Key PointsQuestion
Does intravenous tranexamic acid that is administered after
acute spontaneous intracerebral hemorrhage (ICH) increase
diffusion-weighted imaging hyperintense lesions?
Findings
In this substudy of a randomized clinical trial involving 219
individuals with acute spontaneous ICH, the prevalence or number of
diffusion-weighted imaging hyperintense lesions on brain MRI scans
within 2 weeks did not increase in those who received tranexamic acid
compared with placebo within 8 hours of acute spontaneous ICH.
Meaning
Findings of this substudy suggest that tranexamic acid is
unlikely to increase cerebral ischemic events in acute spontaneous ICH.
Importance
Hyperintense foci on diffusion-weighted imaging (DWI) that are
spatially remote from the acute hematoma occur in 20% of people with
acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a
hemostatic agent that is under investigation for treating acute ICH,
might increase DWI hyperintense lesions (DWIHLs).
Objective
To establish whether tranexamic acid compared with placebo
increased the prevalence or number of remote cerebral DWIHLs within 2
weeks of ICH onset.
Design, Setting, and Participants
This prospective nested magnetic resonance imaging (MRI)
substudy of a randomized clinical trial (RCT) recruited participants
from the multicenter, double-blind, placebo-controlled, phase 3 RCT
(Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage
[TICH-2]) from July 1, 2015, to September 30, 2017, and conducted
follow-up to 90 days after participants were randomized to either the
tranexamic acid or placebo group. Participants had acute spontaneous ICH
and included TICH-2 participants who provided consent to undergo
additional MRI scans for the MRI substudy and those who had clinical MRI
data that were compatible with the brain MRI protocol of the substudy.
Data analyses were performed on an intention-to-treat basis on January
20, 2020.
Interventions
The tranexamic acid group received 1 g in 100-mL intravenous
bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of
ICH onset. The placebo group received 0.9% saline within 8 hours of ICH
onset. Brain MRI scans, including DWI, were performed within 2 weeks.
Main Outcomes and Measures
Prevalence and number of remote DWIHLs were compared between
the treatment groups using binary logistic regression adjusted for
baseline covariates.
Results
A total of 219 participants (mean [SD] age, 65.1 [13.8] years;
126 men [57.5%]) who had brain MRI data were included. Of these
participants, 96 (43.8%) were randomized to receive tranexamic acid and
123 (56.2%) were randomized to receive placebo. No baseline differences
in demographic characteristics and clinical or imaging features were
found between the groups. There was no increase for the tranexamic acid
group compared with the placebo group in DWIHL prevalence (20 of 96
[20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], −0.08; 95% CI, −0.36 to 0.20; P = .59).
In an exploratory analysis, participants who were randomized within 3
hours of ICH onset or those with chronic infarcts appeared less likely
to have DWIHLs if they received tranexamic acid. Participants with
probable cerebral amyloid angiopathy appeared more likely to have DWIHLs
if they received tranexamic acid.
Conclusions and Relevance
This substudy of an RCT found no evidence of increased
prevalence or number of remote DWIHLs after tranexamic acid treatment in
acute ICH. These findings provide reassurance for ongoing and future
trials that tranexamic acid for acute ICH is unlikely to induce cerebral
ischemic events.
Trial Registration
isrctn.org Identifier: ISRCTN93732214
