Hypothermia in Traumatic Brain Injury in Children (HiTBIC)
The purpose of this study is:
- To determine the safety and feasibility of performing an international multi-centre randomized control trial of early and prolonged hypothermia to improve outcome in children with severe traumatic brain injury (TBI).
- To determine whether in children with severe traumatic brain injury, prolonged initial hypothermia (minimum 72 hours at 32-33 degrees) improves the proportion of good outcomes 12 months after injury when compared to initial normothermia (36-37 degrees).
We propose to do a pilot study of 50 children admitted with severe TBI to paediatric intensive care units in Australia and New Zealand. Severe TBI will be defined as children with either (i) Glasgow Coma Scale (GCS) ≤ 8 and an abnormal CT scan or (ii) motor score of ≤ 3 and normal CT scan. Children will be included only if they can be randomised within 6 hours of the injury occurring. Patients will be stratified a priori by (i) centre and (ii) Glasgow Coma Score. One half will be cooled to 32-33°C for 72 hours and then slowly rewarmed. If intracranial hypertension occurs during or after rewarming, the hypothermia group will have cooling continued until intracranial pressure (ICP) is controlled. The other half will have their temperature maintained at 36-37°C. All other aspects of care will be managed with a standardised protocol.
The purpose of this pilot study is to establish the feasibility of doing an outcome study with other international centres. It will also assess the safety of more prolonged cooling and protocol adherence. Primary outcomes will be the frequency of adverse events related to hypothermia, recruitment rates and protocol adherence. These children may also be able to be included in a larger trial.
The primary aim of the outcome study will be to determine whether, in children with severe TBI, prolonged initial hypothermia improves the proportion with good outcome 12 months after injury when compared to initial normothermia. Outcome will be assessed at 6 and 12 months. The primary outcome measure will be a Paediatric Cerebral Performance Category (PCPC) at 12 months after the date of injury, dichotomized to poor outcome (categories 4-6) and good outcome (categories 1-3). Secondary outcome measures will be (i) PCPC at 6 after injury (ii) standardised tests (intelligence and memory, functional outcome, attention, executive functions) 12 months after injury (iii) ICP and cerebral perfusion pressure (CPP) during the first 5 days of treatment (v) frequency and nature of interventions to control ICP/CPP (vi) duration of mechanical ventilation and (vii) potential adverse events.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Traumatic Brain Injury
Royal Alexandra Hospital for Children
New South Wales
Australia and New Zealand Intensive Care Society
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00282269
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Brain Hemorrhage, Traumatic
Bleeding within the brain as a result of penetrating and nonpenetrating CRANIOCEREBRAL TRAUMA. Traumatically induced hemorrhages may occur in any area of the brain, including the CEREBRUM; BRAIN STEM (see BRAIN STEM HEMORRHAGE, TRAUMATIC); and CEREBELLUM.
Coma, Post-head Injury
Prolonged unconsciousness from which the individual cannot be aroused, associated with traumatic injuries to the BRAIN. This may be defined as unconsciousness persisting for 6 hours or longer. Coma results from injury to both cerebral hemispheres or the RETICULAR FORMATION of the BRAIN STEM. Contributing mechanisms include DIFFUSE AXONAL INJURY and BRAIN EDEMA. (From J Neurotrauma 1997 Oct;14(10):699-713)
Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries.
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Head Injuries, Closed
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
The primary goal of this project is to demonstrate the feasibility and clinical benefits of a new rapid treatment for secondary treatment for secondary brain injury called Discrete Cerebra...
The primary hypothesis for this application for a multicenter phase III randomized clinical trial (RCT) is that induced moderate hypothermia (HYPO) (32-33 °C) after severe traumatic brain...
Induction of hypothermia to < 35˚C by < 2.5 hours after severe traumatic brain injury, reaching 33˚C by 4 hours after injury and maintained for 48 hours in patients aged 16-45 will resul...
The purpose of this trial is to determine if hypothermia (body cooling), administered very soon after a severe brain injury improves functional outcome. This pilot trial ended in July 2005...
The purpose of this study is to determine whether the brains of persons with and without traumatic brain injury differ in a meaningful way when advanced technology images of the brain are...
Traumatic brain injury (TBI) is one of the major causes of disability in modern society. The World Health Organization has predicted that, by 2020, traffic accidents will represent the greatest burden...
Impact of Hypotension and Low Cerebral Perfusion Pressure on Outcomes in Children Treated with Hypothermia Therapy following Severe Traumatic Brain Injury: A post hoc Analysis of the Hypothermia Pediatric Head Injury Trial.
Hypotension and low cerebral perfusion pressure are known to be associated with unfavorable outcome in children and adults with traumatic brain injury. Using the database from a previously published,...
Therapeutic hypothermia promotes protection after traumatic brain injury (TBI). The mechanisms underlying hypothermic protection are multifactorial and may include the modulation of microRNA (miRNA) e...
Combinational therapy using hypothermia and the immunophilin ligand FK506 to target altered pial arteriolar reactivity, axonal damage, and blood-brain barrier dysfunction after traumatic brain injury in rat.
This study evaluated the utility of combinational therapy, coupling delayed posttraumatic hypothermia with delayed FK506 administration, on altered cerebral vascular reactivity, axonal injury, and blo...
Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain...