Delayed Cord Clamping with Oxygen In Extremely Low Gestational Age Infants (DOXIE)

极低胎龄婴儿延迟供氧断脐 (DOXIE)

• 批准号: 10549378
• 负责人: Anup C Katheria
• 金额: $ 7.72万
• 依托单位: SHARP MEMORIAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10549378
• 关键词: Advocate; Air; Alveolar; Animals; Birth; Blinded; Blood; Blood flow; Brain; Breathing; Cardiac; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Closure by clamp; Continuous Positive Airway Pressure; Data; Delivery Rooms; Discipline of obstetrics; Disease; Double-Blind Method; Duct (organ) structure; Echocardiography; Enrollment; Extremely low gestational age newborn; Gases; Gestational Age; Head; Heart Rate; Hemorrhage; Hour; Hypoxemia; Hypoxia; Incidence; Infant; Infant Care; Intervention; Legal patent; Life; Lung; Masks; Measurement; Measures; Meta-Analysis; Methods; Milk; Morbidity - disease rate; Movement; Multicenter Trials; Nature; Near-Infrared Spectroscopy; Neonatal; Newborn Infant; Organ; Outcome; Oxygen; Oxygen Therapy Care; Oxygen saturation measurement; Partial Pressure; Peripheral; Physiological; Pilot Projects; Pregnancy; Premature Infant; Protocols documentation; Randomized; Randomized, Controlled Trials; Respiration; Resuscitation; Safety; Stream; Tidal Volume; Trachea; Ultrasonography; Umbilical cord structure; Umbilicus; Venous; Video Recording; Work; arm; design; disability; efficacy evaluation; extreme prematurity; face mask; feasibility testing; glottis; hemodynamics; improved; intraventricular hemorrhage; mortality; organ injury; oxygen toxicity; pilot trial; postnatal; pressure; preterm newborn; prevent; respiratory; safety and feasibility; supplemental oxygen; trial comparing; ventilation

Background: Current newborn care practice is to delay clamping and cutting the umbilical cord to allow for hemodynamic stabilization. Supported by numerous randomized controlled trials and meta-analyses, delayed cord clamping (DCC) is endorsed by both neonatal and obstetrical governing bodies. Limited oxygenation data on DCC in extremely preterm infants suggests they remain hypoxic immediately after birth. This may be due to differences in how infants transition during DCC. Immediately after delivery, extremely preterm infants attempt to initiate lung aeration and gas exchange. Animal studies have demonstrated that delaying clamping of the umbilical cord until breathing is established avoids adverse cerebral and cardiac hemodynamics, which may reduce bleeding in the brain, including severe intraventricular hemorrhage (sIVH). In a multicenter trial comparing DCC to umbilical cord milking, 76 percent of preterm newborns between 230-276 weeks gestation who received DCC without respiratory support initiated respirations prior to cord clamping, yet still had relative hypoxia demonstrated by a low 5-minute arterial oxygen saturation (SpO2 73 percent (95% CI 71.4, 75.6)). Two recent analyses found that preterm infants with a 5-minute SpO2 < 80 percent were more likely to have sIVH or death. Supplemental oxygen provided during DCC with resultant lung aeration may decrease significant morbidities and death in extremely preterm infants. A pilot study with detailed assessments of hemodynamics and organ function immediately after birth is needed to determine the efficacy and safety of providing 100 percent oxygen during DCC. Design: This randomized double-blinded pilot trial will enroll 140 extremely low gestational age infants (230- 276 weeks gestation) who receive DCC of at least 60 seconds with carefully detailed hemodynamic assessments and simultaneous video recordings. The study will evaluate infants providing continuous positive airway pressure (CPAP) and/or positive pressure ventilation (PPV) by face mask with an inspired fractional oxygen (FiO2) of 1.0 (HI Group) during DCC compared to infants given mask CPAP/PPV with an inspired FiO2 of 0.30 during DCC (LO Group). Due to the nature of the intervention, both arms receive CPAP/PPV with identical cord clamping times and respiratory support, the study can be blinded by covering the oxygen blender, avoiding any postnatal treatment bias. Once the cord is clamped and cut, each infant is resuscitated as per usual protocol (CPAP/PPV with a starting FiO2 0.30) by the clinical team. We will collect physiological parameters from birth through the first 24 hours of life (including detailed breathing assessments from video recordings at birth/ resuscitation suite). If we reduce hypoxia in extremely preterm infants by providing supplemental oxygen during the period of delayed cord clamping, there may be a dramatic reduction in morbidity and mortality. Depending on the findings, results will be used to design a more definitive larger, multicenter R01 trial powered for important clinical outcomes such as severe IVH or death and neurodevelopmental outcomes.

背景：当前的新生儿护理实践是延迟夹紧和切断脐带，以允许 血流动力学稳定。在大量随机对照试验和荟萃分析的支持下，延迟 脐带钳夹 (DCC) 得到了新生儿和产科管理机构的认可。有限氧合数据 对极早产儿进行 DCC 的研究表明，他们在出生后立即仍然处于缺氧状态。这可能是由于 DCC 期间婴儿过渡方式的差异。极度早产儿在分娩后立即尝试 启动肺部通气和气体交换。动物研究表明，延迟夹紧 脐带直到呼吸建立可避免不良的脑和心脏血流动力学，这可能 减少脑出血，包括严重脑室内出血 (sIVH)。在一项多中心试验中比较 DCC 到脐带挤奶，76% 的妊娠 230-276 周的早产新生儿接受了脐带挤奶 没有呼吸支持的 DCC 在钳夹脐带之前开始呼吸，但仍然存在相对缺氧 5 分钟动脉血氧饱和度较低（SpO2 73% (95% CI 71.4, 75.6)）即可证明。最近的两个 分析发现，5 分钟 SpO2 < 80% 的早产儿更有可能患有 sIVH 或 死亡。 DCC 期间提供的补充氧气可能会显着减少肺通气量 极早产儿的发病和死亡。详细评估血流动力学的初步研究 出生后立即需要器官功能来确定提供 100% 的有效性和安全性 DCC 期间吸氧。 设计：这项随机双盲试点试验将招募 140 名极低胎龄婴儿（230- 妊娠 276 周）接受至少 60 秒的 DCC 并进行仔细详细的血流动力学评估 和同步视频录制。该研究将评估提供持续气道正压的婴儿 (CPAP) 和/或通过面罩进行正压通气 (PPV)，吸入氧分数 (FiO2) 为 1.0 （HI 组）在 DCC 期间与使用面罩 CPAP/PPV 的婴儿进行比较，DCC 期间吸入 FiO2 为 0.30 （LO 集团）。由于干预的性质，双臂均采用相同的脐带夹紧方式接受 CPAP/PPV 时间和呼吸支持，该研究可以通过覆盖氧气混合器来进行盲法，避免任何产后 治疗偏差。一旦脐带被夹住并剪断，每个婴儿都会按照常规方案（CPAP/PPV 临床团队的初始 FiO2 0.30）。我们将收集从出生到第一次出生的生理参数 生命 24 小时（包括出生时/复苏套件中的视频记录的详细呼吸评估）。如果 我们通过在延迟分娩期间提供补充氧气来减少极早产儿的缺氧 脐带夹紧可能会大大降低发病率和死亡率。根据调查结果、结果 将用于设计更明确的大型多中心 R01 试验，为重要的临床结果提供动力，例如 严重的 IVH 或死亡和神经发育结果。