Clinical trial NCT03364491: Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean
Official title: Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean Delivery: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obstetrical Complications
Hemorrhage
Labor and Delivery
Keywords: Tranexamic Acid
Hemorrhage
Cesarean
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-12-06
Enrollment: 11000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Maternal Death or Transfusion of Packed Red Blood Cells
timeFrame: by hospital discharge or by 7 days postpartum, whichever is sooner
Secondary outcomes:
measure: Number of Participants With Estimated Blood Loss Greater Than 1 Liter During Delivery
timeFrame: From skin incision to transfer from operating room, average of 1 hour
measure: 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
timeFrame: within 6 weeks postpartum
measure: Number of Participants Who Were Transfused With Other Blood Products
timeFrame: within 7 days postpartum
measure: Number of Participants Who Were Transfused With 4 or More Units of Packed Red Blood Cells
timeFrame: within 7 days postpartum
measure: Number of Participants With a Thromboembolic Event (Venous or Arterial), Ischemic Stroke, or Myocardial Infarction
timeFrame: within 6 weeks postpartum
measure: Number of Participants With Seizure Activity That Was Not Seen Prior to Study Enrollment
timeFrame: within 6 weeks postpartum
measure: Number of Participants With Postpartum Infectious Complications
timeFrame: within 6 weeks postpartum
measure: Number of Participants Who Were Treated With Uterotonics Other Than Oxytocin
timeFrame: within 48 hours postpartum
measure: Number of Participants Who Received Surgical or Radiologic Interventions to Control Bleeding and Related Complications
timeFrame: within 7 days postpartum
measure: Change in Hemoglobin
timeFrame: from 4 weeks before delivery to 48 hours postpartum
measure: Number of Participants Who Received Open Label TXA or Other Antifibrinolytic
timeFrame: within 7 days postpartum
measure: Length of Stay
timeFrame: Until hospital discharge, an average of 3 days
measure: Number of Participants Who Received Treatments and Interventions in Response to Bleeding and Related Complications
timeFrame: within 7 days postpartum
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University-Prentice Hospital
state: Illinois
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve-MetroHealth
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Women's Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: The George Washington University Biostatistics Center
name: Rebecca Clifton, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Monica Longo, MD
role: STUDY_DIRECTOR
affiliation: UTMB
name: Louis Pacheco, MD
role: STUDY_CHAIR
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