Corticosteroid Randomisation After Significant Head Injury

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Corticosteroid Randomisation After Significant
Head Injury
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Global Health Statistics
In 1990, road traffic crashes caused 5,563,000
intracranial injuries worldwide

Murray CJL, Lopez AD. Global health statistics.
Boston Harvard University Press, 1996
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Aggregate mortality from 13 randomised trials of
corticosteroids in head injury
Alderson P, Roberts I. BMJ 19973141855-9
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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
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To determine reliably the effects of high dose
corticosteroid infusion on
Aim

• death and disability after head injury
• risk of infection and gastrointestinal bleeding

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Randomisation
Take next numbered treatment pack Fax entry form
to Co-ordinating Centre - Pack number - Patient
details - Hours since injury - GCS - Pupil
reactiveness
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Treatment
1 hour loading infusion of 100mL (2g
steroid/placebo) 48 hour infusion of 20mL/hr or
until discharge, if sooner (0.4g/hr
steroid/placebo)
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Adverse events
Serious and unexpected adverse events suspected
to be related to trial medicine ? Telephone UK
randomisation service and ask for adverse
events
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Unblinding
If care depends importantly on knowing whether
patient received steroid or not ? Telephone UK
randomisation service and ask for unblinding
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Follow-up
No extra tests Single-sided outcome form
completed at discharge, death in hospital, or 14
days Short interview or postal questionnaire
sent at six months
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Trial progress

• Started - April 1999
• Estimated end - March 2005
• Target - 20,000 patients
• Recruitment to date - 2,420 patients

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Projections
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Whos taking part?
105 hospitals in 31 countries
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Recruitment by country
Hospitals Patients Argentina 11 81 Australia 1
Belgium 3 241 Brazil 1 7 Colombia 5 77 Cuba 4
Czech Republic 6 370 Egypt 2 89 Eire 1 76 Ger
many 2 8 Ghana 1 2 Greece 3 Italy 1 1 Malaysia
1 68 Mexico 1 New Zealand 1 9
Hospitals Patients Nigeria 1 13 Paraguay 1 4 Ro
mania 2 96 Singapore 1 9 Slovakia 4 38 South
Africa 1 174 Spain 5 58 Sri Lanka 1 99 Switzerl
and 3 74 Tunisia 1 Turkey 1 Uganda 1 16 UK 36
807 USA 2 Venezuela 3
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Recruitment rates
Hospital Country
Patients/month Research Institute for Special
Surgery and Trauma Czech Republic 9.6 Centre
Hospitalier Regional de Namur Belgium 8.2 Spitalu
l Clinic de Urgenta Bucuresti Romania 7.7 Tygerbe
rg Academic Hospital South Africa 7.3 Makerere
Medical School Uganda 5.5 Mataria Teaching
Hospital Egypt 4.4 Hospital University Science
Malaysia Malaysia 3.9 Hope Hospital UK 3.9 Unive
rsity Hospital of Zurich Switzerland 3.2 Clinica
Las Americas Colombia 3.2 St James's University
Hospital Eire 3.0 Birmingham Heartlands
Hospital UK 2.8 Hospital Universitario Virgen
del Rocio Spain 2.8 Suez Canal
University Egypt 2.8 Hospital San
Bernardo Argentina 2.4 Batticaloa General
Hospital, Teaching Sri Lanka 2.3 NsP
Poprad Slovakia 2.2
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Some results

• Pilot phase 13/4/1999 to 21/12/2000
• 1,000 patients enrolled
• Early outcome (14 days) 99 complete
• Six month outcome 93 complete

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Age and sex
Age group n 16 24 259 (26) 25
34 227 (23) 35 514 (51) Sex Male 781 (78) Femal
e 219 (22)
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Glasgow Coma Scale
GCS n Severe (3-8) 381 (38) Moderate
(9-12) 289 (29) Mild (13-14) 330 (33)
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Time from injury
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Mortality by sex
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Mortality by age
35
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14
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Age group
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Mortality by GCS
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6
GCS
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Management/Complications

• n
• Admitted to ICU 424 43
• 1 3 days 183 19
• 4 days or more 241 24
• Seizure 176 18
• Haematemesis or melaena 4 0
• Wound infection 31 3
• Pneumonia treated by antibiotics 90 9
• Other treatment with antibiotics 286 29
• Neurosurgical operation 195 20
• Major extracranial injury 179 18

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Conclusions to date

• The MRC CRASH Trial is working well in both
  university and general hospitals
• The assumed mortality rate is appropriate
• Large numbers can be successfully followed-up

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www.crash.lshtm.ac.uk
CRASH Co-ordinating Centre 49-51 Bedford Square,
London WC1B 3DP Tel [phone] Fax 44
(0)20 7299 4663 CRASH_at_LSHTM.ac.uk