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）和脑室白细胞乳突（PVL）是早产儿中通常发生的脑病变，并且是长期脑损伤的主要贡献者，对长期的脑损伤及其后期的相关障碍。尽管它的普遍性，长期后果以及巨大的医疗和社会成本，IVH的机制以及预防或治疗其发生的最佳策略的定义很差，尤其是对于极早的婴儿而言。仅在生命的前三天，只有一种药物疗法，预防性放病蛋白可以预防或降低早产儿中IVH的严重程度，但其使用受到有毒副作用和对长期结果的可争议作用的限制。几项小型研究和病例报告表明，延迟的脐带斜率（DCC）也可能会降低早产婴儿IVH的发生率，但迄今为止，这些试验在其绳索夹紧方案中混合了散氨酸治疗。因此，我们将对4个治疗组进行随机，盲目的研究：1）对照（无干预）； 2）单独使用DCC； 3）单独预防性放霉素； 4）关于生存，IVH或PVL的发生率和严重程度，神经发育结果以及相关机械作用的DCC/吲哚美辛的组合。我们的具体目的是：目标1）比较预防性放病蛋白，DCC及其组合的功效和安全性，以影响<28WKS胎龄IVH/PVL的发病率和严重程度（未经严重的IVH或PVL'组中的生存者的主要结果度量的主要成果量度）和更长的Neurocoction; AIM 2）研究预防性吲哚美辛，DCC及其在小于28周妊娠年龄（血容量/循环状态，炎症应激，祖细胞）中的机械作用；目标3）确定治疗组之间临床结果与机械测量之间的关系（n = 400例总病例）。随着极端早产出生的稳定增长和IVH与长期残疾的明确联系，需要改善对这些患者的护理。这个多学科的项目解决了当前实践有明显局限性的研究经验不足的患者人群的重要医疗问题。