• René Post, Menno R Germans, Maud A Tjerkstra, VergouwenMervyn D IMDIDepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Korné Jellema, Radboud W Koot, Nyika D Kruyt, WillemsPeter W APWADepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., WolfsJasper F CJFCDepartment of Neurosurgery, Haaglanden Medical Center, The Hague, Netherlands., Frits C de Beer, Hans Kieft, Dharmin Nanda, Bram van der Pol, Gerwin Roks, Frank de Beer, Patricia H A Halkes, Loes J A Reichman, BrouwersPaul J A MPJAMDepartment of Neurology, Medisch Spectrum Twente, Enschede, Netherlands., Renske M van den Berg-Vos, KwaVincent I HVIHDepartment of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands., Taco C van der Ree, Irene Bronner, Janneke van de Vlekkert, Henri P Bienfait, Hieronymus D Boogaarts, KlijnCatharina J MCJMDepartment of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands., René van den Berg, Bert A Coert, Janneke Horn, MajoieCharles B L MCBLMDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., RinkelGabriël J EGJEDepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., RoosYvo B W E MYBWEMDepartment of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., W Peter Vandertop, Dagmar Verbaan, and ULTRA Investigators.
• Department of Neurosurgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. Electronic address: r.post@amsterdamumc.nl.
• Lancet. 2021 Jan 9; 397 (10269): 112-118.

BackgroundIn patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.MethodsIn this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.FindingsBetween July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.InterpretationIn patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.FundingFonds NutsOhra.Copyright © 2021 Elsevier Ltd. All rights reserved.

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