Darbepoetin Trial to Improve Red Cell Mass and Neurodevelopment in Preterms-CCC

达贝泊汀改善早产儿红细胞质量和神经发育的试验 - CCC

• 批准号: 10152693
• 负责人: ROBIN K OHLS
• 金额: $ 31.61万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-23 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152693
• 关键词: 6 year old; Address; Adult; Adverse effects; Age; Animal Model; Brain; Brain Injuries; Cerebral Palsy; Child; Clinical Trials; Cognition; Cognitive; Control Groups; Development; Developmental Delay Disorders; Dose; Erythrocytes; Erythropoiesis; Erythropoietin; Exposure to; Gestational Age; Goals; Guidelines; Head; Hematocrit procedure; Hematology; Hospitalization; Incidence; Infant; Infant Development; Infrastructure; Institutes; Length; Life; Measures; Multicenter Neonatal Research Network; Multicenter Trials; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Network Infrastructure; Neuraxis; Neurocognitive; Neurodevelopmental Impairment; Neurologic; Outcome; Pharmaceutical Preparations; Placebos; Play; Population; Pregnancy; Premature Infant; Production; Randomized; Randomized Controlled Trials; Recording of previous events; Red Cell Mass result; Risk; Role; Testing; Transfusion; Ultrasonography; Very Low Birth Weight Infant; Weight; angiogenesis; base; care providers; clinical care; clinical practice; cognitive function; collaborative trial; early detection biomarkers; effective therapy; executive function; experience; follow-up; hypoxic ischemic injury; improved; improved outcome; intraventricular hemorrhage; neonatal care; neonatal period; neurodevelopment; neurogenesis; neuroprotection; placebo group; postnatal; prevent; randomized placebo controlled trial; response; standard of care; treatment strategy

PROJECT SUMMARY/ABSTRACT Improving neurodevelopmental outcomes for the nearly 60,000 preterm infants born each year is a major goal for neonatal care providers. A subset of these infants sustain a major intraventricular hemorrhage (IVH) resulting in an increased incidence of developmental delay. Moreover, almost one-third of preterm infants with normal head ultrasounds also develop cognitive delay. Although a variety of treatment strategies have been evaluated, no specific treatment has been identified to improve neurodevelopmental outcomes in preterm infants. One potential therapy involves administering erythropoiesis stimulating agents (ESAs) such as erythropoietin (Epo) and Darbepoetin (Darbe, a longer acting ESA). Initially investigated for their effects on decreasing transfusions in preterm infants, ESAs have been shown to be protective in the developing brain, and thus possibly beneficial for very premature infants who are at risk for IVH, hypoxic-ischemic injury, and developmental delay. We previously evaluated both hematologic and neurodevelopmental outcomes at 18-22 months corrected age in a multicenter trial of 99 preterm infants randomized to receive Epo, Darbe, or placebo through 35 weeks postmenstrual age. ESA-treated infants received fewer transfusions and were exposed to fewer donors. At 18-22 months ESA-treated infants had significantly higher cognitive scores and lower rates of neurodevelopmental impairment, including no cerebral palsy. At 4 and 6 years of age, higher cognitive and executive function scores were measured in ESA compared to placebo recipients. Darbe recipients had improved executive function compared to Epo recipients while receiving one-third the doses, thus providing evidence that Darbe might provide even greater benefit than Epo for preterm infants. This proposal addresses our long-term goal of developing effective treatment strategies to improve outcomes in preterm infants. Understanding the impact of increased hematocrit and decreased transfusions in addition to the non-hematopoietic mechanisms of ESAs is necessary to achieve optimal developmental outcomes. Applying the experience and rigor of the Neonatal Research Network infrastructure in performing randomized placebo controlled trials, our aims are to evaluate the effect of Darbe administered in the first 10 weeks of life to preterm infants born at 23 to 28 completed weeks gestational age on 1) donor and transfusion requirements and measures of red cell mass, and 2) neurocognitive outcome at 22-26 months adjusted age. Hematocrit, transfusions and donor exposures will be collected during hospitalization, and neurodevelopmental outcome will be assessed through comprehensive testing at 22-26 months (Bayley Scales of Infant Development III, executive function, and neurologic exam). If outcomes of the previous study are confirmed, the use of Darbe could become standard of care and significantly improve the lives of thousands of preterm infants.

项目摘要/摘要 改善每年出生的近6万早产儿的神经发育结果是一项重要的工作 新生儿护理提供者的目标。这些婴儿中有一部分患有严重的脑室出血(IVH)。 导致发育迟缓的发生率增加。此外，几乎三分之一的早产儿 头部超声正常时，也会出现认知延迟。尽管各种治疗策略都有 已经进行了评估，还没有确定特定的治疗方法来改善患者的神经发育结果 早产儿。一种可能的治疗方法包括给予红细胞生成刺激剂(ESA)，如 如促红细胞生成素(EPO)和达贝泊丁(Darbe，作用时间更长的ESA)。初步调查了它们的影响 在减少早产儿输血方面，ESA已被证明在发育过程中具有保护作用 大脑，因此可能有益于极早产儿，他们有IVH，缺氧缺血损伤的风险， 和发育迟缓。我们之前评估了血液学和神经发育结果 在一项多中心试验中，99名早产儿随机接受EPO、Darbe或 安慰剂服用至月经后35周。接受ESA治疗的婴儿输血较少， 与更少的捐赠者接触。在18-22个月时，接受ESA治疗的婴儿的认知分数明显较高， 较低的神经发育障碍率，包括无脑性瘫痪。在4岁和6岁时，更高 ESA的认知和执行功能得分被测量，并与安慰剂接受者进行比较。达贝 与EPO接受者相比，接受者在接受三分之一剂量的情况下改善了执行功能， 因此，有证据表明，DARBE可能比EPO对早产儿提供更大的好处。 这项建议符合我们的长期目标，即开发有效的治疗策略以改善 早产儿的结局。了解红细胞压积增加和输血减少的影响 除了ESA的非造血机制外，ESA还是实现最佳发育所必需的 结果。将新生儿研究网络基础设施的经验和严谨应用于执行 随机安慰剂对照试验，我们的目标是评估达贝在前10个月的疗效 23至28周出生的早产儿的生命周1)捐赠者和 红细胞质量的输血需求和测量；2)22-26个月的神经认知结果 调整后的年龄。将在住院期间收集红细胞压积、输血和供者暴露情况，以及 将在22-26个月时通过综合测试评估神经发育结果(Bayley 婴儿发育量表III、执行功能和神经学检查)。如果先前研究的结果 如果得到证实，Darbe的使用可能成为护理的标准，并显著改善 成千上万的早产儿。