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Trial registered on ANZCTR


Registration number
ACTRN12609000764235
Ethics application status
Approved
Date submitted
27/08/2009
Date registered
3/09/2009
Date last updated
11/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The prophylactic hypothermia trial to lessen traumatic brain injury – randomised controlled trial.
Scientific title
Multi-centre randomised trial to evaluate the effect of early hypothermia on neurological function in patients with severe traumatic brain injury.
Secondary ID [1] 291677 0
NCT00987688
Universal Trial Number (UTN)
Trial acronym
POLAR-RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe traumatic brain injury 243599 0
Condition category
Condition code
Neurological 239884 239884 0 0
Other neurological disorders
Injuries and Accidents 239885 239885 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / 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 72hours. Slow rewarming will occur at a rate of 1C/4hrs and will be titrated to intracranial pressure (ICP) control and blood pressure.
Intervention code [1] 241187 0
Treatment: Other
Comparator / control treatment
Standard management patients will be kept at normothermia (37C +/- 0.5C). If they develop a fever >38C they will be treated with paracetamol and surface temperature control equipment will be applied to maintain normothermia for up to 96 hours post randomisation. After 96 hours post randomisation Standard care patients will be managed as per unit protocol. Cooling to 35C is an option for refractory ICP.
Control group
Active

Outcomes
Primary outcome [1] 240670 0
The proportion of favourable neurological outcomes (Glasgow Outcome Score Extended: GOSE 5 to 8)
Timepoint [1] 240670 0
6 months post injury
Secondary outcome [1] 257306 0
Quality of life assessments
*SF-12 (version 1)
*EQ5D
Timepoint [1] 257306 0
6 months post injury
Secondary outcome [2] 257307 0
Mortality
Timepoint [2] 257307 0
6 months post injury, hospital discharge & Intensive Care Unit (ICU)discharge
Secondary outcome [3] 257308 0
Proportion of favourable (GOSE 5-8) neurological outcomes in survivors
Timepoint [3] 257308 0
6 months post injury
Secondary outcome [4] 257309 0
Incidence of adverse events
*Significant bleeding - assessed clinically
*Infection - assessed clinically
Timepoint [4] 257309 0
Assessed as part of normal intensive care management during the study intervention
Secondary outcome [5] 257766 0
Cumulative proportion of patients with Acute Kidney Injury (Injury/Failure Risk Injury Failure Loss End stage (RIFLE) categories) in those receiving cooling v. normothermia
Timepoint [5] 257766 0
Day 7 of hospital admission.
Secondary outcome [6] 257767 0
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. Levels of these biomarkers will be compared in those receiving cooling v. normothermia. Urine NGAL will be measured using the Abbott point-of-care test and other measurements will be performed in accredited laboratories using standardised methods for each biomarker.
Timepoint [6] 257767 0
24hrs, 48 hrs, 72 hrs post Intensive Care admission

Eligibility
Key inclusion criteria
Pre-hospital Inclusion Criteria
*Blunt trauma with clinical diagnosis of severe Traumatic Brain Injury (TBI) and Glasgow Coma Scale <9
*Estimated age = 18 and < 60 years of age
*The patient is intubated or intubation is imminent
Emergency Dept Inclusion Criteria
*Blunt trauma with clinical diagnosis of severe TBI and GCS <9
*Estimated age > or = 18 and < 60 years of age
*The patient is intubated or intubation is imminent
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
***********Pre-hospital Exclusion Criteria
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
Cardiac arrest at the scene or in transit
GCS=3 and un-reactive pupils
Penetrating neck/torso injury
Known or obvious pregnancy
Receiving hospital is not a study site
Evidence of current anti-coagulant treatment
Known to be carer dependent due to a pre-existing neurological condition

***********Emergency Dept Exclusion Criteria
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
Persistent Systolic BP <90mmHg
GCS=3 + un-reactive pupils
Cardiac arrest at the scene or in transit
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
Known to be carer dependent due to a pre-existing neurological condition
In the treating clinician’s opinion, “cooling” is not in the patient’s best interest



Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelope/randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The random allocation sequence will be generated by a computer program. randomisation will be in variable block sizes. Randomisation will be stratified by ambulance base and hospital.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Outcome assessor blinded to treatment allocation
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA,VIC
Recruitment hospital [1] 7824 0
The Alfred - Prahran
Recruitment hospital [2] 7825 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [3] 7826 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 7827 0
Royal Perth Hospital - Perth
Recruitment hospital [5] 7828 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 7829 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 15766 0
4215 - Southport
Recruitment outside Australia
Country [1] 1962 0
New Zealand
State/province [1] 1962 0
Auckland
Country [2] 8792 0
France
State/province [2] 8792 0
Country [3] 8793 0
Switzerland
State/province [3] 8793 0
BERN
Country [4] 8794 0
Qatar
State/province [4] 8794 0
Doha

Funding & Sponsors
Funding source category [1] 237541 0
Government body
Name [1] 237541 0
NHMRC
Address [1] 237541 0
National Health and Medical Research Council
GPO BOx 1421
Canberra
ACT 2601
Country [1] 237541 0
Australia
Funding source category [2] 237542 0
Charities/Societies/Foundations
Name [2] 237542 0
Victorian Neurotrauma Initiative
Address [2] 237542 0
PO Box 2314
Geelong
Vic, 3220
Country [2] 237542 0
Australia
Primary sponsor type
University
Name
Australian and New Zealand Intensive Care-Research Centre, Monash University
Address
Level 3 Burnet building
89 Commercial Rd
Melbourne
Vic, 3004
Country
Australia
Secondary sponsor category [1] 237022 0
None
Name [1] 237022 0
Address [1] 237022 0
Country [1] 237022 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243680 0
The Alfred Human Research & Ethics Committee
Ethics committee address [1] 243680 0
The Alfred
Commercial Rd
Melbourne
Vic, 3004
Ethics committee country [1] 243680 0
Australia
Date submitted for ethics approval [1] 243680 0
16/04/2009
Approval date [1] 243680 0
28/05/2009
Ethics approval number [1] 243680 0
HREC number 154-09

Summary
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 & ventilation, maintaining the fluid balance and draining Cerebrospinal Fluid (CSF) & 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.
Trial website
http://www.anzicrc.monash.org/polar-rct.html
Trial related presentations / publications
Nichol, A., D. Gantner, J. Presneill, L. Murray, T. Trapani, S. Bernard, P. Cameron, G. Capellier, A. Forbes, C. McArthur, L. Newby, S. Rashford, J. V. Rosenfeld, T. Smith, M. Stephenson, D. Varma, T. Walker, S. Webb and D. J. Cooper (2015). "Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury." Crit Care Resusc 17(2): 92-100.
Public notes

Contacts
Principal investigator
Name 30093 0
Prof David 'Jamie' Cooper
Address 30093 0
Australian and New Zealand Intensive Care - Research Centre
School of Public Health and Preventive Medicine
The Department of Epidemiology and Preventive Medicine
Monash University
Level 3, 553 St Kilda Road
Melbourne Vic, 3004
Country 30093 0
Australia
Phone 30093 0
+61 3 99030343
Fax 30093 0
Email 30093 0
amanda.martin@monash.edu
Contact person for public queries
Name 13340 0
Mr MS Lynne Murray
Address 13340 0
ANZIC-RC
Monash University
Level 3 Burnet Building
89 Commercial Rd
Melbourne
Vic, 3004
Country 13340 0
Australia
Phone 13340 0
+61 3 99030513
Fax 13340 0
+61 3 99030071
Email 13340 0
Lynnette.Murray@monash.edu
Contact person for scientific queries
Name 4268 0
Prof Prof Jamie Cooper
Address 4268 0
ANZIC-RC
Monash University
Level 3 Burnet Building
89 Commercial Rd
Melbourne
Vic, 3004
Country 4268 0
Australia
Phone 4268 0
+61 3 90762838
Fax 4268 0
+61 3 99030071
Email 4268 0
Jamie.Cooper@alfred.org.au

No information has been provided regarding IPD availability
'Other' documents specified
al documents can be requested through the custodian
How or where can supporting documents be obtained?
Type [1] 4823 0
Study protocol
Citation [1] 4823 0
on request through the data custodian
Email [1] 4823 0
tony.trapani@monash.edu
Other [1] 4823 0
Attachment [1] 4823 0
Type [2] 4824 0
Other
Citation [2] 4824 0
Terms of reference / data sharing policy
Email [2] 4824 0
Other [2] 4824 0
Attachment [2] 4824 0
Type [3] 4942 0
Statistical analysis plan
Citation [3] 4942 0
Link [3] 4942 0
Email [3] 4942 0
Other [3] 4942 0
Attachment [3] 4942 0
Type [4] 4943 0
Informed consent form
Citation [4] 4943 0
Link [4] 4943 0
Email [4] 4943 0
Other [4] 4943 0
Attachment [4] 4943 0
Type [5] 4944 0
Clinical study report
Citation [5] 4944 0
Link [5] 4944 0
Email [5] 4944 0
Other [5] 4944 0
Attachment [5] 4944 0
Summary results
No Results