Background
Phase 3, double-blind, placebo-controlled RCT (WOMAN trial). 20,060 women with a clinical diagnosis of postpartum hemorrhage (PPH) after vaginal delivery or cesarean section in 193 hospitals across 21 countries. PPH defined as excessive bleeding after delivery at clinician's discretion. Treatment given within 3 hours of delivery.
Interventions and follow up
Arm A: Tranexamic acid (TXA) 1 g IV; second dose of 1 g if bleeding continued at 30 minutes or restarted within 24 hour
Arm B: Placebo
Primary endpoint: Composite of death from PPH or hysterectomy
mFollow up: 42 days postpartum
Arm B: Placebo
Primary endpoint: Composite of death from PPH or hysterectomy
mFollow up: 42 days postpartum
Results
Death from PPH: 1.5% vs 1.9%, RR 0.81 (95% CI 0.65–1.00), P=.045
Hysterectomy: 3.5% vs 3.6%, RR 0.97 (95% CI 0.87–1.09) — NS
Composite primary endpoint: 5.3% vs 5.5%, RR 0.97 (95% CI 0.87–1.09) — NS
Laparotomy for bleeding: 0.8% vs 1.0%, RR 0.64 — significant reduction
Benefit timing: Death from PPH reduced only when TXA given within 3 hours (RR 0.74); no benefit if given later
Hysterectomy: 3.5% vs 3.6%, RR 0.97 (95% CI 0.87–1.09) — NS
Composite primary endpoint: 5.3% vs 5.5%, RR 0.97 (95% CI 0.87–1.09) — NS
Laparotomy for bleeding: 0.8% vs 1.0%, RR 0.64 — significant reduction
Benefit timing: Death from PPH reduced only when TXA given within 3 hours (RR 0.74); no benefit if given later
Adverse events
Main adverse events: Thromboembolic events (DVT, PE, stroke): 0.4% vs 0.4% — no increase with TXA. Seizures: 0.1% vs 0.1%. Overall AE profile similar between arms.
Conclusions
TXA significantly reduced death from PPH but did not reduce hysterectomy, meeting only part of the composite primary endpoint. The mortality reduction was driven by women who received TXA within 3 hours of delivery, supporting early administration as essential.
Key Limitations
Key Limitations: Composite primary endpoint was not significant, though mortality component was. Hysterectomy is a provider decision subject to clinical judgment and variable thresholds across countries. Heterogeneous global populations with highly variable surgical and transfusion resources. Women were enrolled after PPH diagnosis — timing from onset of hemorrhage varied. Lack of protocolized uterotonics or blood product management.
Clinical Context
TXA is now recommended by WHO (2017) and FIGO for all women with PPH, given within 3 hours of delivery. It is included in the WHO Essential Medicines List for obstetric hemorrhage. PPH is the leading cause of maternal mortality globally; TXA's low cost and safety profile make it a key intervention in low-resource settings. All guidelines emphasize <3-hour window for administration.
References
References: WOMAN Trial Collaborators, Lancet 2017 (primary)