollars.
Secondary brain injury is a potentially modifiable contributor to brain injury after
trauma and we have recently demonstrated in a “proof of concept” study (SAFE:TBI)
that a simple choice of resuscitation fluid altered survival and neurological function in
TBI patients. This landmark finding provided optimism that other therapies may also
be effective.
The interventions which have greatest potential to improve neurological outcomes in
TBI patients by attenuating secondary brain injury are: a) early pre-hospital initiation
of prophylactic hypothermia; and b) erythropoietin (EPO) therapy.
a): POLAR Trial
The objective is to complete a multi-centre randomised trial or early cooling in
patients with severe diffuse traumatic brain injury with the primary aim of the study to
determine whether early and sustained prophylactic hypothermia, compared to
standard `normothermic` care, is associated with an increased proportion of
favourable neurological outcomes six months after severe TBI.
b): EPO-TBI Trial
The objective is to complete a stratified, prospective, multi-centre, randomised,
double-blind, placebo-controlled, phase III trial in ICU patients with moderate (GCS
9-12) or severe (GCS 3-8) TBI and to determine whether EPO improves neurological
function 6 months after injury.
Publications:
(as at Feb 2012)
NICHOL A, COOPER DJ and The POLAR and EPO study investigators on behalf of the ANZICS
Clinical trials Group. Can we improve neurological outcomes in severe traumatic brain injury?
Something old (early prophylactic hypothermia) and something new (erythropoietin). Injury.
2009;40(5):471-478.
MOORE EM, BELLOMO R, NICHOL AD, HARLEY N, MACISAAC C, COOPER DJ. The
incidence of acute kidney injury in patients with traumatic brain injury. Renal Failure.
2010;32(9):1060-1065.
NICHOL AD, BAILEY M, COOPER DJ on behalf of the POLAR and EPO investigators. Challenging
issues in randomised controlled trials. Injury. 2010;41 Suppl 1:S20-3.
HIGGINS L, PETTILA V, NICHOL AD, BELLOMO R, COOPER DJ. Expensive care medicineEconomic evaluations in Intensive Care Trials Critical Care Resuscitation. 2010;12(1):62-66.
MOORE E, BELLOMO R, NICHOL A. Biomarker of acute kidney injury in anaesthesia, intensive
care and major surgery: from the bench to clinical research to clinical practice. Minerva
Anaestesiologica. 2010;76(6):425-440.
ROBERTSON MS, NICHOL AD, HIGGINS AM, BAILEY MJ, PRESNEILL JJ, COOPER DJ,
WEBB SA, MCARTHUR C, MACISAAC CM; VTE Point Prevalence Investigators. Venous
Thrombus Embolism Prophylaxis in intensive care units in Australia and New Zealand. Critical Care
Resuscitation. 2010;12(1):9-15.
MOORE E, BELLOMO R, NICHOL A, HARLEY N, MACISAAC C, COOPER D. The incidence of
acute kidney injury in patients with traumatic brain injury. Renal Failure. 2010;32(9):1060-1065.
NICHOL A, ROSENFELD J, COOPER D. Future perspectives for the treatment of TBI patients:
decompressive craniectomy, hypothermia and erythropoietin. In Traumatic brain and spinal cord
injury: challenges and developments in research-Translating Research into Clinical Practice.
Cambridge University Press
MOORE E, BELLOMO R. Erythropoietin (EPO) in acute kidney injury. Annals of Intensive Care
(online journal). 2011;1(3).
NICHOL AD, HIGGINS AM, GABBE BJ, ,MURRAY LJ, COOPER DJ, CAMERON P. Measuring
functional and quality of life outcomes following major head injury: Common scales and checklists.
Injury. 2011;42(3):281-287.
NICHOL A, TRAPANI T, VALLANCE S, COOPER D. Hypothermia in patients with brain injury: the
way forward? Lancet Neurol. 2011;10(5):406-407.
MOORE E, BELLOMO R, NICHOL AD. Erythropoietin (EPO) as a novel brain and kidney protective
agent. Anaesth Intensive Care. 2011 May;39(3):356-72
Presentations:
(as at Feb 2012)
NICHOL A. EPO/POLAR - World leading trials in TBI research. Trauma Melbourne; 2009 November
20-21, Melbourne, Victoria.
NICHOL A. Cooling of our patients: What when, why. ANZIC annual scientific meeting; 2009
October, Perth, Australia.
MURRAY LJ. POLAR study update. ANZICS CTG meeting; 2009 October, Perth, Australia.
NICHOL A. Hypothermia in ICU. The intensive care society of Ireland annual scientific meeting; 2009
May, Dublin, Ireland.
COOPER DJ. POLAR Study Update. ANZICS CTG Spring Research Forum. 2010 October 24-25,
Melbourne, VIC.
RIDLEY E. POLAR BEAR Update. 12th Annual Meeting on Clinical Trials in Intensive Care,
ANZICS Clinical Trials Group. 2010 Mar 25, Noosa, QLD.
NICHOL A. Novel treatments in traumatic brain injury European Society of Intensive Care Medicine.
Acute Brain Injury Conference; 2010 June 10-12, Dublin, Ireland.
COOPER DJ. The magic bullet in TBI- a clinical trials perspective. Trauma Melbourne; 2010
November 19-21, Melbourne, Australia.
NICHOL A. EPO-TBI. ANZICS annual scientific meeting; 2010 October, Perth, Australia.
MOORE E. The incident and implications of acute kidney injury in patients with traumatic brain
injury. 10th International Neurotrauma Symposium (INTS); 2011 April 27- May 1, Shanghai, China.
CAMERON P. Current and Future Clinical Trials: POLAR Trial. Australasian College for Emergency
Medicine Annual Scientific Meeting. 2011 November 20-24. Sydney, Australia.
TRAPANI T. POLAR and EPO-TBI study updates. 9th Victorian ACCCN Annual Symposium on
Critical Care; 2011 March 4, Melbourne, Australia.
COOPER D. Burden of TBI, the Australian experience in TBI. ANZICS Intensive Care Forum; 2011
April 22-24, Singapore.
COOPER D. Australian experience in TBI. 10th International Neurotrauma Symposium (INTS);2011
April 27 - May 1, Shanghai, China.