Safety and Efficacy of Oral Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia: a Pilot Study of the Neonatal Neuroprotection of Asphyxiated Tuscan Infants (NeoNATI) Network
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life
研究概览
简要总结
The purpose of this study is to determine whether the administration of topiramate to newborns with hypoxic-ischemic encephalopathy potentiates the neuroprotective effect of treatment with hypothermia.
详细描述
Neonatal hypoxic-ischemic encephalopathy, due to perinatal asphyxia, is one of the leading causes of cerebral palsy, whose incidence, despite improvements in perinatal practice and neonatal care, has remained essentially unchanged over the recent past decades. It occurs approximately in 2-3 newborns every 1000 live births with a mortality rate of 10% for mild degrees and 60% for severe degrees. About 30% of survivors with mild hypoxic-ischemic encephalopathy and 100% with severe hypoxic-ischemic encephalopathy exhibit variable degrees of neurological disability.
Several studies have demonstrated the therapeutic effects of whole-body or selective head cooling to treat neonates with hypoxic-ischemic encephalopathy. Mild hypothermia, (rectal or esophageal temperature 33-34°C), started within 6 h after birth and protracted for 48-72 h, can significantly improve primary outcome measures such as death or disability at 18 months or improve the neurological outcome in survivors. Consequently, mild hypothermia is at present recommended for the treatment of moderate degrees of encephalopathy.
Topiramate an anticonvulsant agent widely used in adults and children, has been demonstrated to posses neuroprotective properties against hypoxic ischemic brain damage, both in vitro and in animal models and has been included in neuroprotective strategies for ischemic stroke and neonatal hypoxic-ischemic cerebral injury. Recently, topiramate treatment in asphyxiated newborns has been reported safe.
Aim of the present study is to confirm the safety and to evaluate whether the association of topiramate enhances the neuroprotective properties of hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 36 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age > 36 weeks and birth weigh > 1800 g with at least 1 of the following: a) Apgar score < 5 at 10 minutes; b) persisting need for resuscitation, including endotracheal intubation or mask ventilation 10 minutes after birth; c) acidosis (pH <7.0, base deficit >-16 mmol/L in umbilical cord blood or arterial, venous or capillary blood) within 60 minutes from birth;
- •moderate to severe encephalopathy, consisting of altered state of consciousness (irritability, lethargy, stupor, or coma) and > 1 of the following sings: a) hypotonia, b) abnormal reflexes, including oculomotor or pupil abnormalities, c) absent or weak suck, d) clinical seizures.
- •abnormal aEEG
排除标准
- •congenital abnormalities, congenital viral infections or evidence encephalopathy other than HIE.
研究组 & 干预措施
Topiramate
Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate
干预措施: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia (Drug)
结局指标
主要结局
The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life
时间窗: 18 months of life
次要结局
- The secondary aim is to evaluate the efficacy of treatment with topiramate for improving neuroradiological outcome at 3 and 12 months of life(12 months of life)
研究者
Luca Filippi
Dr. Luca Filippi
Azienda Ospedaliero, Universitaria Meyer