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The CRASH-3 Trial has been published.

CRASH-2 demonstrated that early administration of tranexamic acid(within 3 hours of injury) reduced bleeding deaths by one third(1). In CRASH-3, the investigators looked at the effects of tranexamic acid in patients with potential traumatic brain injury.

The Trial

International, multi-centre, randomised, placebo-controlled trial

Big Trial

Eligibility criteria:

  • Within 3 hours of injury
  • GCS <12 or intracranial bleed on CT scan and
  • No major extra cranial bleed

Primary Outcome: Head injury-related death in the hospital within 28 days in patients treated within 3 hours.

n = 4613 patient assigned to tranexamic acid and 4514 assigned to placebo.


  • There was a reduction in head-injury related deaths in patients with mild(GCS of 13-15)-moderate head injury(RR 0.78 [95%CI 0.64-0.95]) when given within 3 hours of injury- these are large confidence intervals
  • We need to remember that the sickest patients ie., the GCS 3, fixed dilated pupils were removed from this study.
  • No clear evidence of reduction in death in those with severe injury (0.99[0.91-1.07])
  • No evidence of adverse effects or complications, although the risk of deep venous thrombosis or pulmonary embolism was not captured in the study.
  • Dose of tranexamic acid used was:
    • loading dose of 1g over 10 minutes followed by
    • IV infusion of 1g over 8 hours

My Take

  • It’s safe
  • It may result in decreased mortality in a particular subgroup: but not statistically significant
  • It’s a discussion to have with the team as the results are not as compelling as CRASH 2.
  • The real result will probably be that patients will get it as they will be getting it for their other trauma, regardless
  • However for isolated intracranial trauma………..I’ll probably give it, if within 3 hours. But I’ll have a discussion with my surgeons well in advance, so we have a protocol.

What will you do?


The CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placeboocntrolled trial. Lancet 2010;376:23-32


  • Patrick Thoma says:

    Overall it seems safe and does not appear to lead to an increase in mortality or negative effects. It also does not appear to provide a significant reduction in mortality, except for some improvement was noted in patients who did not have a severe injury. Determining severe injury appears key, but giving it to the group considered to have a severe injury did not increase mortality and in some instance may provide some reduction in head injury deaths. Overall, it seems safe but needs to be given in the context of expert consultation so as to maximize patient benefit.

  • Prostano says:

    With expert consult and the absence of adverse reactions exhibited in the study, I’d say yes.

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