operative intervention in ich: results of the international surgical trial in intracerebral...

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 29th 2005)

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

7266-7260-66

54-6048-54

42-4836-42

30-3624-30

18-2412-18

6-12<6

%

20

15

10

5

0

Treatment

early surgery

initial conservative

Time since ictus

hrs

Median 20 hrs

STICH Randomisation by Country

ArgentinaAustralia

AustriaBelgium

ChinaCzech Republic

GermanyGreece

HungaryIndiaItaly

JapanLatvia

LithuaniaMacedonia

MalaysiaNetherlands

PolandRussia

SingaporeSouth Africa

SpainSwedenTurkey

UKUkraine

USA

No. Patients

170

160

150

140

130

120

110

100

90

80

70

60

50

40

30

20

10

0

Primary Outcome(Prognosis Based)

Early Surgery Initial Conservative treatment

Favourable 122 (26.1%) 118 (23.8%)

Unfavourable 346 (73.9%) 378 (76.2%)

Primary Outcome:Prognosis Based

Mortality

Early Surgery Initial Conservative treatment

Alive 304 (63.7%) 316 (62.6%)

Dead 173 (36.3%) 189 (37.4%)

Mortality

Survival Functions

days

2101801501209060300

Pro

ba

bili

ty o

f su

rviv

al

1.0

.9

.8

.7

.6

Early Surgery

Initial Conservative Treatment

KaplanMeierPlot ofSurvival

Secondary OutcomeRankin (Prognosis Based)

Early Surgery Initial Conservative treatment

Favourable 152 (32.8%) 137 (28.1%)

Unfavourable 312 (67.2%) 351 (71.9%)

Secondary OutcomeRankin (Prognosis Based)

Secondary OutcomeBarthel (Prognosis Based)

Early Surgery Initial Conservative treatment

Favourable 124 (26.7%) 110 (22.6%)

Unfavourable 341 (73.3%) 377 (77.4%)

Secondary OutcomeBarthel (Prognosis Based)

Primary and Secondary Outcome

• The overall result is NEUTRAL– NOT POSITIVE or NEGATIVE

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

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

Pre-specifiedsubgroupanalysis

Favours surgery Favours control

Depth

Favours surgery Favours control

GCS

Craniotomy

Lobar

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”.

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

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

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)

Overall favourable outcomes – No IVH - 31.4%

– IVH - 15.1%

(p<0.00001)• IVH alone - 19.5%

• IVH + hydrocephalus - 11.5%

(p=0.031)

Midline shift (cm)

> 1.0< = 1.0.00

% f

avo

ura

ble

ou

tco

me

40

30

20

10

0

no IVH

IVH only

IVH + HCP

Volume of haematoma (ml)

> 8040 - 80< = 40

%fa

vou

rab

le o

utc

om

e40

30

20

10

0

no IVH

IVH only

IVH + HCP

Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)

Total Number of patients in that group

Lobar

109 112 27 31 21 270

10

20

30

40

50

60no ivh ES

no ivh ICT

ivh ES

ivh ICT

ivh+hcp ES

ivh+hcp ICT

% f

avo

ura

ble

ou

tco

me Basal ganglionic

94 125 48 33 59 65

Both

31 32 19 11 16 19

Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)

Total Number of patients in that group

Lobar

109 112 27 31 21 270

10

20

30

40

50

60no ivh ES

no ivh ICT

ivh ES

ivh ICT

ivh+hcp ES

ivh+hcp ICT

% f

avo

ura

ble

ou

tco

me Basal ganglionic

94 125 48 33 59 65

Both

31 32 19 11 16 19

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

56 70 126

109 112 221

P=0.095

Lobar haematomas with No IVH and No Hydrocephalus

(prognosis based outcome)

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

Crossovers from intention to treat (ICT = Initial Conservative Treatment)

0

50

100

150

200

250

300

350

400

450

500

Surgery ICT

Non Crossover

Crossover

(M Prasad et al.Ann Arbour 2005)

Crossovers and GCS in ICT group of 140 crossovers to surgery

• Average drop in GCS at crossover was 3 points

GCS

5 7 8

14 15 1317

12

23

1511

0

5

10

15

20

25

5 6 7 8 9 10 11 12 13 14 15

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

Volume of haematoma (CT)

> 100 ml80-10060-8040-6020-40<20 ml

%

100

90

80

70

60

50

40

30

20

10

0

had surgery

no

yes

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

Depth from cortical surface

> 2 cm1- 2 cm< = 1 cm.00

%

100

90

80

70

60

50

40

30

20

10

0

had surgery

no

yes

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

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

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

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

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)

Intraventricular haemorrhage (IVH), Hydrocephalus (HCP), Early Surgery(ES), Initial Conservative treatment (ICT)

Total Number of patients in that group

Lobar

109 112 27 31 21 270

10

20

30

40

50

60no ivh ES

no ivh ICT

ivh ES

ivh ICT

ivh+hcp ES

ivh+hcp ICT

% f

avo

ura

ble

ou

tco

me Basal ganglionic

94 125 48 33 59 65

Both

31 32 19 11 16 19

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

56 70 126

109 112 221

P=0.095

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

56 70 126

109 112 221

P=0.095

Lobar haematomas with No IVH and No Hydrocephalus

(prognosis based outcome)

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

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)

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