The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR-RCT)
Traumatic brain injury (TBI) is a leading cause of death and long term disability, particularly in young adults. Studies from Australia have shown that approximately half of those with severe traumatic brain injury will be severely disabled or dead 6 months post injury. Given the young age of many patients with severe TBI and the long term prevalence of major disability, the economic and more importantly the social cost to the community is very high.
Pre-hospital and hospital management of patients with severe brain injury focuses on prevention of additional injury due primarily to lack of oxygen and insufficient blood pressure. This includes optimising sedation and ventilation, maintaining the fluid balance and draining Cerebrospinal Fluid (CSF) and performing surgery where appropriate. In recent years there has been a research focus on specific pharmacologic interventions, however, to date, there has been no treatment that has been associated with improvement of neurological outcomes.
One treatment that shows promise is the application of hypothermia (cooling). This treatment is commonly used in Australia to decrease brain injury in patients with brain injury following out-of-hospital cardiac arrest. Cooling is thought to protect the brain using a number of mechanisms. There have been a number of animal studies that have looked at how cooling is protective and also some clinical research that suggests some benefit. However at the current time there is insufficient evidence to provide enough proof that cooling should be used routinely for patients with brain injury and like all treatments there can be some risks and side effects.
The POLAR trial has been developed to investigate whether early cooling of patients with severe traumatic brain injury is associated with better outcomes. It is a randomised controlled trial, which is a type of trial that provides the highest quality of evidence.
The null hypothesis is that there is no difference in the proportion of favourable neurological outcomes six months after severe traumatic brain injury in patients treated with early and sustained hypothermia, compared to standard normothermic management.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Multi-centre Randomised Trial to Evaluate the Effect of Early Hypothermia on Neurological Function in Patients With Severe Traumatic Brain Injury. Including Renal Sub Study|
- The proportion of favourable neurological outcomes (Glasgow Outcome Score Extended: GOSE 5 to 8) [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- Quality of life assessments *SF-12 (version 1) *EQ5D [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- Mortality (all cause) [ Time Frame: 6 months post injury ] [ Designated as safety issue: Yes ]
- Proportion of favourable (GOSE 5-8) neurological outcomes in survivors [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- Incidence of adverse events *Significant bleeding - assessed clinically *Infection - assessed clinically [ Time Frame: During the study intervention ] [ Designated as safety issue: Yes ]
- Cumulative proportion of patients with Acute Kidney Injury (Injury/Failure Risk Injury Failure Loss End stage (RIFLE) categories) in those receiving cooling v. normothermia [ Time Frame: Day 7 of hospital admission ] [ Designated as safety issue: No ]
- Levels of biomarkers neutrophil gelatinase-associated lipocalin (NGAL), cystatin C and liver-type fatty acid binding protein (L-FABP) will be measured in plasma and urine from blood and urine specimens obtained from 50 patients. [ Time Frame: 24hrs, 48 hrs, 72 hrs post Intensive Care admission ] [ Designated as safety issue: No ]
- Health Economic Evaluation [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- time to reach 33C and dichotomised GOSE scores [ Time Frame: 6 months post injury ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Early and sustained hypothermia.
exposure: Early and sustained hypothermia. Hypothermia will initially be induced by infusion of up to 2L ice cold saline. Following a safety assessment the patient will be rapidly cooled to 33C using surface temperature control equipment. They will be maintained at 33C 3 days. Rewarming will occur at a rate of 0.17C/hr and will be titrated to intracranial pressure (ICP) control.Other: Normothermia
Standard management. Patients will be kept at normothermia (37C). If they develop a fever >38C they will be treated with paracetamol and surface temperature control equipment will be applied to maintain normothermia. Cooling to 35C is an option for refractory ICP.
No Intervention: Normothermia
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987688
|Contact: Tony V Trapani, BEd BEmH RN||+61 409 798 firstname.lastname@example.org|
|Contact: Lynne Murray||+61 419 155 983||Lynnette.Murray@monash.edu|
|Princess Alexandra Hospital||Recruiting|
|Brisbane, Queensland, Australia|
|Contact: Jason Meyer Jason.Meyer@health.qld.gov.au|
|Principal Investigator: Chris Joyce, MD|
|The Royal Melbourne Hospital||Recruiting|
|Melbourne, Victoria, Australia|
|Contact: Deborah Barge Deborah.Barge@mh.org.au|
|Principal Investigator: Chris Macisaac, MD|
|Prahran, Victoria, Australia, 3004|
|Contact: Shirley Vallance, RN 0390768034 email@example.com|
|Principal Investigator: David J Cooper, MD|
|Australia, Western Australia|
|Royal Perth Hospital||Recruiting|
|Perth, Western Australia, Australia|
|Contact: Elixzabeth Jenkinson Elizabeth.Jenkinson@health.wa.gov.au|
|Principal Investigator: Steve Webb, MD|
|Besancon, Franche Comte, France|
|Contact: Lucie Vettoretti firstname.lastname@example.org|
|Principal Investigator: Sebastien Pilifloury, MD|
|Auckland, North Island, New Zealand|
|Contact: Lynette Newby LynetteN@adhb.govt.nz|
|Principal Investigator: Colin McArthur, MD|
|Waikato District Health Board||Recruiting|
|Waikato, North Island, New Zealand|
|Contact: John Durning John.Durning@waikatodhb.health.nz|
|Principal Investigator: Robert Frengley, MD|
|Study Chair:||Jamie Cooper, BMBS, MD||ANZIC RC|