We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified September 2017 by David James Cooper, Australian and New Zealand Intensive Care Research Centre
Sponsor:
ClinicalTrials.gov Identifier:
NCT00987688
First Posted: October 1, 2009
Last Update Posted: September 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Australian and New Zealand Intensive Care Society Clinical Trials Group
National Health and Medical Research Council, Australia
Transport Accident Commision, Victoria
Monash University
Délégation à la Recherche Clinique et à l'Innovation (DRCI) CHU Besançon
Information provided by (Responsible Party):
David James Cooper, Australian and New Zealand Intensive Care Research Centre
  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
Brain Injuries, Traumatic Other: Hypothermia

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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:


Further study details as provided by David James Cooper, 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 ]
    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).


Secondary Outcome Measures:
  • 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 [ Time Frame: 6 months post injury ]
    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).

  • Quality of life assessments (QOL) o EQ5D o SF12 [ Time Frame: 6 months post injury ]

    Quality of life assessments using the EQ-5D-3L and SF12. The EQ-5D-3L descriptive system that comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems.

    The SF-12® Health Survey (SF-12) is a 12-item questionnaire used to assess health outcomes from the patient's perspective.


  • Average causal effect of hypothermia on GOSE at 6 months comparing hypothermia and control patients who would survive regardless of treatment assignment. [ Time Frame: 6 months post injury ]
    This complier average causal effect (CACE) analysis will be conducted to estimate the average effect of cooling treatment on the primary outcome for patients who would comply with whichever cooling group they were assigned to, considering both the binary and continuous definitions of compliance with cooling.

  • Mortality [ Time Frame: Hospital Discharge and 6 Months post injury ]
    All Cause Mortality

  • Incidence of adverse events, specifically: o Bleeding o Infection. [ Time Frame: Up to study day 10 ]
    The incidence of adverse events will be measured up to day 10 in both groups. The principle adverse events of interest will be bleeding (intracranial or extracranial) and infection (by site).

  • Health economic evaluation [ Time Frame: 6 Months post injury ]
    Cost-effectiveness from the health-care payer perspective will be calculated as a cost per additional patient with a favourable neurological outcome at 6 months following randomisation (defined as GOSE 5-8) and the cost per additional quality-adjusted life year, with quality-adjusted life years calculated using utility scores derived from the EQ-5D-3L conducted at 6 months post randomisation. Costs will be determined based on resource use during the intensive care, acute and post-acute periods up to six months post-randomisation. Where available, total costs of care provided by the state government through the relevant compensation scheme will be obtained for the subgroup of road trauma patients, and this data will be used to determine the cost per additional QALY and cost per additional favourable neurological outcome in this subgroup.

  • Pre-Specified sub group [ Time Frame: 6 Months post injury ]
    The primary and secondary outcomes will be evaluated according to (i) the presence of surgically evacuated intracranial mass lesions (Marshall score V); and (ii) the presence of any intracranial mass lesion whether or not surgically evacuated (Marshall V or VI).

  • Dose effect / Intensity of cooling [ Time Frame: 6 months post injury ]
    Intensity of cooling in intervention arm patients will be categorised according to the time after randomization to first reach one of two core temperature thresholds, being 35°C and also 34°C. Cooling intensity categories are defined as never achieving hypothermia and tertiles of time in those reaching hypothermia. Primary and secondary outcomes of patients in these intensity categories will be compared across categories and to standard care patients.


Estimated Enrollment: 510
Actual Study Start Date: April 2010
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (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 for 72 hours. Rewarming will occur at a rate of 1C/4hrs and will be titrated to intracranial pressure (ICP) control and BP.
No Intervention: Normothermia
Standard management

Detailed Description:
Eligible patients will be randomised in the pre-hospital setting or on admission to the Emergency Department. POLAR study trained paramedics and physicians will screen patients in the pre-hospital setting. Eligible patients will be randomised if they fulfil the inclusion criteria with no pre-hospital exclusion criteria. Those randomised to the normothermia group will follow standard care. For those randomised to the "cooling arm", pre-hospital prophylactic hypothermia will be induced by exposure and by infusing up to 2 litres intravenous cold (4°C) 0.9% sodium chloride aiming for a core temperature of 35°C during transport. In the emergency department the "cooling arm" patients will be assessed to exclude significant bleeding and, once significant bleeding has been excluded, surface cooling vests/wraps will be applied to reach the target core temperature of 33°C. The patient will be then maintained at this temperature for a further 72 hours. Patients with significant bleeding will have cooling withheld until it is safe to decrease the temperature to the target core temperature of 33°C. Patients who have not been randomised pre-hospital will be re-screened in the ED. Eligible patients will be randomised if they fulfil the inclusion criteria with no ED exclusion criteria. Hypothermia will be induced by administration of up to 2L intravenous ice-cold (4°C) 0.9% sodium chloride followed by application of the surface cooling vests/wraps to achieve the target core temperature of 33°C. Patients allocated to standard `normothermic` care will be maintained at a core temperature of 37°C ± 0.5°C.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
    • 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
    • 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00987688


Contacts
Contact: Tony V Trapani, BEd BEmH RN +61 (0) 409 798 892 tony.trapani@monash.edu
Contact: Lynne Murray +61 (0) 419 155 983 Lynnette.Murray@monash.edu

Locations
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia
Contact: Jason Meyer       Jason.Meyer@health.qld.gov.au   
Principal Investigator: Chris Joyce, MD         
Gold Coast University Hospital Recruiting
Gold Coast, Queensland, Australia
Contact: Elizabeth Wake    : 07 568 74149    Elizabeth.Wake@health.qld.gov.au   
Contact       Martin.Wullschleger@health.qld.gov.au   
Principal Investigator: Martin Wullschleger, Prof         
Australia, Victoria
The Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Deborah Barge       Deborah.Barge@mh.org.au   
Principal Investigator: Chris Macisaac, MD         
Alfred Hospital Recruiting
Prahran, Victoria, Australia, 3004
Contact: Shirley Vallance, RN       s.vallance@alfred.org.au   
Principal Investigator: David J Cooper, Prof         
Australia, Western Australia
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia
Contact: Sharon Waterson       Sharon.Waterson@health.wa.gov.au   
Principal Investigator: Steve Webb, Prof         
France
Hôpital St Jacques + CHRU Besançon Recruiting
Besancon, Franche Comte, France
Contact: Lucie Vettoretti       lvettoretti@chu-besancon.fr   
Principal Investigator: Sebastien Pilifloury, MD         
Hôpital La Cavale Blanche + CHRU Brest Recruiting
Brest, France
Contact: Patricia Dias       patricia.dias@chu-brest.fr   
Principal Investigator: Olivier Huet, Prof         
Hôpital Gabriel Montpied + CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, France
Contact: Lucie Vettoretti       lvettoretti@chu-besancon.fr   
Principal Investigator: Russell Chabanne, Dr         
Hôpital Carémeau + CHU de Nimes Recruiting
Nimes, France
Contact: Lucie Vetteroti, Ms.         
Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre Recruiting
Strasbourg, France
Contact: Lucie Vettoretti       lvettoretti@chu-besancon.fr   
Principal Investigator: Michael Lorich, Prof         
New Zealand
Auckland DCCM Recruiting
Auckland, North Island, New Zealand
Contact: Lynette Newby       LynetteN@adhb.govt.nz   
Principal Investigator: Colin McArthur, Prof         
Waikato District Health Board Suspended
Hamilton, North Island, New Zealand
Qatar
Hamad General Hospital Recruiting
Doha, Qatar
Contact: Bianca a Wahlen, Dr       bwahlen@googlemail.com   
Contact: Ayman ElMenyar, Dr         
Saudi Arabia
King Abdulaziz Medical City Recruiting
Riyadh, Saudi Arabia
Contact: Ahmad Deeb       deebah@NGHA.MED.SA   
Contact: Sami Alsolamy, A/Prof       dr.sami.j@gmail.com   
Switzerland
Inselspital, Bern University Hospital Recruiting
Bern, Switzerland
Contact: Marianne Roth       Marianne.Roth@insel.ch   
Contact       Matthias.Haenggi@insel.ch   
Principal Investigator: Matthais Haenggi, Dr.         
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
Transport Accident Commision, Victoria
Monash University
Délégation à la Recherche Clinique et à l'Innovation (DRCI) CHU Besançon
Investigators
Study Chair: Jamie Cooper, BMBS, MD ANZIC RC
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David James Cooper, Director, ANZIC rc, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT00987688     History of Changes
Other Study ID Numbers: ANZIC-RC/DJC003
First Submitted: September 29, 2009
First Posted: October 1, 2009
Last Update Posted: September 21, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by David James Cooper, Australian and New Zealand Intensive Care Research Centre:
trauma
Brain injury
Pre-hospital
cooling

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