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Randomized Controlled Trial
. 2021 Feb;47(1):261-268.
doi: 10.1007/s00068-020-01316-1. Epub 2020 Feb 19.

Tranexamic acid in traumatic brain injury: an explanatory study nested within the CRASH-3 trial

CRASH-3 Intracranial Bleeding Mechanistic Study Collaborators
Collaborators
Randomized Controlled Trial

Tranexamic acid in traumatic brain injury: an explanatory study nested within the CRASH-3 trial

CRASH-3 Intracranial Bleeding Mechanistic Study Collaborators. Eur J Trauma Emerg Surg. 2021 Feb.

Abstract

Purpose: The CRASH-3 trial is a randomised trial of tranexamic acid (TXA) on death and disability in patients with traumatic brain injury (TBI). It is based on the hypothesis that early TXA treatment can prevent deaths from post-traumatic intracranial bleeding. The results showed that timely TXA treatment reduces head injury deaths in patients with reactive pupils and those with a mild to moderate GCS at baseline. We examined routinely collected CT scans in a sample of 1767 CRASH-3 trial patients to explore if, why, and how patients are affected by TXA.

Methods: The CRASH-3 IBMS is an explanatory study nested within the CRASH-3 trial. We measured the volume of intracranial bleeding on CT scans using established methods (e.g. ABC/2).

Results: Patients with any un-reactive pupil had a median intracranial bleeding volume of 60 ml (IQR 18-101 ml) and patients with reactive pupils had a median volume of 26 ml (IQR 1-55 ml). Patients with severe GCS had median intracranial bleeding volume of 37 ml (IQR 3-75 ml) and patients with moderate to mild GCS had a median volume of 26 ml (IQR 0.4-50 ml). For every hour increase from injury to the baseline scan, the risk of new bleeding on a further scan decreased by 12% (adjusted RR = 0.88 [95% CI 0.80-0.96], p = 0.0047).

Conclusion: Patients with reactive pupils and/or mild to moderate GCS may have benefited from TXA in the CRASH-3 trial because they had less intracranial bleeding at baseline. However, because bleeding occurs soon after injury, treatment delay reduces the benefit of TXA.

Keywords: Tranexamic acid; Traumatic brain injury.

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Conflict of interest statement

Abda Mahmood, Adrian Boyle, Antonio Belli, Caroline Leech, Darin Wong, David Davies, Fatahul Laham Mohamed, Haleema Shakur-Still, Hamzah Lotfi, Ian Roberts, Jason Kendall, Kelly Needham, Mark Wilson, Melanie Darwent, Phillip Hopkins, Phil Moss, Sabariah Faizah Jamaluddin and Tim Harris have no conflicts of interest to declare. Antonio Belli was in receipt of a grant from the National Institute for Health Research during the conduct of the study.

Figures

Fig. 1
Fig. 1
Baseline prevalence and type of intracranial bleeding by Glasgow Coma Score (GCS)
Fig. 2
Fig. 2
Baseline intracranial bleeding volume distribution
Fig. 3
Fig. 3
Association between time from injury to baseline scan and intracranial bleeding on baseline scan
Fig. 4
Fig. 4
Association between baseline intracranial bleeding (ml) and baseline midline shift (mm)
Fig. 5
Fig. 5
Association between midline shift and risk of un-reactive (compared to reactive) pupils at baseline
Fig. 6
Fig. 6
Hypothesis: association between bleeding rate and treatment effect
See this image and copyright information in PMC

Comment in

  • CRASH 3: a monumental effort with minimal gain.
    Phadtare CV, Deora H, Sadashiva N. Phadtare CV, et al. Eur J Trauma Emerg Surg. 2021 Feb;47(1):269-271. doi: 10.1007/s00068-020-01424-y. Epub 2020 Jun 24. Eur J Trauma Emerg Surg. 2021. PMID: 32583071 No abstract available.

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