Preterm Epo Neuroprotection Trial (PENUT Trial) CCC

早产儿 Epo 神经保护试验（PENUT 试验）CCC

基本信息

批准号：
8841021
负责人：
Sandra E Juul
金额：
$ 193.95万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8841021
关键词：
9 year old Accounting Acute Acute Brain Injuries Age Anti-Inflammatory Agents Anti-inflammatory Apoptosis Apoptotic Biochemical Biological Markers Blinded Blindness Brain Brain Hypoxia-Ischemia Brain Injuries Caring Cerebellum Cerebral Palsy Cessation of life Chronic Brain Injury Classification Clinical Cognitive Control Groups Data Data Analyses Data Collection Development Diagnosis Diffusion Magnetic Resonance Imaging Documentation Dose Encephalitis Enrollment Erythropoiesis Erythropoietin Evaluation Experimental Models FDA approved Family Funding Gestational Age Goals Health Healthcare Systems Hospital Charges Hospitals Hour Hydrocephalus Impaired cognition Impairment Individual Infant Inflammation Inflammation Mediators Inflammatory Injury Intellectual functioning disability Intervention Leadership Lesion Link Magnetic Resonance Imaging Measurement Measures Monitor Morbidity - disease rate Motor Neonatal Neurodevelopmental Disability Neurodevelopmental Impairment Neurologic Neurological outcome Neuroprotective Agents Newborn Infant Oligodendroglia Outcome Outcome Measure Perinatal Care Phase I/II Trial Physically Handicapped Placebo Control Placebos Pregnancy Premature Infant Publishing Quality Control Randomized Randomized Controlled Trials Recombinant Erythropoietin Reporting Risk Safety Severities Site Structure Survivors System Testing Time Toddler Visual impairment Work angiogenesis arm base cognitive development cohort cost cytokine deafness experience extreme prematurity gray matter high risk high risk infant improved intraventricular hemorrhage mortality motor impairment neonate neurodevelopment neurogenesis neuroprotection novel novel strategies phase 3 study pre-clinical primary outcome prospective recombinant human erythropoietin secondary outcome statistics white matter white matter injury

项目摘要

DESCRIPTION (provided by applicant): In the U.S., approximately 30,600 infants per year are born before 28 weeks of gestation (40 weeks is term). These infants, termed Extremely Low Gestational Age Neonates (ELGANs), experience high morbidity and mortality: 20% of ELGANs admitted to an NICU die before discharge, 20% of survivors have severe and 20% moderate neurodevelopmental impairment (NDI). Perinatal care costs for these infants exceed $18 billion every year and account for approximately half of total hospital charges for newborn care. New approaches are needed to improve these outcomes. Recombinant erythropoietin (Epo) is a promising novel neuroprotective agent. It is widely available, affordable, and has been used safely in neonates to stimulate erythropoiesis. There are extensive preclinical data to support its use as a neuroprotective intervention: Epo decreases acute brain injury following hypoxia ischemia by decreasing inflammation, oxidative and excitotoxic injury which results in decreased apoptosis; Epo also promotes normal brain maturation by increasing neurogenesis, angiogenesis, and by protecting oligodendrocytes. We hypothesize that neonatal Epo treatment of ELGANs will decrease the combined outcome of death or severe NDI from 40% to 30% (primary outcome), or moderate NDI from 60% to 40% (secondary outcome) measured at 24-26 months post menstrual age (PMA). Our specific aims are to compare 376 Epo-treated with 376 control infants to determine: 1) whether Epo decreases the combined outcome of death or NDI at 24-26 months PMA (NDI is defined as the presence of: CP or Bayley III Scales of Infant and Toddler Development cognitive or motor scale < 70); 2) the short-, intermediate- and long-term safety of neonatal high dose Epo administration to ELGANs; 3) whether neonatal Epo treatment decreases serial measures of circulating inflammatory mediators, and biomarkers of brain injury; 4) whether Epo treatment improves brain structure (volume of gray matter, white matter and cerebellum, brain gyrification, and tract-based spatial statistics) at 36 weeks PMA as measured by MRI. In an exploratory aim, we will determine which MRI quantitative measures best predict neurodevelopment at 24-26 months PMA. We anticipate that Epo treatment of ELGANs will confer improved neurodevelopmental outcome at 24-26 months PMA compared to placebo, and will provide a much-needed therapy for this group of vulnerable infants. Furthermore, we anticipate that Epo treatment will be safe, will decrease biomarkers of brain injury and inflammation, and will be associated with less preterm brain injury as determined by MRI at 36 weeks PMA. The CCC will work closely with the linked DCC to accomplish the proposed goals. The CCC will provide the clinical leadership and support for all sites, and the DCC will provide the systems and oversight for data collection, management, quality control, operational support and data analyses for the monitoring and final reporting of the study.

描述（由申请人提供）：在美国，每年约有30,600名婴儿在妊娠28周之前出生（40周是期限）。这些婴儿被称为极低的胎龄新生儿（ELGANS），经历了高发病率和死亡率：20％的Elgans在出院前被NICU死亡，20％的幸存者患有严重的和20％的中度神经发育障碍（NDI）。这些婴儿的围产期护理费用每年超过180亿美元，约占新生儿护理总医院总费用的一半。需要新的方法来改善这些结果。重组红细胞生成素（EPO）是一种有前途的新型神经保护剂。它广泛可用，负担得起，并且已在新生儿安全地使用，以刺激红血病。有广泛的临床前数据来支持其用作神经保护干预：通过减少炎症，氧化性和兴奋性损伤，EPO减少缺血性缺血后急性脑损伤，从而导致细胞凋亡降低； EPO还通过增加神经发生，血管生成和保护少突胶质细胞来促进正常的脑成熟。我们假设新生儿EPO治疗ELGAN将从40％降低到30％（主要结果），或者中度NDI从60％到40％（次要结果）（次要结果）在月经年龄（PMA）（PMA）中测得的40％（次要结果）。我们的具体目的是比较376个与376个对照婴儿进行的EPO处理以确定：1）EPO在24-26个月PMA时是否会降低死亡或NDI的综合结果（NDI定义为：CP或Bayley III的存在：婴儿和幼儿发育和幼儿发育量表或运动量表<70）; 2）新生儿高剂量EPO给ELGAN的短期和长期安全； 3）新生儿EPO治疗是否会减少循环炎性介质的串行测量和脑损伤的生物标志物； 4）如MRI测量的36周PMA时，EPO治疗是否可以改善脑结构（灰质，白质和小脑的体积，脑部旋转和基于道的空间统计）。在探索性目的中，我们将确定哪些MRI定量测量最能预测PMA 24-26个月的神经发育。我们预计，与安慰剂相比，EPO治疗ELGAN将在PMA 24-26个月赋予改善的神经发育结果，并将为这组脆弱的婴儿提供急需的疗法。此外，我们预计EPO治疗将是安全的，会减少脑损伤和炎症的生物标志物，并将与MRI在36周PMA确定的较少的早产脑损伤有关。 CCC将与链接的DCC紧密合作，以实现拟议的目标。 CCC将为所有站点提供临床领导和支持，DCC将为数据收集，管理，质量控制，运营支持和数据分析提供系统和监督，以监视和最终报告研究。