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

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ClinicalTrials.gov Identifier: NCT03364491
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : July 12, 2019
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

Tracking Information
First Submitted Date  ICMJE November 22, 2017
First Posted Date  ICMJE December 6, 2017
Last Update Posted Date July 12, 2019
Actual Study Start Date  ICMJE March 12, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2017)
Maternal death or transfusion of packed red blood cells [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03364491 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2017)
  • Estimated blood loss [ Time Frame: From skin incision to transfer from operating room, average of 1 hour ]
    Estimated blood loss in milliliters, collected from anesthesia record and operative report
  • Maternal death or transfusion of packed red blood cells [ Time Frame: within 7 days postpartum ]
    Maternal death or transfusion of 1 or more units of packed red blood cells.
  • Composite of surgical or radiological interventions to control bleeding and related complications, or maternal death [ Time Frame: within 7 days postpartum ]
    Interventions such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology
  • 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 [ Time Frame: within 6 weeks postpartum ]
  • Transfusion related acute lung injury (TRALI) [ Time Frame: 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
  • Transfusion of other blood products [ Time Frame: within 7 days postpartum ]
    Transfusion of 1 or more units of fresh frozen plasma, cryoprecipitate, or platelets or administration of any factor concentrates
  • Transfusion of 4 or more units of packed red blood cells [ Time Frame: within 7 days postpartum ]
    Amount of packed red blood cells transfused, categorized as 0 to 3 units, or 4 or more units
  • Acute kidney injury [ Time Frame: within 7 days postpartum ]
    Acute elevation of serum creatinine of ≥ 0.3 mg/dL during a period of 48 hours
  • Thromboembolic events (venous or arterial), ischemic stroke, or myocardial infarction [ Time Frame: within 6 weeks postpartum ]
  • New-onset seizure activity [ Time Frame: within 6 weeks postpartum ]
    Maternal seizure activity, confirmed by central review, whose onset is after randomization
  • Postpartum infectious complications [ Time Frame: within 6 weeks postpartum ]
    Infectious complications such as: endometritis, surgical site infection, pelvic abscess
  • Admission to the intensive care unit for more than 24 hours [ Time Frame: within 6 weeks postpartum ]
    Any admission to the intensive care unit that lasts more than 24 hours
  • Maternal death [ Time Frame: within 6 weeks postpartum ]
  • Use of uterotonics other than oxytocin [ Time Frame: within 48 hours postpartum ]
    Any use of uterotonics such as prostaglandins or methergine, but excluding oxytocin
  • Surgical or radiologic interventions to control bleeding and related complications [ Time Frame: within 7 days postpartum ]
    Interventions such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology
  • Change in hemoglobin [ Time Frame: from 4 weeks before delivery to 48 hours postpartum ]
    Change in hemoglobin from before cesarean to lowest post-operative measured
  • TXA side effects [ Time Frame: within 24 hours postpartum ]
    Maternal TXA-related side-effects (nausea, vomiting, dizziness)
  • Open label use of TXA or other antifibrinolytic [ Time Frame: within 7 days postpartum ]
    Use of any amount of open-label TXA (not blinded study drug) or other antifibrinolytic (eg., Amicar)
  • Length of stay [ Time Frame: Until hospital discharge, an average of 3 days ]
    Mother's length of stay from delivery to discharge
  • Hospital re-admission [ Time Frame: within 6 weeks postpartum ]
    Re-admission to the hospital after initial postpartum discharge
  • Any transfusion-associated reactions [ Time Frame: within 7 days postpartum ]
    One more transfusion-associated reactions, such as fever, urticaria, anaphylaxis, alloimmunization
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean
Official Title  ICMJE Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean Delivery: A Randomized Controlled Trial
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • Obstetrical Complications
  • Hemorrhage
  • Labor and Delivery
Intervention  ICMJE
  • 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
  • Drug: Placebo
    50 cc normal saline administered intravenously immediately following umbilical cord clamping (or as soon as possible afterward)
Study Arms  ICMJE
  • Experimental: Tranexamic Acid
    Tranexamic Acid for intravenous administration
    Intervention: Drug: Tranexamic Acid
  • Placebo Comparator: Placebo
    Normal saline for intravenous administration
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 5, 2017)
11000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Pre-operative receipt of TXA
  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 and hematocrit result available from the last 4 weeks, since it is necessary to measure the post-operative change in hemoglobin and hematocrit
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rebecca Clifton, PhD (301) 881-9260 rclifton@bsc.gwu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03364491
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The dataset will be shared per NIH policy after the completion and publication of the main analyses. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu.
Responsible Party The George Washington University Biostatistics Center
Study Sponsor  ICMJE The George Washington University Biostatistics Center
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Rebecca Clifton, Ph.D. The George Washington University Biostatistics Center
Study Director: Menachem Miodovnik, M.D. NICHD Project Scientist
Study Chair: Louis Pacheco, MD UTMB
PRS Account The George Washington University Biostatistics Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP