TY - JOUR
T1 - Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA)
T2 - a randomised controlled trial
AU - ULTRA Investigators
AU - Post, René
AU - Germans, Menno R
AU - Tjerkstra, Maud A
AU - Vergouwen, Mervyn D I
AU - Jellema, Korné
AU - Koot, Radboud W
AU - Kruyt, Nyika D
AU - Willems, Peter W A
AU - Wolfs, Jasper F C
AU - de Beer, Frits C
AU - Kieft, Hans
AU - Nanda, Dharmin
AU - van der Pol, Bram
AU - Roks, Gerwin
AU - de Beer, Frank
AU - Halkes, Patricia H A
AU - Reichman, Loes J A
AU - Brouwers, Paul J A M
AU - van den Berg-Vos, Renske M
AU - Kwa, Vincent I H
AU - van der Ree, Taco C
AU - Bronner, Irene
AU - van de Vlekkert, Janneke
AU - Bienfait, Henri P
AU - Boogaarts, Hieronymus D
AU - Klijn, Catharina J M
AU - van den Berg, René
AU - Coert, Bert A
AU - Horn, Janneke
AU - Majoie, Charles B L M
AU - Rinkel, Gabriël J E
AU - Roos, Yvo B W E M
AU - Vandertop, W Peter
AU - Verbaan, Dagmar
AU - deBeer, Frits C
N1 - Funding Information: This study was funded by the Fonds NutsOhra (project 1202–31). We thank the patients participating in this trial, without whom this trial would have not been possible. We also thank the research teams in all participating centres who contributed to the data collection forms. Funding Information: RvdB reports grants from Cerenovus neurovascular, outside the submitted work; CBLMM reports grants from CVON/Dutch Heart Foundation, European Commission, Dutch Health Evaluation Program, TWIN Foundation, and Stryker, outside the submitted work; and is Shareholder of Nico-Lab, a company that focuses on the use of artificial intelligence for medical image analysis. YBWEMR is a minor shareholder of Nico-Lab. CJMK reports funding from the Dutch Heart Foundation (clinical established investigator grant number 2012T077), and ASPASIA grant from The Netherlands Organisation for Health Research and Development, ZonMw (grant number 015008048), outside the submitted work. MDIV reports funding from the Dutch Heart Foundation (clinical established investigator grant number 2018T0769). All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/9
Y1 - 2021/1/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85098779508&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(20)32518-6
DO - https://doi.org/10.1016/S0140-6736(20)32518-6
M3 - Article
C2 - 33357465
SN - 0140-6736
VL - 397
SP - 112
EP - 118
JO - Lancet
JF - Lancet
IS - 10269
ER -