CRASH‐2 2010.

Methods	Randomised controlled trial.
Participants	20,211 adult (>16 years) trauma patients with, or at risk of, significant bleeding.
Interventions	Tranexamic acid group: loading dose 1g over 10 minutes then infusion of 1 g over 8 hours. Matching placebo. Setting: hospitals in 40 countries participated: details available here: http://www.crash2.lshtm.ac.uk/
Outcomes	Death. Vascular occlusive events. Blood transfusion requirements. Disability. Incranial haemorrhage growth* Brain lesions* Disability* [*collected in Intracranial Bleeding Substudy only]
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator." (pg 24)
Allocation concealment (selection bias)	Low risk	"In hospitals in which telephone randomisation was not practicable we used a local pack system that selected the lowest numbered treatment pack from a box containing eight numbered packs. Apart from the pack number, the treatment packs were identical.... Hospitals with reliable telephone access used the University of Oxford Clinical Trial Service Unit (CTSU) telephone randomisation service." (pg 24)
Blinding of participants and personnel (performance bias) Death, vascular occlusive events, intracranial bleeding	Low risk	"Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation." (pg 24)
Blinding of participants and personnel (performance bias) Surgical intervention, blood transfusion	Low risk	"Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation." (pg 24)
Blinding of outcome assessment (detection bias) Death, surgical intervention, blood transfusion	Low risk	"Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation." (pg 24)
Blinding of outcome assessment (detection bias) Vascular occlusive events, intracranial bleeding	Low risk	"Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation." (pg 24)
Incomplete outcome data (attrition bias) All outcomes	Low risk	"All analyses were undertaken on an intention‐to‐treat basis." (pg 25) The data from four patients were removed from the trial because their consent was withdrawn after randomisation." (pg 25) The review authors judge that the proportion of missing outcomes compared with event risk is not enough to have a clinically relevant impact on the effect estimate.
Selective reporting (reporting bias)	Low risk	Trial prospectively registered (ISRCTN86750102, NCT00375258, DOH‐27‐0607‐1919 [pg 25]). Data on all prespecified outcomes presented in final report.