BLOC-ICH - BLOcking the Cytokine IL-1 in ICH
Research type
Research Study
Full title
Phase II trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH
IRAS ID
252065
Contact name
Adrian Parry-Jones
Contact email
Sponsor organisation
University of Manchester
Eudract number
2018-000249-38
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
R118439, Sponsors reference number
Duration of Study in the UK
1 years, 3 months, 5 days
Research summary
Research Summary
Why - We wish to develop a new treatment for patients with intracerebral haemorrhage; ICH.
In the hours to days after bleeding occurs, we know that inflammation occurs in the brain around the blood clot. Although inflammation is the body's natural response to injury, when it continues unchecked it can worsen damage. We know that inflammation worsens damage after ICH so we want to investigate whether blocking inflammation can improve recovery and overall outcome. ICH accounts for 10% of strokes in the United Kingdom (UK) each year, nearly a third of patients die within one month and over half of those who survive are left with lifelong disability. There are few treatments currently available, this represents a serious unmet need.
What – Interleukin-1 (IL-1) is a naturally occurring protein responsible for inflammation. It has been found to play a key role in early damage after stroke and ICH. Another protein, interleukin-1 receptor antagonist (IL-1Ra) can limit or block the effects of IL-1, potentially reduce brain damage. IL-1Ra is available as Kineret® licensed for rheumatoid arthritis and has been widely tested and found to reduce levels of inflammation. This trial will assess whether reducing inflammation leads to an improvement in outcome after ICH.
Who/where – the trial will recruit patients within 8 hours of ICH from five hospitals in the UK.
How –Following consent, participants will receive 6 injections of IL-1Ra or placebo (dummy drug) over 3 days, the first given within 8 hours of symptom-onset. Research assessments will check safety of the drug and patient well-being. In addition, participants will undergo brain imaging, blood sampling and completion of telephone questionnaires at 30 days and 3 months to assess the impact of trial drug on recovery.
Summary of Results
In the hours to days after stroke caused by bleeding (known as an intracerebral haemorrhage), we know that inflammation develops in the brain around the blood clot. Although inflammation is the body's natural response to injury, when it continues unchecked, it can worsen damage. We conducted a clinical trial of a well-established anti-inflammatory drug (called anakinra) injected under the skin twice a day for three days and compared this to an otherwise identical placebo, or dummy drug. Anakinra blocks inflammation and we aimed to test whether it can reduce brain swelling after intracerebral haemorrhage. We also wanted to test whether there are any safety concerns in intracerebral haemorrhage. We aimed to recruit 80 acute intracerebral haemorrhage patients to the trial. Due to severe pressures related to the COVID-19 pandemic, only 25 patients were recruited by the end of the trial. Of these, 14 received anakinra and 11 received a placebo. Although assignment to anakinra or placebo was random (like flipping a coin), the 14 patients receiving anakinra had much larger bleeds and more severe strokes before starting treatment. Because of the small group size and substantial differences between the patients in each group before treatment, no conclusions can be drawn regarding the effect of the drug. However, no concerns were identified regarding the safety in the 14 patients with intracerebral haemorrhage receiving anakinra in this trial.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
18/YH/0473
Date of REC Opinion
25 Jan 2019
REC opinion
Further Information Favourable Opinion