Recombinant Human Erythropoietin Improve Neurodevelopmental Outcomes in Extremely Preterm Infants
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 440
- 主要终点
- Incidence of neurological disability
研究概览
简要总结
In the ELGAN (Extremely Low Gestational Age Newborn) study, abnormal brain structure and function were associated with intermittent or sustained systemic inflammation (ISSI). Since EPO has anti-inflammatory properties in the kidney and in muscle as well as growth/trophic properties. Based on its potential for neuroprotection, the prospective randomized and masked study was designed to determine whether rhEPO （500u/kg) was also effective in improving developmental outcomes for extremely low gestational age newborns.
详细描述
Exogenous erythropoietin (EPO) is currently used to reduce or prevent the need for red blood cell transfusions in preterm infants. Just two decades ago, erythropoietin (EPO) receptors were first identified in the brain, and astrocytes were found to be capable of synthesizing EPO . Subsequently, it was found that cultured hippocampal and cerebral cortical neurons exposed to EPO were spared some of the glutamate-induced cell death seen in neurons not exposed to EPO. Thus began the concept that EPO protects the brain against adversity. Several follow-up studies of children who had participated in trials of recombinant EPO for the prevention or treatment of anemia, term newborn encephalopathy,or retinopathy of prematurity have also provided evidence of neuroprotective effects.
In the ELGAN (Extremely Low Gestational Age Newborn) study, abnormal brain structure and function were associated with intermittent or sustained systemic inflammation (ISSI) . Since EPO has anti-inflammatory properties in the kidney and in muscle as well as growth/trophic properties, we reasoned that elevated circulating levels might convey information about reduced risk of brain damage in ELGANs.
Although major neurodevelopmental disabilities such as cerebral palsy (CP), mental disabilities, and learning and attention deficits during school age figure prominently in the outcomes of ELBW infants, successful neuroprotective interventions have yet to be developed. Investagators designed a prospective, randomized, masked study to evaluate rhEPO during initial hospitalization and follow up, and hypothesized that rhEPO recipients would receive fewer transfusions during initial hospitalization in extremely preterm infants. Based on its potential for neuroprotection, our study was designed to determine whether rhEPO (500 u/kg) was also effective in improving developmental outcomes for extremely low gestational age newborns.
The neurodevelopmental outcomes of rhEPO in treating extremely preterm infants are not clear. Investigators propose an early-childhood neurodevelopmental follow-up study to compare long-term effects of the rhEPO as measured by, Bayley Scales of Infant Development III. We plan to follow extremely low gestational age children around 24 months' corrected age (CA) who are enrolled in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants admitted to NICU wuth gestational age less than 28 weeks
- •Age less than 3 days;
- •parental informed consent.
排除标准
- •Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)
- •Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities
- •Polycythemia (hematocrit > 65);
- •Hypertension
- •Congenital infection
研究组 & 干预措施
EPO group
In EPO group, The recombinant human erythropoietin (rhEPO) will be given by 500 U/kg/dose intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.
干预措施: Recombinant human erythropoietin (Drug)
Normal saline
Normal saline is administered the same volume with EPO, intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.
干预措施: Normal saline (Drug)
结局指标
主要结局
Incidence of neurological disability
时间窗: 2 years
To assess the incidence of neurological disability of EPO and control groups at 2 years old
Mortality
时间窗: 2 years
To compare the death rate of EPO and control groups at 2 years old
次要结局
- Short-term complicatioins(3 months)
- Early blood biomarkers for poor neurological outcomes(4 weeks)
- Incidence of MDI<70(2 years)
- Incidence of cerebral palsy(2 years)
- Incidence of deafness(2 years)
- Incidence of blindness(2 years)
- Brain imaging biomarkers for poor neurological outcomes(Up to 40 weeks of corrected age)
研究者
Huiqing Sun
Director of preterm infants intensive care unit
Zhengzhou Children's Hospital, China