Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterms - DCC

达贝泊汀改善早产儿红细胞质量和神经保护的试验 - DCC

• 批准号: 10152665
• 负责人: Abhik Das
• 金额: $ 77.77万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152665
• 关键词: 6 year old; Address; Adult; Age; Biometry; Brain; Brain Injuries; Cerebral Palsy; Child; Clinical; Clinical Trials; Cognitive; Collaborations; Companions; Custom; Data; Data Coordinating Center; Data Management Resources; Data Reporting; Development; Developmental Delay Disorders; Dose; Enrollment; Erythrocytes; Erythropoiesis; Erythropoietin; Exposure to; Gestational Age; Goals; Head; Hematocrit procedure; Hematologist; Hematology; Hemoglobin; Hospitalization; Human Resources; Incidence; Infant; Infant Development; Infrastructure; Journals; Knowledge; Leadership; Letters; Life; Logistics; Measures; Monitor; Multi-Institutional Clinical Trial; Multicenter Neonatal Research Network; Multicenter Trials; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Neonatal; Network Infrastructure; Neurocognitive; Neurodevelopmental Impairment; Neurologic; Newborn Infant; Outcome; Peer Review; Pharmaceutical Preparations; Placebos; Population; Premature Infant; Process; Production; Publications; Randomized; Randomized Clinical Trials; Red Cell Mass result; Research; Resources; Risk; Safety; Seminal; Statistical Data Interpretation; Structure; System; Testing; Training; Transfusion; Ultrasonography; Very Low Birth Weight Infant; base; care providers; clinical effect; clinical practice; cognitive function; data management; design; effective therapy; executive function; experience; flexibility; hypoxic ischemic injury; improved; improved outcome; intraventricular hemorrhage; neonatal care; neuroprotection; premature; preterm newborn; prevent; programs; randomized placebo controlled trial; randomized trial; standard of care; treatment strategy; trial comparing

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 specific 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 outcomes 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.

项目总结/摘要 改善每年出生的近60，000名早产儿的神经发育结果是一个主要的 新生儿护理提供者的目标。这些婴儿的一个子集持续严重的脑室内出血（IVH） 导致发育迟缓的发生率增加。此外，近三分之一的早产儿 正常的头部超声波也会导致认知延迟。尽管各种治疗策略 在评估中，尚未确定任何特定的治疗方法来改善神经发育结果， 早产儿一种潜在的疗法涉及施用红细胞生成刺激剂（ESA）， 促红细胞生成素（Epo）和达贝泊汀（Darbe，一种长效ESA）。最初研究它们的影响 在减少早产儿输血方面，ESA已被证明在发育中具有保护作用。 大脑，因此可能有益于处于IVH，缺氧缺血性损伤， 和发育迟缓。我们先前评估了血液学和神经发育结果， 在99名早产儿中进行的一项多中心试验中，校正年龄为18-22个月，随机接受Epo、Darbe或 经后35周内服用安慰剂。ESA治疗的婴儿接受较少的输血， 接触到更少的捐助者。在18-22个月时，ESA治疗的婴儿具有显著更高的认知评分， 神经发育障碍的发生率较低，包括无脑瘫。4岁和6岁时， 与安慰剂接受者相比，测量ESA中的认知和执行功能评分。达尔贝 接受者在接受三分之一剂量的情况下，与Epo接受者相比，执行功能有所改善， 从而提供了Darbe可能为早产儿提供比Epo更大益处的证据。 这项建议涉及我们制定有效治疗策略的长期目标， 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的非造血机制之外， 结果。运用新生儿研究网络基础设施的经验和严谨性， 随机安慰剂对照试验，我们的具体目标是评估Darbe给药在 出生后前10周，早产儿出生时胎龄为23至28周，（1）供体和 输血要求和红细胞量的测量，以及（2）22-26个月时的神经认知结果 调整年龄。将在住院期间收集红细胞压积、输血和供体暴露， 神经发育结果将通过22-26个月的综合测试进行评估（Bayley 婴儿发育量表III、执行功能和神经系统检查）。如果先前研究的结果 证实，Darbe的使用可能成为护理标准，并显着改善患者的生活。 成千上万的早产儿。