Evaluation of Tranexamic Acid in Reducing Postpartum Hemorrhage in Cesarean Deliveries with Placenta Previa: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the effect of a low dose of **tranexamic acid** (TXA) administered within 3 minutes after delivery of the child, in addition to prophylactic uterotonic, on the incidence of red blood cell (RBC) transfusion in women with placenta previa undergoing cesarean delivery, compared to a placebo. This is clinically relevant as it addresses the management of **postpartum hemorrhage**, a significant cause of maternal morbidity and mortality, by potentially reducing the need for blood transfusions.

Secondary objectives include comparing the effect of TXA versus placebo on various outcomes related to blood loss and maternal health:

• Mean gravimetrically estimated blood loss and calculated blood loss.
• Incidence of calculated blood loss exceeding 1000 ml and 1500 ml.
• Incidence of provider-assessed clinically significant postpartum hemorrhage (PPH).
• Mean shock index at specified intervals post-birth.
• Proportion of women requiring supplementary uterotonic treatment and iron sucrose perfusion.
• Mean number of red blood cell units transfused and proportion of women transfused within 24 hours postpartum.
• Proportion of women requiring arterial embolization or emergency surgery for PPH.
• Incidence of maternal postpartum transfer to a higher level of care.
• Mean change in peripartum hemoglobin and hematocrit levels.
• Proportion of breastfeeding at hospital discharge.
• Incidence of maternal death from any cause.
• Occurrence of nausea, vomiting, phosphenes, dizziness, and maternal thromboembolic events.
• Occurrence of neonatal adverse outcomes, including transfer to neonatal ICU.
• Women's satisfaction and psychological status assessed postpartum.

The clinical trial focuses on **postpartum hemorrhage** and involves a study population exclusively comprising females, as the condition pertains to women with placenta previa undergoing cesarean delivery. The participants are adults aged 18 years and older, with a gestational age at delivery of at least 32 weeks. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on specific criteria, including a placental edge below 20mm from the internal cervical os, as diagnosed by the most recent transvaginal ultrasound examination, and affiliation or beneficiary status to a health security system. All participants have provided signed informed consent. The trial does not include male subjects and involves a vulnerable population due to the medical condition and surgical procedure involved. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is designed to evaluate the efficacy of **tranexamic acid** in preventing blood loss following a cesarean delivery in women with placenta previa. This is a multicenter, randomized, double-blind, placebo-controlled trial. The trial aims to compare the effect of a low dose of tranexamic acid (1g) administered within 3 minutes after delivery of the child, in addition to prophylactic uterotonic, versus placebo, on the incidence of red blood cell transfusion between delivery and discharge from postpartum hospital stay. The trial is expected to run from August 7, 2020, to February 28, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), diagnosis of placenta previa, cesarean delivery, gestational age at delivery (≥32 weeks), and signed informed consent. Follow-up visits will occur during the postpartum hospital stay to monitor primary and secondary endpoints, including blood loss, transfusion requirements, and any adverse reactions. The end-of-study visit will assess long-term outcomes, including thromboembolic events and maternal health up to 12 weeks postpartum via a telephone interview.

The expected length of participant involvement is from the time of delivery until 12 weeks postpartum. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will ensure rigorous monitoring to maintain the integrity of the data and the safety of the participants throughout the study duration.

The clinical trial involves the administration of **tranexamic acid**, a chemical compound with the active substance name **tranexamic acid**. It is also known by synonyms such as LB1148, 4-(aminomethyl)cyclohexane-1-carboxylic acid, AMCA, and trans-AMCHA. The pharmaceutical form of tranexamic acid used in this study is a solution for injection, with the administration route being intravenous. The dosage is set at 1 gram, administered within 3 minutes after the delivery of the child. The maximum daily and total dose is 20 milliliters, with a treatment period limited to one day. The primary objective of this trial is to evaluate the effect of tranexamic acid in preventing blood loss in women undergoing cesarean delivery with placenta previa.

The study also includes a non-experimental treatment, **sodium chloride**, which serves as a placebo. Sodium chloride is administered intravenously in a pharmaceutical form identified as PHF00169MIG. The maximum daily and total dose for sodium chloride is 10 milliliters, with a treatment period of one day. This placebo is used to compare the effects of tranexamic acid against a standard saline solution, ensuring the double-blind nature of the trial. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

Efficacy in the clinical trial titled "TRAnexamic Acid for Preventing blood loss following a cesarean delivery in women with placenta pREVIA: a multicenter randomised, double blind placebo controlled trial" will be assessed using both primary and secondary endpoints. The primary endpoint is the incidence of red blood cell transfusion between the delivery of the child and discharge from the postpartum hospital stay. Secondary endpoints include a range of parameters such as mean gravimetrically estimated blood loss, calculated blood loss greater than 1000 mL and 1500 mL, mean calculated blood loss, and mean shock index. The shock index is defined by the ratio of heart rate to systolic blood pressure and will be measured at 15, 30, 45, 60, and 120 minutes after birth, or if postpartum hemorrhage (PPH) occurs.

Additional secondary endpoints include the need for supplementary uterotonic treatment, iron sucrose perfusion until discharge, the number of red blood cell units transfused, and the proportion of women transfused between delivery and 24 hours postpartum. Other outcomes to be measured are arterial embolisation or emergency surgery for PPH, maternal postpartum transfer to a higher level of care, and maternal death for any cause. The trial will also assess the mean change in peripartum hemoglobin and hematocrit levels, occurrence of potential mild adverse reactions of **tranexamic acid** such as nausea and dizziness, and severe unexpected adverse reactions like thromboembolic events. Neonatal outcomes, maternal satisfaction, and psychological status will be evaluated through self-administered questionnaires at day 2 postpartum and 8 weeks postpartum. These efficacy parameters will be collected and analyzed according to the specified timepoints and methods outlined in the trial protocol.