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
| Autor: | Edmund Juszczak, Jo Hajnal, Aniko Deierl, Omar Omar, Brenda Strohm, Geoffrey Charles-Edwards, Ernest B. Cady, David Edwards, Alan Bainbridge, Louise Linsell, Gianlorenzo Fagiolo, Mervyn Maze, Nicholas P. Franks, Denis Azzopardi, Nora Tusor, Basil Kapetanakis, James Griffiths, Nicola J. Robertson |
|---|---|
| Přispěvatelé: | Carburos Metalicos S.E.C.M.S.A, Medical Research Council (MRC) |
| Rok vydání: | 2016 |
| Předmět: |
Male
Xenon Outcome Assessment Hypothermia law.invention 0302 clinical medicine Randomized controlled trial Thalamus law Hypothermia Induced Internal Capsule Outcome Assessment Health Care Single-Blind Method BRAIN NEUROPROTECTION Asphyxia Neonatorum SPECTROSCOPY Standard treatment Gestational age Articles Combined Modality Therapy Magnetic Resonance Imaging Inhalation Anesthesia Hypoxia-Ischemia Brain Anesthetics Inhalation Apgar score Female medicine.symptom Acidosis Life Sciences & Biomedicine medicine.medical_specialty FEASIBILITY Resuscitation Clinical Sciences Clinical Neurology 03 medical and health sciences 030225 pediatrics medicine Humans Lactic Acid HYPOXIC-ISCHEMIC ENCEPHALOPATHY Anesthetics Asphyxia ANESTHESIA Aspartic Acid Intention-to-treat analysis Science & Technology Neurology & Neurosurgery PERINATAL ASPHYXIA business.industry Neonatal encephalopathy Induced NEONATAL ENCEPHALOPATHY Neurosciences Infant Newborn Infant SPATIAL STATISTICS 1103 Clinical Sciences medicine.disease Newborn Perinatal asphyxia Surgery VENTILATION Health Care Brain Injuries Apgar Score Feasibility Studies Neurology (clinical) Neurosciences & Neurology business 1109 Neurosciences 030217 neurology & neurosurgery |
| Zdroj: | The Lancet. Neurology, vol 15, iss 2 The Lancet. Neurology Azzopardi, D; Robertson, NJ; Bainbridge, A; Cady, E; Charles-Edwards, G; Deierl, A; et al.(2015). 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. The Lancet Neurology. doi: 10.1016/S1474-4422(15)00347-6. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3fz9m49s Azzopardi, D, Robertson, N J, Bainbridge, A, Cady, E, Charles-Edwards, G, Deierl, A, Fagiolo, G, Franks, N P, Griffiths, J, Hajnal, J, Juszczak, E, Kapetanakis, B, Linsell, L, Maze, M, Omar, O, Strohm, B, Tusor, N & Edwards, A D 2016, ' 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 ', Lancet Neurology, vol. 15, no. 2, pp. 145–153 . https://doi.org/10.1016/S1474-4422(15)00347-6 |
| ISSN: | 1474-4422 |
| DOI: | 10.1016/s1474-4422(15)00347-6 |
| Popis: | © 2015 Azzopardi et al. Open Access article distributed under the terms of CC BY. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|