Fulltext

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial

Sprigg N 1 , Flaherty K 2 , Appleton JP 2 , Al-Shahi Salman R 3 , Bereczki D 4 , Beridze M 5 Show all authors , Christensen H 6 , Ciccone A 7 , Collins R 8 , Czlonkowska A 9 , Dineen RA 10 , Duley L 11 , Egea-Guerrero JJ 12 , England TJ 13 , Krishnan K 14 , Laska AC 15 , Law ZK 16 , Ozturk S 17 , Pocock SJ 18 , Roberts I 19 , Robinson TG 20 , Roffe C 21 , Seiffge D 22 , Scutt P 2 , Thanabalan J 23 , Werring D 24 , Whynes D 25 , Bath PM 14 , TICH-2 Investigators

Affiliations 

  • 1 Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK; Stroke, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK. Electronic address: nikola.sprigg@nottingham.ac.uk
  • 2 Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK
  • 3 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
  • 4 Department of Neurology, Semmelweis University, Budapest, Hungary
  • 5 The First University Clinic of Tbilisi State Medical University, Tbilisi, Georgia
  • 6 Department of Neurology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
  • 7 Neurology Unit, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy
  • 8 Stroke Service, Adelaide and Meath Hospital, Tallaght, Ireland
  • 9 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
  • 10 Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Queens Medical Centre Campus, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK
  • 11 Nottingham Clinical Trials Unit, University of Nottingham, Queen's Medical Centre, Nottingham, UK
  • 12 UGC de Medicina Intensiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, Spain
  • 13 Vascular Medicine, Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK
  • 14 Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK; Stroke, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK
  • 15 Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
  • 16 Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK; Stroke, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK; Department of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia
  • 17 Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey
  • 18 Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
  • 19 Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK
  • 20 Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK
  • 21 Stroke Research, Faculty of Medicine and Health Sciences, Keele University, Staffordshire, UK
  • 22 Stroke Center, Neurology and Department of Clinical Research, University Hospital, University Basel, Basel, Switzerland
  • 23 Division of Neurosurgery, Department of Surgery, National University of Malaysia, Kuala Lumpur, Malaysia
  • 24 Stroke Research Centre, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College London, London, UK
  • 25 School of Economics, University of Nottingham, University Park, Nottingham, UK
Lancet, 2018 May 26;391(10135):2107-2115.
PMID: 29778325 DOI: 10.1016/S0140-6736(18)31033-X

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications