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Evevident
Original paper
2010LancetEmergency Medicine

CRASH-2

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial

RCTTrauma

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Overview

Early tranexamic acid reduced death due to bleeding in trauma patients with significant hemorrhage, especially when given within 3 hours.

Clinical takeaway

CRASH-2 made TXA a core early medication for bleeding trauma patients, with timing central to benefit.

Key result

All-cause mortality was 14.5% with TXA vs 16.0% with placebo (RR 0.91).

Practice impact

Give TXA early in appropriate bleeding trauma patients, ideally within 3 hours.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

20,211

Follow-up

Death in hospital within 4 weeks of injury.

Geography

Multinational

Clinical question

Does tranexamic acid reduce mortality in trauma patients with or at risk of significant bleeding?

Population

  • Adult trauma patients with significant hemorrhage or at risk of significant hemorrhage, within 8 hours of injury.

Intervention

Tranexamic acid 1 g over 10 minutes, then 1 g over 8 hours.

Comparator

Matching placebo.

Primary outcome

Death in hospital within 4 weeks of injury.

Tranexamic acid reduced all-cause mortality and death from bleeding in trauma patients, with benefit confined to early (within 3 hours) treatment.

Relative risk / 0.91 / CI 95% CI 0.85-0.97 / p=0.0035

Key results

  • All-cause mortality: 14.5% with TXA vs 16.0% with placebo; RR 0.91 (95% CI 0.85-0.97; p=0.0035).
  • Death due to bleeding: 4.9% vs 5.7%; RR 0.85 (95% CI 0.76-0.96; p=0.0077).
  • There was no increase in fatal or nonfatal vascular occlusive events.
  • A later analysis showed benefit only when TXA was given within 3 hours; treatment after 3 hours increased bleeding death.

Harms

  • TXA did not increase vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, or DVT).
  • Administration later than 3 hours after injury was associated with increased death due to bleeding.

Clinical Use

When to cite

  • When considering tranexamic acid for bleeding trauma patients, especially the importance of treatment within 3 hours.

Practice impact

  • Give TXA early in appropriate bleeding trauma patients, ideally within 3 hours.

Applicability

  • Most applicable to adult trauma patients with significant hemorrhage or at risk of it who can be treated within 3 hours of injury.

Limitations

  • Broad pragmatic inclusion across highly variable trauma systems, many resource-limited.
  • Benefit depends strongly on timing; the primary analysis did not initially highlight the time interaction.
  • Enrolled on clinical suspicion of bleeding rather than confirmed hemorrhage.

Common misinterpretations

  • TXA should be given within 3 hours; later administration was associated with increased death from bleeding.
  • The absolute mortality benefit is modest (~1.5 percentage points) and does not license indiscriminate late use.

Citation

CRASH-2 trial collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi:10.1016/S0140-6736(10)60835-5

All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97.