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

Adrian R Parry-Jones, Katie Stocking, Mary Joan MacLeod, Brian Clarke, David J Werring, Keith W Muir, Andy Vail

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalEuropean Stroke Journal
Volume8
Issue number3
Early online date15 Jul 2023
DOIs
Publication statusPublished - 1 Sept 2023

Keywords

  • Intracerebral haemorrhage
  • anakinra
  • clinical trial
  • interleukin-1 receptor antagonist

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