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

The George Washington University Biostatistics Center

Status and phase: Completed; Phase 3

Conditions: Hemorrhage; Obstetrical Complications; Labor and Delivery

Treatments: Drug: Placebo; Drug: Tranexamic Acid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03364491

UG1HD040512 (U.S. NIH Grant/Contract)

UG1HD040545 (U.S. NIH Grant/Contract)

UG1HD087192 (U.S. NIH Grant/Contract)

UG1HD027915 (U.S. NIH Grant/Contract)

UG1HD040560 (U.S. NIH Grant/Contract)

UG1HD040544 (U.S. NIH Grant/Contract)

UG1HD034208 (U.S. NIH Grant/Contract)

UG1HD087230 (U.S. NIH Grant/Contract)

U10HD036801 (U.S. NIH Grant/Contract)

UG1HD053097 (U.S. NIH Grant/Contract)

UG1HD027869 (U.S. NIH Grant/Contract)

HD36801-TXA

UG1HD040485 (U.S. NIH Grant/Contract)

UG1HD040500 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11,000 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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11,000 participants in 2 patient groups, including a placebo group

Tranexamic Acid

Experimental group

Description:

Tranexamic Acid for intravenous administration

Treatment:

Drug: Tranexamic Acid

Placebo

Placebo Comparator group

Description:

Normal saline for intravenous administration

Treatment:

Drug: Placebo