ISRCTN - ISRCTN74236229: Subcutaneous interleukin-1 receptor antagonist (SC IL-1RA) in Stroke Study

Plain English Summary

Background and study aims
A stroke is a serious condition where the blood supply to a part of the brain is cut off, usually by a blood clot blocking an artery (ischaemic stroke) or a bleed (haemorrhagic stroke). A large proportion of stroke victims suffer from long-term complications depending on the area of the brain that is affected, which can affect their ability to move, speak or even their cognitive function (memory loss, difficulty reasoning and confusion). When a person sustains a severe injury chemicals are released in the body to help start the healing process and trigger inflammation (inflammatory biomarkers). Following a stroke, patients have abnormally high levels of inflammatory biomarkers in their blood and brain, including the protein interleukin-1 (IL-1). Increased inflammation is associated with more severe brain damage and the patient is more likely to die or be severely disabled. Interleukin-1 receptor antagonists (IL-1Ra) are drugs which work by blocking the action of IL-1 to reduce inflammation. IL-1Ra is currently licensed as a treatment for rheumatoid arthritis and given to patients via injections under the skin. The aim of this study is to find out if skin injections of IL-1Ra will also work to reduce inflammation after stroke.

Who can participate?
Adults who have had a stroke but are otherwise healthy

What does the study involve?
Participants are randomly allocated to receive twice daily injections of either IL-1Ra or a placebo (dummy drug). The first injection is given within 6 hours of stroke with five further doses given at 12 hourly intervals for 3 days (six injections in total). All participants receive standard care for ischaemic stroke, including treatment to dissolve the blood clot (thrombolysis), if needed. Blood samples are taken at the start of the study. Participants undergo assessments, together with four further blood samples for measurement of inflammatory biomarkers at multiple times over 57 days, to determine whether IL-1Ra causes a decrease in the level of inflammatory biomarkers in the blood within 3 days after stroke and also 57 days after. Participants’ level of disability and length of hospital stay are assessed at 1 and 3 months. Safety data on all participants is collected throughout the study.

What are the possible benefits and risks of participating?
There are no benefits expected from taking part. Risks include those associated with the drug being tested (IL-1Ra). The participant information sheets explain the side-effects relate to it being given as a treatment for rheumatoid arthritis, when it is given for a long time (months or years). The drug is only given for a very short time in this study (3 days). In studies that have given the drug over short periods (for severe infections, subarachnoid haemorrhage or stroke) there has been no evidence of increased infections. However, studies in patients with rheumatoid arthritis who have been on long term treatment have shown a small possibility of an increased risk of infections, some of which were classed as serious. Previous studies also showed that after long-term use of the drug, the body may make antibodies to the drug, with a possible risk of allergy to the drug. This is a rare but potentially serious side-effect. Participants are advised that If they think they may have received this drug or a similar drug, either as part of their general care or as part of another study, they should discuss this with the researcher but they may be excluded from taking part in this study. Some patients also experience a slight skin reaction following injection of the drug. These small red patches usually occur when the drug is given for longer periods e.g. more than 3 days. In the unlikely event this should occur, the participant is given the option to withdraw or to continue and receive the full six injections. The participant is also advised that they may experience some discomfort and bruising as a result of the blood sampling. Researchers try to collect research blood samples at the same time as blood is taken for normal clinical purposes, to reduce discomfort.

Where is the study run from?
Salford Royal NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
March 2015 to October 2016

Who is funding the study?
Stroke Association (UK)

Who is the main contact?
Mrs Sharon Hulme
sharon.hulme@manchester.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Sharon Hulme

ORCID ID

Contact details

Brain Injury Research Team
CSB
Hope Hospital
Stott Lane
Salford
M6 8HD
United Kingdom
+44 (0)161 206 5137
sharon.hulme@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

14764

Study information

Scientific title

Does subcutaneous interleukin-1 receptor antagonist reduce inflammation after ischaemic stroke compared to placebo? (SC IL-1Ra in Stroke study)

Acronym

SC IL-1RA in Stroke Study

Study hypothesis

The aim of this study is to investigate whether skin injections of IL-1Ra twice a day for 3 days will reduce inflammation in the blood of stroke patients.

Ethics approval

NRES Committee North West - Greater Manchester South, 26/9/2013, ref: 13/NW/0460

Study design

Randomised interventional trial; Design type: Treatment

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 to request a patient information sheet

Condition

Topic: Stroke Research Network; Subtopic: Acute Care; Disease: In hospital study

Intervention

Participants will receive twice daily, SC injections of either Kineret© or placebo.

Added 06/04/2017:
Participants will be randomised to subcutaneous administered of Kineret (anakinra) or placebo by a third-party, web-based computerised system. All participants will receive the first dose of study treatment (Kineret or placebo) within 6 hours of stroke onset. Five further doses will be given at 12 hourly intervals; a total of 6 injections over 72 hours. A blood sample will be obtained prior to randomisation and this will be repeated at 7am on the following 3 days. This will be used to measure levels of inflammation in the blood. Participation in the study will not delay clinical care or discharge from the hospital. All participants will be contacted by telephone at 30 days post-stroke, to check for adverse events and at 3 months post-stroke to measure recovery or level of ability using a standard questionnaire called modified Rankin Scale. This will complete study participation.

Intervention type

Drug

Phase

Phase II

Drug names

Anakinra

Primary outcome measures

Current primary outcome measures as of 06/04/2017:
Level of IL6, using ELISA within 3 days of stroke onset

Previous primary outcome measures:
Reduction in inflammatory biomarkers; Timepoints: Between 6 hours and 5-7 days post stroke

Secondary outcome measures

Added 06/04/2017:
1. Levels of other inflammatory markers, measured using ELISA or Luminex at within 3 days of stroke onset
2. Clinical outcome at 3 months following ischaemic stroke, measured using:
2.1. The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS)
2.2. The modified Rankin Score (mRS)
2.3. Survival (mortality) , measured using hospital records
2.4. Length of hospital stay (LOS), measured using a telephone survey

Overall trial start date

01/11/2013

Overall trial end date

30/04/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with confirmed ischaemic stroke who are admitted to the Comprehensive Stroke Centre at Salford Royal NHS Foundation Trust (SRFT) where consent can be obtained and drug administered within 6 hours
2. National Institutes of Health stroke scale (NIHSS) score between 4-26
3. No concomitant health problems that, in the opinion of the Principal Investigator (PI) or designee, would interfere with participation, administration of study treatment or assessment of outcomes including safety, for example, preexisting malignancy
4. Renal function within normal limits (< 177 µmol/l)
5. Willing and able to give informed consent or consent available from a patient representative (personallegal) for study inclusion including agreement in principle to receive study intervention and undergo all study assessments
6. Aged 18 years or above

Healthy volunteers (recruited to provide a one-off 20ml blood sample only)
1. Between 18 and 80 years, in good health

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 120; UK Sample Size: 120; Description: Consists of 80 stroke patients and 40 healthy volunteers.

Participant exclusion criteria

Patient group:
1. Unconfirmed or uncertain diagnosis of ischaemic stroke or rapid improving symptoms
2. Haemorrhagic stroke
3. NIHSS <4 or >26
4. Known allergy to E. coli or any of the constituents of the study medication as established from the patient themselves, reliable representative and clinical records
5. Previous or concurrent treatment with recombinant IL1Ra known at the time of study entry
6. Previous or current treatment with medication suspected of interacting with recombinant IL1Ra, such as TNFa inhibitors
7. Known to have participated in a clinical trial of an investigational agent or device in the previous 30 days or for the period determined by the protocol of the study the patient has taken part in
8. Known or planned pregnancy (pregnancy test to be performed in women of childbearing potential) or breastfeeding
9. Clinically significant concurrent medical condition, at the PIs (or designees) discretion, which could affect the safety, tolerability, or efficacy in this study
10. Previous inclusion in the current study (known prior to inclusion)
11. Evidence of current infection or infection within the past 4 wk
12. Inability or unwillingness of patient or patients personal representative to give written informed consent

Healthy volunteers (recruited to provide a oneoff 20ml blood sample only)
1. Current acute medical problems or taking medication for chronic conditions

Recruitment start date

01/11/2013

Recruitment end date

30/04/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Hope Hospital
Salford
M6 8HD
United Kingdom

Sponsor information

Organisation

Salford Royal NHS Foundation Trust

Sponsor details

R&D Department
Clinical Sciences Building
Stott Lane
Salford
M6 8HD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.srft.nhs.uk/

Funders

Funder type

Charity

Funder name

Stroke Association (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location