Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): A phase 3, randomised controlled trial

P. David Adelson, Stephen R. Wisniewski, John Beca, S. Danielle Brown, Michael Bell, J. Paul Muizelaar, Pamela Okada, Sue R. Beers, Goundappa K. Balasubramani, Deborah Hirtz

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)546-553
Number of pages8
JournalThe Lancet Neurology
Volume12
Issue number6
DOIs
StatePublished - Jun 2013

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Glasgow Outcome Scale
Hypothermia
Randomized Controlled Trials
Pediatrics
Rewarming
Mortality
Wounds and Injuries
National Institute of Neurological Disorders and Stroke
Medical Futility
Induced Hypothermia
Child Mortality
Intention to Treat Analysis
Traumatic Brain Injury
National Institutes of Health (U.S.)
Random Allocation
Brain Injuries
Research Personnel

ASJC Scopus subject areas

  • Clinical Neurology

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Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids) : A phase 3, randomised controlled trial. / Adelson, P. David; Wisniewski, Stephen R.; Beca, John; Brown, S. Danielle; Bell, Michael; Muizelaar, J. Paul; Okada, Pamela; Beers, Sue R.; Balasubramani, Goundappa K.; Hirtz, Deborah.

In: The Lancet Neurology, Vol. 12, No. 6, 06.2013, p. 546-553.

Research output: Contribution to journalArticle

Adelson, PD, Wisniewski, SR, Beca, J, Brown, SD, Bell, M, Muizelaar, JP, Okada, P, Beers, SR, Balasubramani, GK & Hirtz, D 2013, 'Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): A phase 3, randomised controlled trial', The Lancet Neurology, vol. 12, no. 6, pp. 546-553. https://doi.org/10.1016/S1474-4422(13)70077-2
Adelson, P. David ; Wisniewski, Stephen R. ; Beca, John ; Brown, S. Danielle ; Bell, Michael ; Muizelaar, J. Paul ; Okada, Pamela ; Beers, Sue R. ; Balasubramani, Goundappa K. ; Hirtz, Deborah. / Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids) : A phase 3, randomised controlled trial. In: The Lancet Neurology. 2013 ; Vol. 12, No. 6. pp. 546-553.
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abstract = "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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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

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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