Background
Phase 3, double-blind, placebo-controlled RCT (CRASH-2). 20,211 adult trauma patients with significant hemorrhage (systolic BP <90 mmHg or HR >110, or both) or at risk of significant hemorrhage, treated in 274 hospitals across 40 countries. Patients had to be enrolled within 8 hours of injury.
Interventions and follow up
Arm A: Tranexamic acid (TXA) 1 g IV over 10 minutes, then 1 g IV over 8 hour
Arm B: Placebo (matching infusion)
Primary endpoint: In-hospital death within 4 weeks from all cause
mFollow up: 28 days in-hospital
Arm B: Placebo (matching infusion)
Primary endpoint: In-hospital death within 4 weeks from all cause
mFollow up: 28 days in-hospital
Results
All-cause mortality: 14.5% vs 16.0%, RR 0.91 (95% CI 0.85–0.97), P=.0035
Death due to bleeding: 4.9% vs 5.7%, RR 0.85 (95% CI 0.76–0.96), P=.0077
Vascular occlusive events: 1.7% vs 2.0%, RR 0.84 (95% CI 0.68–1.02) — no increase with TXA
Fatal events within 3 hrs of injury: Retrospective subgroup: TXA must be given early (<3 hrs) for maximum benefit; late administration (>3 hrs) may increase bleeding risk
Death due to bleeding: 4.9% vs 5.7%, RR 0.85 (95% CI 0.76–0.96), P=.0077
Vascular occlusive events: 1.7% vs 2.0%, RR 0.84 (95% CI 0.68–1.02) — no increase with TXA
Fatal events within 3 hrs of injury: Retrospective subgroup: TXA must be given early (<3 hrs) for maximum benefit; late administration (>3 hrs) may increase bleeding risk
Adverse events
Main adverse events: Grade ≥3 events not separately tabulated; vascular occlusion (MI, stroke, DVT, PE) did not differ significantly between arms. Seizures rare but known mechanistic concern at high doses — not elevated at standard dosing.
Conclusions
Tranexamic acid given within 8 hours of injury significantly reduced all-cause and hemorrhage-related mortality in adult trauma patients, with no increase in thrombotic complications, establishing TXA as standard care in trauma hemorrhage.
Key Limitations
Key Limitations: Open to possible subgroup analysis bias in the 3-hour window subgroup (post-hoc). Heterogeneous global population with variable surgical capabilities. No protocolized transfusion strategy or hemostatic resuscitation standardization. Long-term neurological outcomes not assessed. Late (>3 hours) administration may be harmful — guideline recommendations now emphasize early use only.
Clinical Context
TXA is now standard of care for trauma hemorrhage across military and civilian trauma systems worldwide (ATLS, EAST, TCCC guidelines), with administration recommended within 3 hours of injury. CRASH-2 was foundational; subsequent CRASH-3 tested TXA in traumatic brain injury. TXA is on the WHO Essential Medicines List. Cost is extremely low, facilitating global adoption.
References