Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Ian
I
Roberts
David
D
Yates
Peter
P
Sandercock
Barbara
B
Farrell
Jonathan
J
Wasserberg
Gabrielle
G
Lomas
Rowland
R
Cottingham
Petr
P
Svoboda
Nigel
N
Brayley
Guy
G
Mazairac
Véronique
V
Laloë
Angeles
A
Muñoz-Sánchez
Miguel
M
Arango
Bennie
B
Hartzenberg
Hussein
H
Khamis
Surakrant
S
Yutthakasemsunt
Edward
E
Komolafe
Fatos
F
Olldashi
Yadram
Y
Yadav
Francisco
F
Murillo-Cabezas
Haleema
H
Shakur
Phil
P
Edwards
D000293:Adolescent; D000328:Adult; D006259:Craniocerebral Trauma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D015600:Glasgow Coma Scale; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D005938:Glucocorticoids; D008775:Methylprednisolone