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The CRASH3 results are out, but do we know what to do? The study enrolled 9202 head-injured patients within 3 hours of injury with a Glasgow Coma Scale (GCS) of ≤12, or any intracranial bleeding on CT scan and randomised them to tranexamic acid (TXA) or placebo. The relative risks (RR) of all-cause mortality (RR: 0.96, 95% CI: 0.89 to 1.04) and head injury death (RR: 0.94, 95% CI: 086 to 1.02) among those receiving TXA were not significant. However, there were significant differences in subgroups who were less severely injured (RR: 0.89, 95% CI: 0.80 to 1.00 if those with GCS=3 or bilateral fixed pupils were excluded, and RR: 0.78, 95% CI: 0.64 to 0.95, in the GCS 9–15 subgroup) or treated earlier (p=0.005 for time effect).1
The results need to be considered in the context of earlier CRASH22 results, which showed a reduction in all-cause mortality (RR: 0.91, 95% CI: 0.85 to 0.97) and death due to bleeding (RR: 0.85, 95% CI: 0.76 to 0.96) if trauma patients who were bleeding or at risk of bleeding were given TXA. In both CRASH2 and CRASH3, the TXA was given in the emergency department.
Both the CRASH2 and CRASH3 studies are on the borderline for power to detect important differences, despite being among the largest ever conducted in trauma care. However, there are unlikely to be better-powered studies ever undertaken, so the current information has to be the basis for clinical decision making. A rigid evidence-based medicine approach (‘this was a negative study—do not use TXA’) risks a lost opportunity to improve care. However, the opposite view (‘TXA is harmless give it to all injured patients’) also risks a lost opportunity to improve care. Looking at Confidence Intervals rather than just thinking about the result as significant/non-significant is helpful, but the translation of the CRASH3 trial …
Correction notice This paper has been updated since first published. In Table 1, Column 'Mortality', data value 0.195 has been revised to 0.195%.
Contributors The article was conceived, written, redrafted and agreed by both authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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