Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

BMC Pediatrics

Renzo Guerrini⁹  Melania Falchi⁹  Tiziana Pisano⁹  Giovanni Cioni⁸  Francesca Tinelli⁸  Gianpaolo Donzelli¹  Maria Luisa Della Bona⁵  Sabrina Malvagia⁵  Giancarlo la Marca⁵  Alberto Spalice⁴  Francesca Del Balzo²  Paola Papoff²  Rosa Scaramuzzo⁶  Matteo Giampietri³  Antonio Boldrini³  Laura Bartalena³  Claudio Fonda⁷  Sara Savelli⁷  Serena Catarzi^1,10  Marta Daniotti^1,10  Patrizio Fiorini^1,10  Luca Filippi^1,10 

[1] Department of Sciences for Woman and Child's Health, University of Florence, “A. Meyer” Children's Hospital, Viale Pieraccini, 24, I-50139, Florence, Italy;Pediatric Emergency and Intensive Care, Department of Pediatrics, La Sapienza University of Rome, Viale del Policlinico, 155, I-00186, Rome, Italy;Neonatal Unit, University of Pisa, Via Roma, 67, I-56126, Pisa, Italy;Division of Child Neurology, Department of Pediatrics, La Sapienza University of Rome, Viale del Policlinico, 155, I-00186, Rome, Italy;Laboratory for diseases of the nervous system and metabolism, “A. Meyer” University Children’s Hospital, Viale Pieraccini, 24, I-50139, Florence, Italy;Istituto di Scienze della Vita, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà, 33, I-56127, Pisa, Italy;Department of Radiological Sciences, “A. Meyer” University Children's Hospital, Viale Pieraccini, 24, I-50139, Florence, Italy;Department of Developmental Neuroscience, Stella Maris Scientific Institute, Viale del Tirreno, 331, I-56128, Calambrone, Pisa, Italy;Paediatric Neurology Unit and Laboratories, “A. Meyer” Children’s Hospital, University of Florence, Viale Pieraccini, 24, I-50139, Florence, Italy;Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department, “A. Meyer” University Children’s Hospital, Viale Pieraccini, 24, I-50139, Florence, Italy

关键词: Topiramate;    Therapeutic hypothermia;    Neonatal hypoxic-ischemic encephalopathy;   

Others  :  1170664
DOI  :  10.1186/1471-2431-12-144

 received in 2012-08-22, accepted in 2012-08-31,  发布年份 2012

【 摘 要 】

Background

Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment.

Methods/Design

Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests.

Discussion

This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns.

Trial registration

Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25

【 授权许可】

   
2012 Filippi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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