Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial
Authors: Polymeris Alexandros A. , Karwacki Grzegorz M. , Siepen Bernhard M. , Schaedelin Sabine , Tsakiris Dimitrios A. , Stippich Christoph , Guzman Raphael , Nickel Christian H. , Sprigg Nikola , Kägi Georg , Vehoff Jochen , Barinka Filip , Thilemann Sebastian , Maurer Marina , Wagner Benjamin , Traenka Christopher , Gensicke Henrik , De Marchis Gian Marco , Bonati Leo H. , Fischer Urs , Z’Graggen Werner J. , Nedeltchev Krassen , Wegener Susanne , Baumgartner Philipp , Engelter Stefan T. , Seiffge David J. , Peters Nils , Lyrer Philippe A. , Clarke Sandra , Falcao Martina , Avramiotis Nikolaos S , Dittrich Tolga , Fisch Urs , Fladt Joachim , Hert Lisa , Schneider Iris , Wiegert Martina , Zietz Annaelle , Beyeler Morin , Goeldlin Martina , Kormann Marianne , Maamari Basel , McEvoy Liselotte , Meinel Thomas R , Müller Madlaina , Vynckier Jan , Ardila Elena , Feuerstein Ingrid , Gantenbein Claudine , Müller Anna , Seljmani Vjosa , Wagner Benedikt , Anders Bettina , Backhaus Roland , Paliantonis Asterios , Taheri Shadi , Thumm Dennis , van Duinen Jannie , Von Bieberstein Lita 
Published: July 2023

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.