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: 9927496
• 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/9927496
• 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.

项目总结/文摘