The Second US National Acute Spinal Cord Study (NASCIS 2) compared 24 hours of methylprednisolone (MP) with placebo in 333 patients with acute spinal cord injury.¹
At six months, patients who had received steroids within eight hours of injury appeared to have greater improvement in motor function, and in sensation to pinprick and touch. Similar results were reported in a Japanese trial of the same regimen.²  Some doctors believe these results are sufficient evidence of benefit to justify treating spinal cord injury patients with corticosteroids, whereas others do not.³  Those who are unconvinced argue that the evidence of benefit is from a sub-group analysis in a relatively small trial.  Without new evidence from a much larger randomised-controlled trial it is unlikely that clinical uncertainty about corticosteroids in spinal cord injury will be resolved. So what are the lessons for the CRASH trial? 

The CRASH trial has been designed to determine reliably the effects of short-term corticosteroid infusion on death and on disability following significant head injury.
With 1200 patients recruited, the CRASH trial is already the largest randomised controlled trial in head injury ever conducted.  Over the next five years the trial aims to recruit a total of 20,000 patients.  A really large trial like CRASH will provide reliable evidence about the effectiveness of corticosteroids in head injury, so that on-going clinical uncertainty, such as for corticosteroids in spinal cord injury, will be considerably reduced. 

There are many reasons for conducting the CRASH trial now:

• Results from animal studies show that high dose methylprednisolone (MP) can reduce post-traumatic neuronal degeneration; 

• 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 touch;

• There are wide variations within and between countries in the use of corticosteroids in head injury; 

• A meta-analysis of randomised controlled 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 benefit.

The CRASH trial is currently recruiting patients in 66 centres in 20 countries and we expect many more centres to join the trial over the next few years.  The enthusiastic response to the CRASH trial from emergency physicians, neurosurgeons, and intensive care physicians, signals the strong international commitment to resolving uncertainties around the effectiveness of interventions in neurotrauma.  Management of the increasing global burden of head injury must be addressed in a similar way to that adopted so successfully in ischaemic heart disease.  Prevention and the understanding of basic pathophysiology must be complemented by well-conducted large simple trials.
 

References

1. Bracken MB, Shepard MJ, Collins WF, et al. A randomised controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. N Eng J Med 1990;322:1405-11.

2. 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.

3. Short DJ, El Masry WS, Jones PW. High dose methylprednisolone in the management of acute spinal cord injury - a systematic review from a clinical perspective. Spinal Cord 2000;38:273-286.