Preterm Epo Neuroprotection Trial (PENUT Trial) DCC

早产儿 Epo 神经保护试验（PENUT 试验）DCC

• 批准号: 8773752
• 负责人: PATRICK J HEAGERTY
• 金额: $ 10.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773752
• 关键词: Accounting; Acute Brain Injuries; Adherence; Age; Apoptosis; Biological Markers; Blindness; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Caring; Cerebellum; Cerebral Palsy; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials Data Monitoring Committees; Cognitive; Committee Members; Communication; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Quality; Databases; Development; Documentation; Dose; Encephalitis; Erythropoiesis; Erythropoietin; Family; Gestational Age; Goals; Guidelines; Healthcare Systems; Hospital Charges; Hospitals; Individual; Infant; Inflammation; Inflammation Mediators; Injury; Internet; Intervention; Leadership; Link; Magnetic Resonance Imaging; Mails; Manuals; Measures; Monitor; Morbidity - disease rate; Motor; National Institute of Neurological Disorders and Stroke; Neonatal; Neurodevelopmental Disability; Neurodevelopmental Impairment; Neuroprotective Agents; Newborn Infant; Oligodendroglia; Online Systems; Outcome; Outcome Measure; Participant; Perinatal Care; Phase III Clinical Trials; Placebo Control; Placebos; Pregnancy; Premature Infant; Preparation; Principal Investigator; Protocols documentation; Publications; Quality Control; Randomized; Recombinant Erythropoietin; Reporting; Research Design; Research Personnel; Safety; Site; Structure; Survivors; System; Testing; Toddler; Training; Universities; Washington; Work; angiogenesis; base; clinical research site; cost; deafness; disability; experience; gray matter; high risk infant; improved; mortality; neonate; neurodevelopment; neurogenesis; neuroprotection; novel; novel strategies; operation; performance site; pre-clinical; premature; primary outcome; public health relevance; randomized trial; recombinant human erythropoietin; secondary outcome; statistics; tool; web site; white matter

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周为足月）。这些婴儿被称为极低胎龄新生儿（elgan），具有很高的发病率和死亡率：入住NICU的elgan中有20%在出院前死亡，20%的幸存者有严重和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）是一种很有前途的新型神经保护剂。它是广泛可用的，负担得起的，并已安全地用于新生儿刺激红细胞生成。有大量的临床前数据支持它