Condition category
Nervous System Diseases
Date applied
04/12/2017
Date assigned
14/12/2017
Last edited
14/12/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Subarachnoid haemorrhage (SAH) is a bleed onto the surface of the brain. It is usually caused when a weakness (aneurysm) in the wall of a blood vessel within the brain suddenly bursts. It affects up to 6,000 people every year in the UK. Up to half of all patients do not survive long enough to receive hospital treatment and those who do survive, often suffer long-term issues that impact on their daily life. In the hours and days after SAH, patients are at risk of further brain damage due to inflammation (swelling). A protein called interleukin-1 (IL-1) is the main culprit and this triggers a number of other chemicals in the circulation which may lead to physical symptoms similar to stroke but can also cause problems with language, mood, anxiety and fatigue all of which impact most on recovery and returning to work. The effect of IL-1 can be blocked, reduced or even reversed by another protein present naturally in our body; interleukin-1 receptor antagonist (IL-1Ra). A company has produced a man-made version of IL-1Ra, which has been used for many years as an anti-inflammatory treatment for rheumatoid arthritis. Inflammation occurs very early after the initial haemorrhage and can continue for up to 21 days, which means IL-1Ra should be given early and through the risk period to prevent or reduce these symptoms. Our group has successfully tested IL-1Ra in patients with subarachnoid haemorrhage and found it reduces inflammation in the circulation and brain and we now want to establish whether IL-1Ra improves recovery after subarachnoid haemorrhage. The aim of this study is to treat patients with SAD using IL-1Ra subcutaneously twice daily to see if this can improve clinical outcomes.

Who can participate?
Adults aged 18 and older who have SAH.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive subcutaneous injections of IL-1Ra twice daily for up to 21 days from the onset of their symptoms. Those in the second group receive a placebo (a dummy) twice daily for 21 days. All participants continue to receive the standard care for subarachnoid haemorrhage and participation in this study will not affect or delay this care. Participants provide blood samples before the treatment, and after 3-5 days to measure levels of inflammatory markers in the blood. Participants are followed up for safety for 30 days and are followed up for six months to assess the impact of the treatment.

What are the possible benefits and risks of participating?
As this is a phase III study it will be made clear to participants that there is no evidence of benefit at this stage. Participants will also be advised that as this study is double-blind and randomised and it will not be known if they will receive study drug or placebo. Evidence from earlier phase studies showed that the study drug reduces inflammation associated with SAH and is safe to use. The results of this study will provide evidence whether reducing inflammation improves outcome and participants may be helping to provide the evidence that may change treatment for SAH in the future.

Where is the study run from?
This study is being run by the University of Manchester (UK) and takes place in hospitals in the UK.

When is the study starting and how long is it expected to run for?
July 2015 to October 2022

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Ms Helen Bradley
helen.bradley@christie.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Helen Bradley

ORCID ID

Contact details

Clinical Trial Project Manager
Manchester Academic Health Science Centre Trial Coordination Unit (MAHSC-CTU)
Block C Withington Hall
The Christie Hospital NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom
+44 161 918 2142
helen.bradley@christie.nhs.uk

Additional identifiers

EudraCT number

2016-003725-42

ClinicalTrials.gov number

Protocol/serial number

35757

Study information

Scientific title

Does Interleukin-1 Receptor Antagonist Improve Outcome following aneurysmal Subarachnoid Haemorrhage (aSAH)? A Phase III trial

Acronym

SC IL-1Ra in SAH - phase III trial

Study hypothesis

Treatment with IL-1Ra subcutaneously (SC) twice daily to patients with aneurysmal subarachnoid haemorrhage will improve clinical outcome at 6 months.

Ethics approval

North West – Haydock Research Ethics Committee, 03/11/2017, ref: 17/NW/0581

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Specialty: Stroke, Primary sub-specialty: Hyperacute; UKCRC code/ Disease: Stroke/ Cerebrovascular diseases

Intervention

This is a double-blind, placebo-controlled trial. Patients with aneurysmal subarachnoid haemorrhage receive subcutaneous injections of IL-1Ra or placebo twice daily for up to 21 days from the onset of their symptoms. Blood samples are taken before the start of the intervention and after 3-5 days to measure levels of inflammatory markers in the blood. Participants are followed up for safety until day 30 after the start of the intervention and are followed up after six months to assess the impact of the intervention on clinical outcome.

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measure

Clinical outcome is measured using the modified Rankin Scale (mRS) questionnaire at 6 months.

Secondary outcome measures

1. Mood is measured using the Hospital Anxiety and Depression Scale questionnaire at 6 months
2. Fatigue is measured using the GM-SAT Fatigue question and Fatigue Severity Score questionnaire at 6 months
3. Quality of life is measured using the EQ-5D-5L questionnaire at 6 months

Overall trial start date

15/07/2015

Overall trial end date

31/10/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients with CT positive spontaneous SAH admitted to a participating neurosurgical centre where written informed consent can be obtained and study drug can be administered within 72 hours of ictus
2. No concomitant health problems that, in the opinion of the PI or designee, would interfere with participation, administration of study drug or assessment of outcomes including safety
3. Willing and able to give informed consent or consent available from a patient representative for trial inclusion including agreement in principle to receive study drug and undergo all study assessments
4. Male or female aged 18 years or above

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1000; UK Sample Size: 1000

Participant exclusion criteria

1. Unconfirmed or uncertain diagnosis of spontaneous SAH
2. Known active tuberculosis or active hepatitis
3. Known active malignancy
4. Neutropenia (ANC <1.5 x 109/L )
5. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) < 30 ml/minute) documented in the last 3 months prior to this SAH
6. Live vaccinations within the last 10 days of this SAH
7. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial
8. Previous or current treatment with medication suspected of interacting with IL-1Ra, listed in the drug SmPC
9. Known to have participated in a clinical trial of an investigational agent or device in the previous 30 days or 5 half-lives of enrolment (whichever is longer) of ictus, or for the period determined by the protocol of the trial / study the patient has taken part in
10. Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant
11. Clinically significant serious concurrent medical condition, pre morbid illnesses, or concurrent serious infection, at the PI’s (or designee’s) discretion, which could affect the safety or tolerability of the intervention
12. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC
13. Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein)

Recruitment start date

31/05/2018

Recruitment end date

30/11/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Royal Stoke University Hospital
Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Hurstwood Park Neurosciences Centre
Lewes Road
West Sussex
RH16 4EX
United Kingdom

Trial participating centre

National Hospital for Neurology and Neurosurgery
Queen Square
London
WC1N 3BG
United Kingdom

Trial participating centre

South West Neurosurgery Centre
Derriford Hospital Derriford Road Crownhill Devon
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Wessex Neurological Centre
Southampton General Hospital Tremona Road Hampshire
Southampton
SO16 6YD
United Kingdom

Trial participating centre

University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

Sponsor information

Organisation

The University of Manchester

Sponsor details

Oxford Road
Manchester
M13 9PL
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Publication in a high-impact peer reviewed journal is planned and is likely to be in the second half of 2023.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes