Transcript CRASH2

CRASH2
Clinical Randomisation of an
Antifibrinolytic in Significant
Haemorrhage
“...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...
“In Switzerland they had brotherly love
- they had 500 years of democracy
and peace, and what did that
produce? The cuckoo clock.”
Scale of problem
• Worldwide:
– 1.6 million deaths annually
– RTC 9th most common cause of death
– Disproportionate impact on younger age groups
• UK:
– 6 million ED attendances
– 720 000 admissions
– 17 000 deaths
CRASH2
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Prospective, multicentre RCT
20 211 patients
274 Hospitals
40 Countries
Commenced May 2005
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
Recruitment
20 211 Randomised
10 096 Tranexamic acid
10 115 Placebo
3 Consent
withdrawn
1 consent withdrawn
10 114 baseline
10 093 baseline
9989 loading
9995 loading
9475 maintenance
9490 maintenance
33 No follow up
47 no follow up
10 060 analysed
10 067 analysed
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
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
Surgery
4814 (47.9%)
4836 (48.0%)
1.00
Transfusion
5067 (50.4%)
5160 (51.3%)
0.98
Median units
3
3
Dependency
Tranexamic acid (n=10 060)
Placebo (n=10 067)
RR
No symptoms
1483 (14.7%)
1334 (13.3%)
1.11
Minor symptoms
3054 (30.4%)
3061 (30.4%)
1.00
Some restriction
2016 (20.0%)
2069 (20.6%)
0.97
Dependent
1294 (12.9%)
1273 (12.6%)
1.02
Fully dependent
696 (6.9%)
676 (6.7%)
1.03
Alive; unknown status
54 (0.5%)
41 (0.4%)
Dead
1463 (14.5%)
1613 (16.0%)
0.91
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
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?
Thank you