{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:45:02Z","timestamp":1790217902271,"version":"4.1.0"},"reference-count":21,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (&amp;gt;10 ng\/mL) have been associated with worse organ dysfunction and mortality.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng\/mL.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng\/kg\/min (n\u2009=\u2009142), or placebo (n\u2009=\u2009137) for 72 hours.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, \u22120.8 to 1.2]; P<\/jats:italic>\u2009=\u2009.70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P<\/jats:italic>\u2009=\u2009.33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P<\/jats:italic>\u2009=\u2009.52). Only 1 serious adverse reaction was observed.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng\/kg\/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04123444<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.32444","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T15:12:26Z","timestamp":1726067546000},"page":"e2432444","source":"Crossref","is-referenced-by-count":14,"title":["Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy"],"prefix":"10.1001","volume":"7","author":[{"given":"Morten H.","family":"Bestle","sequence":"first","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Copenhagen University Hospital\u2013North Zealand, Hilleroed, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, 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Anaesthesia and Intensive Care, Copenhagen University Hospital\u2013North Zealand, Hilleroed, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus T.","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Copenhagen University Hospital\u2013Amager and Hvidovre, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lindhardt","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Copenhagen University Hospital\u2013Zealand University Hospital, Koege, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4r I.","family":"Johansson","sequence":"additional","affiliation":[{"name":"Capital Region Blood Bank, Copenhagen University Hospital\u2013Rigshospitalet, Copenhagen, 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