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The CRASH-2 trial demonstrated that administration of tranexamic acid (TXA) decreased mortality for patients with traumatic hemorrhage (NEJM JW Emerg Med Jul 2010 and Lancet 2010; 376:23). Given that fewer than 250 of the 20,000 patients had isolated traumatic brain injury (TBI), it was unclear whether TXA would have similar benefits in this population (NEJM JW Emerg Med Jan 2012 and BMJ 2011; 343:d3795). The recent CRASH-3 trial, conducted in 29 countries over 6 years, aimed to provide clarification.
Roughly 9200 patients with isolated TBI (Glasgow Coma Scale [GCS] score <13 or any intracranial bleeding on computed tomography scan) who were treated within 3 hours of injury were randomized to TXA (1 g bolus over 10 minutes, followed by 1 g infusion over 8 hours) or placebo. Overall, there was no significant difference in head injury–related death at 28 days (the primary outcome; risk ratio [RR], 0.94; 95% confidence interval, 0.86–1.02). However, preplanned subgroup analyses showed reductions in mortality with TXA for patients with mild-to-moderate injury (GCS >8; RR, 0.78) and those with bilaterally reactive pupils (RR, 0.87). Secondary analyses showed better outcomes with earlier treatment in patients with mild-to-moderate injury (but not those with severe injury) and no difference in survivors' degree of disability or thromboembolic events between the TXA and placebo groups.
The CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): A randomised, placebo-controlled trial. Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)
Comment
We would not expect TXA to decrease mortality in the most severely ill patients, so the finding of a mortality reduction only for patients with mild-to-moderate injury has face validity. Reassuringly, these data also confirm the CRASH-2 findings of improved outcomes with faster treatment and no increase in thrombotic complications after administration of TXA. While some physicians may disagree based on the primary outcome (which included all patients), I'll be administering TXA to patients with intracranial bleeding and mild-to-moderate TBI.