1. CRASH2 Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

2. “...in Italy for 30 years under the Borgias they had warfare, terror, murder, and bloodshed, but they produced Michelangelo, Leonardo da Vinci, and the Renaissance...

3. “In Switzerland they had brotherly love - they had 500 years of democracy and peace, and what did that produce? The cuckoo clock.”

4. Scale of problem Worldwide: – 1.6 million deaths annually – RTC 9 th most common cause of death – Disproportionate impact on younger age groups UK: – 6 million ED attendances – 720 000 admissions – 17 000 deaths

5. CRASH2 Prospective, multicentre RCT 20 211 patients 274 Hospitals 40 Countries Commenced May 2005

6. Design Trauma patients – BP<90mmHg systolic – HR>110 – Clinical suspicion of significant haemorrhage – Within 8 hours of injury Randomised to: – Tranexamic acid, 1g/10min loading then 1g/8hr – Placebo

7. Recruitment 20 211 Randomised 10 096 Tranexamic acid 10 093 baseline 9995 loading 9490 maintenance 10 060 analysed 33 No follow up 3 Consent withdrawn 10 115 Placebo 10 114 baseline 9989 loading 9475 maintenance 10 067 analysed 47 no follow up 1 consent withdrawn

8. Analysis Primary outcome: all cause mortality within four weeks Secondary outcomes: – Vascular occlusive events – Surgical intervention – Blood transfusion – Units blood transfused – Dependancy on discharge/day 28

9. Results Tranexamic acid (n=10 060)Placebo (n=10 067)RR Mortality (all cause)1463 (14.5%)1613 (16.0%)0.91 Mortality (bleeding)489 (4.9%)574 (5.7%)0.85 Mortality (Vascular occlusive events) 33 (0.3%)48 (0.5%)0.69 Vascular occlusive events 168 (1.7%)201 (2.0%)0.84 Surgery4814 (47.9%)4836 (48.0%)1.00 Transfusion5067 (50.4%)5160 (51.3%)0.98 Median units33

10. Dependency Tranexamic acid (n=10 060)Placebo (n=10 067)RR No symptoms1483 (14.7%)1334 (13.3%)1.11 Minor symptoms3054 (30.4%)3061 (30.4%)1.00 Some restriction2016 (20.0%)2069 (20.6%)0.97 Dependent1294 (12.9%)1273 (12.6%)1.02 Fully dependent696 (6.9%)676 (6.7%)1.03 Alive; unknown status54 (0.5%)41 (0.4%) Dead1463 (14.5%)1613 (16.0%)0.91

11. Discussion Significant reduction in mortality Significant increase in fully independent survivors No change in need for surgery No change in need for transfusion or amount transfused – ?surviving longer – ?early estimate of loss inaccurate

12. Summary 1.5% absolute reduction (9% relative risk reduction) in all-cause mortality at 28 days Reduced morbidity No effect on need for operation or transfusion ~£5 per patient Role in ED, Theatre 9, ITU?

13. Thank you