Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial

Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Switzerland. (A.A.P., S.T., M.M., B.W., C.T., H.G., G.M.D.M., L.H.B., U.F., S.T.E., D.J.S., N.P., P.A.L.). Department of Radiology and Nuclear Medicine, Luzerner Kantonsspital, Switzerland (G.M.K.). Department of Neurology, Inselspital, University Hospital and University of Bern, Switzerland (B.M.S., G.K., U.F., W.J.Z., D.J.S.). Graduate School of Health Sciences, University of Bern, Switzerland (B.M.S.). Department of Clinical Research, University Hospital Basel and University of Basel, Switzerland. (S.S.). Division of Hematology, University Hospital Basel, Switzerland (D.A.T.). Department of Neuroradiology and Radiology, Kliniken Schmieder, Allensbach, Germany (C.S.). Department of Neurosurgery, University Hospital Basel and University of Basel, Switzerland. (R.G.). Department of Emergency Medicine, University Hospital Basel and University of Basel, Switzerland. (C.H.N.). Nottingham Stroke Trials Unit, University of Nottingham, United Kingdom (N.S.). Department of Neurology and Stroke Center, Cantonal Hospital St. Gallen, Switzerland (G.K., J.V.). Stroke Center, Klinik Hirslanden Zurich, Switzerland (F.B., N.P.). Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Switzerland (C.T., H.G., S.T.E., N.P.). Reha Rheinfelden, Switzerland (L.H.B.). Department of Neurology and Stroke Center, Cantonal Hospital Aarau, Switzerland (K.N.). Department of Neurology, University Hospital and University of Zurich, Switzerland (S.W., P.B.).

Stroke. 2023

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Abstract
BACKGROUND Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. METHODS We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. RESULTS Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (P(interaction)=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. CONCLUSIONS In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine