{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T07:16:17Z","timestamp":1778224577695,"version":"3.51.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":468,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003142","name":"Fonds NutsOhra","doi-asserted-by":"publisher","award":["1202-031"],"award-info":[{"award-number":["1202-031"]}],"id":[{"id":"10.13039\/501100003142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003142","name":"Fonds NutsOhra","doi-asserted-by":"publisher","award":["1202-031"],"award-info":[{"award-number":["1202-031"]}],"id":[{"id":"10.13039\/501100003142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods:<\/jats:title>\n                    <jats:p>A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0\u20133) at 6\u2009months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0\u20133, 3\u20136 and &amp;gt;6\u2009h).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62\u20131.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p\u2009&amp;lt;\u20090.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6\u2009h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72\u20131.27) with no evidence of effect modification on the time to start of TXA (p\u2009=\u20090.53).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusions:<\/jats:title>\n                    <jats:p>This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6\u2009h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23969873241246591","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T06:51:45Z","timestamp":1712904705000},"page":"658-666","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-4526","authenticated-orcid":false,"given":"Menno R","family":"Germans","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-3435","authenticated-orcid":false,"given":"Maud A","family":"Tjerkstra","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 2"},{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 2"},{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Brenner","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK 4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-1628","authenticated-orcid":false,"given":"Mervyn DI","family":"Vergouwen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabri\u00ebl JE","family":"Rinkel","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-5882","authenticated-orcid":false,"given":"Yvo BWEM","family":"Roos","sequence":"additional","affiliation":[{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"},{"name":"Department of Neurology, Amsterdam University Medical Centers location University of Amsterdam, Amsterdam, The Netherlands 6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"},{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert A","family":"Coert","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 2"},{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5417-0265","authenticated-orcid":false,"given":"W Peter","family":"Vandertop","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 2"},{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Verbaan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands 2"},{"name":"Amsterdam Neuroscience, Neurovascular Disorders, Amsterdam, The Netherlands 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the ULTRA 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