Articles
Introduction
Spontaneous supratentorial intracerebral haemorrhage
affects 20 in 100 000 people every year and community-
based studies have indicated a mortality of more than
40%.
1
Most survivors are disabled. The role of medical
and surgical treatment continues to be controversial.
Much of this controversy relates to the penumbra of
functionally impaired (but potentially viable) tissue
around the haematoma. Such an ischaemic penumbra is
associated with brain oedema related to the presence of
thrombin.
2–6
Simulated removal of the mass lesion
improves perfusion in the surrounding brain tissue.
7,8
However, clinical studies have yielded conflicting
results regarding the importance of such a
penumbra.
9,10
If a penumbra exists in patients
with spontaneous intracerebral haemorrhage, clot
evacuation could then restore function to the
surrounding brain tissue and improve outcome, but
clinical imaging studies have so far failed to provide
conclusive evidence for or against this theory. Elevated
intracranial pressure and reduced cerebral perfusion
pressure have been associated with poor outcome,
lending support to a possible benefit from early
surgical intervention.
11
In 1961, McKissock and colleagues
12
reported the first
prospective randomised controlled trial in neurosurgery
and showed that operative treatment was associated with
a worse outcome than conservative treatment for
patients with spontaneous supratentorial intracerebral
haemorrhage. That trial has affected the management of
this disorder for most of the past half century. In 1989,
Auer and co-workers
13
reported the opposite result in a
trial of endoscopic removal of haemorrhage in
100 patients. In the same year, this finding was
contradicted by Juvela and colleagues
14
(who supported
the view of the McKissock group) but the trial was too
small to detect less than a substantial effect of surgery.
Since these three initial trials, a further six have been
reported and meta-analysis of the first seven has shown
no firm conclusions regarding the role of operative
treatment.
15
A recent trial that used intracavity thrombo-
lysis
16
did not suggest a benefit from surgery, whereas a
trial of CT-guided mechanical aspiration did,
17
but again
in a small number of patients. Many non-randomised
Lancet 2005; 365: 387–97
See Comment page 361
*Investigators listed at the end
of report
Correspondence to:
Prof A David Mendelow, Head of
Department of Neurosurgery,
Newcastle General Hospital,
Newcastle upon Tyne
NE4 6BE, UK
a.d.mendelow@ncl.ac.uk
www.thelancet.com Vol 365 January 29, 2005 387
Early surgery versus initial conservative treatment in
patients with spontaneous supratentorial intracerebral
haematomas in the International Surgical Trial in
Intracerebral Haemorrhage (STICH): a randomised trial
A David Mendelow, Barbara A Gregson, Helen M Fernandes, Gordon D Murray, Graham M Teasdale, D Terence Hope, Abbas Karimi,
M Donald M Shaw, and David H Barer for the STICH investigators*
Summary
Background Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden
neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains
controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative
treatment for patients with intracerebral haemorrhage.
Methods A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of
randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later
evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal
questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the
patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good
prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome
scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis
was by intention to treat.
Findings 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative
treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468
patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496
randomised to initial conservative treatment (odds ratio 0·89 [95% CI 0·66–1·19], p=0·414); absolute benefit 2·3%
(–3·2 to 7·7), relative benefit 10% (–13 to 33).
Interpretation Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no
overall benefit from early surgery when compared with initial conservative treatment.

Articles
studies, including a large observational study of more
than 7000 patients from Japan,
18
have identified
important prognostic criteria in patients with
intracerebral haemorrhage.
Improved surgical techniques, neuroimaging, neuro-
anaesthesia, and perioperative monitoring and care have
all led to improved outcomes from surgery in many
conditions. Hence, a randomised trial of the manage-
ment of patients with spontaneous supratentorial
intracerebral haemorrhage was timely. The International
Surgical Trial in Intracerebral Haemorrhage (STICH)
aimed to assess whether a policy of early surgical
evacuation of the haematoma in patients with sponta-
neous supratentorial intracerebral haemorrhage would
improve outcome, in terms of death and disability,
compared with a policy of initial conservative treat-
ment. Additionally, it aimed to improve definitions of
the indications for early surgery. STICH was designed
as an international, multicentre, parallel-group study.
Methods
Patients
Randomisation commenced in 1995 in Newcastle, UK,
with initial funding from the Stroke Association (UK).
By the beginning of 1998, 11 centres were registered and
further funding was then obtained from the Medical
Research Council (MRC) in the UK for an international,
multicentre trial. By the end of recruitment in February,
2003, 107 centres were registered with the trial and
1033 patients had been recruited. The full trial protocol
was published in 1999.
19
Every centre obtained written
ethical approval according to national and local
guidelines before being eligible to join the study, and
recorded consent to participation as required by local
procedures. Patients were eligible for inclusion if they
had CT evidence of a spontaneous supratentorial
intracerebral haemorrhage that had arisen within 72 h
and if the responsible neurosurgeon was uncertain
about the benefits of either treatment (the clinical
uncertainty principle). Study guidelines recommended
that eligible patients should have a minimum
haematoma diameter of 2 cm and a Glasgow coma score
of five or more.
Patients were not eligible if: the haemorrhage was
probably due to an aneurysm or an angiographically
proven arteriovenous malformation; the haemorrhage
was secondary to a tumour or trauma; patients had a
cerebellar haemorrhage or extension of a supratentorial
haemorrhage into the brainstem; patients had severe
pre-existing physical or mental disability or severe
comorbidity that might interfere with the assessment of
outcome; surgery could not be undertaken within 24 h of
randomisation.
Informed consent according to the criteria set by the
local research ethics committee in every centre had to be
obtained in writing before randomisation. If consent
could not be obtained because the patient was in coma,
confused, or dysphasic, assent was obtained from
relatives (if this was regarded by the local ethics
committee as an acceptable alternative).
Procedures
We used the 24-h telephone randomisation service
provided by the Clinical Trial Service Unit (CTSU) at the
University of Oxford. The responsible neurosurgeon,
having obtained consent or assent, completed a one-
page randomisation form before telephoning the CTSU.
These key baseline data were recorded before treatment
was allocated by the CTSU. A deterministic
minimisation algorithm, based on side of haematoma
and minimum depth from cortical surface, was initially
used to ensure balance between the two groups, within
every country where patients were recruited. However,
the algorithm was later reprogrammed by the CTSU
independently of the trial steering and trial management
committees. As a result, at least 50% of patients were
allocated using simple randomisation alone. This
procedure did not compromise the study, and the
recorded imbalance in overall numbers was entirely
consistent with randomisation when so many strata
were included.
Patients randomised to early surgery had their
haematoma evacuated within 24 h of randomisation by
the method of choice of the responsible neurosurgeon,
combined with the appropriate and best medical
treatment. Patients randomised to initial conservative
treatment had the best medical treatment. Later
evacuation had to be allowed if it became necessary
because of neurological deterioration. Primary outcome
was death or disability using the extended Glasgow
outcome scale 6 months after ictus. Secondary outcomes
included mortality, the Barthel index, and the modified
Rankin scale.
Structured postal questionnaires included questions
required to assess the Glasgow outcome scale,
20
Barthel
index, and modified Rankin scale. Questionnaires were
sent directly to the surviving patients or carers for
completion at 6 months as a technique of masking
surgeons to the outcome. They were translated into
German, Czech, Spanish, Hungarian, Polish, Russian,
Ukrainian, Swedish, Dutch, Chinese, Hindi, Greek,
Turkish, Latvian, and Lithuanian. Patients’ family
practitioners (in the UK) or consultants (outside the UK)
were contacted at 4 months to confirm that the patient
was still alive and to confirm his or her place of
residence.
Questionnaires were sent to patients at 5 months for
completion by the patient, relative, or carer, and a
reminder was sent at 6 months. In a few countries where
the postal system was poor, patients were requested to
attend a follow-up clinic where the questionnaires could
be distributed and obtained. Also in some countries
where literacy or language (or dialect) was problematic,
an independent, masked interviewer questioned the
388 www.thelancet.com Vol 365 January 29, 2005