1. Operative intervention in ICH: Results of the International Surgical Trial in Intracerebral Haemorrhage (STICH) A David Mendelow, Department of Neurosurgery, Newcastle upon Tyne, England On behalf of the STICH Investigators (Lancet January 29 th 2005)

3. Question in STICH Does a policy of “Early Surgery” improve outcome in patients with spontaneous supratentorial intracerebral haemorrhage compared with a policy of “Initial Conservative Treatment”? –Randomisation within 72 hours of ictus –Surgery within 24 hours of randomisation

4. Time since ictus hrs Median 20 hrs

6. Primary Outcome (Prognosis Based) Early SurgeryInitial Conservative treatment Favourable122 (26.1%)118 (23.8%) Unfavourable346 (73.9%)378 (76.2%)

7. Primary Outcome: Prognosis Based

8. Mortality Early SurgeryInitial Conservative treatment Alive304 (63.7%)316 (62.6%) Dead173 (36.3%)189 (37.4%)

9. Mortality

10. Early Surgery Initial Conservative Treatment Kaplan Meier Plot of Survival

11. Secondary Outcome Rankin (Prognosis Based) Early SurgeryInitial Conservative treatment Favourable152 (32.8%)137 (28.1%) Unfavourable312 (67.2%)351 (71.9%)

12. Secondary Outcome Rankin (Prognosis Based)

13. Secondary Outcome Barthel (Prognosis Based) Early SurgeryInitial Conservative treatment Favourable124 (26.7%)110 (22.6%) Unfavourable341 (73.3%)377 (77.4%)

14. Secondary Outcome Barthel (Prognosis Based)

15. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE

16. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus Crossovers Meta-analysis

17. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus Crossovers Meta-analysis

18. Pre- specified subgroup analysis Favours surgery Favours control

19. Depth Favours surgery Favours control GCS Craniotomy Lobar

20. Conclusions While there is no evidence to support a policy of “Early Surgery” compared with a policy of “Initial Conservative Treatment” in patients with spontaneous supratentorial intracerebral haemorrhage (Timing), pre-specified subgroup analysis has suggested that Superficial haematomas treated with craniotomy do better with “Early Surgery”.

21. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus Crossovers Meta-analysis

22. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus DANGER Crossovers Meta-analysis

24. Post-hoc analysis of IVH and hydrocephalus (All CT scans read per protocol – Neurosurgery Focus 2003) Of 902 readable CT scans: 42% (377) had IVH of whom 55% (208) had hydrocephalus. (Paramasweram Battathiri et al. Ann Arbour 2005)

25. Overall favourable outcomes –No IVH - 31.4% –IVH - 15.1% (p<0.00001) IVH alone- 19.5% IVH + hydrocephalus - 11.5% (p=0.031)

28. Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT) Total Number of patients in that group % favourable outcome

30. Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT) Total Number of patients in that group % favourable outcome

31. Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis based outcome) Early surgery Initial Conservative Treatment Favourable outcome 53 (49%)42 (37%)95 Unfavourable outcome 5670126 109112221 P=0.095

32. Lobar haematomas with No IVH and No Hydrocephalus (prognosis based outcome)

33. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus Crossovers (26% ICT group) Meta-analysis

34. Crossovers from intention to treat (ICT = Initial Conservative Treatment) (M Prasad et al. Ann Arbour 2005)

35. Crossovers and GCS in ICT group of 140 crossovers to surgery Average drop in GCS at crossover was 3 points

36. Volume in ICT group of 140 crossovers to surgery (in red)

37. Depth from cortical surface in ICT group of 140 crossovers (in red)

38. Factors that drove crossovers to surgery from Initial Conservative Treatment (ICT) Deterioration in Glasgow Coma Score (GCS) Larger volume Bigger midline shift Superficial Focal deficit NOT –IVH –hydrocephalus

39. Primary and Secondary Outcome The overall result is NEUTRAL –NOT POSITIVE or NEGATIVE Can we now use this information to help with decision making in our patients? Subgroups –Pre-specified: published in Lancet paper –Post-hoc: IVH and hydrocephalus Crossovers Meta-analysis

40. Meta-analysis of 12 trials of surgery for ICH (Mortality only)

41. Meta-analysis of 12 trials of surgery for ICH (Death or disability)

42. Conclusions While there is no evidence to support a policy of “Early Surgery” compared with a policy of “Initial Conservative Treatment” in patients with spontaneous supratentorial intracerebral haemorrhage (Timing), pre-specified subgroup analysis has suggested that Superficial haematomas treated with craniotomy do better with “Early Surgery”. Meta-analysis suggests: –Superficial clots – consider craniotomy –Deep clots – consider aspiration New Meta-analysis to evaluate lobar vs. deep with no IVH (12 trials) Patients with IVH and/or hydrocephalus have much poorer outcomes and should be considered separately (new trials)

43. Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT) Total Number of patients in that group % favourable outcome

44. Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis based outcome) Early surgery Initial Conservative Treatment Favourable outcome 53 (49%)42 (37%)95 Unfavourable outcome 5670126 109112221 P=0.095

45. Lobar haemorrhages with No IVH and No Hydrocephalus (prognosis based outcome) Early surgery Initial Conservative Treatment Favourable outcome 53 (49%)42 (37%)95 Unfavourable outcome 5670126 109112221 P=0.095

46. Lobar haematomas with No IVH and No Hydrocephalus (prognosis based outcome)

47. STICH II Supratentorial LOBAR ICH with no IVH or hydrocephalus Randomisation within 48 hours of ictus Surgery within 12 hours of randomisation Outcome as in STICH I 600 patients needed Funding applied for from UK MRC

48. How do we manage a patient with Supratentorial ICH? Observation clinically or with ICP/CPP monitoring and operate with deterioration Craniotomy if there is deterioration from GCS between 9 and 12 and if the clot is superficial Aspiration if the clot is deep: another large trial is needed (data from meta-analysis of aspiration methods)

49. Acknowledgements UK Stroke Association UK Medical Research Council (MRC) NIH, Northern Brainwave Appeal and NNF Investigators, patients and relatives from 107 centres in 27 countries MRC Steering Committee MRC Data Monitoring and Ethics Committee All Co-investigators and Fellows