The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial

Roberts, Ian; Shakur, Haleema; Afolabi, Adefemi; Brohi, Karim; Coats, Timothy J; Dewan, Yashbir; Gando, Satoshi; Guyatt, Gordon; Hunt, Beverley J.; Morales, Carlos; Perel, Pablo; Prieto‐Merino, David; Woolley, Tom

doi:10.1016/s0140-6736(11)60278-x

Cited by 867 publications

(242 citation statements)

References 13 publications

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“…Antifibrinolytic drugs are used worldwide to decrease the requirement for blood transfusions, reduce the risk of reoperation for bleeding, and lower mortality associated with hemorrhage following major trauma 1, 2, 3. The most commonly used antifibrinolytic drugs include tranexamic acid (TXA), ɛ‐aminocaproic acid (EACA), and aprotinin 1.…”

mentioning

confidence: 99%

Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

208

158

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Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26

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mentioning

confidence: 99%

Tranexamic acid–associated seizures: Causes and treatment

Lecker

Wang

Whissell

et al. 2015

Annals of Neurology

208

158

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“…14 If tranexamic acid is effective after traumatic brain injury, it should also be most effective when given soon after injury, when intracranial bleeding is ongoing. 8 The potential for harm also exists however.…”

mentioning

confidence: 99%

Does tranexamic acid improve outcomes in traumatic brain injury?

Mahmood

Roberts

Shakur

et al. 2016

BMJ

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“…However, whilst the trial was underway, new research suggested a shorter therapeutic window than 8 hours 12, 13 . The new data showed that tranexamic acid is most likely to improve outcome if given soon after injury and would be unlikely to improve outcome if given beyond three hours of injury.…”

Section: Trial Methodsmentioning

confidence: 99%

“…This was based on the CRASH-2 trial results which showed that giving tranexamic acid to patients with traumatic extra-cranial bleeding within eight hours of injury reduces death due to bleeding and all-cause mortality 11 . However, pre-specified subgroup analyses showed that the effect of tranexamic acid depends on the time interval between the injury and start of treatment 12 . Treatment within three hours of injury substantially reduced death due to bleeding and all-cause mortality whereas treatment started after three hours appeared to increase death due to bleeding and had no effect on all-cause mortality.…”

Section: Statistical Analysis Planmentioning

confidence: 99%

“…Tranexamic acid also reduces mortality in bleeding trauma patients. In 2011, the CRASH-2 trial showed that administration of tranexamic acid to poly-trauma patients within three hours of injury reduces deaths due to bleeding by about one third 11, 12 . In 2017, the WOMAN trial showed that administration of tranexamic acid to women with post-partum haemorrhage within three hours of delivery reduces deaths due to bleeding by about one third 13 .…”

Section: Introductionmentioning

confidence: 99%

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Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial

Roberts¹,

Belli²,

Brenner³

et al. 2018

Wellcome Open Res

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Background: Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide reliable evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients to an intravenous infusion of tranexamic acid or matching placebo in addition to usual care. This paper presents a protocol update (version 2.1) and statistical analysis plan for the CRASH-3 trial. Results: The primary outcome is head injury death in hospital within 28 days of injury for patients treated within 3 hours of injury (deaths in patients treated after 3 hours will also be reported). Because there are strong scientific reasons to expect that tranexamic acid will be most effective in patients treated immediately after injury and less effective with increasing delay, the effect in patients treated within one hour of injury is of particular interest. Secondary outcomes are all-cause and cause-specific mortality, vascular occlusive events (myocardial infarction, pulmonary embolism, deep vein thrombosis, stroke), disability based on the Disability Rating Scale and measures suggested by patient representatives, seizures, neurosurgical intervention, neurosurgical blood loss, days in intensive care and adverse events. Sub-group analyses will examine the effect of tranexamic acid on head injury death stratified by time to treatment, severity of TBI and baseline risk. Conclusion: The CRASH-3 trial will provide reliable evidence of the effectiveness and safety of tranexamic acid in patients with acute TBI. Registration: International Standard Randomised Controlled Trials registry ( ISRCTN15088122) 19/07/2011, and ClinicalTrials.gov ( NCT01402882) 25/07/2011.

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The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial

Cited by 867 publications

References 13 publications

Tranexamic acid–associated seizures: Causes and treatment

Tranexamic acid–associated seizures: Causes and treatment

Does tranexamic acid improve outcomes in traumatic brain injury?

Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial

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