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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00987688
Registration number
NCT00987688
Ethics application status
Date submitted
29/09/2009
Date registered
1/10/2009
Date last updated
22/08/2018
Titles & IDs
Public title
The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury
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Scientific 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
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Secondary ID [1]
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ANZIC-RC/DJC003
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Universal Trial Number (UTN)
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Trial acronym
POLAR-RCT
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Brain Injuries, Traumatic
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Condition category
Condition code
Injuries and Accidents
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Other injuries and accidents
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Neurological
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Other neurological disorders
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Skin
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Other skin conditions
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Hypothermia
Experimental: Hypothermia - Early and sustained hypothermia.
No Intervention: Normothermia - Standard management
Other interventions: 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.
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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The proportion of favourable neurological outcomes (Glasgow Outcome Score Extended: GOSE 5 to 8)
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Assessment method [1]
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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).
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Timepoint [1]
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6 months post injury
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Secondary outcome [1]
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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
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Assessment method [1]
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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).
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Timepoint [1]
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6 months post injury
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Secondary outcome [2]
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Quality of life assessments (QOL) o EQ5D o SF12
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Assessment method [2]
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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.
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Timepoint [2]
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6 months post injury
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Secondary outcome [3]
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Average causal effect of hypothermia on GOSE at 6 months comparing hypothermia and control patients who would survive regardless of treatment assignment.
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Assessment method [3]
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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.
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Timepoint [3]
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6 months post injury
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Secondary outcome [4]
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Mortality
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Assessment method [4]
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All Cause Mortality
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Timepoint [4]
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Hospital Discharge and 6 Months post injury
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Secondary outcome [5]
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Incidence of adverse events, specifically: o Bleeding o Infection.
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Assessment method [5]
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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).
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Timepoint [5]
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Up to study day 10
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Secondary outcome [6]
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Health economic evaluation
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Assessment method [6]
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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.
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Timepoint [6]
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6 Months post injury
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Secondary outcome [7]
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Pre-Specified sub group
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Assessment method [7]
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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).
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Timepoint [7]
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6 Months post injury
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Secondary outcome [8]
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Dose effect / Intensity of cooling
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Assessment method [8]
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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.
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Timepoint [8]
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6 months post injury
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
60
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people assessing the outcomes
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Intervention assignment
Parallel
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Other design features
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Phase
Not Applicable
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/04/2010
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
15/06/2018
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Sample size
Target
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Accrual to date
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Final
511
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Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
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Recruitment hospital [1]
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Princess Alexandra Hospital - Brisbane
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Recruitment hospital [2]
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Gold Coast University Hospital - Gold Coast
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Recruitment hospital [3]
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The Royal Melbourne Hospital - Melbourne
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Recruitment hospital [4]
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Alfred Hospital - Prahran
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Recruitment hospital [5]
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Royal Perth Hospital - Perth
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Recruitment postcode(s) [1]
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- Brisbane
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Recruitment postcode(s) [2]
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- Gold Coast
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Recruitment postcode(s) [3]
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- Melbourne
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Recruitment postcode(s) [4]
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3004 - Prahran
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Recruitment postcode(s) [5]
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- Perth
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Recruitment outside Australia
Country [1]
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France
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State/province [1]
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Franche Comte
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Country [2]
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France
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State/province [2]
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Brest
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France
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State/province [3]
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Clermont-Ferrand
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France
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State/province [4]
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Nimes
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Country [5]
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France
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State/province [5]
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Strasbourg
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Country [6]
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New Zealand
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State/province [6]
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North Island
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Country [7]
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Qatar
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State/province [7]
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Doha
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Country [8]
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Saudi Arabia
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State/province [8]
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Riyadh
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Country [9]
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Switzerland
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State/province [9]
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Bern
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Funding & Sponsors
Primary sponsor type
Other
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Name
Australian and New Zealand Intensive Care Research Centre
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Australian and New Zealand Intensive Care Society Clinical Trials Group
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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National Health and Medical Research Council, Australia
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Address [2]
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Country [2]
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Other collaborator category [3]
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Other
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Name [3]
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Transport Accident Commision, Victoria
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Address [3]
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Country [3]
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Other collaborator category [4]
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Other
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Name [4]
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Monash University
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Address [4]
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Other collaborator category [5]
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Other
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Name [5]
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Délégation à la Recherche Clinique et à l'Innovation (DRCI) CHU Besançon
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Address [5]
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Ethics approval
Ethics application status
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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 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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00987688
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Trial related presentations / publications
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.
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.
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Public notes
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Contacts
Principal investigator
Name
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Jamie Cooper, BMBS, MD
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Address
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ANZIC RC
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Phone
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Fax
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Email
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00987688
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