Anest. intenziv. Med. 2011;22(2):103-114

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo controlled trialIntensive Care Medicine - Original Paper

Trenkler Štefan^1,*, Laincz Anton², Valky Jozef³, Yaghi Ajtham⁴, Svoboda Petr⁵

¹ Klinika anestéziológie a intenzívnej medicíny, Univerzita P. J. Šafárika a Univerzitná nemocnica L. Pasteura Košice, Slovensko

² Oddelenie anestéziológie a intenzívnej medicíny, Nemocnica Poprad, a. s., Slovensko

³ Oddelenie anestéziológie a intenzívnej medicíny, Fakultná nemocnica s Poliklinikou F. D. Roosevelta Banská Bystrica

⁴ Klinika anestéziológie a intenzívnej medicíny, Univerzitná nemocnica Bratislava, Nemocnica Ružinov

⁵ Úrazová nemocnice v Brně

Background:
Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.

Methods:
This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were blinded to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat.
This study is registered as ISRCTN86750102, Clinicaltrials.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919.
Findings:
Total 10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1,463 [14.5%] in the tranexamic acid group vs 1,613 [16.0%] in the placebo group; relative risk 0.91, 95% CI 0.85-0.97; p = 0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 5.74 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p = 0.0077).
Interpretation:
Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.
Funding:
UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Keywords: tranexamic acid; trauma; bleeding; RCT; CRASH-2

Received: December 23, 2010; Accepted: February 3, 2011; Published: April 1, 2011  Show citation