1. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial
- Author
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René Post, Menno R Germans, Maud A Tjerkstra, Mervyn D I Vergouwen, Korné Jellema, Radboud W Koot, Nyika D Kruyt, Peter W A Willems, Jasper F C Wolfs, 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, Paul J A M Brouwers, Renske M van den Berg-Vos, Vincent I H Kwa, Taco C van der Ree, Irene Bronner, Janneke van de Vlekkert, Henri P Bienfait, Hieronymus D Boogaarts, Catharina J M Klijn, René van den Berg, Bert A Coert, Janneke Horn, Charles B L M Majoie, Gabriël J E Rinkel, Yvo B W E M Roos, W Peter Vandertop, Dagmar Verbaan, Menno R. Germans, Maud A. Tjerkstra, Mervyn D.I. Vergouwen, Radboud W. Koot, Nyika D. Kruyt, Peter W.A. Willems, Jasper F.C. Wolfs, Frits C. de Beer, Patricia H.A. Halkes, Loes J.A. Reichman, Paul J.A.M. Brouwers, Renske M. van den Berg-Vos, Vincent I.H. Kwa, Taco C. van der Ree, Henri P. Bienfait, Hieronymus D. Boogaarts, Catharina J.M. Klijn, Martine van Bilzen, H.J.G. Dieks, Koen de Gans, J.B.M. ten Holter, Jelle R. de Kruijk, Charlie T.J.M. Leijzer, Delmar Molenaar, Robbert J. van Oostenbrugge, Jeske van Pamelen, Fianne H.M. Spaander, Sarah E. Vermeer, J. Manuela Voorend, Bert A. Coert, Charles B.L.M. Majoie, Gabriël J.E. Rinkel, Yvo B.W.E.M. Roos, W. Peter Vandertop, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, Neurology, Radiology and nuclear medicine, VU University medical center, ACS - Atherosclerosis & ischemic syndromes, Graduate School, ANS - Systems & Network Neuroscience, ANS - Neurovascular Disorders, Experimental Vascular Medicine, Radiology and Nuclear Medicine, and ACS - Microcirculation
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Intention-to-treat analysis ,Antifibrinolytic ,business.industry ,medicine.drug_class ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,General Medicine ,Odds ratio ,030204 cardiovascular system & hematology ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Randomized controlled trial ,law ,Modified Rankin Scale ,Anesthesia ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,Prospective cohort study ,business ,Tranexamic acid ,medicine.drug - Abstract
BACKGROUND: In 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.METHODS: In 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.FINDINGS: Between 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.INTERPRETATION: In 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.FUNDING: Fonds NutsOhra.
- Published
- 2021