Tranexamic acid should not be used routinely in patients with intracerebral haemorrhage, according to results of an Australian-led study, which show early administration of the antifibrinolytic agent has no affect on haematoma growth.
The Stopping Intracerebral Haemorrhage with Tranexamic Acid for Hyperacute onset Presentation including Mobile Stroke Units (STOP-MSU) was an investigator-led, double-blind phase 2 trial conducted at 25 sites – including hospitals and one mobile stroke unit – across Australia, Finland, New Zealand, Taiwan and Vietnam.
Eligible participants were aged 18 years or older and presented with acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT.
Some 201 participants (median age 66, 41% female) were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 minutes followed by 1 g over 8 hours) or placebo (saline; matched regimen) within two hours of symptom onset.
The median onset to treatment time was 105 minutes and baseline imaging to treatment time was 26 minutes, which were the fastest reported for such trials.
Haematoma growth was defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 hours (target range 18–30 h) from baseline scan.
Findings published in the Lancet Neurology [link here] showed haematoma growth occurred in 38% of 97 assessable patients in the placebo group and 43% of 101 assessable patients in the tranexamic acid group (adjusted odds ratio [aOR] 1.31).
Median absolute haematoma growth was 1.2 mL in both groups, which was a small absolute increase and an unexpected finding in the placebo group compared with a previous trial that recorded a 3.4 mL median growth, the authors noted.
Major thromboembolic events – defined as ischaemic stroke, myocardial infarction or pulmonary embolism – at 90 days occurred in one of 98 participants in the placebo group and three of 103 in the tranexamic acid group (risk difference 0.02).
Each group recorded eight deaths (8%) by day 7 (aOR 1.08), and by 90 days, 15% of the placebo group and 18% of the tranexamic acid group had died (aOR 1.61).
No deaths were considered related to the study treatment.
The researchers, led by neurologists at the Melbourne Brain Centre at The Royal Melbourne Hospital, also observed no effects on other imaging endpoints, functional outcomes at 90 days, or safety.
“Accumulating evidence suggests that any effect of tranexamic acid on haematoma growth might be very small in absolute terms,” they wrote.
“Therefore, on the one hand, individuals who have substantial haematoma growth might not benefit in a meaningful way from antifibrinolytic therapy. On the other hand, individuals who do not have haematoma growth… might dilute any potential observable effect of antifibrinolytic therapy.
“We attempted to investigate whether tranexamic acid might have had an effect at the more extreme levels of growth by analysing absolute growth at the 25th and 75th percentiles (as well as the median) but did not see any significant effects in these analyses.”
They said tranexamic acid might potentially have effects on outcomes in intracerebral haemorrhage that were independent of haematoma growth attenuation, including effects on perihaematomal oedema or inflammation.
Results from ongoing phase 3 trials would add context as to whether the low cost and readily accessible agent had a future role for this indication, they said.
Some authors have previously received funding from pharmaceutical companies.