Prevention of Postpartum Hemorrhage With Tranexamic Acid

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Three doses of Tranexamic acid (5 mg/kg, 10 mg/kg, and 15 mg/kg) will be used in a dose escalation fashion by cohort with the lowest dose first.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose of Tranexamic acid 5mg/kg will be administered. | Drug: Tranexamic Acid<br>* Tranexamic acid dosage (5 mg/kg, 10 mg/kg and 15 mg/kg) administered in a dose escalating fashion by cohort with the lowest dose first.<br>* Other names: TXA; Cyklokapron;|
| Experimental: Cohort 2<br>Dose of Tranexamic acid 10 mg/kg will be administered. | Drug: Tranexamic Acid<br>* Tranexamic acid dosage (5 mg/kg, 10 mg/kg and 15 mg/kg) administered in a dose escalating fashion by cohort with the lowest dose first.<br>* Other names: TXA; Cyklokapron;|
| Experimental: Cohort 3<br>Dose of Tranexamic acid 15 mg/kg will be administered. | Drug: Tranexamic Acid<br>* Tranexamic acid dosage (5 mg/kg, 10 mg/kg and 15 mg/kg) administered in a dose escalating fashion by cohort with the lowest dose first.<br>* Other names: TXA; Cyklokapron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Tranexamic Acid | Serum Assay of TXA in blood and breast milk to determine clearance. | Different time points ranging from surgery (T0) to 1 day postpartum. | 
| Pharmacodynamics of Tranexamic acid | Pharmacodynamics: maximum lysis (ML) and other coagulation markers such as d-dimer and plasmin-anti-plasmin complexes | Different time points ranging from surgery (T0) to 1 day postpartum. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated blood loss | Intraoperative blood loss | During surgery | 
| Safety parameters | Safety parameters such as adverse events and serious adverse events | During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid, postpartum hemorrhage