Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH)

Parry-Jones, A. R., Stocking, K., MacLeod, M. J., Clarke, B., Werring, D. J., Muir, K. W. and Vail, A. (2023) Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH). European Stroke Journal, 8(3), pp. 819-827. (doi: 10.1177/23969873231185208) (PMID:37452707) (PMCID:PMC10472954)

Abstract

Purpose: Recombinant human interleukin-1 receptor antagonist (anakinra) is an anti-inflammatory with efficacy in animal models of stroke. We tested the effect of anakinra on perihaematomal oedema in acute intracerebral haemorrhage (ICH) and explored effects on inflammatory markers. Methods: We conducted a multicentre, randomised, double-blind, placebo-controlled trial in patients with acute, spontaneous, supratentorial ICH between May 2019 and February 2021. Patients were randomised to 100 mg subcutaneous anakinra within 8 h of onset, followed by five, 12-hourly, 100 mg subcutaneous injections, or matched placebo. Primary outcome was oedema extension distance (OED) on a 72 h CT scan. Secondary outcomes included plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Findings: 25 patients (target = 80) were recruited, 14 randomised to anakinra, 11 to placebo. Mean age was 67 and 52% were male. The anakinra group had higher median baseline ICH volume (12.6 ml, interquartile range[IQR]:4.8–17.9) versus placebo (5.5 ml, IQR:2.1–10.9). Adjusting for baseline, 72 h OED was not significantly different between groups (mean difference OED anakinra vs placebo -0.05 cm, 95% confidence interval [CI]: −0.17–0.06, p = 0.336). There was no significant difference in area-under-the-curve to Day 4 for IL-6 and CRP, but a post-hoc analysis demonstrated IL-6 was 56% (95% CI: 2%–80%) lower at Day 2 with anakinra. There were 10 and 2 serious adverse events in anakinra and placebo groups, respectively, none attributed to anakinra. Conclusion: We describe feasibility for delivering anakinra in acute ICH and provide preliminary safety data. We lacked power to test for effects on oedema thus further trials will be required.

• Item Type: Articles
• Additional Information: This report is independent research arising from a Clinician Scientist Award to APJ (CS-2014-14-005) supported by the National Institute for Health Research.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith
• Authors: Parry-Jones, A. R., Stocking, K., MacLeod, M. J., Clarke, B., Werring, D. J., Muir, K. W., and Vail, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: European Stroke Journal
• Publisher: SAGE Publications
• ISSN: 2396-9873
• ISSN (Online): 2396-9881
• Published Online: 15 July 2023
• Copyright Holders: Copyright © European Stroke Organisation 2023
• First Published: First published in European Stroke Journal 8(3): 819 - 827
• Publisher Policy: Reproduced under a Creative Commons licence