CRASH-2 timing analysis

The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.

CRASH-2 collaborators, Roberts I, Shakur H, et al. Lancet (London, England) 2011 · PMID 21439633 · doi:10.1016/s0140-6736(11)60278-x

Question

Does the effect of tranexamic acid on death from bleeding depend on how soon after injury it is given?

Design

Exploratory subgroup analysis of the CRASH-2 randomised placebo-controlled trial by time from injury to treatment.

Patients

CRASH-2 participants grouped by treatment within 1 hour, 1-3 hours and more than 3 hours from injury.

Intervention

Tranexamic acid given at varying times after injury

Comparison

Placebo

Primary outcome

Death due to bleeding

Key result

Treatment within 1 hour, and between 1 and 3 hours, significantly reduced bleeding deaths, whereas treatment after 3 hours appeared to increase the risk of death from bleeding.

Limitations

This was a post hoc subgroup analysis, so the time interaction should be viewed as hypothesis-generating, although it was biologically plausible.

Impact on practice

Underpins the UK rule that tranexamic acid should be given as early as possible and not started more than 3 hours after injury, driving prehospital administration.