Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 15474134 · doi:10.1016/S0140-6736(04)17188-2
What was done
In an international multicenter randomized placebo-controlled trial, 10,008 adults with clinically significant head injury (Glasgow Coma Score ≤ 14 within 8 hours of injury) were randomized to receive a 48-hour infusion of corticosteroids (methylprednisolone) or placebo. Analysis was conducted by intention to treat. The reported outcome was death from all causes within 2 weeks of injury.
What was found
Death from all causes within 2 weeks was significantly higher in the corticosteroid group compared to placebo (1,052 [21.1%] vs 893 [17.9%]; relative risk 1.18, 95% CI 1.09–1.27; p=0.0001). The increase in relative mortality risk did not significantly differ across injury severity (p=0.22) or time since injury (p=0.05).
Why it matters
This landmark study refuted decades of clinical practice and prior smaller reviews, showing that intravenous corticosteroids increase short-term mortality after acute head injury.
Limits
The trial was halted early on safety grounds after recruiting 10,008 of a planned 20,000 participants; 6-month disability outcomes are not reported here, and the biological cause of increased mortality was not determined.
Cited by
- supports The CRASH trial evaluating corticosteroid anti-inflammatories for head injury found an absolute increase in death rate of 3.8% compared to placebo.