Tranexamic acid does not prevent intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage, an Australian-led randomised controlled trial has shown.
The STOP-AUST study was conducted in 100 patients with acute ICH at 13 stroke centres in Australia, Finland and Taiwan, and found no difference between the antifibrinolytic and placebo in reducing intracerebral haemorrhage growth at 24 hours.
However the treatment was safe, with no increase in thromboembolic complications, and the door is still open to investigate tranexamic acid in larger studies with more realistic and simpler eligibility criteria, the investigators say.
The trial was hampered by slow recruitment due to the requirement to obtain CT angiography and assess for a spot sign, which is not part of the routine care for ICH patients, noted the study authors, led by Professor Steven Davis of the Melbourne Brain Centre at the Royal Melbourne Hospital.
In the study, which ran from 2013 to 2019, adult patients were enrolled if they presented with acute ICH and had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 hours of symptom onset and within one hour of CT angiography.
Patients were randomly assigned to receive either 1g of intravenous tranexamic acid over 10 minutes followed by 1g over 8 hours or matching placebo, started within 4·5 hours of symptom onset.
For the primary outcome of intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 hours, there was no significant difference between the tranexamic acid group (22 patients, 44%) and placebo group (26 patients, 52%).
Functional outcomes at three months were also not different between groups.
There was no significant difference in deaths (16% vs 26% for placebo vs tranexamic acid) or thromboembolic complications (4% vs 2%) between the groups.
The study investigators concluded that the evidence to date does not justify routine use of tranexamic acid in patients with acute intracerebral haemorrhage.
However they said that given the high mortality of ICH and lack of treatments, it is still worth exploring a simpler and more streamlined protocol for using tranexamic acid in acute ICH.
“With an inexpensive and safe therapy such as tranexamic acid, the benefits of strict patient selection and narrow target population might be lost, especially because many patients have haemorrhage growth without the spot sign,” they wrote in Lancet Neurology.
“In this setting, it might be wiser in future trials to concentrate on an early time window instead of the spot sign. Because of long recovery periods in patients with intracerebral haemorrhage, we think that the preferred trial functional outcome would be 6-month mRS,” they added.
An accompanying commentary backed this approach, suggesting that the STOP-AUST trial might have failed to detect a clinically meaningful benefit because of its requirement for additional imaging before using tranexamic acid.
With a delay of around 40 minutes from baseline CT to treatment, this meant substantial haematoma growth might have already occurred before treatment, said Professor David Werring of the UCL Institute of Neurology, London.
He noted that there were several other trials of tranexamic acid in ICH underway and said there was still the potential for “well powered and pragmatic trials” to show an effect on haematoma expansion, mortality, and longer-term outcomes.