Clinical trial NCT00282269: Hypothermia in Traumatic Brain Injury in Children (HiTBIC)
Official title: Pilot Study of Early and Prolonged Hypothermia in Severe Traumatic Brain Injury in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Children
Hypothermia
Outcome
Intensive Care
Magnetic resonance Imaging
Lead sponsor: Australia and New Zealand Intensive Care Society
Sponsor class: OTHER
First posted: 2006-01-26
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* have a severe traumatic brain injury as defined by either a GCS ≤ 8 and an abnormal CT scan (intracranial hemorrhage, cerebral edema or diffuse axonal injury) or a motor score ≤ 3 and normal CT scan
* are aged between 1 and 16 years
* are mechanically ventilated

Exclusion Criteria:

* are not randomized by 6 hours after injury
* have penetrating brain injuries
* have fixed dilated pupils and GCS = 3
* have proven cervical spinal cord injury
* have more than mild neurodevelopmental disability prior to injury
* have an acute isolated epidural hematoma and are expected to recover rapidly after surgical removal
* have had a post-traumatic seizure with a normal CT scan
* have refractory shock, defined as systolic blood pressure more than 2 standard deviations (SD) below the mean for age despite 80ml/kg intravenous fluid resuscitation

Primary outcomes:
measure: Paediatric Cerebral Performance Category (PCPC) at 12 months after injury
timeFrame: 12 months
measure: Recruitment Rates
timeFrame: Recruitment completion
measure: Adverse Events
timeFrame: Recruitment completion
Secondary outcomes:
measure: Intracranial pressure(ICP)/Cerebral perfusion pressure(CPP) control
timeFrame: Recruitment completion
measure: Duration of mechanical ventilation
timeFrame: Recruitment completion
measure: Intensive care and hospital length of stay
timeFrame: Recruitment completion
measure: Neuropsychological Outcome
timeFrame: 12 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Royal Alexandra Hospital for Children
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Paediatric Intensive Care Services
state: Queensland
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital
state: Western Australia
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
Study officials:
affiliation: Starship Children's Hospital, Auckland, New Zealand
name: John Beca, FJFICM
role: PRINCIPAL_INVESTIGATOR
References: