Hypothermia in Traumatic Brain Injury in Children (HiTBIC)

Pilot Study of Early and Prolonged Hypothermia in Severe Traumatic Brain Injury in Children

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).

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Procedure: Induced Hypothermia

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • Sydney Children's Hospital
    • Sydney, New South Wales, Australia
      • Royal Alexandra Hospital for Children
  • Queensland
    • Brisbane, Queensland, Australia
      • Queensland Paediatric Intensive Care Services
  • South Australia
    • Adelaide, South Australia, Australia
      • Women's and Children's Hospital
  • Victoria
    • Melbourne, Victoria, Australia
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia
      • Princess Margaret Hospital
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Paediatric Cerebral Performance Category (PCPC) at 12 months after injury	12 months
Recruitment Rates	Recruitment completion
Adverse Events	Recruitment completion

Secondary Outcome Measures

Outcome Measure	Time Frame
Intracranial pressure(ICP)/Cerebral perfusion pressure(CPP) control	Recruitment completion
Duration of mechanical ventilation	Recruitment completion
Intensive care and hospital length of stay	Recruitment completion
Neuropsychological Outcome	12 months

Collaborators and Investigators

• Sponsor: Australia and New Zealand Intensive Care Society
• Investigators: Principal Investigator: John Beca, FJFICM, Starship Children's Hospital, Auckland, New Zealand

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 25, 2006
• First Submitted That Met QC Criteria: January 25, 2006
• First Posted (Estimate): January 26, 2006

Study Record Updates

• Last Update Posted (Estimate): June 22, 2010
• Last Update Submitted That Met QC Criteria: June 18, 2010
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Children; Outcome; Hypothermia; Intensive Care; Traumatic Brain Injury; Magnetic resonance Imaging
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Body Temperature Changes; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Hypothermia
• Other Study ID Numbers: NTX/06/02/002