Filippi Luca, Fiorini Patrizio, Catarzi Serena, Berti Elettra, Padrini Letizia, Landucci Elisa, Donzelli Gianpaolo, Bartalena Laura, Fiorentini Erika, Boldrini Antonio, Giampietri Matteo, Scaramuzzo Rosa Teresa, la Marca Giancarlo, Della Bona Maria Luisa, Fiori Simona, Tinelli Francesca, Bancale Ada, Guzzetta Andrea, Cioni Giovanni, Pisano Tiziana, Falchi Melania, Guerrini Renzo
a Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department , "A. Meyer" University Children's Hospital , Florence , Italy.
b Department of Health Sciences, Section of Clinical Pharmacology and Oncology , University of Florence , Florence , Italy.
J Matern Fetal Neonatal Med. 2018 Apr;31(8):973-980. doi: 10.1080/14767058.2017.1304536. Epub 2017 Mar 28.
To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE).
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.
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.
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.
探讨在缺氧缺血性脑病（HIE）新生儿中，基于托吡酯（TPM）联合中度低温治疗开展一项研究的可行性。
多中心随机对照试验。根据其放大的脑电图模式，选择具有HIE早熟代谢、临床和脑电图（EEG）体征的足月儿，并随机分为接受TPM（出生后前三天每天10mg/kg）联合中度低温治疗组或仅接受低温治疗组。通过监测心肺参数和采集血样以检查肾脏、肝脏、代谢平衡及TPM药代动力学来评估安全性。以死亡率和严重神经功能障碍的联合发生率作为主要结局指标评估疗效。将磁共振损伤、癫痫、失明、听力损失、18 - 24个月龄时的神经发育情况的发生率作为次要结局指标进行评估。
44例窒息新生儿纳入研究。21例新生儿（10例中度HIE和11例重度HIE）被分配至低温联合TPM治疗组，23例（12例中度HIE和11例重度HIE）被分配至低温治疗组。在安全性、主要或次要结局指标方面未观察到统计学或临床显著差异。然而，联合TPM治疗的新生儿癫痫患病率有所降低。
该初步试验结果表明，在HIE新生儿中使用TPM是安全的，但并未降低死亡率和严重神经功能障碍的联合发生率。TPM联合治疗在预防后续癫痫方面的作用值得进一步研究。
