Traumatic Brain InjuryPhase 3NCT00222742
Hypothermia in Children After Trauma
A Phase 3 study testing induced moderate hypothermia in people with Traumatic Brain Injury, run by Phoenix Children's Hospital at 30 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- induced moderate hypothermia
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 30 sitesin 6 countries
- Study dates
- Nov 2007to Mar 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients with a GCS </= 8
- Glasgow Motor Score < 6
- Closed head injury
- Age 0 < 18 y
Who cannot join
- Unavailable to initiate cooling within 6 hours of injury
- Glasgow Coma Scale (GCS) score = 3 and abnormal brainstem function
- Normal initial CT scan (No blood, fracture, swelling, and/or shift)
- Penetrating brain injury
- No known mechanism of injury
- Unknown time of injury
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- Uncorrectable coagulopathy (PT/PTT > 16/40 sec, INR > 1.7)
- Hypotensive episode (Systolic Blood Pressure <5th percentile for age>10 min)
- Documented Hypoxic episode (O2 saturation < 94% for > 30 min)
- Pregnancy
Trial locations and contacts
30 sites in 6 countries.
30 sites in 6 countries
United States17 sites
Carolinas Medical Center
Charlotte, North Carolina, 28203
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 47229-3039
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas, Southwestern
Dallas, Texas, 75235
Duke University
Durham, North Carolina, 27710
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Miami
Miami, Florida, 33136
Cohen's Children's Hospital
New Hyde Park, New York, 11040
Weill Cornell Medical Center
New York, New York, 10950
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
University of Pittsburgh/Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of California, Davis Medical Center
Sacramento, California, 95817
University of Washington
Seattle, Washington, 98104
Washington University
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Australia7 sites
Royal Children's Hospital, Brisbane
Brisbane, Queensland, 4029
Mater Children's Hospital
Brisbane, Queensland, 4101
Children's Youth and Women's Health Service
North Adelaide, South Australia, 5006
Royal Children's Hospital Melbourne
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Subiaco, Perth, Western Australia, 6008
Sydney Children's Hospital, Randwick
Sydney, New South Wales, 2031
Children's Hospital at Westmead
Westmead, New South Wales, 2145
Canada2 sites
Stollery Children's Hospital
Edmonton, Alberta, T6G2B7
British Columbia Children's Hospital
Vancouver, British Columbia, V4A 5X3
United Kingdom2 sites
Birmingham Children's Hospital
Birmingham, West Midlands, UK B4 6NH
Institute of Child Health, Univ. College London & Great Ormond
Bloomsbury, London, WC1N 3JH
About this study
Official title: 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).
Read the 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).
- Conditions
- Traumatic Brain Injury
- Being tested
- induced moderate hypothermia
- Keywords
- hypothermia, pediatric TBI
- Medical subject headings
- Brain Injuries, Traumatic, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
induced moderate hypothermiaProcedure or surgery
Subjects assigned to the treatment arm will be cooled to 32-33 °C for 48 hours and then slowly warmed.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Induced moderate hypothermia (32-33 C) Receives: Procedure: induced moderate hypothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 month post injury
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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).
Measured: 7 days post injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startNov 2007
- Primary completionMay 2011
- Study completionMar 2012
Why it stopped: Futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phoenix Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- P. David Adelson, MD, Principal investigator, Phoenix Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00222742
- Sponsor's protocol ID
- 1R01-NS052478-01
- Other IDs
- 1R01NS052478-01
- Status last verified
- Jul 2012
- First submitted
- 16 Sep 2005
- Last updated
- 11 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 29370008Adelson 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.
PubMed 23664370
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric Traumatic Brain Injury Consortium: Hypothermia
- ClinicalTrials.gov ID
- NCT00222742
- Acronym / sponsor ID
- 1R01-NS052478-01
- Conditions
- Traumatic Brain Injury
- Keywords
- hypothermia, pediatric TBI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Phoenix Children's HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Nov 2007
- Primary completion
- May 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Procedure: induced moderate hypothermiaInduced moderate hypothermia (32-33 C) |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Patients with a GCS </= 8
- Glasgow Motor Score < 6
- Closed head injury
- Age 0 < 18 y
Key exclusion criteria (10 listed)
- Unavailable to initiate cooling within 6 hours of injury
- Glasgow Coma Scale (GCS) score = 3 and abnormal brainstem function
- Normal initial CT scan (No blood, fracture, swelling, and/or shift)
- Penetrating brain injury
- No known mechanism of injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| induced moderate hypothermiaSubjects assigned to the treatment arm will be cooled to 32-33 °C for 48 hours and then slowly warmed. | Procedure or surgery | A |
Primary outcome
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.
Time frame: 3 month post injury
3 secondary outcomes
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.
Time frame: 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.
Time frame: 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).
Time frame: 7 days post injury
Results and safety
The study was stopped early (reason given: Futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2012.
- Derived from this study: PubMed 29370008Meinert 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.
- Derived from this study: PubMed 23664370Adelson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
P. David Adelson, MD principal investigator
Phoenix Children's Hospital
30 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing induced moderate hypothermia in people with Traumatic Brain Injury, run by Phoenix Children's Hospital at 30 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Australia, Canada, United Kingdom, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Futility). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 3 month post injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00222742, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2012.