Indomethacin and Delayed Umbilical Cord Clamp for Preterm Infant IVH
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 256
- 试验地点
- 1
- 主要终点
- Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
研究概览
简要总结
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. The investigators are conducting 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. 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.
详细描述
The investigators will compare efficacy and safety of prophylactic indomethacin, DCC, and their combination, in affecting the incidence and severity of IVH/PVL in infants <30wks gestational age (primary outcome measure of 'fraction of survivors with no severe IVH or PVL' among the 4 groups), and longer term neurocognitive function. Other secondary endpoints and investigations include mechanistic effects of prophylactic indomethacin, DCC, and their combination (blood volume/circulatory status, inflammatory stress, progenitor cells) as well as defining relationships between clinical outcomes and mechanistic measurements among treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 24 Weeks 至 30 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •pregnant women admitted >24weeks and <30weeks gestational age,
- •in-hospital birth (allowing for cord clamp randomization)
排除标准
- •preterm infant <24weeks or >30weeks at birth
- •maternal risks identified by obstetrician
- •fetal risks identified by obstetrician
- •any congenital abnormality of newborn infant
- •placental abruption/placental previa
- •delivery less than 2hrs from consenting to study participation
研究组 & 干预措施
immediate cord clamp & placebo IV solution
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
干预措施: placebo infusion (Drug)
immediate cord clamp & placebo IV solution
This Arm will receive immediate clamp of umbilical cord at birth, and an intravenous delivery of placebo drug solution (diluent for active drug, indomethacin) within the first 12hrs of life.
干预措施: immediate cord clamp at birth (Procedure)
delay cord clamp & placebo IV solution
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
干预措施: delay in umbilical cord clamp at birth (Procedure)
delay cord clamp & placebo IV solution
A delay in cord clamp for 45 seconds will be instituted in the delivery room. Placebo drug solution will be administered within 12hrs post-birth.
干预措施: placebo infusion (Drug)
immediate cord clamp & indomethacin IV
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
干预措施: Indomethacin (Drug)
immediate cord clamp & indomethacin IV
Umbilical cord will be clamped immediately at birth. Indomethacin will be administered IV, starting within 12hrs of life (0.1mg/kg every 24 hrs for three total doses.This intervention is considered 'standard care' at many Neonatology medical facilities. The dose of indomethacin has been shown to be effective in reducing brain bleeds in preterm infants (although there are also data showing safety concerns).
干预措施: immediate cord clamp at birth (Procedure)
indomethacin iv & delayed cord clamp
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
干预措施: Indomethacin (Drug)
indomethacin iv & delayed cord clamp
A delay in cord clamp of 45 seconds will be instituted in the delivery room. In addition, indomethacin will be administered iv (initiated within 12hrs of life), 0.1mg/kg every 24 hrs for three total doses.
干预措施: delay in umbilical cord clamp at birth (Procedure)
结局指标
主要结局
Percent of Survivors With no Severe IVH (Grades 3 or 4) or PVL
时间窗: within first 60 days of life
determined by head ultrasound in Neonatal Intensive Care Unit (NICU) and single head MRI at 38weeks corrected gestational age
次要结局
- Number of Participants With Acute Kidney Injury(first 60 days of life)
研究者
Hong Huang
Research Protocol Manager/Clinical/UKHC
University of Kentucky