Pharmacokinetics and Safety of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Area Under Plasma Concentration-time at Time t (AUC0-t) for Caffeine
研究概览
简要总结
Hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia is common and often fatal. Therapeutic hypothermia reduces mortality and morbidity in infants with HIE. Even with the widespread use of therapeutic hypothermia, ~60% of infants with HIE die or have neurodevelopmental impairment. As a result, there is an urgent, unmet public health need to develop adjuvant therapies to improve survival and neurodevelopmental outcomes in this population.
Caffeine may offer neuroprotection for infants with HIE by blocking adenosine receptors in the brain and reducing neuronal cell death. In animal models of HIE, caffeine reduces white matter brain injury. Drugs in the same class as caffeine (i.e., methylxanthines) have been shown to be protective against acute kidney injury in the setting of HIE. However, their safety and efficacy have not been studied in the setting of therapeutic hypothermia and their effect on neurological outcomes is not known. Since these drugs reduce injury to the kidney in infants with HIE, they may also reduce injury to the brain.
This phase I study will evaluate the pharmacokinetics, safety, and preliminary effectiveness of caffeine as an adjuvant therapy to improve neurodevelopmental outcomes in infants with HIE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent from parent or guardian
- •≥ 36 weeks gestational age at birth
- •Receiving therapeutic hypothermia for a diagnosis of HIE
- •Intravenous (IV) access
- •Postnatal age < 24 hours
排除标准
- •Receiving > 1 anti-epileptic drug for seizures
- •Sustained (>4 hours) heart rate > 180 beats per minute
- •Known major congenital anomaly
- •Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
研究组 & 干预措施
Low Dose Caffeine (5 mg/kg)
Within 24 hours of delivery, participants will receive low dose administration of Caffeine citrate.
干预措施: Caffeine Citrate 5 mg/kg (Drug)
High Dose Caffeine (10 mg/kg)
Within 24 hours of delivery, participants will receive high dose administration of Caffeine citrate.
干预措施: Caffeine Citrate 10 mg/kg (Drug)
结局指标
主要结局
Area Under Plasma Concentration-time at Time t (AUC0-t) for Caffeine
时间窗: 7 samples will be collected with the following optimal sampling windows: 0-15 minutes, 30-60 minutes, 1-3 hours, 3-6 hours, 6-12 hours, 12-18 hours, 15 minutes prior to next dose.
AUC0-t defines area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
次要结局
- Number of Participants With Seizures Requiring >1 Anti-Epileptic Medication(From the first dose of caffeine to 7 days following the final dose.)
- Number of Participants With Necrotizing Enterocolitis(From the first dose of caffeine to 7 days following the final dose.)
- Number of Participants With Abnormal MRI Brain Findings Based on NICHD Neonatal Research Network Score(During initial hospitalization, approximately 7-14 postnatal days)
- Number of Participants With a Bayley Scales of Infant Development (BSID-III) Cognitive, Language, or Motor Composite Score < 85(18-24 months of age)