STICH II Surgical Trial in Intracerebral Haemorrhage Recruitment

STICH II Surgical Trial in Intracerebral Haemorrhage Recruitment and data collection progress to date Dr. Alina Andras Database 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 ISRCTN 22153967 * 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 Outside Europe (38) Registered Centres 111 Further with Ethics Expressed Interest 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 28 99 • 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 (x 2) • 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 (x 2) • Vishakhapatnam, India • Zagazig, Egypt Europe (55) • Amberg, Germany • Athens, Greece • Berlin, Germany (x 2) • Bialystok, Poland • Bilbao, Spain • Borsod County, Hungary • Brno, Czech Republic (x 2) • 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 (x 2) • Novosibirsk, Russia • Olomouc, Czech Republic • Ostrava, Czech Republic • Pecs, Hungary • Poznan, Poland • Prague, Czech Republic • Riga, Latvia (x 2) • Rome, Italy • Saarbruecken, Germany • Saarland, Germany • Santander, Spain • Siegen, Germany • Skopje, Macedonia • Tbilisi, Georgia • Thessaloniki, Greece (x 2) • Timisoara, Romania • Trondheim, Norway • Uppsala, Sweden • Valladolid, Spain • Vienna, Austria • Wiesbaden, Germany • Yerevan State, Armenia

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 (1 cm 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 100 ml (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. Included • • 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 1 cm of the cortical surface of the brain. It extends from the lobar region into the basal ganglia. There is evidence also of intraventricular haemorrhage. 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

• 0 Armenia - Yerevan Australia - Melbourne China - Shanghai Czech Republic - Brno Czech Republic - Liberec Czech Republic - Prague Egypt - Mansoura Germany - Amberg Germany - Charite Berlin Germany - Dessau Germany - Dusseldorf Germany - Erlangen Germany - Griefswald Germany - Heidelberg Germany - Helios Berlin Germany - Homburg/Saar Germany - Jena Germany - Lubeck Germany - Munster Germany - Wiesbaden Greece - Athens Greece - Ippokration Hungary - Borsod Hungary - Pecs India - Bangalore India - Ludhiana India - New Delhi India - Trivandrum India - Viskhapatanam India- Maharshtra Italy - Rome Japan - Tokyo Lativia - Riga (PS) Latvia - Riga (G) Lithuania - Klaipeda Macedonia - Skopje Mexico - Tlalpan Nepal - Dharan Nepal - Lalitpur Pakistan - Lahore Pakistan - Peshawar Poland - Bialystok Poland - Poznan Romania - Cluj Romania - Timisoara Russia - Novosibirsk Spain - Santander Spain - Valladolid Sri Lanka - Colombo Turkey - Istanbul UK - Cambridge UK - Dundee UK - Edinburgh UK - Brighton UK - Leeds UK - St. George's, London UK - Middlesbrough UK - Newcastle UK - Preston UK - Salford UK - Southampton USA - Hartford USA - Jacksonville USA - Macon USA - Penn State USA - Temple Recruitment by Centre 66 out of 111 (60%) centres have recruited at least one patient 40 35 30 25 20 15 10 5

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

Patient Demographics Age Gender (%) Figures produced for 432 cases Median Age = 65 years Min = 17 years, Max = 94 years

Haematoma Characteristics Volume (ml) Depth (mm from Cortex) Median depth = 1 mm Median volume =37 ml Min = 10 ml Max = 100 ml Figures produced for 432 cases Side (%) 48% 52%

Total GCS at randomisation Median GCS = 13 Figures produced on 31/03/2011 for 432 cases.

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% Pre-ICH Mobility: Mobility Score % with score 1 - able to walk 200 m outside 93% 2 – able to walk indoors 6% 3 – unable to walk without help 1%

Status at 2 weeks: • 35% Discharged from hospital • 32% Still on neurosurgical ward • 26% Transferred • 7% Dead

Study Flow Chart Diagnostic CT Equipoise Consent to STICH II Telephone randomisation service (24 hours) or web service Initial Conservative Treatment Early Surgery • 5 Days GCS Monitoring • Day 5 CT • Discharge / 2 week form 6 month outcome questionnaire

Commitments from collaborators • • • 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

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