TY - JOUR
T1 - Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH)
AU - Parry-Jones, Adrian R
AU - Stocking, Katie
AU - MacLeod, Mary Joan
AU - Clarke, Brian
AU - Werring, David J
AU - Muir, Keith W
AU - Vail, Andy
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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.
AB - 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.
KW - Intracerebral haemorrhage
KW - anakinra
KW - clinical trial
KW - interleukin-1 receptor antagonist
UR - http://www.scopus.com/inward/record.url?scp=85165264517&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/1b747488-8e4c-3263-adac-7a7eb15b4bae/
U2 - 10.1177/23969873231185208
DO - 10.1177/23969873231185208
M3 - Article
C2 - 37452707
SN - 2396-9873
VL - 8
SP - 819
EP - 827
JO - European Stroke Journal
JF - European Stroke Journal
IS - 3
ER -