Tranexamic Acid Not Effective as Intracerebral Hemorrhage Treatment
The first trial of tranexamic acid in patients with known ongoing intracerebral hemorrhage shows insignificance compared with placebo, with future studies of simpler recruitment methods needed.
Atte Meretoja, MD, PhD, MSc, FRACP
Results from the phase 2 STOP-AUST trial (NCT01702636) revealed that tranexamic acid does not prevent intracerebral hemorrhage growth, despite the treatment being safe with no increases in thromboembolic complications.
In the prospective, double-blind, randomized, placebo-controlled trial, 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had the primary outcome of intracerebral hemorrhage growth at 24 hours (odds ratio [OR], 0.72; 95% CI, 0.32–1.59; P = 0.41). Additionally, an exploratory post-hoc analysis showed no change in the primary outcome if adjusted for time from onset to therapy in addition to baseline volume (OR, 0.72; 95% CI, 0.32–1.59; P = .43).
Atte Meretoja, MD, PhD, MSc, FRACP, director, Helsinki University Central Hospital, and colleagues aimed to assess whether tranexamic acid reduced intracerebral hemorrhage growth after pre-existing research suggested it may decrease hemorrhage in conditions such as acute trauma and menorrhea.
All told, the investigators noted similar rates of patients who died or had thromboembolic complications between the groups. In total, 8 (16%) and 13 (26%) patients in the placebo and tranexamic acid groups died, respectively. Two (4%) patients in the placebo group reported thromboembolic complications compared to 1 (2%) in the tranexamic group. One death was due to sepsis while all others were due to stroke progression. None of the deaths were considered related to study medication by site investigators or by a central assessor.
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Predefined subgroups within the study including stroke to treatment time, intracerebral hemorrhage baseline volume and location, Glasgow Coma Scale score, age, gender, and protocol compliance, showed no significant interaction with the treatment effect. A post-hoc analysis of interaction of time to treatment as a continuous variable had a P value of 0.059.
“Because hemorrhage growth is a major cause of morbidity and mortality in acute intracerebral hemorrhage, new, safe, and effective treatments to stem ongoing hemorrhage are urgently required.” Meretoja et al concluded.
At 3 months, the distribution of functional outcome did not fulfil the proportional odds assumptions, and the assumption-free analysis showed no difference between the treatment groups (generalized OR, 1.01; 95% CI 0.63–1.61; P = .97).
Patients included in the study were eligible if they had an acute intracerebral hemorrhage fulfilling clinical criteria (Glasgow Come Scale score of >7, intracerebral hemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 hours, and no use of anticoagulation). Each patient was randomly assigned 1:1 to receive either 1g of intravenous tranexamic acid over 10 minutes followed by 1 g over 8 hours or matching placebo, started within 4.5 hours of symptom onset.
The median intracerebral hemorrhage growth from baseline to 24 hours was 2.7 mL (interquartile range [IQR], 0.1–13.7), being 3.4 mL (IQR, 0.0–16.) for patients in the placebo group and 1.9 mL (IQR, 0.2–9.5) for those in the tranexamic acid group (P = .81).
There were 28 protocol violations within the study occurring in 26 participants, most of which were related to problems with delivering the therapy within 1 hour of baseline imaging.
The authors of the study noted that larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.
