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J R Soc Med. 2002 March; 95(3): 162.
PMCID: PMC1279495


The Medical Research Council CRASH Trial (Corticosteroid Randomisation After Significant Head Injury) is a large-scale randomized controlled trial, among adults with head injury and impaired consciousness, of the effects of a short-term infusion of corticosteroids on death and on neurological disability. Following a successful pilot phase that included over 1000 randomized participants, the main phase of the trial is now underway. Over the next five years the trial aims to recruit 20 000 patients. Such large numbers will only be possible if doctors and nurses worldwide join the trial.

There are many reasons for conducting the CRASH Trial now: (1) results from animal studies show that high-dose methylprednisolone can reduce post-traumatic neuronal degeneration1,2; (2) patients with spinal cord injury who are treated with corticosteroids rather than placebo within 8 hours of injury appear to have greater improvement in motor function, and in sensation to pinprick and touch3,4; (3) there are wide variations within and between countries in the use of corticosteroids in head injury5; (4) a meta-analysis of randomized trials of corticosteroids in head injury shows that existing trials are too small to demonstrate or to refute the possibility of a moderate but clinically important benefit6.

Head-injured adults with impaired consciousness are eligible for inclusion in the trial if the responsible doctor is for any reason substantially uncertain whether or not to use corticosteroids. Patients with head injury and impaired consciousness may be unable to give properly informed consent, and in this emergency situation it may not be appropriate to delay the start of treatment until relatives' consent can be obtained. Hence, the doctor in charge should take responsibility for entering such patients, just as he or she would take responsibility for choosing other treatments. However, the requirements of the relevant research ethics committee must be adhered to. Numbered drug or placebo packs will be available in each participating emergency department. Randomization involves calling a 24-hour free phone service. The outcome measures are death from any cause within two weeks of injury, and death or dependence at six months. In-hospital deaths, complications and short-term recovery are recorded on a single-sided outcome form that can be completed entirely from the hospital notes and no extra tests are needed. Long-term recovery is assessed at six months either by a simple postal questionnaire, sent directly to each trial participant from the national coordinating centre, or by telephone interview, and will not involve any additional work for collaborating hospitals.

The identification of effective treatments for head injury is of global health importance. Will readers who would like to take part please register their interest via the trial website [ ] or write to the CRASH trial coordinating centre.


1. Hall E. High dose glucocorticoid treatment improves neurological recovery in head-injured mice. J Neurosurg 1985;62: 882-7 [PubMed]
2. Ildan F, Polat S, Oner A, et al. The effect of the treatment of high-dose methyl- prednisolone on Na(+)-K(+)/Mg(+2) ATPase activity and lipid peroxidation and ultrastructural findings following cerebral contusion in rat. Surg Neurol 1995;44: 573-80 [PubMed]
3. Bracken M, Shepard MJ, Collins WF, et al. A randomised controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. N Engl J Med 1990;322: 1405-11 [PubMed]
4. Otani K, Abe H, Kadoya S, et al. Beneficial effect of methylprednisolone sodium succinate in the treatment of acute spinal cord injury (translation of Japanese). Sekitsui Sekizui J 1994;7: 633-47
5. Matta B, Menon D. Severe head injury in the United Kingdom and Ireland: A survey of practice and implications for management. Crit Care Med 1996;24: 1743-8 [PubMed]
6. Alderson P, Roberts I. Corticosteroids in acute traumatic brain injury: a systematic review of randomised trials. BMJ 1997;314: 1855-9 [PMC free article] [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press