Previous research has presented convincing evidence that the administration of tranexamic acid (TXA) after cesarean delivery can reduce the incidence of postpartum hemorrhage (PPH) and the associated mortality and morbidity. Although there have been several significant studies on this topic, they are limited by small sample sizes, which make the studies difficult to generalize and limit their statistical power. This study aimed to address that gap and assess clinical outcomes related to the administration of TXA in a large sample.

This was a multicenter, double-blind, randomized controlled trial including 31 hospitals participating in the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Eligibility criteria included scheduled or unscheduled cesarean delivery of a singleton or twin gestation. Exclusion criteria included maternal age younger than 18 years, blood transfusion before randomization, plan for transfusion after randomization, contraindications to TXA, patient decision not to use blood products, or administration of antifibrolytic agents or uterotonic agents other than oxytocin. The primary outcome was maternal death or blood transfusion before hospital discharge or 7 days after delivery, whichever came first. Secondary outcomes included intraoperative blood loss of more than 1 L and treatments or interventions in response to bleeding or related complications within 7 days of delivery, as well as infectious complications within 6 weeks of delivery.

Final analyses included 11,000 patients, with 5529 in the TXA group and 5471 in the placebo group. Baseline characteristics were not significantly different between groups, and no center-dependent differences were observed. The primary outcome was observed in 3.6% of patients in the TXA group and 4.3% of patients in the placebo group (adjusted relative risk, 0.89; P = 0.19). Intraoperative blood loss of more than 1 L was recorded in 7.3% and 8.0% in the tranexamic and placebo groups, respectively (relative risk, 0.90; 95% CI, 0.79–1.05). Treatments and interventions in response to bleeding occurred in 16.1% of individuals in the TXA group and 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82–0.97). Infectious complications were reported in 3.2% and 2.5% in the TXA and placebo groups, respectively (relative risk, 1.28; 95% CI, 1.02–1.61). Sensitivity analysis showed similar results to initial analysis, and no significant differences were seen between groups in major safety outcomes.

This analysis indicates that the administration of TXA during cesarean delivery did not lower the risk of maternal death or blood transfusion. These results are in direct contradiction to previous research showing that TXA is effective at reducing these outcomes. This trial was stronger than any previous studies in sample size and careful randomization ensuring equal representation of scheduled and unscheduled cesarean deliveries, which makes the contradiction to previous research especially relevant. Some limitations of this trial included limitations in time of administration of TXA as well as dosage. Outcomes related to these 2 variables are still largely unknown. This trial also excluded patients at high risk of thromboembolic phenomena, and the effect of TXA in this population is still unknown. Further research should focus on more diverse populations, as well as understanding variations in outcomes with timing and dosage, which this study did not address.