Prevention of Postpartum Hemorrhage With Tranexamic Acid

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic Acid

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • James Slota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Dose of Tranexamic acid 5mg/kg will be administered.	Drug: Tranexamic Acid; 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.; Other Names: TXA; Cyklokapron
EXPERIMENTAL: Cohort 2; Dose of Tranexamic acid 10 mg/kg will be administered.	Drug: Tranexamic Acid; 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.; Other Names: TXA; Cyklokapron
EXPERIMENTAL: Cohort 3; Dose of Tranexamic acid 15 mg/kg will be administered.	Drug: Tranexamic Acid; 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.; Other Names: TXA; Cyklokapron

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Homa Ahmadzia, MD, George Washington University

Publications and helpful links

General Publications

• Ahmadzia HK, Luban NLC, Li S, Guo D, Miszta A, Gobburu JVS, Berger JS, James AH, Wolberg AS, van den Anker J. Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women. Am J Obstet Gynecol. 2021 Jul;225(1):85.e1-85.e11. doi: 10.1016/j.ajog.2020.11.035. Epub 2020 Nov 26.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2018
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: June 27, 2017
• First Submitted That Met QC Criteria: September 18, 2017
• First Posted (ACTUAL): September 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: tranexamic acid; postpartum hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: IND134701; UL1TR001876 (NIH); KL2TR001877 (NIH); K23HL141640 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No