René Post1, Menno R Germans2, Maud A Tjerkstra3, Mervyn D I Vergouwen4, Korné Jellema5, Radboud W Koot6, Nyika D Kruyt7, Peter W A Willems4, Jasper F C Wolfs8, Frits C de Beer9, Hans Kieft10, Dharmin Nanda9, Bram van der Pol11, Gerwin Roks12, Frank de Beer13, Patricia H A Halkes14, Loes J A Reichman15, Paul J A M Brouwers16, Renske M van den Berg-Vos17, Vincent I H Kwa17, Taco C van der Ree18, Irene Bronner19, Janneke van de Vlekkert19, Henri P Bienfait20, Hieronymus D Boogaarts21, Catharina J M Klijn22, René van den Berg23, Bert A Coert3, Janneke Horn24, Charles B L M Majoie23, Gabriël J E Rinkel4, Yvo B W E M Roos25, W Peter Vandertop3, Dagmar Verbaan3. 1. Department of Neurosurgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. Electronic address: r.post@amsterdamumc.nl. 2. Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland. 3. Department of Neurosurgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 4. Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. 5. Department of Neurology, Haaglanden Medical Center, The Hague, Netherlands. 6. Department of Neurosurgery, Leids University Medical Center, Netherlands. 7. Department of Neurology, Leids University Medical Center, Netherlands. 8. Department of Neurosurgery, Haaglanden Medical Center, The Hague, Netherlands. 9. Department of Neurosurgery, Isala Hospital, Zwolle, Netherlands. 10. Department of Intensive Care, Isala Hospital, Zwolle, Netherlands. 11. Department of Neurosurgery, Elisabeth Tweesteden ziekenhuis, Tilburg, Netherlands. 12. Department of Neurology, Elisabeth Tweesteden ziekenhuis, Tilburg, Netherlands. 13. Department of Neurology, Spaarne Gasthuis, Haarlem, Netherlands. 14. Department of Neurology, Noordwest Ziekenhuisgroep, Alkmaar, Netherlands. 15. Department of Neurology, Ziekenhuisgroep Twente, Almelo, Netherlands. 16. Department of Neurology, Medisch Spectrum Twente, Enschede, Netherlands. 17. Department of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands. 18. Department of Neurology, Dijklander Hospital, Hoorn, Netherlands. 19. Department of Neurology, Flevo Hospital, Almere, Netherlands. 20. Department of Neurology, Gelre Hospital, Apeldoorn, Netherlands. 21. Department of Neurosurgery, Radboud University Medical Center, Nijmegen, Netherlands. 22. Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands. 23. Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 24. Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 25. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
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 acidand 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.
RCT Entities:
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.
Authors: C Beynon; M Bernhard; T Brenner; M Dietrich; M O Fiedler; C Nusshag; M A Weigand; C J Reuß; D Michalski; C Jungk Journal: Anaesthesist Date: 2021-08-10 Impact factor: 1.041
Authors: Benjamin W Y Lo; Hitoshi Fukuda; Anderson C O Tsang; David J Langer; Satoru Miyawaki; Masaomi Koyanagi; Matthew Wai-Man Lui Journal: Surg Neurol Int Date: 2021-04-14