A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 133
- 试验地点
- 5
- 主要终点
- The primary endpoint is the maximum safe and tolerated dose of Levetiracetam
研究概览
简要总结
The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 30 minute seizure burden/hour. This will make the final results of study more generalizable.
If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site.
Funding Source- FDA OOPD
详细描述
Aims/Hypotheses:
Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity.
If 60mg/kg LEV does not control seizures, subjects will be randomised to receive either additional LEV or PHB. LEV dose will be escalated in 30mg/kg increments to a maximal dose of 150mg/kg total loading dose. We will use a continual reassessment method to determine the maximal safe and tolerated dose.
Secondary/exploratory aims:
- To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity.
- To estimate the additional efficacy of higher doses of LEV in neonates with seizures of mild to moderate severity.
- To improve technologies for the prompt detection of neonatal seizures: We will assess the latest version of Persyst's neonatal seizure detector.
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
- None
入排标准
- 年龄范围
- — 至 1 Month（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •at risk for seizures or suspected to be having seizures;
- •all seizure aetiologies except correctable metabolic abnormalities such as hypoglycaemia and hypocalcaemia;
- •Term neonates (corrected gestational age between 35 and 44 weeks, postnatal age less than 28 days);
- •weight > 2200g.
- •Parental ability to comprehend and provide written informed consent
排除标准
- •Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative seizure burden of 30 minutes/hour or more in phase 3;
- •Renal failure defined as anuria in the first 24 hours of life;
- •Subjects in whom death seems imminent;
- •Seizures caused by correctable metabolic abnormality, such as hypocalcaemia, hypoglycaemia.
研究组 & 干预措施
Dose escalation with LEV
Additional LEV at a higher dose (30 mg/kg, 60 mg/kg, or 90 mg/kg depending on the stage of the study).
干预措施: Levetiracetam Injection (Drug)
Standard of care Phenobarbital
Treatment with Phenobarbital 20mg/kg IV and if needed a further 20mg/kg totalling 40mg/kg
干预措施: Phenobarbital Sodium Injection (Drug)
结局指标
主要结局
The primary endpoint is the maximum safe and tolerated dose of Levetiracetam
时间窗: 4 years
A continual reassessment method will be used to determine the maximal safe and tolerated dose
次要结局
- Long-term outcome(8 years)
- Levetiracetam CL(4 years)
- Levetiracetam Vd(4 years)
- Adverse event rates(4 years)
- Seizure burden reduction(4 years)
- Estimate of efficacy of higher dose LEV(4 years)
- Seizure freedom rates(4 years)
研究者
Richard H. Haas
Professor
University of California, San Diego