Treatment of poor-grade subarachnoid haemorrhage trial 2
| ISRCTN | ISRCTN15960635 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15960635 |
| Protocol serial number | 7842 |
| Sponsor | Newcastle upon Tyne Hospitals NHS Foundation Trust |
| Funder | Efficacy and Mechanism Evaluation Programme |
- Submission date
- 01/09/2016
- Registration date
- 05/09/2016
- Last edited
- 11/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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 December 2018 (updated 04/03/2021, previously: 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)
TOPSAT2@ncl.ac.uk
Contact information
Public
Institute of Neuroscience
Newcastle University
3-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
Public
Newcastle Clinical Trials Unit
Newcastle University
3-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
| Phone | +44 191 2084591 |
|---|---|
| TOPSAT2@ncl.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multi-centre prospective randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| 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 acronym | TOPSAT2 |
| Study objectives | 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(s) | Yorkshire & The Humber - Leeds East Research Ethics Committee, 20/06/2016, ref: 16/YH/0234 |
| Health condition(s) or problem(s) studied | Subarachnoid haemorrhage |
| Intervention | 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 | Procedure/Surgery |
| Primary outcome measure(s) |
Functional outcome is measured by ordinal analysis of modified Rankin Score (mRS) at 12 months. |
| Key secondary outcome measure(s) |
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 |
| Completion date | 18/12/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | All |
| Target sample size at registration | 346 |
| Total final enrolment | 305 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 12/09/2016 |
| Date of final enrolment | 10/09/2019 |
Locations
Countries of recruitment
- United Kingdom
- England
- Czech Republic
- Estonia
- Hungary
- Latvia
- Lithuania
- Poland
Study participating centres
Newcastle upon Tyne
NE7 7DN
United Kingdom
Stoke-on-Trent
TS4 3BW
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Leeds
LS1 3EX
United Kingdom
Haywards Heath
RH16 4EX
United Kingdom
Sheffield
S5 7AU
United Kingdom
Sheffield
S10 2JF
United Kingdom
Liverpool
L9 7LJ
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/07/2021 | 05/04/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 2 | 25/01/2019 | 11/08/2022 | No | No |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN15960635_PROTOCOL_V2_25Jan19.pdf
- Protocol file
Editorial Notes
11/08/2022: Protocol file uploaded.
05/04/2022: Publication reference and total final enrolment number added.
04/03/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2021 to 18/12/2018.
2. The plain English summary was updated to reflect these changes.
04/12/2019: The recruitment end date was changed from 31/03/2020 to 10/09/2019.
