Indomethacin and delayed umbilical cord clamp for preterm infant IVH

吲哚美辛联合延迟脐带钳治疗早产儿 IVH

• 批准号: 8628142
• 负责人: John Anthony Bauer
• 金额: $ 64.62万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628142
• 关键词: Abbreviations; Address; Adverse effects; Affect; Apoptotic; Biological Markers; Birth; Birth Weight; Blinded; Blood; Blood Volume; Brain; Brain Injuries; Brain imaging; Caring; Case Study; Cephalic; Cerebral Palsy; Child; Clinical; Cognitive; Communities; Costs and Benefits; Data; Developmental Delay Disorders; Developmental Disabilities; Effectiveness; Evaluation; Extremely Low Birth Weight Infant; FDA approved; Frequencies; Gestational Age; Goals; Head; Health Care Costs; Hemorrhage; Incidence; Indomethacin; Infant; Inflammatory; Intervention; Intestinal Perforation; Investigation; Kidney; Lesion; Life; Link; Magnetic Resonance Imaging; Measurement; Medical; Medical center; Mental Retardation; Mothers; Neonatology; Neurocognitive; Neurologic; Neurons; Newborn Infant; Organ failure; Outcome; Outcome Measure; Patient Care; Pediatric Hospitals; Performance; Periventricular Leukomalacia; Phenotype; Premature Infant; Prevalence; Prevention; Prevention therapy; Protocols documentation; Randomized; Research; Risk; Safety; Severities; Site; Stem cells; Stress; Surveys; Survivors; Testing; Toxic effect; Ultrasonography; Umbilical cord structure; clinical care; comparative efficacy; cost; design; disability; follow-up; hemodynamics; high risk; improved; intraventricular hemorrhage; patient population; premature; prevent; primary outcome; prophylactic; public health relevance; social; vascular inflammation

DESCRIPTION (provided by applicant): Intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) are brain lesions that commonly occur in preterm infants and are well-recognized major contributors to long-term brain injury and related disabilities later in life. Despite its prevalence, long term consequences, and enormous medical and social costs, mechanisms of IVH and optimal strategies to prevent or treat its occurrence are poorly defined, especially for extremely premature infants. Only one medical therapy, prophylactic indomethacin during the first 3 days of life, has been shown to prevent or decrease the severity of IVH in preterm infants, but its use is limited by toxic side effects and debatable effects on long-term outcomes. Several small studies and case reports suggest that delayed umbilical cord-clamping (DCC) may also decrease the incidence of IVH in premature infants, but thus far these trials have indomethacin treatment mixed within their cord clamping protocols. We will therefore conduct a randomized, blinded investigation of 4 treatment groups: 1) Control (no intervention); 2) DCC alone; 3) Prophylactic indomethacin alone; 4) Combination of DCC/indomethacin, with respect to survival, IVH or PVL incidence and severity, neurodevelopmental outcomes, and relevant mechanistic effects. Our Specific Aims are: Aim 1) Compare efficacy and safety of prophylactic indomethacin, DCC, and their combination, in affecting the incidence and severity of IVH/PVL in infants <28wks gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL' among the 4 groups), and longer term neurocognitive function; Aim 2) Investigate mechanistic effects of prophylactic indomethacin, DCC, and their combination in infants less than 28wks gestational age (blood volume/circulatory status, inflammatory stress, progenitor cells); and Aim 3) Determine relationships between clinical outcomes and mechanistic measurements among treatment groups (n=400 total cases). With the steady rise in extreme prematurity births and clear links of IVH to long-term disabilities there is a need to improve care for these patients. This multi-disciplinary project addresses an important medical problem for an understudied patient population, where the current practice has clear limitations.

描述（由申请人提供）：脑室内出血（IVH）和脑室周围白质软化（PVL）是早产儿中常见的脑部病变，并且是公认的导致长期脑损伤和日后相关残疾的主要原因。尽管其普遍存在、长期后果以及巨大的医疗和社会成本，但 IVH 的机制和预防或治疗其发生的最佳策略尚不清楚，特别是对于极早产儿。只有一种药物疗法，即出生后 3 天内预防性使用吲哚美辛，已被证明可以预防或减轻早产儿 IVH 的严重程度，但其使用受到毒副作用和对长期结果的有争议的影响的限制。几项小型研究和病例报告表明，延迟脐带结扎 (DCC) 也可能降低早产儿 IVH 的发生率，但到目前为止，这些试验在其脐带结扎方案中混合了吲哚美辛治疗。因此，我们将对 4 个治疗组进行随机、盲法调查： 1) 对照组（无干预）； 2）单独DCC； 3)单独预防性使用吲哚美辛； 4) DCC/吲哚美辛的组合，对于生存、IVH 或 PVL 发生率和严重程度、神经发育结果以及相关机制效应。我们的具体目标是： 目标 1) 比较预防性吲哚美辛、DCC 及其组合对胎龄 <28 周婴儿 IVH/PVL 的发生率和严重程度的疗效和安全性（主要结果指标是 4 组中“无严重 IVH 或 PVL 的幸存者比例”）以及长期神经认知功能；目标 2) 研究预防性吲哚美辛、DCC 及其组合对胎龄小于 28 周婴儿的机制影响（血容量/循环状态、炎症应激、祖细胞）；目标 3) 确定治疗组之间临床结果和机械测量之间的关系（总共 400 例病例）。随着极端早产率的稳步上升以及 IVH 与长期残疾的明显联系，有必要改善对这些患者的护理。这个多学科项目为未充分研究的患者群体解决了一个重要的医学问题，目前的实践有明显的局限性。