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.
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 masked 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.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.


RESULTS
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 (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] 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 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).


CONCLUSIONS
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.


BACKGROUND
UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
Clinical Trials Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Shakur
Haleema
H
Roberts
Ian
I
Bautista
Raúl
R
Caballero
José
J
Coats
Tim
T
Dewan
Yashbir
Y
El-Sayed
Hesham
H
Gogichaishvili
Tamar
T
Gupta
Sanjay
S
Herrera
Jorge
J
Hunt
Beverley
B
Iribhogbe
Pius
P
Izurieta
Mario
M
Khamis
Hussein
H
Komolafe
Edward
E
Marrero
María-Acelia
MA
Mejía-Mantilla
Jorge
J
Miranda
Jaime
J
Morales
Carlos
C
Olaomi
Oluwole
O
Olldashi
Fatos
F
Perel
Pablo
P
Peto
Richard
R
Ramana
P V
PV
Ravi
R R
RR
Yutthakasemsunt
Surakrant
S
D000328:Adult; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001803:Blood Transfusion; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D014148:Tranexamic Acid / Q000627:therapeutic use*; D014947:Wounds and Injuries / Q000150:complications*
D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid