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EFFECT OF INTRAVENOUS CORTICOSTEROIDS ON DEATH WITHIN 14 DAYS IN 10,008 ADULTS WITH CLINICALLY SIGNIFICANT HEAD INJURY (MRC CRASH TRIAL):RANDOMISED PLACEBO-

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Presentation on theme: "EFFECT OF INTRAVENOUS CORTICOSTEROIDS ON DEATH WITHIN 14 DAYS IN 10,008 ADULTS WITH CLINICALLY SIGNIFICANT HEAD INJURY (MRC CRASH TRIAL):RANDOMISED PLACEBO-"— Presentation transcript:

1 EFFECT OF INTRAVENOUS CORTICOSTEROIDS ON DEATH WITHIN 14 DAYS IN 10,008 ADULTS WITH CLINICALLY SIGNIFICANT HEAD INJURY (MRC CRASH TRIAL):RANDOMISED PLACEBO- CONTROLLED TRIAL Dr. Hussein Ssenyonjo Resident, Neurosurgery Mulago Hospital

2 Summary Cortical steroids have been used to treat head injuries for more than 30 years.In 1997,findings after systematic review suggested that these drugs reduce the risk of death by 1-2%.The CRASH trial- a muliticentre international collaboration aimed to confirm or refute such an effect by recruiting 20,000 patients.In May,2004, the data monitoring committee disclosed the unmasked results to the steering committee,which stopped recruitment.

3 Patients and methods Adults 16 yrs and above who presented within 8 hrs of injury and were noted in hospital to be having GCS of 14 and less.These were recruited if the treating doctor was uncertain whether or not to use steroids-(UNCERTANITY PRINCIPLE)

4 Procedures Patients randomised in one of two ways. 1.reliable telephone access 2.Local pack system We randomly allocated patients to 48 h infusion of either methylprednisolone or placebo.Loading dose 2g over 1 h in 100mls of infusion.Maintenance dose 0.4g/h for 48h at rate of 20ml/h. Primary outcome measures were death from any cause within 2 weeks of injury and death or disability at 6 months.

5 Statistical analysis Estimated risk of death allocated to placebo –15%. 2% survival difference would be clinically important so the trial size had to be large enough to detect a difference of this size.A trial of 20,000 patients would have a good chance of showing a 2% survival difference at convincing levels of significance ie >90% power to achieve p<0.01 Precision-95%CI for overall risk and 99%CI for subgroup results Homogenicity in treatment effects assessed within subgroups by X2 test at 5% significance level.

6 Results 239 hospitals from 49 countries. 10,008 patients randomised to steroid or placebo infusion 62 8h after injury, 3 stopped at request of a relative.

7 Baseline characteristics Age <25 STEROID n= (30%) PLACEBO n= (29%) (23%)1217(24%) (31%)1485(30%) >55821(16%)849(17%)

8 GCSCP Severe(3-8)1985(40%)1981(39%) Moderate(9-12) Mild(13-14) 1557(31%) 1465(29%) 1483(30%) 1537(31%) Baseline characteristics-cont

9 Time of injury <11350(27%)1347(27%) >1<31532(31%)1483(30%) >3<82125(42%)2087(42%) Baseline characteristics-cont

10 Cause of Injury R-T Crash3249(65%)3169(63%) Fall>2m608(12%)699(14%) other1085(22%)1053(21%) Not Known65(1%)80(2%) Baseline characteristics-cont

11 Brain CT Scan Done Yes 3,916(78%)3,896(78%) No/Not Known1,091(22%) 1,105(22%) Baseline characteristics-cont

12 CT Scan ResultsCP Normal23%22% 1 petechial Hrrge29%28% 3 rd V and basal cistern obliteration23%24% SAH31%32% Shift>514%15% Non evacuated haematoma27% Evacuated H12%13% Cortical contusion > 1cm22%23% Baseline characteristics-cont

13 Adherence to treatment-9,848(98%) 9,748(99%)received full loading dose. Mortality data obtained for 9,964 patients,4,985- CS M-1.052(21%) in 2wks, 4,979-P M- 893(18%) RR of death from all causes in 2wks in CS group with placebo 1.18 RR of death at 2wks didn’t differ by injury severity (p=0.22) or time since injury(p=0.05) Baseline characteristics-cont

14 Effects of CS allocation on death in 2wks,by injury severity Injury severityC n=(5007)P=(5001) GCS(3-8)785/1972(39.8%)687/1972(34.8%) Moderate (9-12)205/1553(13.2%0143/1476(9.7%) Mild(13-14)62/1460(4.2%)63/1531(4.1%) Time since Injury <1h227/1341(16.9%)209/1342(15.6%) >1<3h308/15309(20.14)296/1560(19%) >3<8h X2 6.03,p= /2114(24.5%)388/2077(18.7%) All patients 95%CI 1052/4985(21.1%)893/4979(17.9%)

15 Effects of CS allocation on death from all causes in 2 weeks by CT scan results. Normal Ct CS n= /897(4.7%) P n= /878(3.6%) One or more petechial 313/1139(27.5%)270/1098(24.6%) Obliteration 3 rd V or basal cistern 396/906(43.7%)381/920(41.4%) SAH406/1226(33.1%)378/1231(30.7%) Shift >5mm279/556(50.2%)269/579(46.5%) Non evacuated H366/1061(34.5%)322/1050(30.7%) Evacuated H137/486(28.2%)144/500(28.8%) Cortical contusion> 1289/869(33.3%)252/886(28.4%)

16 Comment on results Relative Risk of death at 2wks wasn’t different in any of the 8 Ct diagnosis subgroups examined

17 Conclusion Corticosteroids should not be used routinely to use had injury whatever the severity.


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