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Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)—a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Berthelsen, Rasmus Ehrenfried
dc.contributor.author Ostrowski, Sisse Rye
dc.contributor.author Bestle, Morten Heiberg
dc.contributor.author Johansson, Per Ingemar
dc.date.accessioned 2020-03-23T15:51:39Z
dc.date.available 2020-03-23T15:51:39Z
dc.date.issued 2019-09-05
dc.identifier.citation Berthelsen, R.E., Ostrowski, S.R., Bestle, M.H. et al. Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)—a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy. Critical Care 23, 301 (2019). https://doi.org/10.1186/s13054-019-2573-8
dc.identifier.issn 1364-8535
dc.identifier.uri https://hdl.handle.net/20.500.11815/1649
dc.description Publisher's version (útgefin grein). The CO-ILEPSS trial was approved by the ethics committee in The Capital Region of Denmark with protocol number: H-3-2014-087.
dc.description.abstract Background: Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome. Method: The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 μg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test. Results: We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin (p = 0.03) and nucleosomes (p = 0.02) in the placebo group and decreasing levels of sE-Selectin (p = 0.007) and sVEGFR1 (p = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group (p = 0.049) and increased from baseline to day 7 in the active treatment group (p = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h (p = 0.048) and onwards (p = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h (p = 0.024) and onwards in the active treatment group. Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality. Conclusion: Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial. Trial registration: Clinicaltrials.com, NCT02204852 (July 30, 2014); EudraCT no. 2014-002440-41
dc.description.sponsorship Funding was provided by Professor Per I. Johansson, Senior Physician, DMSC, MPA, The Capital Region Blood Bank, and Rigshospitalet. We would like to acknowledge all the nurses and doctors at the intensive care unit and the nurses at the post-operative care unit at NOH for the work associated with the trial treatment including randomisation, preparation of trial medication and blood sampling.
dc.format.extent 301
dc.language.iso en
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartofseries Critical Care;23(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Endothelium
dc.subject Eptifibatide
dc.subject Iloprost
dc.subject Infection
dc.subject Pathologic processes
dc.subject Platelet aggregation inhibitors
dc.subject Platelets
dc.subject Septic shock
dc.subject Æðaþel
dc.subject Sýkingar
dc.subject Meinafræði
dc.subject Lyfleysur
dc.title Co-administration of iloprost and eptifibatide in septic shock (CO-ILEPSS)—a randomised, controlled, double-blind investigator-initiated trial investigating safety and efficacy
dc.type info:eu-repo/semantics/article
dcterms.license Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.description.version Peer Reviewed
dc.identifier.journal Critical Care
dc.identifier.doi 10.1186/s13054-019-2573-8
dc.contributor.department Rannsóknarsetur í kerfislíffræði (HÍ)
dc.contributor.department Center for Systems Biology (UI)

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