If It Bleeds, It Can Get TXA?

When trauma bleeds: TXA! When women bleed: TXA! When the nose bleeds: TXA! When your freckles need lightening: TXA!

But, what about inside the brain?

This is TICH-2, an international, randomized, placebo-controlled trial testing tranexamic acid versus placebo for patients with primary intracerebral hemorrhage. The intervention arm received 1g of IV TXA as a bolus, followed by 1g over the subsequent 8 hours. The primary outcome was functional status at day 90 measured – inappropriately so, of course – as shift on the modified Rankin Scale. We’ve critiqued the ordinal shift several times as, effectively, statistically magnifying unimportant differences as a crutch for trials struggling to find a difference using a traditional, dichotomous endpoint.

However, regardless, their efforts are for naught: their primary endpoint still failed to reach statistical significance. Across five years and 2,325 randomized participants, nearly all patient-oriented outcomes showed no difference: 29% of TXA patients were mRS ≥2 at 90 days, compared with 29% of placebo. The numbers of deaths by day 90 were virtually identical, as were measures of quality of life, functional status, and days at home. Adjusted analyses and various subgroups generated odds ratios whose confidence intervals almost broke free of unity, but not quite.

The major quirk – over two-thirds of the trial was randomized greater than 3 hours from onset. The trauma literature focuses on early anti-fibrinolytic treatment, and it is reasonable to suggest the delay in treatment was too great to demonstrate a benefit. Then, even though no patient-oriented benefit was observed, hematoma expansion was attenuated in the TXA cohort. This is not the first time an ICH trial has seen benefits with regard to hematoma expansion absent patient-oriented outcome improvements, but it still seems a valid surrogate for, at least, a small effect size for which this trial may (or not) be underpowered to detect.

My takeaway is this trial hasn’t done much to move the needle with regard to evaluating TXA in ICH. It does show, at least, as administered in this trial, it is unlikely to have substantial benefit. However, TXA is inexpensive and seems to demonstrate a reasonable margin of safety. It is still reasonable to consider its use in as timely a fashion as possible, with the expectation the true NNT may be ~50 to 200, while awaiting further data from other trials currently underway.

“Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial”
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31033-X/fulltext