Clinical trial NCT03856164: Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery
Official title: Use of Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Post Partum Hemorrhage
Fibrinolysis; Hemorrhage
Blood Loss
Keywords: Tranexamic acid
TXA
Anti-fibrinolytics
Postpartum hemorrhage
Obstetric hemorrhage
Fibrinolysis
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-02-27
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The investigators prepared a novel study of tranexamic acid (TXA) designed to estimate the quantity of blood loss in women undergoing elective repeat cesarean deliveries. This is the first trial to utilize a prophylactic dose of TXA prior to incision followed by a subsequent prophylactic dose at placental delivery in obstetric patients undergoing scheduled cesareans. The purpose of this study is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The central hypothesis is that TXA administration reduces blood loss and fibrinolysis in women undergoing repeat cesarean sections.

Detailed description: Obstetric hemorrhage has been identified as a contributory cause for the United States' suboptimal and inequitable outcomes among pregnant women. As such, obstetric hemorrhage has become a formal focus point in a national agenda to improve maternal outcomes. Strategies to identify maternal hypovolemia and treating obstetric hemorrhage are undergoing organized scrutiny in many states including Texas. Tranexamic acid (TXA) treatment is receiving increased emphasis in obstetric care because TXA inhibits fibrinolysis. Increased clot stability offers the possibility of preventing blood loss (prophylaxis) as well as mitigating ongoing hemorrhage. TXA therapy has been principally studied in nonpregnant populations; results of studies in pregnant women have been lacking.

Tranexamic acid is an antifibrinolytic agent that acts as a competitive inhibitor at the lysine binding sites of plasminogen and inhibits the ability of protease plasmin to cleave the fibrin clot. In large randomized controlled trials, it has been reported to be effective in decreasing perioperative blood loss in a variety of circumstances primarily involving trauma patients. Shakur and co-authors in a trial of 20,000 non-pregnant trauma patients reported a significant reduction in all-cause mortality after TXA administration. In another large study (WOMAN Trial), 20,000 pregnant women with hemorrhage were randomized to TXA or placebo. TXA was associated with a significant decrease in death due to bleeding.

Tranexamic acid's role in treating hemorrhage have been widely studied in non-pregnant populations. Studies of TXA in obstetrics are limited. The American College of Obstetricians and Gynecologists believes the data is insufficient to recommend tranexamic acid for prophylaxis.

The investigators designed a randomized placebo-controlled trial comparing TXA dosing prior to incision for cesarean delivery with a repeat dose given at placental delivery. The purpose is to quantify blood loss during uncomplicated repeat cesarean deliveries with and without TXA. The investigators elected to study scheduled elective cesareans because such procedures are at low risk for profound hemorrhage. It is the intent to have a study cohort where the two treatment groups (TXA or placebo) are as comparable as possible, so the efficacy of TXA is not tested in women with highly variable volumes of obstetric hemorrhage.

Eligibility criteria: Inclusion Criteria:

1. Intrauterine pregnancy
2. Age ≥ 18
3. Gestation age ≥ 37 weeks 0 days
4. Scheduled cesarean delivery
5. Second or third cesarean delivery
6. Singleton pregnancy

Exclusion Criteria:

1. First cesarean delivery
2. Four or more cesarean deliveries
3. Intrauterine fetal death
4. Fetal anomalies
5. Documented coagulopathy (Elevated Prothrombin Time (PT), Elevated Partial Thromboplastin Time (PTT), Elevated International Normalized Ratio (INR))
6. Thrombocytopenia (Platelet count \< 100k)
7. Internal bleeding, external bleeding, easy bruising
8. History of thrombotic event
9. Hypertension
10. Diagnosis of renal insufficiency (Creatinine\> 1 mg/dL)
11. Insulin-treated diabetes
12. Suspected morbidly adherent placenta
13. Placenta previa
14. Multiple Gestations
15. BMI ≥ 50
16. Hematocrit ≤ 25
17. Blood transfusion within 24 hours prior to cesarean delivery
18. History of abnormal bleeding or blood disorder
19. Planned general anesthesia

Primary outcomes:
measure: Blood Volume Loss
timeFrame: 24 hours postpartum.
Secondary outcomes:
measure: D-Dimer (µg/mL)
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
measure: Fibrinogen (mg/dL)
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
measure: Tissue Plasminogen Activator Antigen (ng/mL)
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
measure: Plasminogen Activator Inhibitor-Type-1 (Units/mL)
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
measure: Rotational Thromboelastometry INTEM and EXTEM Clotting Time
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
measure: Rotational Thromboelastometry INTEM, EXTEM, FIBTEM Maximum Clot Firmness
timeFrame: Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Parkland Hospital
state: Texas
Study officials:
affiliation: UT Southwestern
name: Olutoyosi Ogunkua, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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