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CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. Jul 2010: 3-4.
In a nutshell
Surgery and trauma both trigger fibrinolysis. Tranexamic acid inhibits this process, and reduces blood loss. The CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage 2) study is a placebo-controlled trial of the effects of early administration of tranexamic acid. 20,211 adult trauma patients with significant haemorrhage (systolic blood pressure <90mmHg or a heart rate above 110 beats per minute, or both), or who were considered at risk of significant haemorrhage, and who were within eight hours of injury, were randomised in over 40 countries to a loading dose of 1g tranexamic acid over 20 minutes and then 1g over eight hours, or placebo. All cause mortality was 14.5% with tranexamic acid v 16% with placebo (p=0.12). RR of death with tranexamic acid =0.91. Only deaths from stroke (eight vs five) were higher in the drug group. The risk of death due to bleeding was significantly reduced, even on the day of randomisation. There was no significant difference in the use of blood products. 14.7% v 13.3% had no symptoms at discharge, with drug and placebo, respectively. No difference in risk of requiring surgical intervention, or of gastrointestinal bleeding.
Second opinion
The CRASH study is a large, randomised trial. Participants and physicians were blinded as to treatment received. The study outcomes should therefore inform our clinical practice. Some commentators nevertheless suggest the benefits need to be compared with those of the myriad other factors that influence emergency and intensive care outcomes before widespread adoption. It’s also noted that the drug has been associated with seizures in cardiac surgery, although at higher doses. The study was designed with drug administration early in the disease process, aiming to reduce haemorrhage without increasing later vascular occlusive events. Future work might focus on whether there is additional benefit to earlier (Emergency Department), or longer, periods of drug administration. It is also recognised that whilst tranexamic acid inhibits fibrinolysis, this was not actually measured in the trial. Other work would suggest this is nevertheless the mode of drug action, but further study of the in vivo action of tranexamic acid in these patients might shed light on the process of pathological fibrinolysis and indicate novel avenues for drug design and intervention.
The verdict
- This was a large multi-centred randomised controlled trial.
- There was significant reduction in all cause mortality at four weeks in trauma patients with significant haemorrhage.
- The result supports serious consideration of inclusion of tranexamic acid in the physician’s armoury for these patients.
Paul Brennan
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