The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury (POLAR-RCT)
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|ClinicalTrials.gov Identifier: NCT00987688|
Recruitment Status : Active, not recruiting
First Posted : October 1, 2009
Last Update Posted : June 19, 2018
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 or disease||Intervention/treatment||Phase|
|Brain Injuries, Traumatic||Other: Hypothermia||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||511 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|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|
|Actual Study Start Date :||April 2010|
|Actual Primary Completion Date :||November 10, 2017|
|Estimated Study Completion Date :||June 2018|
Early and sustained 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
- 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).
- 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.
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
|Princess Alexandra Hospital|
|Brisbane, Queensland, Australia|
|Gold Coast University Hospital|
|Gold Coast, Queensland, Australia|
|The Royal Melbourne Hospital|
|Melbourne, Victoria, Australia|
|Prahran, Victoria, Australia, 3004|
|Australia, Western Australia|
|Royal Perth Hospital|
|Perth, Western Australia, Australia|
|Hôpital St Jacques + CHRU Besançon|
|Besancon, Franche Comte, France|
|Hôpital La Cavale Blanche + CHRU Brest|
|Hôpital Gabriel Montpied + CHU Clermont-Ferrand|
|Hôpital Carémeau + CHU de Nimes|
|Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre|
|Auckland, North Island, New Zealand|
|Waikato District Health Board|
|Hamilton, North Island, New Zealand|
|Hamad General Hospital|
|King Abdulaziz Medical City|
|Riyadh, Saudi Arabia|
|Inselspital, Bern University Hospital|
|Study Chair:||Jamie Cooper, BMBS, MD||ANZIC RC|