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TXA: Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean

Sponsor
The George Washington University Biostatistics Center (Other)
Overall Status
Completed
CT.gov ID
NCT03364491
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
11,000
Enrollment
12
Locations
2
Arms
42.6
Actual Duration (Months)
916.7
Patients Per Site
21.5
Patients Per Site Per Month

Study Details

Study Description

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
  • 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

Study Type:
Interventional
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 intravenouslyParticipants 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 :
Mar 12, 2018
Actual Primary Completion Date :
Aug 31, 2021
Actual Study Completion Date :
Sep 30, 2021

Arms and Interventions

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 Names:
  • 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

    Primary Outcome Measures

    1. Maternal death or transfusion of packed red blood cells [by hospital discharge or by 7 days postpartum, whichever is sooner]

      Maternal death or transfusion of 1 or more units of packed red blood cells.

    Secondary Outcome Measures

    1. Estimated blood loss [From skin incision to transfer from operating room, average of 1 hour]

      Estimated blood loss in milliliters, collected from anesthesia record and operative report

    2. Maternal death or transfusion of packed red blood cells [within 7 days postpartum]

      Maternal death or transfusion of 1 or more units of packed red blood cells.

    3. Composite of surgical or radiological interventions to control bleeding and related complications, or maternal death [within 7 days postpartum]

      Interventions such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology

    4. Composite of maternal death, thromboembolic events (venous or arterial), ischemic stroke, myocardial infarction, new-onset seizure activity, or admission to the intensive care unit for more than 24 hours [within 6 weeks postpartum]

    5. Transfusion related acute lung injury (TRALI) [within 7 days postpartum]

      Ratio of partial pressure of oxygen to inspired fraction of oxygen below 300 within 6 hours of receiving a blood product with bilateral pulmonary edema on chest x-ray

    6. Transfusion of other blood products [within 7 days postpartum]

      Transfusion of 1 or more units of fresh frozen plasma, cryoprecipitate, or platelets or administration of any factor concentrates

    7. Transfusion of 4 or more units of packed red blood cells [within 7 days postpartum]

      Amount of packed red blood cells transfused, categorized as 0 to 3 units, or 4 or more units

    8. Acute kidney injury [within 7 days postpartum]

      Acute elevation of serum creatinine of ≥ 0.3 mg/dL during a period of 48 hours

    9. Thromboembolic events (venous or arterial), ischemic stroke, or myocardial infarction [within 6 weeks postpartum]

    10. New-onset seizure activity [within 6 weeks postpartum]

      Maternal seizure activity, confirmed by central review, whose onset is after randomization

    11. Postpartum infectious complications [within 6 weeks postpartum]

      Infectious complications such as: endometritis, surgical site infection, pelvic abscess

    12. Admission to the intensive care unit for more than 24 hours [within 6 weeks postpartum]

      Any admission to the intensive care unit that lasts more than 24 hours

    13. Maternal death [within 6 weeks postpartum]

    14. Use of uterotonics other than oxytocin [within 48 hours postpartum]

      Any use of uterotonics such as prostaglandins or methergine, but excluding oxytocin

    15. Surgical or radiologic interventions to control bleeding and related complications [within 7 days postpartum]

      Interventions such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology

    16. Change in hemoglobin [from 4 weeks before delivery to 48 hours postpartum]

      Change in hemoglobin from before cesarean to lowest post-operative measured

    17. TXA side effects [within 24 hours postpartum]

      Maternal TXA-related side-effects (nausea, vomiting, dizziness)

    18. Open label use of TXA or other antifibrinolytic [within 7 days postpartum]

      Use of any amount of open-label TXA (not blinded study drug) or other antifibrinolytic (eg., Amicar)

    19. Length of stay [Until hospital discharge, an average of 3 days]

      Mother's length of stay from delivery to discharge

    20. Hospital re-admission [within 6 weeks postpartum]

      Re-admission to the hospital after initial postpartum discharge

    21. Any transfusion-associated reactions [within 7 days postpartum]

      One more transfusion-associated reactions, such as fever, urticaria, anaphylaxis, alloimmunization

    22. Composite of treatments and interventions in response to bleeding and related complications [within 7 days postpartum]

      Treatments and interventions 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

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 University of Alabama - Birmingham Birmingham Alabama United States 35233
    2 Northwestern University-Prentice Hospital Chicago Illinois United States 60611
    3 Columbia University New York New York United States 10032
    4 University of North Carolina - Chapel Hill Chapel Hill North Carolina United States 27599
    5 Case Western Reserve-MetroHealth Cleveland Ohio United States 44109
    6 Ohio State University Hospital Columbus Ohio United States 43210
    7 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    8 Magee Women's Hospital of UPMC Pittsburgh Pennsylvania United States 15213
    9 Brown University Providence Rhode Island United States 02905
    10 University of Texas Medical Branch Galveston Texas United States 77555
    11 University of Texas - Houston Houston Texas United States 77030
    12 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

    • 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)

    None provided.

    More Information

    Publications

    Responsible Party:
    The George Washington University Biostatistics Center
    ClinicalTrials.gov Identifier:
    NCT03364491
    Other Study ID Numbers:
    • HD36801-TXA
    • U10HD036801
    • UG1HD087230
    • UG1HD027869
    • UG1HD040500
    • UG1HD034208
    • UG1HD027915
    • UG1HD040485
    • UG1HD053097
    • UG1HD040544
    • UG1HD040545
    • UG1HD040560
    • UG1HD040512
    • UG1HD087192
    First Posted:
    Dec 6, 2017
    Last Update Posted:
    Jun 15, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Hemorrhage
    Tranexamic Acid

    Study Results

    No Results Posted as of Jun 15, 2022