Prevention of Postpartum Hemorrhage With Tranexamic Acid

Phase 2

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Cohort 2	Tranexamic Acid	Dose of Tranexamic acid 10 mg/kg will be administered.
Cohort 1	Tranexamic Acid	Dose of Tranexamic acid 5mg/kg will be administered.
Cohort 3	Tranexamic Acid	Dose of Tranexamic acid 15 mg/kg will be administered.

Primary Outcome Measures

Name	Time	Method
PK Model Parameter Estimates	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	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).

Secondary Outcome Measures

Name	Time	Method
Estimated Blood Loss	During surgery	Intraoperative blood loss
Safety Parameters	During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum	Safety parameters such as adverse events (including nausea/vomiting) and serious adverse events