Developmental Clinical Studies - Does subcutaneous IL-1RA reduce inflammation following subarachnoid haemorrhage?

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SAH occurs when a blood vessel within the brain bursts; affecting up to 6,000 people every year in the UK. It is often due to a weakening in the blood vessel wall (aneurysm) and can occur without warning. Up to half of all patients who have a SAH do not survive long enough to receive hospital treatment. Of those who survive, blood flow to the brain may be reduced due to blood from the haemorrhage irritating the outer surface of brain arteries causing them to spasm and become narrower. Reduction in blood flow prevents oxygen reaching brain cells causing them to die. This is known as cerebral ischaemia (CI) and causes patients to experience symptoms similar to a stroke. However, these symptoms may not be immediately apparent as they commonly occur between 3-15 days after the initial haemorrhage. This is known as Delayed Cerebral Ischaemia (DCI).A protein called interleukin-1 (IL-1) is an important trigger for damage happening after CI. After SAH, IL-1 causes the release of other proteins which cause inflammation in the circulation and the brain. IL-1 can be blocked, limited or even reversed by another protein present naturally in our body; interleukin-1 receptor antagonist (IL-1RA). A company has duplicated IL-1RA; marketing it as an anti-inflammatory treatment for rheumatoid arthritis (Kineret?). Our group has successfully tested Kineret? and found that when given in high doses at the onset of CI; it reduces inflammation and ischaemia. As ischaemia in SAH is delayed, it may be possible to give Kineret? as a preventative measure rather than a treatment; allowing smaller doses to be used. We want to establish whether injections of Kineret?, given in small amounts, reduces inflammation in brain blood vessels and the subsequent incidence of DCI. To do this, we will recruit up to 140 SAH patients from our neurosurgical centre (Salford Royal NHS Foundation Trust) over 2? years. Patients will be randomised by an independent third party to receive either Kineret? or placebo in twice daily injections for up to 21 days after the bleed. We will perform a number of assessments and blood tests at pre-determined time points. Patients will continue to receive the standard care for SAH and participation in this study will not affect or delay this care. Throughout the study we will consult with Patient-Public Involvement groups, building on previous work and strengthening our relationship with the lay community.