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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 : December 5, 2018
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)
Estimated 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 12, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

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. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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

  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 [ Time Frame: within 6 weeks postpartum ]
  5. 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

  6. 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

  7. 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

  8. 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

  9. Thromboembolic events (venous or arterial), ischemic stroke, or myocardial infarction [ Time Frame: within 6 weeks postpartum ]
  10. New-onset seizure activity [ Time Frame: within 6 weeks postpartum ]
    Maternal seizure activity, confirmed by central review, whose onset is after randomization

  11. Postpartum infectious complications [ Time Frame: 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 [ Time Frame: within 6 weeks postpartum ]
    Any admission to the intensive care unit that lasts more than 24 hours

  13. Maternal death [ Time Frame: within 6 weeks postpartum ]
  14. Use of uterotonics other than oxytocin [ Time Frame: 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 [ Time Frame: within 7 days postpartum ]
    Interventions such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology

  16. 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

  17. TXA side effects [ Time Frame: within 24 hours postpartum ]
    Maternal TXA-related side-effects (nausea, vomiting, dizziness)

  18. 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)

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

  20. Hospital re-admission [ Time Frame: within 6 weeks postpartum ]
    Re-admission to the hospital after initial postpartum discharge

  21. Any transfusion-associated reactions [ Time Frame: within 7 days postpartum ]
    One more transfusion-associated reactions, such as fever, urticaria, anaphylaxis, alloimmunization


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. 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.
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


Contacts
Contact: Uma Reddy, M.D. 301-496-1074 reddyu@mail.nih.gov
Contact: Elizabeth Thom, Ph.D. (301) 881-9260 e_thom@bsc.gwu.edu

Locations
United States, Alabama
University of Alabama - Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Stacy Harris, BSN    205-996-6262    stacylharris@uabmc.edu   
Principal Investigator: Alan TN Tita, MD         
United States, Illinois
Northwestern University-Prentice Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Gail Mallett, RN BSN CCRC    312-503-3200    g-mallett@northwestern.edu   
Principal Investigator: William Grobman, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Sabine Bousleiman    212-305-4348    sb1080@columbia.edu   
Principal Investigator: Cynthia Gyamfi-Bannerman, MD         
United States, North Carolina
University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Kelly Clark, RN    919-350-6117    kelly_clark@med.unc.edu   
Principal Investigator: John M Thorp, Jr., MD         
United States, Ohio
Case Western Reserve-MetroHealth Recruiting
Cleveland, Ohio, United States, 44109
Contact: Wendy Dalton, RN    216-778-7533    wdalton@metrohealth.org   
Principal Investigator: Edward Chien, MD         
Ohio State University Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Anna Bartholomew, RN, BSN    614-685-3229    anna.bartholomew@osumc.edu   
Principal Investigator: Catalin S Buhimschi, MD         
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jennifer Craig, BSN    212-662-3926    jennifer.craig@uphs.upenn.edu   
Principal Investigator: Samuel Parry, MD         
Magee Women's Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Melissa Bickus, BS, RN    412-641-4072    mbickus@mail.magee.edu   
Principal Investigator: Hyagriv Simhan, MD, MS         
United States, Rhode Island
Brown University Recruiting
Providence, Rhode Island, United States, 02905
Contact: Donna Allard, RNC    401-274-1122    dallard@wihri.org   
Principal Investigator: Dwight J Rouse, MD         
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
Contact: Ashley Salazar, MSN    409-772-0312    assalaza@utmb.edu   
Principal Investigator: George R Saade, MD         
University of Texas - Houston Recruiting
Houston, Texas, United States, 77030
Contact: Felecia Ortiz, RN BSN    713-500-6467    Felecia.Ortiz@uth.tmc.edu   
Principal Investigator: Suneet Chauhan, MD         
United States, Utah
University of Utah Medical Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Kim Hill, RN    801-585-7645    Kim.Hill@hsc.utah.edu   
Principal Investigator: Michael W Varner, MD         
Sponsors and Collaborators
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Elizabeth Thom, Ph.D. The George Washington University Biostatistics Center
Study Director: Uma Reddy, M.D. NICHD Project Scientist
More Information
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Publications:

Responsible Party: The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier: NCT03364491     History of Changes
Other Study ID Numbers: HD36801-TXA
U10HD036801 ( U.S. NIH Grant/Contract )
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
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. Requests for datasets can be sent to mfmudatasets@bsc.gwu.edu.

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
Obstetric Labor Complications
Pathologic Processes
Pregnancy Complications
Tranexamic Acid
 Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants