Dr. Gaurav Kumar

Emergency Medicine Resident

Aiims9/27/2014 1

Background

STICH –pontaneous supratentorial lobar intracerebral haematomas.

9/27/2014 2

Background

Spontaneous intracerebral haemorrhage (ICH) accounts for 10 to

40% of all cases of stroke

The morbidity and mortality exceed 60%.

Young disabled survivors are a significant burden to both Health Services and family.

9/27/2014 3

BackgroundWithin the spectrum of spontaneous intracerebral haemorrhage there

are some patients with large or space occupying haemorrhage who

require surgery for neurological deterioration .

And others with small haematomas who should be managed

conservatively.

There is equipoise about the management of patients between these

two extremes.

9/27/2014 4

Findings of previous trials

The first randomised trial of Surgical Treatment of ICH, published in

1961.

But it did not show a significant advantage for either surgical or

conservative treatment.

Many other studies were done after this but none showed benefit of

one over other method of Rx.

9/27/2014 5

STICH I

The need to gain evidence to support clinical decision making led to

the initiation of the Surgical Trial in Intracerebral Haemorrhage

(STICH).

Started in 1998, this trial is the largest to date and successfully

recruited 1033 patients from 87 centres around the world.

9/27/2014 6

RESULT OF STICH I

Showed a small non-significant advantage for surgery (Mendelow et

al. 2005)

9/27/2014 7

UNFORTUNATE OUTCOME OF STICH I

Had been that many people misinterpreted the

results to argue that there was no need to operate on

patients with ICH at all !

9/27/2014 8

Neurosurgeons know that early removal of an intracranial

haemorrhage is highly effective in the context of trauma.

It seems unlikely that surgery would be of benefit in one scenario and

not in the other.

Hence the STICH II Trial.

9/27/2014 9

TRIAL DESIGN

Prospective, randomized, parallel group trial.

In all, 129 NSx units in 39 countries.

Only patients for whom the treating neurosurgeon is in equipoise

about the benefits of early craniotomy compared to initial conservative

treatment are eligible for the trial.

Outcome is measured at six months via a postal questionnaire

9/27/2014 10

INCLUSION CRITERIAAll of the following :

Evidence of a spontaneous lobar ICH on CT scan (1 cm or less from the cortex surface of the brain)

Patient within 48 hours of ictus.

Best MOTOR score on the Glasgow Coma Scale (GCS) of 5 or 6 and best EYE score on the GCS of 2 or more

Volume of haematoma between 10 and 100 ml [Calculated using (a × b × c)/2 method].

9/27/2014 11

Eligible CT

9/27/2014 12

EXCLUSION CRITERIAAny of them :

Clear evidence that the haemorrhage is due to an aneurysm or

angiographically proven arteriovenous malformation.

Intraventricular haemorrhage of any sort.

ICH secondary to tumour or trauma.

9/27/2014 13

Not CT

9/27/2014 14

EXCLUSION CRITERIA

Basal ganglia, thalamic, cerebellar or brainstem haemorrhage or

extension of a lobar haemorrhage into any of these regions

If surgery cannot be performed within 12 hours.

Patients who did not consent to participate

9/27/2014 15

INTERVENTIONSPatients were randomly allocated to either early surgery or initial

conservative treatment.

All patient must have an baseline CT head.

In the early surgery group, surgeons were expected to undertake evacuation of the haematomas within 12 h.

In the initial conservative treatment group, delayed evacuation was permitted if judged clinically appropriate.

9/27/2014 16

RANDOMIZATION

It is not possible to blind either patients or treating surgeons to when

the patient has had surgery or whether they have had surgery.

To minimise possible sources of bias randomisation is undertaken

centrally by an independent organization.

Centre for Healthcare Randomised Trials, Aberdeen.

9/27/2014 17

RANDOMIZATION

Randomisation must take place within 48 hours of ictus

Eligible patients randomly assigned in a 1:1 ratio to early surgery or

early medical treatment group.

Randomization done with the use of telephone and internet based

system with stratification according to country and planned operation.

9/27/2014 18

STUDY END POINTSPrimary end point :

DEATH.

Severe disability.

9/27/2014 19

STUDY END POINTS

Secondary end point :

mortality,

time to death,

prognosis-based dichotomised Rankin and GOSE, and Rankin

and EuroQol; all measured at 6 months.

9/27/2014 20

Statistical analysis

Analysis will be on an “intention to treat” basis

a sample size of 566 (283 in each group) was needed to show a 12%

benefit from surgery (two-sided significance level of 0·05) with 80%

power.

Hence a sample size of 600 patients to allow for withdrawals and

crossovers.

9/27/2014 21

Statistical analysis

Primary outcome analysis was a simple categorical frequency

comparison by use of the χ2 test for prognosis-based favourable and

unfavourable outcome on GOSE(GLASGOW OUTCOME SCALE-

EXTENDED)

Secondary analysis consisted of a Kaplan-Meier survival curve with

log-rank test, χ2 test for mortality at 6 months, and 6 month prognosis-

based Rankin

9/27/2014 22

RESULTS

9/27/2014 23

No. of patients in study=601

294307

no. of patients

conervaticve gp. surgery gp.9/27/2014 24

STUDY OUTLINE

The two groups were well matched at baseline,

57% of total were male and median age was 65.

50% of patient in early surgery group and 49% in early conservative group had a GCS of 14 or 15 at the time of randomization.

9/27/2014 26

Characteristics of haematomas

EARLY SURGERY GROUP CONSERVATIVE GROUP

VOLUME(ML)

MEDIAN 38 36

MEAN 41.4 41.0

DEPTH(MM)

MEDIAN 1 1

MEAN 1.6 1.6

SIDE OF H’AGE

LEFT 158 (52%) 149 (51%)

RIGHT 147 (48%) 142 (49%)9/27/2014 27

outcome

9/27/2014 28

Early surgery group Early conservative group

Primary outcome

Prognosis based

Unfavourable 174(59%) 178(62%)

Favourable 123(41%) 108(38%)

Secondary outcome

Mortality at 6 months

Dead 54(18%) 69(24%)

Alive 244(82%) 222(76%)

Prognosis based modified Rankin

Unfavourable 155 (53%) 158 (56%)

Favourable 140 (47%) 126 (43%)

SUBGROUP ANALYSIS

KAPLAN-MEIER SURVIVAL CURVE

Source: The Lancet 2013; 382:397-408 (DOI:10.1016/S0140-6736(13)60986-1)

Discussion

DID not find significant evidence to support that early surgery

compared with initial conservative treatment (with delayed surgery if

the patient deteriorates) improves outcome in conscious patients in

whom there is a superficial intracerebral haemorrhage of 10—100 mL

and no evidence of intraventricular haemorrhage.

9/27/2014 31

Strengths of the study

Prospective randomized trial.

Baseline characteristics of patients similar.

Early randomization and early surgery.

9/27/2014 32

Limitations of the study

Cross over : 62 (21%) of 291 patients assigned to initial conservative

treatment went on to have delayed surgery.But because of the

intention-to-treat analysis they remained in the initial conservative

treatment group.

9/27/2014 33

Limitations of the study

More than half of the patients had good prognosis(i.e. 66% pt inearly

surgery group and 64% pt inconsevative group)

But the patients who benefited most from surgery were poor

prognosis group.

9/27/2014 34

Critical Appraisal

Was the randomization list concealed ? yes

Was the follow up of the patients sufficiently long and complete ? yes

Were the patients, clinicians and the study personnel kept “blind” to treatment ? No

Were the groups treated equally ? yes

Were the groups similar at the start of the trial ? yes

Does these results apply to our patient ? ?

9/27/2014 35

SUBGROUP ANALYSIS