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: 9045658
• 负责人: John Anthony Bauer
• 金额: $ 65.62万
• 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/9045658
• 关键词: 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; Disabled Persons; Effectiveness; Evaluation; FDA approved; Frequencies; Gestational Age; Goals; Head; Health; 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; Patients; 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; extreme prematurity; follow-up; handicapping condition; hemodynamics; high risk; improved; intraventricular hemorrhage; patient population; prevent; primary outcome; prophylactic; social; treatment group; 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acia （PVL）是常见于早产儿的脑部病变，是公认的长期脑损伤和相关残疾的主要原因。尽管IVH的流行、长期后果以及巨大的医疗和社会成本，但其机制和预防或治疗其发生的最佳策略仍不明确，特别是对极早产儿而言。只有一种药物治疗，即在出生后3天内预防性使用吲哚美辛，已被证明可以预防或降低早产儿IVH的严重程度，但其使用受到毒副作用的限制，对长期预后的影响尚存争议。一些小型研究和病例报告表明，延迟脐带夹紧（DCC）也可能降低早产儿IVH的发生率，但到目前为止，这些试验在其脐带夹紧方案中混合使用吲哚美辛治疗。因此，我们将对4个治疗组进行随机、盲法调查：1)对照组（不干预）；2)单独DCC；3)预防性单独使用吲哚美辛；4) DCC/吲哚美辛联用，在生存率、IVH或PVL发生率和严重程度、神经发育结局及相关机制作用方面。我们的具体目标是：目的1)比较预防性吲哚美辛、DCC及其联合使用对<28周胎龄婴儿IVH/PVL发生率和严重程度的影响（主要结局指标为“4组中无严重IVH或PVL的幸存者比例”）和长期神经认知功能的有效性和安全性；目的2)探讨预防性吲哚美辛、DCC及其联合应用对小于28周胎龄婴儿的作用机制（血容量/循环状况、炎症应激、祖细胞）；目的3)确定各治疗组临床结果与机制测量之间的关系（n=400例）。随着极端早产的稳步上升以及体外受精与长期残疾的明确联系，有必要改善对这些患者的护理。这个多学科项目为研究不足的患者群体解决了一个重要的医疗问题，目前的做法有明显的局限性。