Professor Pippa Tyrrell
University of Manchester
United Kingdom
Does subcutaneous interleukin-1 receptor antagonist reduce inflammation after ischaemic stroke compared to placebo?
The Stroke Association
277,280
01/07/2013
3
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.