Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants - a Randomized, Double-blind, Placebo-controlled, Prospective, and Multicenter Clinical Study
试验速览
- 阶段
- 3 期
- 入组人数
- 120
- 试验地点
- 8
- 主要终点
- Neurodevelopmental outcome
研究概览
简要总结
The purpose of this randomized and placebo-controlled EpoRepair trial is to evaluate the effect of intravenously administered recombinant human erythropoietin (Epo) as compared to placebo in preterm infants with brain damage on neurological development until five years od age.
详细描述
Worldwide, 1% of all infants are born very preterm with less than 32 weeks of gestation, which is more than 2 months before expected date of delivery. If these smallest infants suffer in addition to prematurity a second hit, such as intraventricular hemorrhage or parenchymal infarction, they are at high risk for learning disabilities, mental retardation, and cerebral palsy in later life.
Intraventricular hemorrhage and parenchymal infarction occur in about 12% of very preterm infants, mostly in the very smallest and within the first few days after birth, and can be recorded by cranial ultrasound. Except for shunt insertion to divert cerebrospinal fluid in infants with posthemorrhagic hydrocephalus and possibly the removal of blood clots, there is no treatment for established intracerebral bleeding, and no medical therapies exist to ameliorate the neurodevelopmental sequelae.
Apart from stimulating production of red blood cells in the bone marrow, recombinant human erythropoietin (Epo) has been shown to exert neuroprotective action in a variety of animal models and in clinical studies. Epo administration has been found to be beneficial and safe in randomized controlled trials (RCT) involving adult and infant patients.
Observational data suggest that Epo administered to very preterm infants in order to prevent from anemia improves long-term cognitive outcomes until school-age especially in those infants who had suffered intracerebral bleeding. These data, however, are observational and therefore do not allow for any firm conclusions or recommendations. The hypothesis generated by these data calls for confirmation or refutation by an RCT designed to address this question.
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
- 23 Weeks 至 31 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants with less than 32 weeks of gestation and/or less than 1500 g weight at birth
- •Intraventricular hemorrhage and/or hemorrhagic parenchymal infarction
- •Less than 8 days of life
- •Informed written parental consent
排除标准
- •Genetically defined syndrome
- •Severe congenital malformation adversely affecting life expectancy and/or neurodevelopment
- •A priory palliative care
- •Unlikely to participate at 5-year follow-up examination
研究组 & 干预措施
recombinant human Erythropoietin (Epo)
Epo 2000 U in normal saline per ml/kg of body weight 5 times intravenously, total dosage 10000 U per 5ml/kg.
In detail: For loading 3 times beginning at day 5 of life (± 2 days), followed at 24 hours and 48 hours later. For maintenance 2 times, at day 10 and day 17 after the first study medication.
干预措施: recombinant human Erythropoietin (Drug)
Control
Placebo 1 ml normal saline/kg of body weight 5 times intravenously, total dosage 5 ml/kg.
In detail: For loading 3 times beginning at day 5 of life (± 2 days), followed at 24 hours and 48 hours later. For maintenance 2 times, at day 10 and day 17 after the first study medication.
干预措施: Placebo (Drug)
结局指标
主要结局
Neurodevelopmental outcome
时间窗: 5 years
With 5 years of age, composite intelligence quotient to be assessed by standardized IQ tests.
次要结局
- Biomarker serial cranial ultrasound(Infants will be followed for the duration of hospital stay, an expected average of 14 weeks)
- Safety(Infants will be followed for the duration of hospital stay, an expected average of 14 weeks)
- Overall developmental outcome(5 years)
- Biomarker cranial MRI(40 weeks postmenstrual age)
- Neurodevelopmental outcome(2 years)