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症（PVL）是早产儿常见的脑部病变，是公认的长期脑损伤和日后相关残疾的主要原因。尽管其流行，长期的后果，以及巨大的医疗和社会成本，IVH的机制和最佳的策略，以防止或治疗其发生的定义很差，特别是对于极早产儿。只有一种药物治疗，即在生命的前3天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和对长期结局的影响的限制。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了吲哚美辛治疗。因此，我们将对4个治疗组进行随机、盲法研究：1）对照（无干预）; 2）单独DCC; 3）单独预防性吲哚美辛; 4）DCC/吲哚美辛联合治疗，研究生存率、IVH或PVL发生率和严重程度、神经发育结局和相关机制效应。我们的具体目标是：目的1）比较吲哚美辛、DCC及其联合应用对<28周胎龄儿IVH/PVL发生率和严重程度的影响（4组中“无严重IVH或PVL的存活者比例”的主要结局指标）和长期神经认知功能;目的2）探讨吲哚美辛、DCC及其联合应用对小于28周胎龄儿的预防作用机制（血容量/循环状态、炎症应激、祖细胞）;和目的3）确定治疗组之间的临床结果和机械测量之间的关系（n=400个总病例）。随着极端早产的稳步上升以及IVH与长期残疾的明确联系，有必要改善对这些患者的护理。这个多学科项目解决了一个重要的医疗问题，为一个研究不足的患者群体，目前的做法有明显的局限性。