Tranexamic Acid for the Prevention of Obstetrical Hemorrhage After Cesarean

Phase 3

Completed

Conditions: Labor and Delivery
Obstetrical Complications
Hemorrhage

Interventions: Drug: Placebo
Drug: Tranexamic Acid

Registration Number: NCT03364491

Lead Sponsor: The George Washington University Biostatistics Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 11000

Inclusion Criteria

Scheduled or unscheduled cesarean delivery
Singleton or twin gestation

Exclusion Criteria

Age less than 18 years
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
Recent diagnosis or history of venous thromboembolism or arterial thrombosis because TXA is a risk factor for thromboembolism, and its use is contraindicated
Known congenital or acquired thrombophilias, including antiphospholipid antibody syndrome, because of the increased risk of thrombosis
Seizure disorder (including eclampsia) because TXA is a GABA receptor antagonist, and its use has been associated with postoperative seizures
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.
Sickle cell disease, because of substantial use of perioperative transfusion unrelated to hemorrhage. Sickle cell trait is not an exclusion per se.
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
Need for therapeutic dose of anticoagulation before delivery, because the risk of thrombosis may be increased with TXA
Treatment with clotting factor concentrates, because the risk of thrombosis may be increased with TXA
Presence of frank hematuria, because the risk of ureteral obstruction in those with upper urinary tract bleeding may be increased with TXA
Patient refusal of blood products because the primary outcome is then pre-determined
Receipt of TXA; or planned or expected use of TXA prophylaxis
Active cancer, because of risk of thromboembolism
Congestive heart failure requiring treatment, because of risk of thrombosis
History of retinal disease, because the risk of central retinal artery or vein obstruction may be increased with TXA
Acquired defective color vision or subarachnoid hemorrhage, since TXA is contraindicated
Hypersensitivity to TXA or any of the ingredients
No hemoglobin result available from the last 4 weeks, since it is necessary to measure the post-operative change in hemoglobin
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.
Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
Participating in another intervention study where the primary outcome includes postpartum bleeding or thromboembolism, or the study intervention directly affects postpartum bleeding or thromboembolism
Receipt of uterotonics, other than oxytocin, or planned or expected use of uterotonic prophylaxis
Symptomatic for COVID-19 infection within 14 days prior to delivery

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Normal saline for intravenous administration
Tranexamic Acid	Tranexamic Acid	Tranexamic Acid for intravenous administration

Primary Outcome Measures

Name	Time	Method
Number of Participants With Maternal Death or Transfusion of Packed Red Blood Cells	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

Name	Time	Method
Number of Participants Who Received Surgical or Radiologic Interventions to Control Bleeding and Related Complications	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
Number of Participants Who Received Open Label TXA or Other Antifibrinolytic	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)
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	within 6 weeks postpartum
Number of Participants Who Were Transfused With Other Blood Products	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
Number of Participants With Estimated Blood Loss Greater Than 1 Liter During Delivery	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
Number of Participants With Seizure Activity That Was Not Seen Prior to Study Enrollment	within 6 weeks postpartum	This is the number of mothers who experienced seizure activity, confirmed by central review, whose onset is after enrollment
Number of Participants With Postpartum Infectious Complications	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
Change in Hemoglobin	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
Length of Stay	Until hospital discharge, an average of 3 days	Mother's length of stay from delivery to discharge
Number of Participants Who Were Transfused With 4 or More Units of Packed Red Blood Cells	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
Number of Participants With a Thromboembolic Event (Venous or Arterial), Ischemic Stroke, or Myocardial Infarction	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.
Number of Participants Who Were Treated With Uterotonics Other Than Oxytocin	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.
Number of Participants Who Received Treatments and Interventions in Response to Bleeding and Related Complications	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

Trial Locations

Locations (12): Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Magee Women's Hospital of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
University of Texas - Houston
🇺🇸
Houston, Texas, United States
University of Utah Medical Center
🇺🇸
Salt Lake City, Utah, United States
Northwestern University-Prentice Hospital
🇺🇸
Chicago, Illinois, United States
University of Alabama - Birmingham
🇺🇸
Birmingham, Alabama, United States
University of North Carolina - Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Columbia University
🇺🇸
New York, New York, United States
Brown University
🇺🇸
Providence, Rhode Island, United States
Case Western Reserve-MetroHealth
🇺🇸
Cleveland, Ohio, United States
Ohio State University Hospital
🇺🇸
Columbus, Ohio, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States