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Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxi...

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Autores principales: Azzopardi, Denis, Robertson, Nicola J, Bainbridge, Alan, Cady, Ernest, Charles-Edwards, Geoffrey, Deierl, Aniko, Fagiolo, Gianlorenzo, Franks, Nicholas P, Griffiths, James, Hajnal, Joseph, Juszczak, Edmund, Kapetanakis, Basil, Linsell, Louise, Maze, Mervyn, Omar, Omar, Strohm, Brenda, Tusor, Nora, Edwards, A David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lancet Pub. Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710577/
https://www.ncbi.nlm.nih.gov/pubmed/26708675
http://dx.doi.org/10.1016/S1474-4422(15)00347-6
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author Azzopardi, Denis
Robertson, Nicola J
Bainbridge, Alan
Cady, Ernest
Charles-Edwards, Geoffrey
Deierl, Aniko
Fagiolo, Gianlorenzo
Franks, Nicholas P
Griffiths, James
Hajnal, Joseph
Juszczak, Edmund
Kapetanakis, Basil
Linsell, Louise
Maze, Mervyn
Omar, Omar
Strohm, Brenda
Tusor, Nora
Edwards, A David
author_facet Azzopardi, Denis
Robertson, Nicola J
Bainbridge, Alan
Cady, Ernest
Charles-Edwards, Geoffrey
Deierl, Aniko
Fagiolo, Gianlorenzo
Franks, Nicholas P
Griffiths, James
Hajnal, Joseph
Juszczak, Edmund
Kapetanakis, Basil
Linsell, Louise
Maze, Mervyn
Omar, Omar
Strohm, Brenda
Tusor, Nora
Edwards, A David
author_sort Azzopardi, Denis
collection PubMed
description BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. FINDINGS: The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. INTERPRETATION: Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. FUNDING: UK Medical Research Council.
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spelling pubmed-47105772016-02-11 Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial Azzopardi, Denis Robertson, Nicola J Bainbridge, Alan Cady, Ernest Charles-Edwards, Geoffrey Deierl, Aniko Fagiolo, Gianlorenzo Franks, Nicholas P Griffiths, James Hajnal, Joseph Juszczak, Edmund Kapetanakis, Basil Linsell, Louise Maze, Mervyn Omar, Omar Strohm, Brenda Tusor, Nora Edwards, A David Lancet Neurol Articles BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. FINDINGS: The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. INTERPRETATION: Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. FUNDING: UK Medical Research Council. Lancet Pub. Group 2016-02 /pmc/articles/PMC4710577/ /pubmed/26708675 http://dx.doi.org/10.1016/S1474-4422(15)00347-6 Text en © 2016 Azzopardi et al. Open Access article distributed under the terms of CC BY http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Azzopardi, Denis
Robertson, Nicola J
Bainbridge, Alan
Cady, Ernest
Charles-Edwards, Geoffrey
Deierl, Aniko
Fagiolo, Gianlorenzo
Franks, Nicholas P
Griffiths, James
Hajnal, Joseph
Juszczak, Edmund
Kapetanakis, Basil
Linsell, Louise
Maze, Mervyn
Omar, Omar
Strohm, Brenda
Tusor, Nora
Edwards, A David
Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title_full Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title_fullStr Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title_full_unstemmed Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title_short Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial
title_sort moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (toby-xe): a proof-of-concept, open-label, randomised controlled trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710577/
https://www.ncbi.nlm.nih.gov/pubmed/26708675
http://dx.doi.org/10.1016/S1474-4422(15)00347-6
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