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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- PK Model Parameter Estimates
研究概览
简要总结
Postpartum hemorrhage is a significant contributor to maternal morbidity and mortality and is worldwide. TXA has recently been proven to reduce mortality when given to women in setting of diagnosed PPH. US obstetricians and anesthesiologists are hesitant to use TXA in the peripartum period especially for prevention of PPH due to uncertainty of an optimal dose and safety profile. The purpose of this study is to characterize the pharmacokinetics of TXA when given prophylactically at time of delivery. In addition investigators will determine the pharmacodynamics of TXA in the peripartum period.
详细描述
Conduct a prospective, open-label, dose finding PK study in 30 pregnant 3rd trimester women scheduled for non-emergent cesarean section who are at risk for hemorrhage. Three doses of the drug will be administered in an escalating fashion by cohort with the lowest dose first. A maximum of 1 gram will be administered. TXA serum levels at several time points after delivery will be assayed. A PK model will be constructed for determining the optimal TXA dose administered at parturition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women who are undergoing medically indicated cesarean section at greater than 34+0 weeks gestation or women undergoing elective cesarean section at 39+0 weeks gestation in accordance with recommendations from the American Congress of Obstetricians and Gynecologists
- •Pregnant women with normal serum creatinine (serum creatinine < 0.9)
- •Women between the ages of 18 and 50 years old
排除标准
- •Patients younger than 18 or older than 50
- •women with active thrombotic or thromboembolic disease
- •Women with a history of arterial or venous thromboembolic event
- •Women with inherited thrombophilia or preexisting conditions that predisposes them to thromboembolic events (i.e. lupus, antiphospholipid syndrome)
- •Women with a subarachnoid hemorrhage
- •Women with acquired defective color vision
- •history of seizure disorder
- •known renal dysfunction
- •multiple gestations (Twin or triplet pregnancies)
- •Hypersensitivity to Tranexamic acid or anti-fibrinolytic therapy
- •History of liver dysfunction
研究组 & 干预措施
Cohort 1
Dose of Tranexamic acid 5mg/kg will be administered.
干预措施: Tranexamic Acid (Drug)
Cohort 2
Dose of Tranexamic acid 10 mg/kg will be administered.
干预措施: Tranexamic Acid (Drug)
Cohort 3
Dose of Tranexamic acid 15 mg/kg will be administered.
干预措施: Tranexamic Acid (Drug)
结局指标
主要结局
PK Model Parameter Estimates
时间窗: Different time points ranging from surgery (T0) to 1 day postpartum.
Data obtained from assays of TXA in blood, dose group and patient characteristics; parameter estimates in 2 compartment model includes the clearance of the drug (L/hr).
Pharmacodynamics of Tranexamic Acid
时间窗: Different time points ranging from surgery (T0) to 1 day postpartum.
PD model parameters included concentration of TXA causing 50% of maximal fractional inhibition (IC50).
次要结局
- Estimated Blood Loss(During surgery)
- Safety Parameters(During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum)
研究者
Homa K. Ahmadzia
PI
George Washington University