October 15, 2019

Background: Evidence from the CRASH-2 trial showed an absolute reduction in mortality of 1.5% (NNT = 67) in patients with extracranial bleeding treated with tranexamic acid  (TXA) within 3 hours of injury. However, CRASH-2 did not answer the question of effect on mortality in patients with intracranial hemorrhage (ICH), as these patients were excluded from the trial.  It makes biologic sense that administration of TXA in patients with traumatic brain injury (TBI) might prevent or reduce ICH expansion and thus avert brain herniation and death.  There were two smaller RCTs [2] that showed a reduction in death with TXA in patients with ICH. However, both of these trials were small and considered to be hypothesis generating only. TICH-2 [3] was an international, randomized, double-blind, placebo-controlled phase 3 trial in adults with ICH from acute stroke with ≈2300 patients and showed no difference between groups in functional status at day 90. TICH-2 did show a small improvement in hematoma expansion at day 2 and death by day 7.  Due to the fact that these  findings were secondary outcomes they were also hypothesis generating. All of the above positive findings therefore required confirmation in a larger randomized trial, which has finally arrived…CRASH-3.