OPTIMUM OB-TXA: Optimal TIMing, route and dose of tranexamic acid prior to UMbilical cord clamp for postpartum hemorrhage prevention

最佳 OB-TXA：脐带钳夹前氨甲环酸预防产后出血的最佳时间、途径和剂量

• 批准号: 11000587
• 负责人: Homa Khorrami Ahmadzia
• 金额: $ 57.1万
• 依托单位: INOVA HEALTH CARE SERVICES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-09 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/11000587
• 关键词: OPTIMUM; OB; TXA; Optimal; TIMing

Project Summary The primary goal of this proposal is to fill critical gaps related to timing, route and dose of tranexamic acid (TXA) in prevention of postpartum hemorrhage (PPH) to maximize maternal benefit while minimizing fetal-neonatal and maternal risks. With my clinical background in Maternal-Fetal Medicine, research experiences in epidemiologic and translational coagulation methods, and prior preliminary data, I have the expertise and strong scientific premise to successfully complete these aims. The proposed innovative study focuses on three unique subpopulations (vaginal delivery, cesarean delivery, morbid obesity) and has three routes of TXA administration (intravenous over 2 minutes, intravenous over 10 minutes and intramuscular) immediately prior to childbirth. Neonatal exposure will be assessed through TXA concentrations in umbilical cord blood and breast milk, as well as clinical outcomes at delivery, 2 weeks and 6 weeks postpartum. The specific aims are as follows: 1a) Determine the optimal timing, route and dose of prophylactic TXA for prevention of PPH 1b) Determine neonatal exposure to TXA through transplacental transfer and breast milk when TXA is administered pre-cord clamp, and 2) Characterize prothrombotic and fibrinolytic biomarkers in maternal circulation following TXA. The innovative nature of this grant is multifold: a) repurposing an inexpensive generic drug to address disparities in obstetric hemorrhage; b) exploring rapid administration via IM and 2min infusion to improve access in low resource settings; c) pre-cord clamp TXA administration as a novel approach not yet considered in large obstetric clinical trials; d) refinement of dosing in unique subpopulations (morbidly obese, vaginal delivery); e) biomarker safety including a no drug group and f) a robust team of multidisciplinary experts with regional and international expertise. Specifically, team members have expertise in clinical pharmacology, neonatal medicine, lab medicine, thrombosis and hemostasis, clinical trials in pregnant women and newborns, pharmacometrics and epidemiology/biostatistics. I have an ideal working environment, rooted in the Clinical and Translational Science Institute partnering GW and Children’s National Hospital but also extended through supplemental sites at University of Maryland Center for Translational Medicine and University of North Carolina Coagulation Lab. In summary, this proposal sets forth aims that are significant, innovative, feasible, and will help the obstetric community better understand how peripartum hemostasis can be optimized using TXA while being sure to minimize fetal/neonatal risks. Ultimately, our work will answer important questions that are part of the solution for how to prevent maternal morbidity and mortality for the 140 million women worldwide that give birth each year.

项目摘要 这项建议的主要目标是填补与氨甲环酸(TXA)的时间、路线和剂量相关的关键空白 在预防产后出血(PPH)方面，以最大限度地增加产妇利益，同时最大限度地减少胎儿-新生儿和 母性风险。以我母胎医学的临床背景，流行病学的研究经验 和转化法凝血，以及前期的初步数据，我有专业知识和较强的科学性 成功完成这些目标的前提。拟议的创新研究侧重于三个独特的 亚群(阴道分娩、剖腹产、病态肥胖)，并有三种血栓素A给药途径 (静脉注射超过2分钟，静脉注射超过10分钟，肌肉注射)。 新生儿的暴露也将通过脐带血和母乳中的TXA浓度进行评估 观察分娩时、产后2周、6周的临床结局。具体目标如下：1) 确定预防性血栓素A预防PPH的最佳时机、途径和剂量 当脐带夹前注射TXA时，通过胎盘转移和母乳暴露于TXA，以及 2)分析TXA后母血中血栓前状态和纤溶状态的生物标志物。创新的 这项赠款的性质是多方面的：a)改变一种廉价仿制药的用途，以解决产科方面的差距 出血；b)探索通过IM和2分钟输液快速给药，以改善获得低资源的机会 设置；c)脐带前夹住TXA是一种尚未在大型产科临床上考虑的新方法 试验；d)改进独特亚群(病态肥胖、阴道分娩)的剂量；e)生物标记物的安全性 包括一个非毒品小组和f)一个强大的多学科专家团队，具有区域和国际合作 专业知识。具体地说，团队成员拥有临床药理学、新生儿医学、实验室医学、 血栓形成和止血，孕妇和新生儿的临床试验，药物计量学和 流行病学/生物统计学。我有一个理想的工作环境，植根于临床和翻译科学 研究所与乔治华盛顿大学和国立儿童医院合作，还通过以下补充网站扩展 马里兰大学转化医学中心和北卡罗来纳大学凝血实验室。在……里面 总结，这项建议阐述了重大的、创新的、可行的目标，并将帮助产科 社区更好地了解如何使用TXA优化围产期止血，同时确保 将胎儿/新生儿风险降至最低。最终，我们的工作将回答作为解决方案一部分的重要问题 关于如何预防全球1.4亿生育妇女的孕产妇发病率和死亡率 年。