부산대학교 도서관

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S0140-6736(18)31033-X Byline: Prof Nikola Sprigg, FRCP [nikola.sprigg@nottingham.ac.uk] (a,b,*), Katie Flaherty, MSc (a), Jason P Appleton, MRCP (a), Prof Rustam Al-Shahi Salman, FRCPEdin (c), Prof Daniel Bereczki, MD (d), Prof Maia Beridze, MD (e), Prof Hanne Christensen, DMSci (f), Alfonso Ciccone, MD (g), Ronan Collins, MD (h), Prof Anna Czlonkowska, MD (i), Robert A Dineen, FRCR (j,k), Prof Lelia Duley, FRCOG (l), Juan Jose Egea-Guerrero, MD (m), Timothy J England, FRCP (n), Kailash Krishnan, PhD (a,b), Ann Charlotte Laska, MD (o), Zhe Kang Law, MRCP (a,b,p), Prof Serefnur Ozturk, MD (r), Prof Stuart J Pocock, PhD (s), Prof Ian Roberts, FRCP (t), Prof Thompson G Robinson, FRCP (u), Prof Christine Roffe, FRCP (v), David Seiffge, MD (w), Polly Scutt, MSc (a), Jegan Thanabalan, MS (q), Prof David Werring, FRCP (x), Prof David Whynes, PhD (y), Prof Philip M Bath, FMedSci (a,b) for the TICH-2 Investigators ([Dagger]) Summary Background Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. Methods We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. Findings We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0*88, 95% CI 0*76--1*03, p=0*11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0*73, 0*53--0*99, p=0*0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0*92, 95% CI 0*77--1*10, p=0*37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]). Interpretation Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect. Funding National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation. Author Affiliation: (a) Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK (b) Stroke, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK (c) Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK (d) Department of Neurology, Semmelweis University, Budapest, Hungary (e) The First University Clinic of Tbilisi State Medical University, Tbilisi, Georgia (f) Department of Neurology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark (g) Neurology Unit, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy (h) Stroke Service, Adelaide and Meath Hospital, Tallaght, Ireland (i) 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (j) Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Queens Medical Centre Campus, Nottingham, UK (k) NIHR Nottingham Biomedical Research Centre, Nottingham, UK (l) Nottingham Clinical Trials Unit, University of Nottingham, Queen's Medical Centre, Nottingham, UK (m) UGC de Medicina Intensiva, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, Seville, Spain (n) Vascular Medicine, Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK (o) Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (p) Department of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia (q) Division of Neurosurgery, Department of Surgery, National University of Malaysia, Kuala Lumpur, Malaysia (r) Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey (s) Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK (t) Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK (u) Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK (v) Stroke Research, Faculty of Medicine and Health Sciences, Keele University, Staffordshire, UK (w) Stroke Center, Neurology and Department of Clinical Research, University Hospital, University Basel, Basel, Switzerland (x) Stroke Research Centre, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College London, London, UK (y) School of Economics, University of Nottingham, University Park, Nottingham, UK * Correspondence to: Prof Nikola Sprigg, Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, UK (footnote)[Dagger] A complete list of the TICH-2 trial investigators is provided in the