Brenner, A;
Belli, A;
Chaudhri, R;
Coats, T;
Frimley, L;
Jamaluddin, SF;
Jooma, R;
Mansukhani, R;
Sandercock, P;
Shakur-Still, H;
et al.
Brenner, A; Belli, A; Chaudhri, R; Coats, T; Frimley, L; Jamaluddin, SF; Jooma, R; Mansukhani, R; Sandercock, P; Shakur-Still, H; Shokunbi, T; Roberts, I; CRASH-3 trial collaborators
(2020)
Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial.
Crit Care, 24 (1).
p. 560.
ISSN 1466-609X
https://doi.org/10.1186/s13054-020-03243-4
SGUL Authors: Jarman, Heather
|
PDF
Published Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
|
![]() |
Microsoft Word (.docx) (Supplementary tables)
Published Version
Available under License Creative Commons Attribution. Download (25kB) |
Abstract
BACKGROUND: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. METHODS: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. RESULTS: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58-0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69-1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83-1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70-0.87) and death within 28 days (RR 0.88, 95% CI 0.82-0.94). CONCLUSIONS: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. TRIAL REGISTRATION: ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011.
Item Type: | Article | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Additional Information: | © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | |||||||||||||||||||||
Keywords: | CRASH-3 trial, Emergence care, Epidemiology, Intracranial haemorrhage, Randomised controlled trial, Tranexamic acid, Traumatic brain injury, Antifibrinolytic Agents, Brain Injuries, Humans, Multiple Trauma, Neuroprotective Agents, Protective Factors, Tranexamic Acid, CRASH-3 trial collaborators, Humans, Brain Injuries, Multiple Trauma, Tranexamic Acid, Neuroprotective Agents, Antifibrinolytic Agents, Protective Factors, Traumatic brain injury, Tranexamic acid, CRASH-3 trial, Randomised controlled trial, Intracranial haemorrhage, Epidemiology, Emergence care, Emergency & Critical Care Medicine, 11 Medical and Health Sciences | |||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Population Health Research Institute (INPH) | |||||||||||||||||||||
Journal or Publication Title: | Crit Care | |||||||||||||||||||||
ISSN: | 1466-609X | |||||||||||||||||||||
Language: | eng | |||||||||||||||||||||
Dates: |
|
|||||||||||||||||||||
Publisher License: | Creative Commons: Attribution 4.0 | |||||||||||||||||||||
Projects: |
|
|||||||||||||||||||||
PubMed ID: | 33172504 | |||||||||||||||||||||
Web of Science ID: | WOS:000589473900001 | |||||||||||||||||||||
Go to PubMed abstract | ||||||||||||||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/114272 | |||||||||||||||||||||
Publisher's version: | https://doi.org/10.1186/s13054-020-03243-4 |
Statistics
Actions (login required)
![]() |
Edit Item |