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Corticosteroid Randomisation After Significant Head Injury

Corticosteroid Randomisation After Significant Head Injury. 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. 40%. 39%. 37%. DEAD. 35%. DEAD.

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Corticosteroid Randomisation After Significant Head Injury

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  1. Corticosteroid Randomisation After Significant Head Injury

  2. 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

  3. 40% 39% 37% DEAD 35% DEAD 422 out of 396 1087 out of 1061 30% Steroid Control Aggregate mortality from 13 randomised trials of corticosteroids in head injury Alderson P, Roberts I. BMJ 1997;314:1855-9

  4. 20% Smallest absolute risk reductiondetectable in study of given size* 15% Smallest absolute risk reduction detectable 10% 5% 0% 20 40 80 160 320 640 1,280 2,560 5,120 10,240 20,480 Study size (number randomised) (*baseline risk = 0.2, power = 80%)

  5. 20% Smallest absolute risk reductiondetectable in study of given size* 15% Smallest absolute risk reduction detectable 62 trials 10% 45 37 36 5% 15 5 3 0% 20 40 80 160 320 640 1,280 2,560 5,120 10,240 20,480 Study size (number randomised) (*baseline risk = 0.2, power = 80%)

  6. 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

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

  8. Randomisation • Take next numbered treatment pack • Fax entry form to Co-ordinating Centre • - Pack number • - Patient details • - Hours since injury • - GCS • - Pupil reactiveness

  9. 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)

  10. Adverse events Serious and unexpected adverse events suspected to be related to trial medicine  Telephone UK randomisation service and ask for “adverse events”

  11. Unblinding If care depends importantly on knowing whether patient received steroid or not  Telephone UK randomisation service and ask for “unblinding”

  12. 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

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

  14. Projections

  15. Who’s taking part? 105 hospitals in 31 countries

  16. 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 Germany 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 Romania 2 96 Singapore 1 9 Slovakia 4 38 South Africa 1 174 Spain 5 58 Sri Lanka 1 99 Switzerland 3 74 Tunisia 1 Turkey 1 Uganda 1 16 UK 36 807 USA 2 Venezuela 3

  17. 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 Spitalul Clinic de Urgenta Bucuresti Romania 7.7 Tygerberg 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 University 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

  18. 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

  19. Age and sex Age group n % 16 – 24 259 (26) 25 – 34 227 (23) 35 + 514 (51) Sex Male 781 (78) Female 219 (22)

  20. Glasgow Coma Scale GCS n % Severe (3-8) 381 (38) Moderate (9-12) 289 (29) Mild (13-14) 330 (33)

  21. 400 300 200 100 0 0-1 1-2 2-3 3-4 4-5 5-6 6-7 7-8 Hours Time from injury

  22. 16% 22% Mortality by sex

  23. Mortality by age 35% 23% 14% 8% Age group

  24. Mortality by GCS 31% 11% 6% GCS

  25. 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

  26. 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

  27. www.crash.lshtm.ac.uk CRASH Co-ordinating Centre 49-51 Bedford Square, London WC1B 3DP Tel: +44 (0)20 7299 4684 Fax: +44 (0)20 7299 4663 CRASH@LSHTM.ac.uk

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