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

TICH-2 Investigators

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2107-2115
Number of pages9
JournalThe Lancet
Volume391
Issue number10135
DOIs
Publication statusPublished - 26 May 2018

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Tranexamic Acid
Cerebral Hemorrhage
Placebos
Stroke
Odds Ratio
Hemorrhage
Biomedical Technology Assessment
National Institutes of Health (U.S.)
Random Allocation
Hematoma
Registries
Therapeutics
Randomized Controlled Trials
Logistic Models
Delivery of Health Care

ASJC Scopus subject areas

  • Medicine(all)

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

In: The Lancet, Vol. 391, No. 10135, 26.05.2018, p. 2107-2115.

Research output: Contribution to journalArticle

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title = "Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial",
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.",
author = "{TICH-2 Investigators} and Nikola Sprigg and Katie Flaherty and Appleton, {Jason P.} and Salman, {Rustam Al Shahi} and Daniel Bereczki and Maia Beridze and Hanne Christensen and Alfonso Ciccone and Ronan Collins and Anna Czlonkowska and Dineen, {Robert A.} and Lelia Duley and Egea-Guerrero, {Juan Jose} and England, {Timothy J.} and Kailash Krishnan and Laska, {Ann Charlotte} and Law, {Zhe Kang} and Serefnur Ozturk and Pocock, {Stuart J.} and Ian Roberts and Robinson, {Thompson G.} and Christine Roffe and David Seiffge and Polly Scutt and Jegan Thanabalan and David Werring and David Whynes and Bath, {Philip M.}",
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TY - JOUR

T1 - Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2)

T2 - an international randomised, placebo-controlled, phase 3 superiority trial

AU - TICH-2 Investigators

AU - Sprigg, Nikola

AU - Flaherty, Katie

AU - Appleton, Jason P.

AU - Salman, Rustam Al Shahi

AU - Bereczki, Daniel

AU - Beridze, Maia

AU - Christensen, Hanne

AU - Ciccone, Alfonso

AU - Collins, Ronan

AU - Czlonkowska, Anna

AU - Dineen, Robert A.

AU - Duley, Lelia

AU - Egea-Guerrero, Juan Jose

AU - England, Timothy J.

AU - Krishnan, Kailash

AU - Laska, Ann Charlotte

AU - Law, Zhe Kang

AU - Ozturk, Serefnur

AU - Pocock, Stuart J.

AU - Roberts, Ian

AU - Robinson, Thompson G.

AU - Roffe, Christine

AU - Seiffge, David

AU - Scutt, Polly

AU - Thanabalan, Jegan

AU - Werring, David

AU - Whynes, David

AU - Bath, Philip M.

PY - 2018/5/26

Y1 - 2018/5/26

N2 - 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.

AB - 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.

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