Hypothermia in Traumatic Brain Injury in Children (HiTBIC)

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282269
• Other study ID #: NTX/06/02/002
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 25, 2006
• Last updated: June 18, 2010
• Start date: November 2006
• Est. completion date: June 2010

Study information

• Verified date: June 2009
• Source: Australia and New Zealand Intensive Care Society
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia New Zealand: Paediatric Study Group (PSG) of ANZICS Clinical Trials Group (CTG)
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 16 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Hypothermia
• Traumatic Brain Injury

Intervention

Procedure:
• Induced Hypothermia
Induced Hypothermia within 6 hours of injury and maintained for a minimum of 72 hours

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Australia and New Zealand Intensive Care Society

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Paediatric Cerebral Performance Category (PCPC) at 12 months after injury		12 months	Yes
Primary	Recruitment Rates		Recruitment completion	No
Primary	Adverse Events		Recruitment completion	Yes
Secondary	Intracranial pressure(ICP)/Cerebral perfusion pressure(CPP) control		Recruitment completion	Yes
Secondary	Duration of mechanical ventilation		Recruitment completion	Yes
Secondary	Intensive care and hospital length of stay		Recruitment completion	Yes
Secondary	Neuropsychological Outcome		12 months	Yes