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

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posted on 2018-06-12, 10:27 authored by Nikola Sprigg, Katie Flaherty, Jason P. Appleton, Rustam Al-Shahi Salman, Daniel Bereczki, Maia Beridze, Hanne Christensen, Alfonso Ciccone, Ronan Collins, Anna Czlonkowska, Robert A. Dineen, Lelia Duley, Juan Jose Egea-Guerrero, Timothy J. England, Kailash Krishnan, Ann Charlotte Laska, Zhe Kang Law, Serefnur Ozturk, Stuart J Pocock, Ian Roberts, Thompson G. Robinson, Christine Roffe, David Seiffge, Polly Scutt, Jegan Thanabalan, David Werring, David Whynes, Philip M. Bath, TICH-2 Investigators
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.

Funding

Funding: National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

History

Citation

Lancet, 2018, 391 (10135), pp. 2107-2115

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Lancet

Publisher

Elsevier

issn

0140-6736

eissn

1474-547X

Acceptance date

2018-04-30

Copyright date

2018

Available date

2018-06-12

Publisher version

https://www.sciencedirect.com/science/article/pii/S014067361831033X?via=ihub

Language

en

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