Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery (TXA)

January 12, 2021 updated by: Olutoyosi Ogunkua, MD, University of Texas Southwestern Medical Center

Use of Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery

The investigators prepared a novel study of tranexamic acid (TXA) designed to estimate the quantity of blood loss in women undergoing elective repeat cesarean deliveries. This is the first trial to utilize a prophylactic dose of TXA prior to incision followed by a subsequent prophylactic dose at placental delivery in obstetric patients undergoing scheduled cesareans. The purpose of this study is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The central hypothesis is that TXA administration reduces blood loss and fibrinolysis in women undergoing repeat cesarean sections.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Obstetric hemorrhage has been identified as a contributory cause for the United States' suboptimal and inequitable outcomes among pregnant women. As such, obstetric hemorrhage has become a formal focus point in a national agenda to improve maternal outcomes. Strategies to identify maternal hypovolemia and treating obstetric hemorrhage are undergoing organized scrutiny in many states including Texas. Tranexamic acid (TXA) treatment is receiving increased emphasis in obstetric care because TXA inhibits fibrinolysis. Increased clot stability offers the possibility of preventing blood loss (prophylaxis) as well as mitigating ongoing hemorrhage. TXA therapy has been principally studied in nonpregnant populations; results of studies in pregnant women have been lacking.

Tranexamic acid is an antifibrinolytic agent that acts as a competitive inhibitor at the lysine binding sites of plasminogen and inhibits the ability of protease plasmin to cleave the fibrin clot. In large randomized controlled trials, it has been reported to be effective in decreasing perioperative blood loss in a variety of circumstances primarily involving trauma patients. Shakur and co-authors in a trial of 20,000 non-pregnant trauma patients reported a significant reduction in all-cause mortality after TXA administration. In another large study (WOMAN Trial), 20,000 pregnant women with hemorrhage were randomized to TXA or placebo. TXA was associated with a significant decrease in death due to bleeding.

Tranexamic acid's role in treating hemorrhage have been widely studied in non-pregnant populations. Studies of TXA in obstetrics are limited. The American College of Obstetricians and Gynecologists believes the data is insufficient to recommend tranexamic acid for prophylaxis.

The investigators designed a randomized placebo-controlled trial comparing TXA dosing prior to incision for cesarean delivery with a repeat dose given at placental delivery. The purpose is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The investigators elected to study scheduled elective cesareans because such procedures are at low risk for profound hemorrhage. It is the intent to have a study cohort where the two treatment groups (TXA or placebo) are as comparable as possible, so the efficacy of TXA is not tested in women with highly variable volumes of obstetric hemorrhage.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75235
        • Parkland Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Intrauterine pregnancy
  2. Age ≥ 18
  3. Gestation age ≥ 37 weeks 0 days
  4. Scheduled cesarean delivery
  5. Second or third cesarean delivery
  6. Singleton pregnancy

Exclusion Criteria:

  1. First cesarean delivery
  2. Four or more cesarean deliveries
  3. Intrauterine fetal death
  4. Fetal anomalies
  5. Documented coagulopathy (Elevated Prothrombin Time (PT), Elevated Partial Thromboplastin Time (PTT), Elevated International Normalized Ratio (INR))
  6. Thrombocytopenia (Platelet count < 100k)
  7. Internal bleeding, external bleeding, easy bruising
  8. History of thrombotic event
  9. Hypertension
  10. Diagnosis of renal insufficiency (Creatinine> 1 mg/dL)
  11. Insulin-treated diabetes
  12. Suspected morbidly adherent placenta
  13. Placenta previa
  14. Multiple Gestations
  15. BMI ≥ 50
  16. Hematocrit ≤ 25
  17. Blood transfusion within 24 hours prior to cesarean delivery
  18. History of abnormal bleeding or blood disorder
  19. Planned general anesthesia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tranexamic acid
Tranexamic Acid for intravenous administration.
Drug: Tranexamic Acid
Two doses of Tranexamic Acid (1 gram), diluted in 100 cc of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.
Other Names:
  • Cyklokapron
Placebo Comparator: Placebo
Normal saline for intravenous administration.
Drug: Placebo
100 mL of normal saline. Administered intravenously at least 10 minutes prior to skin incision and repeated immediately after placental delivery.
Other Names:
  • Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Volume Loss
Time Frame: 24 hours postpartum.
Total blood volume loss will be calculated in milliliters.
24 hours postpartum.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
D-Dimer (µg/mL)
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Measured from blood sample collection.
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Fibrinogen (mg/dL)
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Measured from blood sample collection.
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Tissue Plasminogen Activator Antigen (ng/mL)
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Measured from blood sample collection.
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Plasminogen Activator Inhibitor-Type-1 (Units/mL)
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Measured from blood sample collection.
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Rotational Thromboelastometry INTEM and EXTEM Clotting Time
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter).
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Rotational Thromboelastometry INTEM, EXTEM, FIBTEM Maximum Clot Firmness
Time Frame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter).
Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

  • Principal Investigator: Olutoyosi Ogunkua, M.D., UT Southwestern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 17, 2019

Primary Completion (Actual)

January 10, 2020

Study Completion (Actual)

August 31, 2020

Study Registration Dates

First Submitted

February 21, 2019

First Submitted That Met QC Criteria

February 25, 2019

First Posted (Actual)

February 27, 2019

Study Record Updates

Last Update Posted (Actual)

January 19, 2021

Last Update Submitted That Met QC Criteria

January 12, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU-2018-0315

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

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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