Clinical trial NCT00222742: Hypothermia in Children After Trauma
Official title: Pediatric Traumatic Brain Injury Consortium: Hypothermia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Traumatic Brain Injury
Keywords: hypothermia
pediatric TBI
Lead sponsor: Phoenix Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2005-09-22
Enrollment: 90
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 month post injury
Secondary outcomes:
measure: 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.
timeFrame: at 6 and 12 months post injury
measure: 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.
timeFrame: 3, 6 and 12 months post injury
measure: To determine the effect of HYPO after severe TBI in children on reducing intracranial hypertension and maintaining adequate cerebral perfusion pressure (CPP).
timeFrame: 7 days post injury
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New Hyde Park
country: United States
facility: Cohen's Children's Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh/Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas, Southwestern
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Sydney
country: Australia
facility: Sydney Children's Hospital, Randwick
state: New South Wales
city: Westmead
country: Australia
facility: Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Children's Hospital, Brisbane
state: Queensland
city: Brisbane
country: Australia
facility: Mater Children's Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Children's Youth and Women's Health Service
state: South Australia
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne
state: Victoria
city: Subiaco, Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Rondebosch
country: South Africa
facility: University of Cape Town
state: Cape Town
city: Bloomsbury
country: United Kingdom
facility: Institute of Child Health, Univ. College London & Great Ormond
state: London
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
Study officials:
affiliation: Phoenix Children's Hospital
name: P. David Adelson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.