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The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR-RCT)

This study is currently recruiting participants.
Verified April 2012 by Australian and New Zealand Intensive Care Research Centre
Sponsor:
Collaborators:
Australian and New Zealand Intensive Care Society Clinical Trials Group
National Health and Medical Research Council, Australia
Victorian Neurotrauma Initiative
Information provided by (Responsible Party):
Siouxzy Morrison, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier:
NCT00987688
First received: September 29, 2009
Last updated: April 12, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Severe Traumatic Brain Injury
 Other: Hypothermia
Other: Normothermia
 Phase 3

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Australian and New Zealand Intensive Care Research Centre:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Quality of life assessments *SF-12 (version 1) *EQ5D [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
  • Mortality [ 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 ]

Estimated Enrollment: 512
Study Start Date: April 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypothermia
Early and sustained hypothermia.
 Other: 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
Standard management

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
    • 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
    • Able to be intubated without drugs
    • GCS=3 + un-reactive pupils
    • Persistent Systolic BP <90mmHg

    • Clinically significant bleeding likely to require haemostatic intervention, for example:

      • Bleeding into the chest, abdomen or retro-peritoneum likely to require surgery +/- embolisation
      • Pelvic fracture likely to require surgery +/- embolisation
      • More than two long bone fractures requiring operative fixation
    • Penetrating neck/torso injury
    • Positive urine or blood pregnancy test
    • Evidence of current anti-coagulant treatment
    • In the treating clinician's opinion, "cooling" is not in the patient's best interest
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987688

Contacts
Contact: Tony V Trapani, BEd BEmH CCRN +61399030034 tony.trapani@monash.edu

Locations
Australia, Victoria
Alfred Hospital Recruiting
Prahran, Victoria, Australia, 3004
Contact: Shirley Vallance, RN     0390768034     s.vallance@alfred.org.au    
Principal Investigator: David J Cooper, MD            
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
Australian and New Zealand Intensive Care Society Clinical Trials Group
National Health and Medical Research Council, Australia
Victorian Neurotrauma Initiative
Investigators
Study Chair: Jamie Cooper, BMBS, MD ANZIC RC
  More Information

No publications provided by Australian and New Zealand Intensive Care Research Centre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Siouxzy Morrison, Executive Officer, ANZIC rc, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT00987688     History of Changes
Other Study ID Numbers: DJC003
Study First Received: September 29, 2009
Last Updated: April 12, 2012
Health Authority: Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
New Zealand: Health and Disability Ethics Committees

Additional relevant MeSH terms:
Hypothermia
Brain Injuries
Body Temperature Changes
Signs and Symptoms
Brain Diseases
 Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on May 16, 2013