Professor Pippa Tyrrell
University of Manchester
Does subcutaneous interleukin-1 receptor antagonist reduce inflammation after ischaemic stroke compared to placebo?
The Stroke Association
Thrombolysis and stroke unit care have improved stroke outcomes, but there remains an urgent need to reduce neuronal injury following stroke. The cytokine interleukin-1 (IL-1) mediates brain injury. IL-1 enhances endothelial reactivity and recruitment of circulating inflammatory cells whereas inhibition of IL-1, using IL-1 receptor antagonist (IL-1Ra), markedly reduces experimental brain injury and could be a widely applicable treatment for stroke. We have shown that intravenous IL-1Ra reduces markers of inflammation in blood and cerebrospinal fluid following stroke and subarachnoid haemorrhage; and that IL-1Ra is safe and well tolerated. Subcutaneous IL-1Ra is the form of IL-1Ra that is currently available for clinical use and this route of administration has proved effective experimentally in stroke. It is essential to examine whether SC IL-1Ra reduces inflammation in stroke patients, prior to a full clinical trial.
We will undertake a single-centre, double-blind, randomised, placebo-controlled Phase II study of IL-1Ra (30 per group), administered SC, twice daily for three days in patients with ischaemic stroke.
Primary outcome: reduction in concentrations of IL-6 to day 3.
Secondary clinical outcomes will be collected up to three months. The results will inform a Phase III efficacy study.