Corticosteroid Randomisation After Significant Head Injury

In 1990, road traffic crashes caused 5,563,000 intracranial injuries worldwide Murray CJL, Lopez AD. Global health statistics. Boston: Harvard University Press, 1996 Global Health Statistics

% 5% 10% 15% 20% Study size (number randomised ) Smallest absolute risk reduction detectable Smallest absolute risk reduction detectable in study of given size* ,2802,5605,12010,24020,480 Size and power of head injury trials Number of trials of given size (*baseline risk = 0.2, power = 80%)

A large simple placebo controlled trial, among adults with head injury and impaired consciousness, of the effects of a 48-hour infusion of corticosteroids on death and neurological disability

Aggregate mortality from 13 randomised trials of steroids in head injury 39% DEAD 422 out of % DEAD 396 out of % 35% 40% SteroidControl Alderson P, Roberts I. BMJ 1997;314:1855-9

Meta-analysis of mortality in previous trials of steroids in head injury

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 990;322: “After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function, sensation to pinprick and touch.”

To determine reliably the effects of high dose corticosteroid infusion on: death and disability after head injury risk of infection and gastrointestinal bleeding Aim

Eligibility Adult with head injury and impaired consciousness No clear indication for or contraindication to steroids

Randomisation Freephone and give: patient details hours since injury GCS pupil reactiveness Treatment pack number will be allocated

Randomisation Take next numbered treatment pack Fax entry form to co-ordinating centre pack number patient details hours since injury GCS pupil reactiveness

Treatment 1 hour loading infusion of 100mL (2gm steroid/placebo) 48 hour infusion of 20mL/hr (0.4gm/hr steroid/placebo for 48 hrs)

Adverse events Serious and unexpected adverse event suspected to be related to trial medicine ask for “adverse events”

Unblinding If care depends importantly on knowing whether patient received steroid or not ask for “unblinding”

Follow up No extra tests Single-sided outcome form completed at discharge, death in hospital, or 2 weeks (whichever first)

CRASH Co-ordinating Centre Bedford Square, London, WC1B 3DP Tel: +44 (0) Fax: +44 (0)