Tranexamic Acid for Prevention of Hemorrhage in Cesarean Delivery

Phase 2

Completed

Conditions: Post Partum Hemorrhage
Blood Loss
Fibrinolysis; Hemorrhage

Interventions: Drug: Placebo
Drug: Tranexamic Acid

Registration Number: NCT03856164

Lead Sponsor: University of Texas Southwestern Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 110

Inclusion Criteria

Intrauterine pregnancy
Age ≥ 18
Gestation age ≥ 37 weeks 0 days
Scheduled cesarean delivery
Second or third cesarean delivery
Singleton pregnancy

Exclusion Criteria

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

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
Blood Volume Loss	24 hours postpartum.	Total blood volume loss will be calculated in milliliters.

Secondary Outcome Measures

Name	Time	Method
D-Dimer (µg/mL)	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Measured from blood sample collection.
Fibrinogen (mg/dL)	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Measured from blood sample collection.
Tissue Plasminogen Activator Antigen (ng/mL)	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Measured from blood sample collection.
Plasminogen Activator Inhibitor-Type-1 (Units/mL)	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Measured from blood sample collection.
Rotational Thromboelastometry INTEM and EXTEM Clotting Time	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter).
Rotational Thromboelastometry INTEM, EXTEM, FIBTEM Maximum Clot Firmness	Collection prior to first drug infusion, immediately before second infusion and 24 hours postpartum.	Rotational thromboelastometry is a whole blood viscoelastic test that analyzes deficits in clotting factors, clot strength, and clot breakdown. EXTEM, INTEM, and FIBTEM tests measure the extrinsic pathway, intrinsic pathway, and fibrinogen levels, respectively. Compared to non-pregnant patients, FIBTEM/EXTEM/INTEM amplitudes and the FIBTEM maximum clot firmness are higher in pregnant women. The EXTEM and INTEM clotting time are shorter, indicating the relative hypercoagulability of pregnancy. Reference ranges for INTEM Clotting Time (100-240 seconds), INTEM Maximum Clot Firmness (50-72 millimeter), EXTEM Clotting Time (38-79 seconds), EXTEM Maximum Clot Firmness (50-72 millimeter), FIBTEM Maximum Clot Firmness (9-25 millimeter).