The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury

NCT00987688 | Completed DMC

• 1 other identifier: ANZIC-RC/DJC003
• Study Type: interventional
• Target: 511
• Locations: 6 countries
• Sites: 15

Brief Summary

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.

Conditions

Brain Injuries, Traumatic

Keywords

trauma; Brain injury; Pre-hospital; cooling

Outcome Measures

Primary Outcomes (1)

• The proportion of favourable neurological outcomes (Glasgow Outcome Score Extended: GOSE 5 to 8)

  The Glasgow Outcome Scale Extended (GOSE) is an ordinal rating scale. The 8 scores in the scale are: Dead (1), Vegetative State (2), Lower Severe Disability (3), Upper Severe Disability (4), Lower Moderate Disability (5), Upper Moderate Disability (6), Lower Good Recovery (7), and Upper Good Recovery (8).

  6 months post injury

Secondary Outcomes (8)

• Probability of an equal or greater GOSE level at 6 months compared to the probability of a lesser GOSE level, using a proportional odds model or partial proportional odds model

  6 months post injury

• Quality of life assessments (QOL) o EQ5D o SF12

  6 months post injury

• Average causal effect of hypothermia on GOSE at 6 months comparing hypothermia and control patients who would survive regardless of treatment assignment.

  6 months post injury

• Mortality

  Hospital Discharge and 6 Months post injury

• Incidence of adverse events, specifically: o Bleeding o Infection.

  Up to study day 10

Study Arms (2)

Hypothermia

EXPERIMENTAL

Early and sustained hypothermia.

Other: Hypothermia

Normothermia

NO INTERVENTION

Standard management

Interventions

Hypothermia OTHER

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 for 72 hours. Rewarming will occur at a rate of 1C/4hrs and will be titrated to intracranial pressure (ICP) control and BP.

Hypothermia

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Blunt trauma with clinical diagnosis of severe TBI and GCS \<9
• Estimated age ≥ 18 and \< 60 years of age
• The patient is intubated or intubation is imminent

You may not qualify if:

• Pre-hospital:
• Clinical diagnosis of drug or alcohol intoxication as predominant cause of coma
• Randomisation unable to be performed within 3 hrs of estimated time of injury
• Estimated transport time to study hospital \>2.5hrs
• Able to be intubated without drugs
• Systolic BP \<90mmHg
• Heart rate \> 120bpm
• GCS=3 + un-reactive pupils
• Penetrating neck/torso injury
• Known or obvious pregnancy
• Receiving hospital is not a study site
• Evidence of current anti-coagulant treatment
• Emergency Dept:
• Clinical diagnosis of drug or alcohol intoxication as predominant cause of coma
• Randomisation unable to be performed within 3 hrs of estimated time of injury

Sponsors & Collaborators

• Australian and New Zealand Intensive Care Research Centre: lead
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator
• National Health and Medical Research Council, Australia: collaborator
• Transport Accident Commision, Victoria: collaborator
• Monash University: collaborator
• Délégation à la Recherche Clinique et à l'Innovation (DRCI) CHU Besançon: collaborator

Study Sites (15)

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Alfred Hospital

Prahran, Victoria, 3004, Australia

Location

Royal Perth Hospital

Perth, Western Australia, Australia

Location

Hôpital St Jacques + CHRU Besançon

Besançon, Franche Comte, France

Location

Hôpital La Cavale Blanche + CHRU Brest

Brest, France

Location

Hôpital Gabriel Montpied + CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

Hôpital Carémeau + CHU de Nimes

Nîmes, France

Location

Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre

Strasbourg, France

Location

Auckland DCCM

Auckland, North Island, New Zealand

Location

Waikato District Health Board

Hamilton, North Island, New Zealand

Location

Hamad General Hospital

Doha, Qatar

Location

King Abdulaziz Medical City

Riyadh, Saudi Arabia

Location

Inselspital, Bern University Hospital

Bern, Switzerland

Location

Related Publications (5)

• Nichol A, Gantner D, Presneill J, Murray L, Trapani T, Bernard S, Cameron P, Capellier G, Forbes A, McArthur C, Newby L, Rashford S, Rosenfeld JV, Smith T, Stephenson M, Varma D, Walker T, Webb S, Cooper DJ. Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury. Crit Care Resusc. 2015 Jun;17(2):92-100.

  PMID: 26017126 BACKGROUND

• Presneill J, Gantner D, Nichol A, McArthur C, Forbes A, Kasza J, Trapani T, Murray L, Bernard S, Cameron P, Capellier G, Huet O, Newby L, Rashford S, Rosenfeld JV, Smith T, Stephenson M, Varma D, Vallance S, Walker T, Webb S, James Cooper D; POLAR investigators and the ANZICS Clinical Trials Group. Statistical analysis plan for the POLAR-RCT: The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial. Trials. 2018 Apr 27;19(1):259. doi: 10.1186/s13063-018-2610-y.

  PMID: 29703266 BACKGROUND

• Ridley EJ, Davies AR, Bernard S, McArthur C, Murray L, Paul E, Trapani A, Cooper DJ; ANZICS Clinical Trials Group. Measured energy expenditure in mildly hypothermic critically ill patients with traumatic brain injury: A sub-study of a randomized controlled trial. Clin Nutr. 2021 Jun;40(6):3875-3882. doi: 10.1016/j.clnu.2021.05.012. Epub 2021 May 24.

  PMID: 34130035 DERIVED

• Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, Kasza J, Murray L, Newby L, Presneill JJ, Rashford S, Rosenfeld JV, Stephenson M, Vallance S, Varma D, Webb SAR, Trapani T, McArthur C; POLAR Trial Investigators and the ANZICS Clinical Trials Group. Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury: The POLAR Randomized Clinical Trial. JAMA. 2018 Dec 4;320(21):2211-2220. doi: 10.1001/jama.2018.17075.

  PMID: 30357266 DERIVED

• Moore EM, Nichol AD, Bernard SA, Bellomo R. Therapeutic hypothermia: benefits, mechanisms and potential clinical applications in neurological, cardiac and kidney injury. Injury. 2011 Sep;42(9):843-54. doi: 10.1016/j.injury.2011.03.027. Epub 2011 Apr 9.

  PMID: 21481385 DERIVED

Related Links

• POLAR home (Monash university)
• POLAR SAP update\_signed\_20180612
• POLAR SAP update\_figures1 and 2\_signed\_20180613

MeSH Terms

Conditions

Brain Injuries, Traumatic; Wounds and Injuries; Brain Injuries

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System

Study Officials

• Jamie Cooper, BMBS, MD

  ANZIC RC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, ANZIC rc

Study Record Dates

• First Submitted: September 29, 2009
• First Posted: October 1, 2009
• Study Start: April 1, 2010
• Primary Completion: November 10, 2017
• Study Completion: June 15, 2018
• Last Updated: August 22, 2018

Record last verified: 2018-08

Locations

NZ (2); AU (5); FR (5); QA (1); CH (1); SA (1)