Hypothermia in Traumatic Brain Injury in Children (HiTBIC)

June 18, 2010 updated by: Australia and New Zealand Intensive Care Society

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)

Phase

Phase 2
Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 16 years (Child)

Accepts Healthy Volunteers

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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 Time Frame: 12 months	12 months
Recruitment Rates Time Frame: Recruitment completion	Recruitment completion
Adverse Events Time Frame: Recruitment completion	Recruitment completion

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Australia and New Zealand Intensive Care Society

Investigators

Principal Investigator: John Beca, FJFICM, Starship Children's Hospital, Auckland, New Zealand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)