Study Design Summary: Multinational randomized, placebo controlled study that compared giving TXA vs placebo to patients with TBI and no extracranial bleeding, primary outcome was brain injury related death at 28 days.
Notes: This study has many signs pointing towards a biased study. They have many secondary endpoints and changed their definitions of inclusion criteria (8 hours vs 3 hours from injury) and yet were still underpowered. After the study they pushed propaganda hard to make TXA standard of care for TBI patients with misleading information on videos and posters. The listed primary outcome on clinicaltrials.gov was all cause mortality which is also different from the paper.
The TXA vs placebo groups were pretty balanced in both prestudy points such as age, sex, time since injury, GCS. The TXA group had somewhat less VTE (1.8% vs 2.4%), DVT was equal in both groups, PE slightly higher in placebo group (0.3% vs 0.8%). There were very few patients lost to followup in either group, and this study is the largest RCT to date to look at TXA in TBI.
Overall the head injury related deaths in TXA vs placebo group was 18.5% vs 19.8% (CI 0.86-1.02) thus making the trial a negative trial by their pre-definition. A subanalysis of the data excluding pts with GCS of 3 or bilateral unreative pupils showed outcome was 12.5% vs 14.0% (0.80-1.00). Still a relatively negative study. Keep in mind the overall study was underpowered and thus the subanlaysis is further under powered.
The study broke down head injury related deaths based on GCS as another subanalysis. Patients with a GCS 3-8 had no difference in TXA vs placebo, patients with GCS 9-15 had difference favoring TXA (5.8% head injury related mortality in TXA group vs 7.5% in placebo group). Again, as the whole study was underpowered, these sub groups are further underpowered. They did not include a subanalysis of patients with GCS 8-12 which would have been interesting to see.
They compared TXA vs placebo group survivors in Disability Rating Scale and there was no difference.
There were less head injury related deaths in the TXA group at 24 hours, but when the endpoint was expanded to 28 days this effect was muted, some suggest this is due to increase in non-bleeding related causes of head injury related deaths. There was a subanalysis that compared TXA vs placebo in patients treated <1h, 1-3h, or >3 hours from injury and there were no differences observed. Some suggest that patients treated soon after injury likely had worse injuries and thus confounding the results.
I would be extremely weary of interpreting data from a study that had so many changes in its endpoints and after a negative study pushed propaganda hard that the study was positive.
Unpublished data apparently showed overall mortality benefit in TXA group but hard to evaluate since it was unpublished.
Study Conclusion: TXA given within 3 hours of injury reduces head injury related deaths in patients with TBI and no extracranial bleeding.
Fusion Beat Bottom Line Impression: While the study is underpowered, it demonstrated low side effect profile of TXA when considering VTE. In patients with GCS 9-15 who are less than 3 hours from injury, TXA may provide some benefit with reduction of head injury related deaths. No true definitive conclusion can be drawn as the resulting positive benefit was seen in an underpowered subgroup analysis but is worth noting as potential generator of further directed research. Giving TXA to patients in this select group that showed benefit is likely worthwhile but should not be tying up cognitive bandwidth early on in the resuscitation.
A Fusion Beat 