STICH IISurgical Trial in Intracerebral Haemorrhage

Recruitment and data collection progress to date

Dr. Alina AndrasDatabase Manager

STICH II• Funded by Medical Research Council (UK) and

now managed by NIHR on behalf of the MRC-NIHR partnership (Efficiency and Mechanism Evaluation (EME) Programme) *

• Sponsored by Newcastle upon Tyne Hospitals NHS Foundation Trust

• Registered with Current Controlled Trials ISRCTN22153967

* The view and opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of Health

STICH II - Objectives

• To establish whether a policy of earlier surgical evacuation of the haematoma in selected patients with spontaneous lobar ICH will improve outcome compared to a policy of initial conservative treatment.

• To better define the indications for early surgery.

STICH II Main Features

• Multicentre randomised parallel group prospective trial

• Spontaneous lobar intracerebral haemorrhage

• Treating neurosurgeon must be in equipoise over treatment

• 600 patients

• Outcome at six months

Centre Recruitment:111 centres – 31 March 2011

Centre Recruitment

Registered Centres 111Further with Ethics 28

Expressed Interest 99

UK (18)• Aberdeen• Brighton• Cambridge• Dundee• Edinburgh• Hull• Leeds• Liverpool• London -St George’s • National Hospital• Newcastle upon Tyne• N. Staffordshire• Middlesbrough• Oxford• Preston• Salford• Southampton• Swansea

Europe (55)• Amberg, Germany• Athens, Greece• Berlin, Germany (x2)• Bialystok, Poland• Bilbao, Spain• Borsod County, Hungary• Brno, Czech Republic (x2)• Chisinau, Moldova• Cluj, Romania• Dessau, Germany• Dusseldorf, Germany• Erlangen, Germany• Granada, Spain• Griefswald, Germany• Groningen, Netherlands• Heidelberg, Germany• Istanbul, Turkey• Jena, Germany• Kassel, Germany• Klaipeda, Lithuania• Lübeck, Germany• Liberec, Czech Republic• Magdeburg, Germany• Münster, Germany (x2)• Novosibirsk, Russia• Olomouc, Czech Republic• Ostrava, Czech Republic• Pecs, Hungary• Poznan, Poland• Prague, Czech Republic• Riga, Latvia (x2)• Rome, Italy• Saarbruecken, Germany• Saarland, Germany• Santander, Spain• Siegen, Germany• Skopje, Macedonia• Tbilisi, Georgia• Thessaloniki, Greece (x2)• Timisoara, Romania• Trondheim, Norway• Uppsala, Sweden• Valladolid, Spain• Vienna, Austria• Wiesbaden, Germany• Yerevan State, Armenia

Outside Europe (38)• Albany, NY, USA• Bangalore, India• Beijing, China• Bloomington, USA• Calcutta, India• Colombo, Sri Lanka• Dhaklria, India• Dharan, Nepal• Edmonton, Canada• Guadalajara, Mexico• Gwarko, Nepal• Haifa, Israel • Hartford USA• Haryana, India• Hyderabad, India (x2)• Kansas, USA• Kubang Kieran, Malaysia• Lahore, Pakistan• Loyola, USA• Ludhiana, India• Macon, USA • Maharashtra, India• Mansoura, Egypt• Mayo, Jacksonville, USA• Melbourne, Australia • New Delhi, India• Penn State, USA• Peshawar, Pakistan• Riyadh, KSA• Seoul, South Korea• Shanghai, China• Temple, USA• Tianjin, China• Tlalpan, Mexico• Tokyo, Japan• Trivandrum, India (x2)• Vishakhapatnam, India• Zagazig, Egypt

STICH II patients’ recruitment

– Eligibility– Randomisation– Data collection

• Randomisation• Two week• CTs• Adverse Events• Outcome

STICH II- Inclusion criteria

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

• Patient within 48 hours of ictus

• Best MOTOR score on GCS of 5 or 6 and best EYE score on GCS of 2 or more

• Volume of haematoma between 10 and 100ml (using Broderick method)

• Clinical equipoise

STICH II- exclusion criteria

• Clear evidence that the ICH is due to an aneurysm or angiographically proven AVM

• Intraventricular haemorrhage of any sort

• Hydrocephalus

• ICH secondary to tumour or trauma

• Basal ganglia, thalamic, cerebellar or brainstem ICH or extension of lobar ICH into any of these regions

• Severe pre-existing physical or mental disability or severe co-morbidity that might interfere with assessment of outcome

• If surgery cannot be performed within 12 hours

Example CT scans of patients with intracerebral haematomas that would and would not be eligible for

STICH II

• Example 1• This picture shows a scan of a patient who would be eligible• for STICH II. The patient has a lobar intracerebral haematoma, • close to the cortical surface. The volume of the haematoma is • within the 10 – 100 ml criterion. There is no evidence of • hydrocephalus or intraventricular haemorrhage and the • haematoma does not extend into the basal ganglia, and is not

associated with trauma, tumour or aneurysm.

• Example 2• In contrast this picture shows the scan of a patient who has a

haematoma that would exclude them from STICH II. The• haematoma is not within 1cm of the cortical surface of the brain. • It extends from the lobar region into the basal ganglia. There is

evidence also of intraventricular haemorrhage.

Included Excluded

STICH II - Recruitment• Patient satisfies criteria

– has had a CT scan to confirm the diagnosis, size and location of the haematoma.

• Consent or assent obtained– Information sheet is given to patient/relative with time to ask questions– Written witnessed informed consent from

• the patient or• the person with the closest personal relationship with the patient who is themselves

capable and willing to assent on behalf of the patient. – Copies given to patient and filed in notes and site project file

• Complete pre-randomisation record

• Web and phone 24 hour randomisation service based in Aberdeen HSRU

• Allocation – stratified by country and method of surgery – with a minimisation algorithm based on age group and neurological deficit with

a random component

Patient Recruitment:432 patients, 111 centres – 31 March 2011

Recruitment by Centre• 66 out of 111 (60%) centres have recruited at least one patient

Recruitment by Country• Patients have been recruited from 25 countries.

Patient Demographics

Gender (%)

Age

Figures produced for 432 cases

Median Age = 65 yearsMin = 17 years, Max = 94 years

Haematoma Characteristics

Side (%)

Volume (ml) Depth (mm from Cortex)

Figures produced for 432 cases

Median volume =37 mlMin = 10mlMax = 100ml

Median depth = 1mm

48%

52%

Total GCS at randomisation

Figures produced on 31/03/2011 for 432 cases.

Median GCS = 13

Neurological Deficits:

% Normal % Weak % Paralysed

ARM 27 41 32

LEG 32 46 22

OVERALL 27 40 33

Hours to Randomisation

Median = 22 hours

Past medical history:

• 66% history of hypertension

• 47% on anti-hypertensives

• 5% previous MI

• 10% previous stroke

Medical treatment

• At time of ICH– 7% anti coagulants– 11% anti platelet therapy– 1% recent thrombolytic therapy

• Following ICH– 1% Factor VII– 11% other coagulants

• 26% had an angiogram – 93% no sig vascular lesion, 5% AVM, 3% Aneurysm

Previous functional status:

Pre-ICH Rankin Score:Rankin Score % with score

0 - well 78%

1 – Minor symptoms 15%

2 – Minor handicap 5%

3 – Moderate handicap 1%

4 – Needs lots of help with ADL 1%

5 – Needs constant care 0%

Mobility Score % with score

1- able to walk 200m outside 93%

2 – able to walk indoors 6%

3 – unable to walk without help 1%

Pre-ICH Mobility:

Status at 2 weeks:

• 35% Discharged from hospital

• 32% Still on neurosurgical ward

• 26% Transferred

• 7% Dead

Study Flow Chart

• 5 Days GCS Monitoring• Day 5 CT • Discharge / 2 week form

6 month outcome questionnaire

Diagnostic CT

Equipoise

Consent to STICH II

Telephone randomisation service (24 hours) or web service

Initial Conservative Treatment

Early Surgery

• Randomisation forms• CT scans• Discharge/ 2 week follow-up form• (Cross-over forms)• Adverse Event Form• 6 month follow up:

– Cover letter– Form

• Screening logs

Commitments from collaborators

MRC Good clinical trials guidelines

• Trial Management Team• Trial Steering Committee• Data Monitoring Committee (DMC)• Ethical Approval and R & D Approval (UK)• Sub agreement

Acknowledgements

• Steering and Data Monitoring Committees

• All Co-investigators

• All patients and carers

• Medical Research Council

www.research.ncl.ac.uk/stich

email: stich@ncl.ac.uk