Prevention of postpartum hemorrhage: identifying pregnant women at risk and determining the safe and effective use of tranexamic acid using state-of-the-art pharmacokinetic/pharmacodynamics modeling

预防产后出血：利用最先进的药代动力学/药效学模型识别处于危险中的孕妇并确定氨甲环酸的安全有效使用

• 批准号: 10160946
• 负责人: Homa Khorrami Ahmadzia
• 金额: $ 15.52万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160946
• 关键词: Address; Alteplase; Antifibrinolytic Agents; Applications Grants; Area; Award; Biological Assay; Biological Availability; Biometry; Blood; Blood Transfusion; Blood specimen; Cardiac; Cesarean section; Cessation of life; Child; Childhood; Clinical; Clinical Sciences; Closure by clamp; Coagulation Process; Collaborations; Data; Development; Discipline of obstetrics; Dose; Drug Formulations; Drug Kinetics; Educational workshop; Enrollment; Ensure; Environment; Epidemiologist; Fetal Research; Fibrinolysis Pathway; Functional disorder; Funding; Future; Goals; Half-Life; Health Care Costs; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospitalization; Hospitals; Hour; In Vitro; Incidence; Inpatients; Institutes; Institution; International; Intervention; Intravenous; Lead; Maternal Mortality; Maternal-fetal medicine; Medical; Medical Faculty; Medical center; Mentors; Mentorship; Methods; Modeling; National Institute of Child Health and Human Development; Nature; Oral; Orthopedics; Patients; Perinatal; Pharmaceutical Preparations; Pharmacodynamics; Plant Roots; Population; Positioning Attribute; Postpartum Hemorrhage; Pregnant Women; Prevention; Preventive; Randomized Clinical Trials; Registries; Research; Research Personnel; Resources; Rice; Risk; Risk Factors; Role; Safety; Sampling; Sensitivity and Specificity; Serum; Subgroup; Therapeutic; Third Pregnancy Trimester; Thromboembolism; Thrombophilia; Thrombosis; Time; Training; Tranexamic Acid; Transfusion; Translational Research; Trauma; Umbilical cord structure; United States National Institutes of Health; Vagina; Validation; Whole Blood; Woman; base; career; career development; data registry; design; epidemiology study; experience; health care service utilization; high risk; improved; innovation; maternal morbidity; mid-career faculty; mortality; multidisciplinary; novel; pharmacodynamic model; pharmacokinetic model; predictive modeling; pregnant; prevent; prophylactic; prospective; research study; risk prediction model; serological marker; success; tool; transfusion medicine; translational study

Project Summary/Abstract The primary goal of this proposal is to help further my development into an independent investigator in the area translational and clinical peripartum hemostasis research. With my clinical background in Maternal-Fetal Medicine and research experiences in epidemiologic and translational study methods, I am ideally positioned to succeed through the NIH K23 Career Mentored Development Award mechanism. The proposed study focuses on improving methods to identify women at risk for postpartum hemorrhage and evaluate the optimal dosing of tranexamic acid (TXA) for prevention in at risk women. The specific aims are as follows: 1) To improve the statistical risk prediction model for deliveries requiring blood transfusion, 2) To conduct a prospective clinical pharmacokinetic study using TXA prophylactically at time of delivery, and 3) To determine the pharmacodynamics (PD) of TXA in peripartum period and explore pre-delivery markers to predict peripartum blood transfusion. Collectively, these aims will better identify women at greatest risk for severe postpartum hemorrhage and determine the optimal dosing and effects of TXA on hemostasis when used for prevention of hemorrhage. I have identified excellent mentors and collaborators/advisors on her research team to help accomplish the outlined aims. The multidisciplinary nature of the project justifies a larger mentorship team in order for me to be successful. The primary mentor is Dr. John van den Anker, an internationally recognized expert in pharmacokinetic research and translational studies who is well-funded by NIH. My three other co-mentors include Dr. Madeline Rice, a senior epidemiologist at the GW Biostatistics Center, Dr. Richard Amdur, a senior biostatistician at GW Medical Faculty Associates and Dr. Naomi Luban, an internationally recognized and NIH-funded pediatric transfusion medicine expert. Important to my successful completion of Aim 2 is collaboration with GW obstetric anesthesiologist Dr. Jeffrey Berger. Finally, two additional senior investigators and internationally recognized experts are Dr. Alisa Wolberg and Dr. Andra James. Their collaboration and career mentorship will help ensure my success during and especially beyond this award. I will participate in coursework and focused workshops as well as hands-on training designed to promote investigator independence. I will benefit from an ideal working environment, rooted in the Clinical and Translational Science Institute partnering GW and Children’s National Medical Center but also extended through supplemental training at the GW Biostatistics Center and Dr. Wolberg’s hemostasis and thrombosis lab. In summary, this proposal sets forth aims that are significant, innovative and feasible, and will provide me with the tools and mentorship to develop into an independent investigator working to better understand how peripartum hemostasis can be optimized using tranexamic acid.

项目概要/摘要 该提案的主要目标是帮助我进一步发展成为该领域的独立调查员 凭借我在母胎方面的临床背景，进行转化和临床围产期止血研究。 流行病学和转化研究方法方面的医学和研究经验，我处于理想的位置 通过 NIH K23 职业指导发展奖机制取得成功。 重点是改进方法来识别有产后出血风险的妇女并评估最佳方案 氨甲环酸 (TXA) 的剂量用于预防高危女性的具体目标如下： 1) 改进需要输血的分娩的统计风险预测模型，2) 进行 在分娩时预防性使用 TXA 进行前瞻性临床药代动力学研究，以及 3) 确定 围产期 TXA 的药效学 (PD) 并探索产前标志物进行预测 总的来说，这些目标将更好地识别重症风险最高的女性。 产后出血并确定 TXA 用于止血时的最佳剂量和效果 我在她的研究团队中找到了优秀的导师和合作者/顾问。 帮助实现所概述的目标 该项目的多学科性质证明需要更大的指导。 约翰·范·登·安克 (John van den Anker) 博士是我取得成功的主要导师。 药代动力学研究和转化研究领域公认的专家，得到 NIH 的大力资助 我的三个。 其他共同导师包括 GW 生物统计中心的高级流行病学家 Madeline Rice 博士、 Richard Amdur 是 GW 医学院的高级生物统计学家，Naomi Luban 博士是 国际公认的、由 NIH 资助的儿科输血医学专家对我的成功非常重要。 目标 2 的完成是与 GW 产科麻醉师 Jeffrey Berger 博士的合作。 最后，还有两个目标。 其他高级研究人员和国际公认的专家是 Alisa Wolberg 博士和 Andra 博士 詹姆斯。他们的合作和职业指导将有助于确保我在期间和之后的成功。 我将参加旨在获得该奖项的课程和重点研讨会以及实践培训。 促进研究者的独立性，我将受益于植根于临床和临床的理想工作环境。 转化科学研究所与 GW 和儿童国家医疗中心合作，但也扩大了合作范围 通过GW生物统计中心和Wolberg博士的止血和血栓形成补充培训 总之，该提案提出了重大、创新和可行的目标，并将为我提供帮助。 借助工具和指导，发展成为一名独立调查员，更好地了解如何 使用氨甲环酸可以优化围产期止血。