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Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean (TXA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03364491
Recruitment Status : Completed
First Posted : December 6, 2017
Results First Posted : January 19, 2023
Last Update Posted : February 21, 2023
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
The George Washington University Biostatistics Center

Study Description
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Brief Summary:
A randomized placebo-controlled trial of 11,000 women to assess whether tranexamic acid as prophylaxis lowers the risk of postpartum hemorrhage in women undergoing a cesarean delivery.

Condition or disease Intervention/treatment Phase
Obstetrical Complications Hemorrhage Labor and Delivery Drug: Tranexamic Acid Drug: Placebo Phase 3

Detailed Description:

Obstetrical hemorrhage is a common cause of maternal morbidity and mortality worldwide. The frequency and severity of hemorrhage is significantly higher after cesarean delivery than vaginal delivery. Recent evidence has emerged about the importance of the fibrinolytic pathway in the pathophysiology of hemorrhage in different clinical scenarios including trauma-associated bleeding, cardiovascular surgery, and obstetrical hemorrhage. Tranexamic acid (TXA) inhibits fibrinolysis and is used routinely to prevent hemorrhage in trauma cases and high risk surgeries. Randomized trials of TXA as a prophylaxis to prevent hemorrhage in cesarean delivery have been small and of mixed quality; however meta-analysis suggests that it is effective.

This study is a randomized placebo-controlled trial of 11,000 women to assess whether tranexamic acid as prophylaxis lowers the risk of postpartum hemorrhage in women undergoing a cesarean delivery.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to receive either TXA (1 gram [10cc] mixed with 40 cc of normal saline) administered intravenously or a placebo control of 50 cc of normal saline administered intravenously
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The patient nor the clinical staff will be aware of the treatment assignment. The TXA or placebo solutions will be prepared by the center research pharmacies.
Primary Purpose: Prevention
Official Title: Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean Delivery: A Randomized Controlled Trial
Actual Study Start Date : March 15, 2018
Actual Primary Completion Date : July 24, 2021
Actual Study Completion Date : October 29, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tranexamic Acid
Tranexamic Acid for intravenous administration
 Drug: Tranexamic Acid
A single dose of Tranexamic Acid (1 gram) in normal saline for a total of 50cc, administered intravenously immediately following umbilical cord clamping (or as soon as possible afterward)
Other Name: TXA
Placebo Comparator: Placebo
Normal saline for intravenous administration
 Drug: Placebo
50 cc normal saline administered intravenously immediately following umbilical cord clamping (or as soon as possible afterward)


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Maternal Death or Transfusion of Packed Red Blood Cells [ Time Frame: by hospital discharge or by 7 days postpartum, whichever is sooner ]
    Participants were monitored from delivery until hospital discharge or 7 days after delivery (postpartum), whichever is sooner. This is the number of mothers who died for any reason, or had a blood transfusion of 1 or more units (of packed red blood cells, including whole blood or cell saver).


Secondary Outcome Measures :
  1. Number of Participants With Estimated Blood Loss Greater Than 1 Liter During Delivery [ Time Frame: From skin incision to transfer from operating room, average of 1 hour ]
    [Major secondary outcome] The surgeon or anesthesiologist estimated the blood loss during the delivery in milliliters, which was recorded in the anesthesia record and/or operative report

  2. Number of Mothers Who Died or Had Thromboembolic Events (Venous or Arterial), Ischemic Stroke, Myocardial Infarction, New-onset Seizure Activity, or Were Admitted to the Intensive Care Unit for More Than 24 Hours [ Time Frame: within 6 weeks postpartum ]
  3. Number of Participants Who Were Transfused With Other Blood Products [ Time Frame: within 7 days postpartum ]
    This is the number of mothers who received during the first 7 days after delivery a transfusion of 1 or more units of fresh frozen plasma, cryoprecipitate, or platelets, or received any factor concentrates

  4. Number of Participants Who Were Transfused With 4 or More Units of Packed Red Blood Cells [ Time Frame: within 7 days postpartum ]
    Participants were categorized according to the amount of packed red blood cells or whole blood transfused, either as 0 to 3 units, or 4 or more units

  5. Number of Participants With a Thromboembolic Event (Venous or Arterial), Ischemic Stroke, or Myocardial Infarction [ Time Frame: within 6 weeks postpartum ]
    [Key secondary outcome] This is the number of mothers who experienced a thromboembolic event, ischemic stroke, or myocardial infarction during the 6 weeks after delivery.

  6. Number of Participants With Seizure Activity That Was Not Seen Prior to Study Enrollment [ Time Frame: within 6 weeks postpartum ]
    This is the number of mothers who experienced seizure activity, confirmed by central review, whose onset is after enrollment

  7. Number of Participants With Postpartum Infectious Complications [ Time Frame: within 6 weeks postpartum ]
    [Key Secondary Outcome] This is the number of mothers who experienced any of the following infectious complications in the 6 weeks after delivery: endometritis, surgical site infection, pelvic abscess

  8. Number of Participants Who Were Treated With Uterotonics Other Than Oxytocin [ Time Frame: within 48 hours postpartum ]
    This is the number of mothers who were treated with uterotonics such as prostaglandins or methergine, but excluding oxytocin, from delivery through 48 hours after delivery.

  9. Number of Participants Who Received Surgical or Radiologic Interventions to Control Bleeding and Related Complications [ Time Frame: within 7 days postpartum ]
    This is the number of mothers who required any of the following types of surgical procedures to control bleeding: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology

  10. Change in Hemoglobin [ Time Frame: from 4 weeks before delivery to 48 hours postpartum ]
    [Key secondary outcome] Change in hemoglobin from the most recent measured before delivery to lowest measured in the 48 hours after delivery

  11. Number of Participants Who Received Open Label TXA or Other Antifibrinolytic [ Time Frame: within 7 days postpartum ]
    This is the number of mothers who were treated with any amount of open-label TXA (not blinded study drug) or another antifibrinolytic (eg., Amicar)

  12. Length of Stay [ Time Frame: Until hospital discharge, an average of 3 days ]
    Mother's length of stay from delivery to discharge

  13. Number of Participants Who Received Treatments and Interventions in Response to Bleeding and Related Complications [ Time Frame: within 7 days postpartum ]
    [Key secondary outcome] This is the number of mothers who received treatments and interventions to control bleeding such as: uterotonics such as prostaglandins or methergine, but excluding oxytocin; open label TXA or other antifibrinolytics; transfusion of 1 or more units of fresh frozen plasma, cryoprecipitate, or platelets or administration of any factor concentrates; laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Scheduled or unscheduled cesarean delivery
  2. Singleton or twin gestation

Exclusion Criteria:

  1. Age less than 18 years
  2. Transfusion or planned transfusion of any blood products during the current admission because the primary outcome is already pre-determined and the need for transfusion will be unrelated to perioperative hemorrhage
  3. Recent diagnosis or history of venous thromboembolism or arterial thrombosis because TXA is a risk factor for thromboembolism, and its use is contraindicated
  4. Known congenital or acquired thrombophilias, including antiphospholipid antibody syndrome, because of the increased risk of thrombosis
  5. Seizure disorder (including eclampsia) because TXA is a GABA receptor antagonist, and its use has been associated with postoperative seizures
  6. Serum creatinine 1.2 or higher or on dialysis, with renal disease, or a history of renal insufficiency, because TXA is substantially excreted by the kidney, and impaired renal function may increase the risk of toxic reactions.
  7. Sickle cell disease, because of substantial use of perioperative transfusion unrelated to hemorrhage. Sickle cell trait is not an exclusion per se.
  8. Autoimmune diseases such as lupus, rheumatoid arthritis, Sjogren's disease, and inflammatory bowel disease because of hypercoagulability and the increased risk of thrombosis or thromboembolism
  9. Need for therapeutic dose of anticoagulation before delivery, because the risk of thrombosis may be increased with TXA
  10. Treatment with clotting factor concentrates, because the risk of thrombosis may be increased with TXA
  11. Presence of frank hematuria, because the risk of ureteral obstruction in those with upper urinary tract bleeding may be increased with TXA
  12. Patient refusal of blood products because the primary outcome is then pre-determined
  13. Receipt of TXA; or planned or expected use of TXA prophylaxis
  14. Active cancer, because of risk of thromboembolism
  15. Congestive heart failure requiring treatment, because of risk of thrombosis
  16. History of retinal disease, because the risk of central retinal artery or vein obstruction may be increased with TXA
  17. Acquired defective color vision or subarachnoid hemorrhage, since TXA is contraindicated
  18. Hypersensitivity to TXA or any of the ingredients
  19. No hemoglobin result available from the last 4 weeks, since it is necessary to measure the post-operative change in hemoglobin
  20. Scheduled cesarean delivery and quota for scheduled deliveries already met. Quotas on the number of scheduled and unscheduled deliveries will be placed to ensure approximately equal distribution of scheduled and unscheduled cesarean deliveries.
  21. Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
  22. Participating in another intervention study where the primary outcome includes postpartum bleeding or thromboembolism, or the study intervention directly affects postpartum bleeding or thromboembolism
  23. Receipt of uterotonics, other than oxytocin, or planned or expected use of uterotonic prophylaxis
  24. Symptomatic for COVID-19 infection within 14 days prior to delivery
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03364491


Locations
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United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States, 35233
United States, Illinois
Northwestern University-Prentice Hospital
Chicago, Illinois, United States, 60611
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case Western Reserve-MetroHealth
Cleveland, Ohio, United States, 44109
Ohio State University Hospital
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Magee Women's Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
University of Texas - Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Rebecca Clifton, Ph.D. The George Washington University Biostatistics Center
Study Director: Monica Longo, MD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Chair: Louis Pacheco, MD UTMB
  Study Documents (Full-Text)

Documents provided by The George Washington University Biostatistics Center:
Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] April 8, 2021

More Information
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Publications:

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Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT03364491    
Other Study ID Numbers: HD36801-TXA
U10HD036801 ( U.S. NIH Grant/Contract )
UG1HD087230 ( U.S. NIH Grant/Contract )
UG1HD027869 ( U.S. NIH Grant/Contract )
UG1HD040500 ( U.S. NIH Grant/Contract )
UG1HD034208 ( U.S. NIH Grant/Contract )
UG1HD027915 ( U.S. NIH Grant/Contract )
UG1HD040485 ( U.S. NIH Grant/Contract )
UG1HD053097 ( U.S. NIH Grant/Contract )
UG1HD040544 ( U.S. NIH Grant/Contract )
UG1HD040545 ( U.S. NIH Grant/Contract )
UG1HD040560 ( U.S. NIH Grant/Contract )
UG1HD040512 ( U.S. NIH Grant/Contract )
UG1HD087192 ( U.S. NIH Grant/Contract )
First Posted: December 6, 2017    Key Record Dates
Results First Posted: January 19, 2023
Last Update Posted: February 21, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses. Data be will accessible through the NICHD Data and Specimen Hub.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The George Washington University Biostatistics Center:
Tranexamic Acid
Hemorrhage
Cesarean
Additional relevant MeSH terms:
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Hemorrhage
Pathologic Processes
Tranexamic Acid
Antifibrinolytic Agents
 Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants