TY - JOUR
T1 - Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids)
T2 - A phase 3, randomised controlled trial
AU - Adelson, P. David
AU - Wisniewski, Stephen R.
AU - Beca, John
AU - Brown, S. Danielle
AU - Bell, Michael
AU - Muizelaar, J. Paul
AU - Okada, Pamela
AU - Beers, Sue R.
AU - Balasubramani, Goundappa K.
AU - Hirtz, Deborah
N1 - Funding Information:
SRW has received grant support from Eli Lilly and has done consulting for Cyberonics Inc, lmaRx Therapeutics Inc, Bristol-Myers Squibb Company, Organon, Case-Western University, Singapore Clinical Research Institute, Dey Pharmaceuticals, and Venebio. All other authors declare that they have no conflicts of interest.
Funding Information:
We thank the National Institute of Neurological Disorders and Stroke and the National Institutes of Health (NIHU01NS052478) for funding this project, and all the members of the Paediatric Traumatic Brain Injury Consortium for their support and willingness to participate in this study. Additionally, we would like to thank the Data and Safety Monitoring Board for their oversight and counsel during the course of this trial. We would also like to thank Christina Casanova for administrative assistance in the preparation of this paper.
PY - 2013/6
Y1 - 2013/6
N2 - Background: On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury. Methods: In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. Findings: The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. Interpretation: Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. Funding: National Institute of Neurological Disorders and Stroke and National Institutes of Health.
AB - Background: On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury. Methods: In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742. Findings: The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events. Interpretation: Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury. Funding: National Institute of Neurological Disorders and Stroke and National Institutes of Health.
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U2 - 10.1016/S1474-4422(13)70077-2
DO - 10.1016/S1474-4422(13)70077-2
M3 - Article
C2 - 23664370
AN - SCOPUS:84877919716
SN - 1474-4422
VL - 12
SP - 546
EP - 553
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 6
ER -