Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial

Lancet Neurology
Ronit M PresslerNEonatal seizure treatment with Medication Off-patent (NEMO) consortium

Abstract

Preclinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov, number NCT01434225. Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephal...Continue Reading

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References

Nov 1, 1981·Journal of Clinical Pharmacology·R E BrummettD Himes
Jan 1, 1997·Biology of the Neonate·A M Lopez-SamblasM W Modi
Aug 12, 1999·The New England Journal of Medicine·M J PainterJ Alvin
Jan 24, 2002·Therapeutic Drug Monitoring·Gérard PonsYann Merlé
Oct 14, 2005·The New England Journal of Medicine·Seetha ShankaranUNKNOWN National Institute of Child Health and Human Development Neonatal Research Network
Oct 18, 2005·Nature Medicine·Volodymyr I DzhalaKevin J Staley
Sep 14, 2006·Statistics in Medicine·Sarah Zohar, John O'Quigley
Nov 18, 2006·Lancet Neurology·Yehezkel Ben-Ari, Gregory L Holmes
Dec 7, 2007·Journal of the Association for Research in Otolaryngology : JARO·Ruth Rebecca TaylorAndrew Forge
Jul 22, 2008·Pediatric Neurology·Faye S Silverstein, Donna M Ferriero
Oct 3, 2009·The New England Journal of Medicine·Denis V AzzopardiUNKNOWN TOBY Study Group
Apr 3, 2013·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Tammy N TsuchidaUNKNOWN American Clinical Neurophysiology Society Critical Care Monitoring Committee
May 22, 2013·Seminars in Fetal & Neonatal Medicine·Ronit M Pressler, B Mangum
May 28, 2013·Seminars in Fetal & Neonatal Medicine·Geraldine B BoylanSampsa Vanhatalo
Jul 28, 2013·The Journal of Pediatrics·Elisa SmitMarianne Thoresen

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Citations

Oct 10, 2015·The European Journal of Neuroscience·S K KangS D Kadam
Jan 7, 2016·Annals of Clinical and Translational Neurology·Joseph Glykys, Kevin J Staley
Jan 7, 2016·Annals of Clinical and Translational Neurology·Nathan J StevensonGeraldine B Boylan
Dec 18, 2015·European Journal of Pharmacology·Maria D DonovanBrendan T Griffin
Nov 26, 2015·Nature Medicine·Stephan Lawrence MarguetDirk Isbrandt
Nov 17, 2015·Seizure : the Journal of the British Epilepsy Association·Niamh E LynchGeraldine B Boylan
Mar 12, 2016·Nature Reviews. Neurology·Gilles Huberfeld, Charles J Vecht
Mar 18, 2016·Neuron·Nicolas DoyonYves De Koninck
Mar 25, 2016·Expert Review of Neurotherapeutics·Chao DuXuenfeng Wang
May 6, 2016·Frontiers in Cellular Neuroscience·Yehezkel Ben-AriEric Lemonnier
Apr 29, 2015·Nature Reviews. Neurology·Marianne Thoresen, Hemmen Sabir
Mar 15, 2015·Lancet Neurology·Hannah C Glass
Jul 3, 2016·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Lauren C WeekeUNKNOWN NEonatal seizure treatment with Medication Off -patent (NEMO)consortium
Sep 7, 2016·Current Neurology and Neuroscience Reports·Tristan T Sands, Tiffani L McDonough
Sep 15, 2016·Expert Opinion on Drug Metabolism & Toxicology·Anne SmitsKarel Allegaert
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Abhishek BanerjeeMriganka Sur
Nov 18, 2016·Nature Communications·Hannah AlfonsaAndrew J Trevelyan
Nov 20, 2016·Journal of Neurochemistry·Miguel A S Martín-Aragón BaudelMark G Darlison
Nov 9, 2016·PloS One·Nathan J StevensonSampsa Vanhatalo
Apr 6, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Knut KirmseKnut Holthoff
Oct 6, 2016·Statistical Methods in Medical Research·Caroline PetitSarah Zohar
Apr 30, 2017·The European Journal of Neuroscience·Yuri BozziSimona Casarosa
Jan 14, 2017·Neuropharmacology·Natalia Rodriguez-AlvarezDavid C Henshall
Apr 9, 2017·Archives of Disease in Childhood. Fetal and Neonatal Edition·Kathryn MartinelloNicola J Robertson
Aug 5, 2017·Paediatric Drugs·Elissa YozawitzRonit M Pressler
Dec 15, 2017·Frontiers in Cellular Neuroscience·Sergei KirischukWerner Kilb
Aug 12, 2015·World Journal of Clinical Pediatrics·Maggie Lo-Yee YauPak Cheung Ng
Aug 24, 2018·Developmental Neurobiology·Shivani C KharodShilpa D Kadam
Dec 2, 2017·Archives of Disease in Childhood. Fetal and Neonatal Edition·Anthony Richard Hart, James J P Alix
Nov 8, 2018·Expert Opinion on Pharmacotherapy·Alessandra MoranoCarlo Di Bonaventura
Dec 9, 2017·Epilepsy Currents·Laura A Jansen
Feb 23, 2019·Epilepsia·Hannah C GlassUNKNOWN Neonatal Seizure Registry study group
Nov 2, 2018·Italian Journal of Pediatrics·Carlotta SpagnoliFrancesco Pisani
Jan 23, 2020·Epilepsy Currents·Stephen F TraynelisUNKNOWN National Institutes of Neurological Disorders and Stroke (NINDS)/American Epilepsy Society (AES) Epilepsy Research Benchmark
Jan 13, 2016·Clinical Neuropharmacology·Philippe DamierYeheskel Ben-Ari
Oct 6, 2015·Epilepsia·Renzo GuerriniIngmar Blumcke
Jul 3, 2016·Cold Spring Harbor Perspectives in Medicine·Gregory L Holmes, Jeffrey L Noebels

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