title: Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study.
abstract: OBJECTIVE
  To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE).
  
  
  METHODS
  Multicenter randomized controlled trial. Term newborns with precocious metabolic, clinical and electroencephalographic (EEG) signs of HIE were selected according to their amplified integrated EEG pattern and randomized to receive either TPM (10 mg/kg once a day for the first three days of life) plus moderate hypothermia or hypothermia alone. Safety was assessed by monitoring cardiorespiratory parameters and blood samples collected to check renal, liver, metabolic balance and TPM pharmacokinetics. Efficacy was evaluated by the combined frequency of mortality and severe neurological disability as primary outcome. Incidence of magnetic resonance injury, epilepsy, blindness, hearing loss, neurodevelopment at 18-24 months of life was assessed as secondary outcomes.
  
  
  RESULTS
  Forty-four asphyxiated newborns were enrolled in the study. Twenty one newborns (10 with moderate and 11 with severe HIE) were allocated to hypothermia plus TPM and 23 (12 moderate and 11 severe HIE) to hypothermia. No statistically or clinically significant differences were observed for safety, primary or secondary outcomes. However, a reduction in the prevalence of epilepsy was observed in newborns co-treated with TPM.
  
  
  CONCLUSIONS
  Results of this pilot trial suggest that administration of TPM in newborns with HIE is safe but does not reduce the combined frequency of mortality and severe neurological disability. The role of TPM co-treatment in preventing subsequent epilepsy deserves further studies.
authors.affiliation: a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
authors.affiliation: a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Fiorini
authors.affiliation: a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Catarzi
authors.affiliation: a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Elettra
authors.initials: E
authors.lastname: Berti
authors.affiliation: a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Padrini
authors.affiliation: b Department of Health Sciences, Section of Clinical Pharmacology and Oncology , University of Florence , Florence , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Landucci
authors.affiliation: c Department of Neurofarba , University of Florence , Florence , Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Donzelli
authors.affiliation: d Neonatal Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bartalena
authors.affiliation: d Neonatal Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Fiorentini
authors.affiliation: d Neonatal Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Boldrini
authors.affiliation: d Neonatal Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Giampietri
authors.affiliation: d Neonatal Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Rosa Teresa
authors.initials: RT
authors.lastname: Scaramuzzo
authors.affiliation: e Laboratory for Diseases of the Nervous System and Metabolism , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.affiliation: e Laboratory for Diseases of the Nervous System and Metabolism , "A. Meyer" University Children's Hospital , Florence , Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Della Bona
authors.affiliation: f Department of Developmental Neuroscience , Stella Maris Scientific Institute , Pisa , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fiori
authors.affiliation: f Department of Developmental Neuroscience , Stella Maris Scientific Institute , Pisa , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tinelli
authors.affiliation: f Department of Developmental Neuroscience , Stella Maris Scientific Institute , Pisa , Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Bancale
authors.affiliation: f Department of Developmental Neuroscience , Stella Maris Scientific Institute , Pisa , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guzzetta
authors.affiliation: f Department of Developmental Neuroscience , Stella Maris Scientific Institute , Pisa , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cioni
authors.affiliation: g Pediatric Neurology Unit and Laboratories , "A. Meyer" Children's Hospital, University of Florence , Florence , Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pisano
authors.affiliation: g Pediatric Neurology Unit and Laboratories , "A. Meyer" Children's Hospital, University of Florence , Florence , Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Falchi
authors.affiliation: g Pediatric Neurology Unit and Laboratories , "A. Meyer" Children's Hospital, University of Florence , Florence , Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D005240:Feasibility Studies; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose
keywords: Newborn; asphyxia; hypoxic-ischemic encephalopathy; neuroprotection