Mild Encephalopathy in the Newborn Treated With Darbepoetin (MEND)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Normal Neurodevelopment
研究概览
简要总结
This is a Phase II multicenter placebo-controlled randomized, feasibility/safety trial. Infants >34 week gestational age with perinatal acidemia and mild neonatal encephalopathy on the modified Sarnat neurologic examination at less than six hours of age. Participants will be randomized to receive either one dose of Darbepoetin, or placebo within 24 hours of birth. Neurodevelopmental testing (Bayley (III or IV) and Gross Motor Function Assessment) will be performed at 24 months of age. Pharmacokinetics will be assessed on those infants that received Darbe.
详细描述
Therapeutic hypothermia (TH) is the standard of care for newborns diagnosed with moderate to severe neonatal encephalopathy (NE) presumably due to hypoxic ischemia. In order to be eligible for TH an infant must have perinatal acidemia and evidence of moderate or severe encephalopathy on a standardized neurologic examination (Sarnat). However, the majority of newborns with perinatal acidemia do not have a neurologic examination abnormal enough to be classified as moderate or severe NE. In a retrospective review, DuPont et al. found that as many as 20% of newborns with perinatal academia and mild NE have abnormal short-term outcomes such as seizures, death from progressive asphyxia insult, brain MRI findings consistent with NE, abnormal neurologic examination at discharge, gastrostomy tube feeding, or feeding difficulties. Preliminary data from a prospective trial investigating mild NE (PRIME study, NCT01747863) found that 39% had either abnormal electroencephalography at < 9h of age, an abnormal brain MRI finding, or abnormal neurological exam at discharge. Murray et al. recently reported on 5-year outcomes of infants with mild encephalopathy and showed that 25% had neurodevelopmental disability. These data suggest that mild NE likely carries a higher risk of impaired neurological outcome then reported previously. Thus it would appear that neuroprotective strategies would be beneficial in this group of infants. Preliminary data suggest that erythropoiesis stimulating agents (ESA) provide neuroprotection, and improve short and long-term neurologic outcome in neonatal brain injury. ESA may work through several mechanisms including reduced inflammation, limited oxidative stress, decreased apoptosis and white matter injury, as well as via pro-angiogenic and neurogenic properties. Darbepoetin alfa (Darbe), a recombinant human erythropoietin (EPO)-derived molecule has established safety and pharmacokinetics in newborns. Because Darbe has an extended circulating half-life with comparable biological activity to EPO, it has the advantage of requiring less frequent administration
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Hour 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants will be eligible for the MEND trial if they have a gestational age > 34 weeks by best obstetric estimate, are <24 hours old and have evidence of mild encephalopathy as defined by Shankaran et al based on a modified Sarnat examination performed at <6 hours of age.
- •History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality, or meconium staining)
- •Infant is evaluated for hypothermia therapy and DOES NOT meet clinical criteria for TH.
- •Infant has an IV for clinical treatment
排除标准
- •Moderate/Severe encephalopathy on modified Sarnat examination at < 6 hours of age
- •Major congenital and/or chromosomal abnormalities
- •Prenatal diagnosis of brain abnormality or hydrocephalus
- •Severe growth restriction (< 3%)
- •Central venous hematocrit >65%, platelet count >600,000/dL, and/or neutropenia (ANC<500 μL)
- •Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist
研究组 & 干预措施
Darbepoetin Alpha
IV,10 mcg/kg/dose, Darbepoetin Alpha, one dose at <24 hours of age
干预措施: Darbepoetin Alfa (Drug)
Placebo
IV, Normal saline (placebo dose), one dose at <24 hours of age
干预措施: Normal Saline (Drug)
结局指标
主要结局
Normal Neurodevelopment
时间窗: 9 - 12 months of age
The Bayley III and Neuromuscular Assessment were completed between 9-12 months of age. Subjects were abnormal if they had a Bayley III score of less than 70 and/or an abnormal neurological examination.
次要结局
- Percent of Infants With Adverse Events(30 days or until hospital discharge whichever comes first)
- Percentage of Infants Who Need Gavage Feeds or Gastrostomy at Discharge Home(30 days or until hospital discharge whichever comes first)
- Percent of Infants With Seizures(30 days or until hospital discharge whichever comes first)