Levetiracetam Efficacy and Safety as First-line Treatment of Neonatal Seizures Occuring in Hypoxic-ischemic Encephalopathy Context
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 6
- 主要终点
- Levetiracetam Short-Term Toxicity
研究概览
简要总结
LEVNEONAT is a multicentre French clinical trials with the aim to develop new treatment strategies for the treatment of neonatal seizures using Levetiracetam. The purpose of this study is to determine the correct dosing, safety and efficacy for intravenous levetiracetam as first line treatment in term newborn babies with seizures in hypoxic-ischemic encephalopathy context. This new anticonvulsivant drug is a promising treatment for seizures in newborns.
详细描述
Article Focus
- The principal aim of LEVNEONAT-1 is to determine the levetiracetam optimal dose defined as the highest efficient dose under toxicity restrictions for treating neonatal seizures.
- LEVNEONAT-1 is an open-label, sequential dose-finding study with 3 increasing dose levels of levetiracetam.
Strenghts and limitation of study
- For the first time, levetiracetam will be used as the first-line treatment of neonatal seizures and not as an add-on therapy.
- Statistical model is designed for a rare clinical situation with a sequential adaptive method updating in real time the dose allocation for next patient by using all available data from previous participants.
- The targeted population, i.e. the newborn less than 3 days of life, is particularly sensitive and the written consent of both parents is required before the levetiracetam administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 36 Weeks 至 43 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Suspected or confirmed brain malformation, inborn error of metabolism, genetic syndrome or major congenital malformation
- •Congenital (in utero) infection (TORCH)
- •Babies who have received phenobarbital or any other anticonvulsive medication other than a bolus of midazolam for intubation
- •Anuria/renal failure defined as serum creatinine > 150 micromol/L
- •Seizures secondary to treatable metabolic etiology as hypoglycemia and hypocalcemia
- •Corrected QT interval (QTc) greater than 450 milliseconds on the electrocardiogram (ECG) prior to inclusion in the presence or absence of a condition that promotes QT prolongation (hypokalemia, maternal treatment during childbirth or treatment of the child with drugs known to prolong QT),
- •Participation to an interventional research study
研究组 & 干预措施
Intravenous levetiracetam
1 loading dose of 30, 40 or 50 mg/kg administered intra-venously. Maintenance treatment: one intra-venous injection /8h, 8 doses in total for a 3-day treatment. Maintenance dose corresponds to the loading dose quarter i.e. 7.5, 10 or 12.5 mg/kg.
干预措施: Intravenous Levetiracetam (Drug)
结局指标
主要结局
Levetiracetam Short-Term Toxicity
时间窗: 6 days from the loading dose
Short-term toxicity focuses on 4 adverse events potentially attributable to LEV occurring in the 6 days following the loading dose: i) Severe apnoea leading to mechanical ventilation during the 4-hour period following the LEV infusion; ii) Anaphylactic shock occurring during the 30 minutes following the LEV infusion; iii) Toxic epidermic necrosis; iv) Stevens-Jonhson Syndrome. Short-term toxicity has been designed to trigger quickly a decreasing dose allocation to the next potential participant through a e-CRF alert.
Levetiracetam Efficacy on EEG recording
时间窗: the period just before the LEV loading dose (from 20 min to 3 hours) and the 3 hour time-interval from 1 hour 15 min (T11/4) to 4 hours 15 min (T41/4) after the starting of loading dose infusion (T0)
Efficacy has been defined as an 80% reduction of seizure burden on EEG recording.
Levetiracetam Long-Term Toxicity
时间窗: 30 days from the loading dose
Long-term toxicity includes all the adverse events observed and declared to the pharmacovigilance unit up to the hospital discharge or the 30th day of life at the latest.
次要结局
- Levetiracetam Distribution Volume(at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.)
- Levetiracetam Elimination Clearance(at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last levetiracetam maintenance dose, respectively.)
- Plasmatic Levetiracetam Maximal Concentration(30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion)
- Levetiracetam Entire Treatment Area Under Curve(at 30 min, 4 hours and 7 hours after the end of loading dose infusion, respectively and at 1 to 3 hours and 12 hours to 18 hours after the last Levetiracetam maintenance dose, respectively.)
- Levetiracetam Loading Dose Area under Curve(30 min, 4 hours and 7 hours after the end of Levetiracetam loading dose infusion)
- Seizure recurrence from the Efficacy criteria completion to day 6(from 4h15 after the loading dose to 6 days)
- Levetiracetam Efficacy according to the seizure burden intensity prior to loading dose(after the complete recruting period)