Adverse events within 28d of randomization.Vascular occlusive events (MI, CVA, DVT, and PE).Early head injury-related death (within 24h after injury).Primary: Head injury-related death in hospital within 28 days of injury in patients treated within 3 hours of injury.Patients randomly assigned to receive tranexamic acid (loading dose 1g over 10 min then infusion of 1g over 8hr) or matching placebo (0.9% normal saline).Adults with TBI who were within 3 hrs of injury, had a GCS score of ≤12 or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible (The original protocol had eligibility listed as 8hr but in 2016 the protocol was changed to limit recruitment to patients to ≤3hrs from injury).
ANTIDOTE 8 CRASH TRIAL
Randomized, placebo-controlled trial done in 175 hospitals in 29 countries.All of the above positive findings therefore required confirmation in a larger randomized trial, which has finally arrived…CRASH-3. Due to the fact that these findings were secondary outcomes they were also hypothesis generating. TICH-2 did show a small improvement in hematoma expansion at day 2 and death by day 7. TICH-2 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. However, both of these trials were small and considered to be hypothesis generating only. There were two smaller RCTs that showed a reduction in death with TXA in patients with ICH.
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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.
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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. 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.