Condition category
Circulatory System
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims
A spontaneous subarachnoid haemorrhage (SAH) is a type of stroke caused by sudden bleeding over the surface of the brain. It is usually caused when a bulge in a blood vessel wall (brain aneurysm) bursts (ruptures) because the vessel wall has become weakened over time. Following the rupture, blood pools inside the skull (which cannot expand due to its rigid structure) leading to increased pressure on the brain and oxygen starvation (cerebral ischaemia), leading to brain damage. Recovery largely depends on the extent of this damage, and is assessed using the WFNS (World Federation of Neurosurgical Societies) grading system. Patients with WFNS grade 1-3 usually recover well, but patients with high WFNS grade (4-5) often end up with a bad outcome such as death or severe disability. Grade 1-3 patients are treated early, based on high quality evidence from studies. However, there is no good evidence base for determining the best way of treating those with grade 4-5 SAH. There are currently two strategies for treating these patients: early treatment or treatment after neurological (brain and nervous system) recovery. The aim of this study is to compare these two approaches to find out which is the better treatment option. A sample of patients also take part in a sub-study, in which they undergo MRI scanning, in order to find out the relationship between brain markers and outcome, and whether they might be used to identify patients who would benefit from each treatment strategy.

Who can participate?
Adults who have had an SAH graded WFNS 4 or 5.

What does the study involve?
Patients are randomly allocated to one of two groups. Those in the first group are kept under close observation, and have aneurysm treatment after they recover consciousness. Those in the second group receive treatment for their aneurysm within 24 hours. Participants in both groups have their recovery monitored over the next 12 months using questionnaires. The questionnaire takes about 20 minutes to complete, and is sent out by post, along with a pre-paid reply envelope. Participants are asked to complete and return the questionnaire, with the help of a friend or relative, or with a member of the research team by telephone to go through the questions if necessary, or online via the trial website. Around one third of the participants also take part in a related study, in which they attend a hospital appointment at the start of the study and after six months to have their brain scanned using an MRI machine.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved for those participating in the main study. The total effective dose from patients participating in the MRI sub study can therefore be taken as approximately 6 mSv which is equivalent to approximately 2.5 years of exposure to average UK natural background radiation, placing the study into the ‘intermediate’ risk category.

Where is the study run from?
Royal Victoria Infirmary (lead centre) and eight other NHS hospitals in England (UK)

When is the study starting and how long is it expected to run for?
December 2015 to March 2021

Who is funding the study?
National Institute for Health Research Efficacy and Mechanism Evaluation Programme (UK)

Who is the main contact?
1. Professor Philip White (scientific)
2. Ms Philippa Watts (public)

Trial website

Contact information



Primary contact

Prof Philip White


Contact details

Institute of Neuroscience
Newcastle University
3-4 Claremont Terrace
Newcastle upon Tyne
United Kingdom



Additional contact

Ms Philippa Watts


Contact details

Newcastle Clinical Trials Unit
Newcastle University
3-4 Claremont Terrace
Newcastle upon Tyne
United Kingdom
+44 191 2084591

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Randomised Controlled Study for patients with high grade Subarachnoid haemorrhage to determine whether or not early (within 24 hours) treatment or treatment after neurological recovery has a better outcome than the other



Study hypothesis

The aim of this study is to establish the efficacy of a strategy of early aneurysm treatment (within 72h of ictus) in a population of World Federation of Neurosurgical Societies grade 4-5 (high grade) aneurysmal subarachnoid haemorrhage (aSAH) patients in comparison with the conventional strategy of treatment of aneurysm after neurological improvement (to WFNS grade 1-3).

Ethics approval

Yorkshire & The Humber - Leeds East Research Ethics Committee, 20/06/2016, ref: 16/YH/0234

Study design

Multi-centre prospective randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Subarachnoid haemorrhage


Participants are randomised to undergo either endovascular (coiling) or neurosurgical (clipping) treatment for their aneurysm within 24 hours of ictus or upon neurological improvement. Both are standard procedures and are performed whether or not they are in the study. At the time of enrolment all patients will be unconscious and therefore unable to consent, and so REC/HRA approval for assent has been sought. There are no further treatments and no study bloods are being taken.

Participants will be followed up for a total period of 12 months within the trial site that patients were admitted to until day 30 or discharge (whichever is the sooner), and then at 6 and 12 months later by way of postal or online mRS and EQ5D questionnaires completed by the participants.

Intervention type



Drug names

Primary outcome measures

Functional outcome is measured by ordinal analysis of modified Rankin Score (mRS) at 12 months.

Secondary outcome measures

1. mRS is measured by dichotomisation of scores 0-3 (no or significant symptoms) vs 4-6 (severe symptoms and mortality) and 0-2 (no or few symptoms) v 3-6 (significant symptoms and mortality) at 12 months
2. Mortality rate is measured by -survival analysis at 30 days, six months and 12 months
3. Re-bleeding rate is measured by the number of re-bleeds that have occurred at 12 months
4. Treatment related complication rate & SAE report rates are measured by the number of treatment related complications and SAEs that have occurred at 12 months
5. Time to hospital discharge is measured by length of time in hospital from randomisation at discharge date
6. Length of ITU/HDU stay is measured by length of time in ITU/HDU from randomisation at discharge date
7. Functional outcome is measured by ordinal analysis of modified Rankin Score (mRS) at 6 months

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Aged 18-80 years
2. WFNS grade 4 or 5 SAH (grade for trial eligibility purposes is the WFNS grade recorded at first medical assessment following: hospital attendance AND confirmation of the diagnosis of SAH – by CT (or MRI) and/or lumbar puncture)
3. Assent obtained from next of kin, professional consultee or welfare attorney/nearest relative

Participant type


Age group




Target number of participants


Participant exclusion criteria

1.WFNS grade 1-3, or uncertain WFNS grade (where patient recovers quickly and proves not to be of true high grade):
1.1. Patients of uncertain grade on transfer to a neuroscience unit where a formal sedation hold is undertaken at the neurosciences centre and the patient is established to be truly grade 4 or 5 will be eligible for trial
1.2. This will also apply to patients of uncertain grade undergoing sedation hold after insertion of external ventricular drain (EVD) or other early intervention for hydrocephalus
2. Signs of coning or brain death not promptly reversed by anti-cerebral oedema treatment
3. Pure intraventricular haemorrhage (no SAH)
4. Large intracerebral haematoma which requires immediate clot evacuation
5. Significant aneurysmal SAH-related haemodynamic instability
6. Lack of clinical equipoise
7. Lack of assent/consent
8. Pregnancy
9. Pre SAH modified Rankin score >2
10. Pre-existing severe co-morbidity such that clinical follow up at 12 months is judged unlikely
11. Non-saccular, Mycotic, giant or other atypical aneurysm

For MRI sub study only
Known absolute contra indication to MRI

Recruitment start date


Recruitment end date



Countries of recruitment

Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, United Kingdom

Trial participating centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
United Kingdom

Trial participating centre

Royal Stoke University Hospital
Newcastle Road
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
United Kingdom

Trial participating centre

Queen's Medical Centre
Derby Road
United Kingdom

Trial participating centre

Leeds General Infirmary
Great George Street
United Kingdom

Trial participating centre

Hurstwood Park Neurological Centre
Lewes Road
Haywards Heath
RH16 4EX
United Kingdom

Trial participating centre

Northern General Hospital
Herries Road
S5 7AU
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
S10 2JF
United Kingdom

Trial participating centre

The Walton Centre
Lower Lane
L9 7LJ
United Kingdom

Sponsor information


Newcastle upon Tyne Hospitals NHS Foundation Trust

Sponsor details

Newcastle Joint Research Office
Level 1
Regent Point
Regent Farm Road
Newcastle upon Tyne
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Efficacy and Mechanism Evaluation Programme

Alternative name(s)

NIHR Efficacy and Mechanism Evaluation programme, EME

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Progress and final outcomes will be disseminated at relevant neurosurgical, stroke, neuroradiology, MRI and critical care conferences by platform and poster presentations. Five to six research publications based on the findings are expected to be published in international peer reviewed journals. Results will also be reported to the Sponsor and Funder, and will be available on their websites. Manuscripts, abstracts and other modes of presentation will be reviewed by the Trial Steering Committee and Funder prior to submission. Individuals will not be identifiable in any study report.
A procedural safety paper will be submitted within weeks of the end of randomisation. There will also be multiple outputs around MR imaging techniques in high grade SAH. More detailed subgroup analysis and modelling of care are additional papers, identified as likely outputs of the TOPSAT2 study. The Stroke Research component embedded within NIHR Research Division 2, Newcastle University, professional societies (British Society Neurological Surgeons, British Society Neuroradiologists, UK Neurointerventional Group, British Neurovascular Group), Royal Colleges and contacts with the Clinical Senates, UK Stroke Forum and the Stroke Association will be utilised to disseminate the findings more widely to the public. This will include use of web-based information, newsletters and press releases.
The study team will feed back to centres via newsletters, the website and trial close down meetings and publications, and to participants via website, newsletter and the publicity generated. More direct personal or small group feedback will be given to the PPI groups involved in developing, contributing to and supporting TOPSAT 2. Feedback in the form of a lay summary will be provided to participants via the general section of the trial website, participant-specific newsletter at the end of trial (if they indicated they wished to receive it) and by wider publicity generated.

Intention to publish date


Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes