TY - JOUR

T1 - A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients

AU - Emsley, H. C. A.

AU - Smith, C. J.

AU - Georgiou, R. F.

AU - Vail, A.

AU - Hopkins, S. J.

AU - Rothwell, N. J.

AU - Tyrrell, P. J.

PY - 2005/10

Y1 - 2005/10

N2 - Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5-7 day brain infarct volume was measured by computed tomography. Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.

AB - Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5-7 day brain infarct volume was measured by computed tomography. Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.

U2 - 10.1136/jnnp.2004.054882

DO - 10.1136/jnnp.2004.054882

M3 - Journal article

C2 - 16170078

AN - SCOPUS:25444517949

VL - 76

SP - 1366

EP - 1372

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 10

ER -