By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College
SOURCE: Meretoja A, Yassi N, Wu TY, et al. Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): A multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Neurol 2020;19:980-987.
Primary intracerebral hemorrhage is a major cause of severe neurological disability and carries a high rate of death. Worldwide, it comprises 5% of all human deaths. Patients are treated in multidisciplinary specialized stroke units and neurological intensive care units, with the best possible results, but there are no specific, targeted therapies that are evidence-based and have shown benefit in the treatment of these patients. The major determinants of survival and clinical outcome are the patient’s age, level of consciousness at onset, and volume of the hematoma. In addition, it has been demonstrated in multiple studies that the hematoma size increases over the first several hours and up to 24 hours. One approach to therapy has been to prevent hematoma growth by administering a hemostatic agent. Recombinant activated coagulation factor VII was tested in two large trials with 1,240 patients treated within four hours of symptom onset, without showing a significant benefit in outcomes. Tranexamic acid was tested in a study of 2,325 patients with intracerebral hemorrhage within eight hours of symptom onset, but again, did not significantly improve neurological outcome.
The current investigators of the STOP-AUST trial led a prospective, double-blind, randomized, placebo-controlled Phase II trial at 13 stroke centers in Australia, Finland, and Taiwan to determine if administration of tranexamic acid within four and a half hours of symptom onset would reduce hematoma growth and have an effect on neurological outcome. Patients were eligible to be enrolled if they were 18 years of age or older with an acute intracerebral hemorrhage, a Glasgow Coma Scale score > 7, intracerebral brain hemorrhage (ICH) volume less than 70 mL, no secondary cause of hemorrhage, no thromboembolic events in the previous 12 months, no planned surgery, no use of anticoagulants, and the presence of contrast extravasation on computed tomography angiography (spot sign). Infusion of tranexamic acid had to be started within four and a half hours of symptom onset. The primary outcome was growth of the intracerebral hemorrhage at 24 hours. A total of 100 participants were enrolled and randomly assigned to tranexamic acid treatment or placebo. There were 50 participants in each group. The median age was 71 years and the median intracerebral hemorrhage volume was 14.6 mL. The primary outcome, which was growth of hemorrhage at 24 hours, was not significantly different between the two groups. Fifty-two percent of patients in the placebo group and 44% in the tranexamic acid group had intracerebral hemorrhage growth of greater than 33% at 24 hours. There was no difference between the groups in mortality or thromboembolic complications. Although this study did not demonstrate benefit of treatment with tranexamic acid, the investigators suggested that earlier treatment should be studied and might be of benefit.