Multi-centre randomised controlled trials of early acute interventions (hypothermia, and erythropoietin) to improve outcomes after traumatic brain injury

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 (ANZICS-CTG) 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.