Tranexamic Acid Timing and Mortality Impact After Trauma - 02/08/25

Doi : 10.1016/j.annemergmed.2025.06.609

Adnan Ali, MBBS, PhD ^a, Russell L. Gruen, MBBS, PhD ^b,^c,^⁎ , Stephen A. Bernard, MBBS, MD ^d,^e,^f, Brian Burns, MB BCh, MSc ^g,^h, Andrew B. Forbes, PhD ⁱ, Dashiell C. Gantner, MBBS, PhD ^d,^e,^j, Colin J. McArthur, MBChB ^k,^l, Marc Maegele, MD ^m,ⁿ, Biswadev Mitra, MBBS, PhD ^d,^o
on behalf of
PATCH-Trauma trial investigators^†
The PATCH-Trauma Trial investigators are listed in the Supplementary Appendix .
^a Clinical Hub for Interventional Research, John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia
^b Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR
^c School of Medicine and Psychology, The Australian National University, Canberra, Australian Capital Territory, Australia
^d Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
^e Department of Intensive Care, Alfred Hospital, Melbourne, Victoria, Australia
^f Ambulance Victoria, Melbourne, Victoria, Australia
^g Aeromedical Operations, NSW Ambulance, Sydney, New South Wales, Australia
^h Sydney Medical School, Sydney University, Sydney, New South Wales, Australia
ⁱ School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia
^j Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia
^k Auckland City Hospital, Auckland, New Zealand
^l Medical Research Institute of New Zealand, Wellington, New Zealand
^m Cologne-Merheim Medical Center, Department of Traumatology, Orthopaedic Surgery and Sports Medicine, University of Witten-Herdecke, Cologne, Germany
ⁿ Institute for Research in Operative Medicine, University Witten-Herdecke, Cologne, Germany
^o Alfred Health Emergency Services, Melbourne, Victoria, Australia

^∗Corresponding Author.

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Abstract

Study objective

Trauma resuscitation guidelines across the world have incorporated the administration of tranexamic acid (TXA) within 3 hours of injury. The 3-hour window was deduced from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial and has not been replicated. The aim of this study was to determine whether death within 28 days after trauma varied according to time from injury to the first TXA dose and, if so, precisely determine the therapeutic window.

Methods

This was an exploratory analysis of the Prehospital Tranexamic Acid for Severe Trauma (PATCH-Trauma) trial, which enrolled adults with major trauma and suspected trauma-induced coagulopathy. Eligible patients were randomized to receive either TXA (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1 g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. In this analysis, we examined the effect of time from injury to first treatment dose on death within 28 days utilizing a continuous scale with linear, first-degree fractional polynomial, and second-degree fractional polynomial functions of time from injury to first treatment dose. Further log-binomial regression analyses were performed in subgroups based on the information obtained from the previous step.

Results

The intention-to-treat study cohort comprised 1,287 patients, of which 635 had been allocated to the placebo arm and 652 to the TXA arm. The median time from injury to first treatment dose was 79 (interquartile range [IQR] 55 to 112) minutes. Risk of death within 28 days increased as the time to first dose of treatment increased, with benefit most pronounced up to 90 minutes. Beyond 90 minutes, the upper 95% confidence interval (CI) crossed the line of equivalence (risk ratio, 1). Administration of TXA within 90 minutes significantly reduced the risk of death within 28 days (67/393 [17%] in the TXA group versus 91/363 [25%] in placebo group; adjusted risk ratio 0.64, 95% CI 0.50 to 0.82), whereas administration beyond 90 minutes did not decrease mortality at 28 days (adjusted risk ratio 1.04, 95% CI 0.74 to 1.47).

Conclusion

The optimal therapeutic window for TXA after trauma may be within 90 minutes.

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Keywords : Tranexamic acid, Injury, Trauma, Randomized controlled trial

Plan

Introduction

Background

Importance

Goals of This Investigation

Methods

Study Design and Setting

Selection of Participants

Characteristics of study subjects

Main Results

Limitations

Discussion

	Supervising editor : Allan B. Wolfson, MD. Specific detailed information about possible conflict of interest for individual editors is available at editors .
	Author contributions: AA, RG, SB, and BM conceptualized the study. PATCH trial investigators collected and curated data. AA undertook the analysis. All authors reviewed the manuscript. RG takes responsibility for the paper as a whole.
	Data sharing statement: Deidentified data will be made available to researchers who provide a methodologically sound proposal to undertake hypothesis driven research for review to corresponding author and will be reviewed by the PATCH-trauma trial management committee and/or the Australian and New Zealand Intensive Care Society Clinical Trials Group.
	All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
	Funding and support: By Annals’ policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org/ ). The PATCH-Trauma Trial is funded by grants from the Australian National Health and Medical Research Council (NHMRC APP1044894 and APP165275 ), the Health Research Council of New Zealand (GA216F), the New Zealand Lottery Grants Board (34033), and the German Research Funding Agency (Deutsche Forschungsge-meinschaft) (MA 2569/6-1). All authors report no conflict of interest.
	Trial registration number: The trial is registered with clinicaltrials.gov id NCT02187120.
	Please see page XX for the Editor’s Capsule Summary of this article.