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Interleukin-1 beta is an early pro-inflammatory cytokine and a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>To determine the effect of treatment with recombinant human interleukin-1 receptor antagonist anakinra on perihematomal oedema (PHO) formation in patients with spontaneous ICH compared to standard medical management, and investigate whether this effect is dose-dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>ACTION is a phase-II, prospective, randomised, three-armed (1:1:1) trial with open-label treatment and blinded end-point assessment (PROBE) at three hospitals in The Netherlands. We will include 75 patients with a supratentorial spontaneous ICH admitted within 8\u2009h after symptom onset. Participants will receive anakinra in a high dose (loading dose 500\u2009mg intravenously, followed by infusion with 2\u2009mg\/kg\/h over 72\u2009h; n\u2009=\u200925) or in a low dose (loading dose 100\u2009mg subcutaneously, followed by 100\u2009mg subcutaneous twice daily for 72\u2009h; n\u2009=\u200925), plus standard care. The control group (n\u2009=\u200925) will receive standard medical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes:<\/jats:title>\n                    <jats:p>Primary outcome is PHO, measured as oedema extension distance on MRI at day 7\u2009\u00b1\u20091. Secondary outcomes include the safety profile of anakinra, the effect of anakinra on serum inflammation markers, MRI measures of blood brain barrier integrity, and functional outcome at 90\u2009\u00b1\u20097\u2009days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>The ACTION trial will provide insight into whether targeting interleukin-1 beta in the early time window after ICH onset could ameliorate secondary brain injury. This may contribute to the development of new treatment options to improve clinical outcome after ICH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23969873231200686","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:55:42Z","timestamp":1694778942000},"page":"265-273","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-5652","authenticated-orcid":false,"given":"MP","family":"Cliteur","sequence":"first","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands 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