Hypothermia in Children After Trauma

Pediatric Traumatic Brain Injury Consortium: Hypothermia

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 injury (TBI) in children and maintained for 48 hours will improve mortality at 3 months and 12 month functional outcome as assessed by the Glasgow Outcome Scale (GOS).

Study Overview

• Status: Terminated
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Procedure: induced moderate hypothermia

Detailed Description

The primary specific aim of this RCT is to determine the effect of induced moderate HYPO (32-33 °C) after severe TBI in children on mortality at 3 months post injury. The primary outcome measure will be the GOS; the primary time point for evaluation is 3 months. Further secondary functional outcome measures will include the GOS - Extended Pediatrics (GOS - E Peds), and Vineland Adaptive Behavior Scale (VABS) and will be assessed in conjunction with the GOS at 6 and 12 months post injury.

The secondary hypotheses are based on the results and analysis of the Pilot Clinical Trial (completed and recently published [Adelson et al. NEUROSURGERY. 56 (4): 740-754, 2005]). These secondary hypotheses include that induced moderate hypothermia (HYPO) (32-33 °C) after severe TBI in children and maintained for 48 h:

• will improve other outcome assessments including neurocognitive status on performance-based neuropsychological testing across the domains of intellectual development, learning and memory, language, motor and psychomotor skills, visuo-spatial abilities, attention and executive function, and behavior at only 6 and 12 months after injury;
• HYPO will improve long term outcome of all age ranges and across genders in infants, young, preadolescent, and adolescent children; AND
• HYPO will lessen intracranial hypertension and lessen the intensity of therapy necessary for control of ICP.

Based on these hypotheses, further secondary specific aims are proposed:

• Specific Aim 2: To determine the effect of early induced moderate HYPO (32-33°C) after severe TBI in children on global function and neurocognitive outcomes in the areas of intellectual ability/ development, memory and learning, and behavior at 6 and 12 months post injury.
• Specific Aim 3: To determine the effect of early induced moderate HYPO after severe TBI in children of different age ranges (< 6 y and 6- < 16 y) on mortality and 6 and 12 months functional and neurocognitive outcomes.
• Specific Aim 4: To determine the effect of early moderate HYPO after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Sydney Children's Hospital, Randwick
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Children's Hospital, Brisbane
    • Brisbane, Queensland, Australia, 4101
      • Mater Children's Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Children's Youth and Women's Health Service
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne
  • Western Australia
    • Subiaco, Perth, Western Australia, Australia, 6008
      • Princess Margaret Hospital for Children
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2B7
      • Stollery Children'S Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V4A 5X3
      • British Columbia Children's Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Starship Children's Hospital
• South Africa
  • Cape Town
    • Rondebosch, Cape Town, South Africa, 7700
      • University of Cape Town
• United Kingdom
  • London
    • Bloomsbury, London, United Kingdom, WC1N 3JH
      • Institute of Child Health, Univ. College London & Great Ormond
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, UK B4 6NH
      • Birmingham Children's Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen's Children's Hospital
    • New York, New York, United States, 10950
      • Weill Cornell Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 47229-3039
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh/Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas, Southwestern
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with a GCS </= 8
2. Glasgow Motor Score < 6
3. Closed head injury
4. Age 0 < 18 y

Exclusion Criteria

1. Unavailable to initiate cooling within 6 hours of injury
2. Glasgow Coma Scale (GCS) score = 3 and abnormal brainstem function
3. Normal initial CT scan (No blood, fracture, swelling, and/or shift)
4. Penetrating brain injury
5. No known mechanism of injury
6. Unknown time of injury
7. Uncorrectable coagulopathy (PT/PTT > 16/40 sec, INR > 1.7)
8. Hypotensive episode (Systolic Blood Pressure <5th percentile for age>10 min)
9. Documented Hypoxic episode (O2 saturation < 94% for > 30 min)
10. Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Induced moderate hypothermia (32-33 C)	Procedure: induced moderate hypothermia; Subjects assigned to the treatment arm will be cooled to 32-33 °C for 48 hours and then slowly warmed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary specific aim of this RCT is to determine the effect of induced moderate HYPO (32-33 °C) after severe TBI in children on mortality.	3 month post injury

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the effect of HYPO after severe TBI in children on global function and neurocognitive outcomes in the areas of intellectual ability/development, memory and learning, and behavior.	at 6 and 12 months post injury
To determine the effect of HYPO after severe TBI in children of different age ranges (< 6y; 6-<16y; and 16-<18y) on mortality and 6 and 12 months functional and neurocognitive outcomes.	3, 6 and 12 months post injury
To determine the effect of HYPO after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).	7 days post injury

Collaborators and Investigators

• Sponsor: Phoenix Children's Hospital
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: P. David Adelson, MD, Phoenix Children's Hospital

Publications and helpful links

General Publications

• Meinert E, Bell MJ, Buttram S, Kochanek PM, Balasubramani GK, Wisniewski SR, Adelson PD; Pediatric Traumatic Brain Injury Consortium: Hypothermia Investigators. Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia. Pediatr Crit Care Med. 2018 Apr;19(4):345-352. doi: 10.1097/PCC.0000000000001471.
• Adelson PD, Wisniewski SR, Beca J, Brown SD, Bell M, Muizelaar JP, Okada P, Beers SR, Balasubramani GK, Hirtz D; Paediatric Traumatic Brain Injury Consortium. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial. Lancet Neurol. 2013 Jun;12(6):546-53. doi: 10.1016/S1474-4422(13)70077-2. Epub 2013 May 8.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): July 11, 2012
• Last Update Submitted That Met QC Criteria: July 10, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: hypothermia; pediatric TBI
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Body Temperature Changes; Brain Injuries; Brain Injuries, Traumatic; Hypothermia
• Other Study ID Numbers: 1R01-NS052478-01; 1R01NS052478-01