ANZCTR - Registration

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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]

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

Condition category

Condition code

Neurological

Other neurological disorders

Injuries and Accidents

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]

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]

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

Timepoint [1]

6 months post injury

Secondary outcome [1]

Quality of life assessments
*SF-12 (version 1)
*EQ5D

Timepoint [1]

6 months post injury

Secondary outcome [2]

Mortality

Timepoint [2]

6 months post injury, hospital discharge & Intensive Care Unit (ICU)discharge

Secondary outcome [3]

Proportion of favourable (GOSE 5-8) neurological outcomes in survivors

Timepoint [3]

6 months post injury

Secondary outcome [4]

Incidence of adverse events
*Significant bleeding - assessed clinically
*Infection - assessed clinically

Timepoint [4]

Assessed as part of normal intensive care management during the study intervention

Secondary outcome [5]

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]

Day 7 of hospital admission.

Secondary outcome [6]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/04/2010

Actual

20/04/2010

Date of last participant enrolment

Anticipated

1/10/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

500

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,WA,VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment hospital [2]

Royal Melbourne Hospital - Royal Park campus - Parkville

Recruitment hospital [3]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [4]

Royal Perth Hospital - Perth

Recruitment hospital [5]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [6]

Gold Coast University Hospital - Southport

Recruitment postcode(s) [1]

4215 - Southport

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Country [2]

France

State/province [2]

Country [3]

Switzerland

State/province [3]

BERN

Country [4]

Qatar

State/province [4]

Doha

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
GPO BOx 1421
Canberra
ACT 2601

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Victorian Neurotrauma Initiative

Address [2]

PO Box 2314
Geelong
Vic, 3220

Country [2]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Alfred Human Research & Ethics Committee

Ethics committee address [1]

The Alfred
Commercial Rd
Melbourne 
Vic, 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/04/2009

Approval date [1]

28/05/2009

Ethics approval number [1]

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

Prof David 'Jamie' Cooper

Address

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

Australia

Phone

+61 3 99030343

Fax

amanda.martin@monash.edu

Contact person for public queries

Name

MS Lynne Murray

Address

ANZIC-RC
Monash University
Level 3 Burnet Building
89 Commercial Rd
Melbourne
Vic, 3004

Country

Australia

Phone

+61 3 99030513

Fax

+61 3 99030071

Lynnette.Murray@monash.edu

Contact person for scientific queries

Name

Prof Jamie Cooper

Address

ANZIC-RC
Monash University
Level 3 Burnet Building
89 Commercial Rd
Melbourne
Vic, 3004

Country

Australia

Phone

+61 3 90762838

Fax

+61 3 99030071

Jamie.Cooper@alfred.org.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

Current supporting documents:

Updated to:

Doc. No.	Type	Citation	Link	Other Details
23157	Other
23158	Other	Terms of reference / data sharing policy	https://www.monash.edu/__data/assets/pdf_file/0008/1852316/2019-07-23-ANZIC-RC-Terms-of-Ref.pdf
23159	Statistical analysis plan
23160	Informed consent form
23161	Clinical study report
23799	Other			al documents can be requested through the custodia... [More Details]

Results publications and other study-related documents

Documents added manually

Current Study Results

No documents have been uploaded by study researchers.

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4265	Study results article	Yes			308414-(Uploaded-16-09-2019-16-11-07)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Statistical analysis plan for the POLAR-RCT: The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial.	2018	https://dx.doi.org/10.1186/s13063-018-2610-y
Embase	Measured energy expenditure in mildly hypothermic critically ill patients with traumatic brain injury: A sub-study of a randomized controlled trial.	2021	https://dx.doi.org/10.1016/j.clnu.2021.05.012

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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Documents added manually

Documents added automatically