Tranexamic acid modestly reduced a composite postpartum hemorrhage outcome among patients with placenta previa undergoing cesarean delivery, according to findings from a multicenter, double-blind, placebo-controlled phase 3 randomized controlled trial published in BMJ.
The trial enrolled 1,732 patients with placenta previa at 24 maternity units in China from July 2023 to March 2025. After withdrawals and postrandomization exclusions, 1,694 patients were included in the intention-to-treat population, and primary outcome data were available for 1,691 patients.
Patients were randomly assigned to receive prophylactic oxytocin plus either intravenous tranexamic acid 1 g or placebo. Tranexamic acid or placebo was administered intravenously over 10 minutes and initiated within 5 minutes of umbilical cord clamping.
The primary outcome was postpartum hemorrhage, defined in the trial as calculated estimated blood loss of at least 1,000 mL or red cell transfusion within 2 days following delivery.
Postpartum hemorrhage occurred in 29.7% of patients in the tranexamic acid group vs 35.1% of patients in the placebo group, corresponding to a relative risk of 0.85 (95.2% CI, 0.75–0.96), indicating a statistically significant but modest reduction in the composite endpoint.
Calculated estimated blood loss of at least 1,000 mL occurred in 25.7% of patients receiving tranexamic acid vs 31.6% receiving placebo. Red cell transfusion within 2 days following delivery occurred in 18.8% vs 21.6%, respectively; however, the transfusion component alone did not show a statistically significant reduction, with a relative risk of 0.88 (95% CI, 0.74–1.03).
The number needed to treat was 19 (95% CI, 10–104) to prevent 1 primary outcome event and 17 (95% CI, 10–63) to prevent 1 episode of calculated estimated blood loss of at least 1,000 mL.
"This trial found that among women with placenta [previa] who underwent caesarean delivery and received prophylactic oxytocin, treatment with tranexamic acid resulted in a statistically significant yet modest reduction in the incidence of postpartum [hemorrhage]," wrote lead study author Lizi Zhang, of the Department of Obstetrics and Gynaecology at The Third Affiliated Hospital, Guangzhou Medical University in China, and colleagues.
Eligible patients were aged 18 years or older, had singleton or multiple pregnancy at 34 weeks' gestation or later, were undergoing cesarean delivery, and had a hemoglobin level greater than 90 g/L within the previous week. Key exclusion criteria included thromboembolic risk factors, a history of epilepsy or seizures, active malignancy, cardiovascular disorders, kidney or liver dysfunction, autoimmune diseases, and hypersensitivity to tranexamic acid.
All patients had placenta previa, a condition associated with postpartum hemorrhage in approximately one third of affected pregnancies, and 17.9% had co-existing placenta accreta spectrum disorders. The researchers noted that the proportion of patients with placenta accreta spectrum disorders reflected tertiary referral patterns and was not intended to represent prevalence in the general population.
Results for secondary bleeding measures were mixed. Gravimetrically estimated blood loss of at least 1,000 mL occurred in 15.0% of patients receiving tranexamic acid vs 20.6% receiving placebo. A hemoglobin decrease greater than 20 g/L occurred in 17.9% vs 22.9%, respectively. Mean calculated estimated blood loss was 841 mL vs 1,003 mL.
However, mean gravimetrically estimated blood loss was similar between the groups, and the trial did not show clear differences in transfusion by discharge, intensive care unit or obstetric high-dependency unit transfer, additional operations, hysterectomy, hypovolemic shock, readmission, hospital stay, or maternal death.
Subgroup analyses did not show statistically significant heterogeneity by maternal age, placenta previa type, antepartum hemorrhage status, or placenta accreta spectrum disorder status. The researchers cautioned that subgroup estimates were not adjusted for multiplicity and should not be used for hypothesis testing.
Serious adverse events occurred in 0.5% of patients in both groups in the safety population through 6 weeks postpartum. Thromboembolic events occurred in 1 patient receiving tranexamic acid and 3 patients receiving placebo. No maternal deaths, myocardial infarctions, seizures, or kidney-function impairments requiring treatment were reported.
The researchers acknowledged several limitations, including incomplete documentation of all ineligible patients and reasons for exclusion, exploratory secondary outcome analyses, and 6-week follow-up data collected through telephone interviews that relied on patient recall. They also noted that the single-country study design may limit generalizability because of differences in body mass index, placenta accreta spectrum prevalence, and clinical management practices across regions.
Disclosures can be found in the published study.
Source: The BMJ
