Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial
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Abstract
Corticosteroids have been used to treat head injuries for more than 30 years. In 1997,
findings of a systematic review suggested that these drugs reduce risk of death by
1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm
or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring
committee disclosed the unmasked results to the steering committee, which stopped
recruitment.
10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within
8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone)
or placebo. Primary outcomes were death within 2 weeks of injury and death or disability
at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at
randomisation and on time from injury to randomisation. Analysis was by intention
to treat. Effects on outcomes within 2 weeks of randomisation are presented in this
report. This study is registered as an International Standard Randomised Controlled
Trial, number ISRCTN74459797.
Compared with placebo, the risk of death from all causes within 2 weeks was higher
in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative
risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids
did not differ by injury severity (p=0.22) or time since injury (p=0.05).
Our results show there is no reduction in mortality with methylprednisolone in the
2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is
unclear.