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

被引:23
作者
Berthelsen, Rasmus Ehrenfried [1 ]
Ostrowski, Sisse Rye [2 ,3 ]
Bestle, Morten Heiberg [1 ,3 ]
Johansson, Per Ingemar [4 ,5 ,6 ]
机构
[1] Roskilde Univ Copenhagen, Dept Anesthesiol & Intens Care, Zealand Univ Hosp, Roskilde, Denmark
[2] Copenhagen Univ Hosp, Dept Clin Immunol, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark
[3] Univ Copenhagen, Dept Clin Med, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark
[4] Rigshosp, Capital Reg Blood Bank, Sect Transfus Med, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark
[5] Univ Iceland, Ctr Syst Biol, Sturlugata 8, IS-101 Reykjavik, Iceland
[6] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Ctr Translat Injury Res CeTIR, 7000 Fannin,Suite 1800, Houston, TX 77030 USA
关键词
Septic shock; Pathologic processes; Infection; Endothelium; Platelets; Iloprost; Eptifibatide; Platelet aggregation inhibitors; LOW-DOSE PROSTACYCLIN; SEVERE SEPSIS; THROMBUS RESOLUTION; PROTEIN-C; ENDOTHELIUM; INHIBITION; ENDOTOXEMIA; DYSFUNCTION; EXPRESSION; PATHWAY;
D O I
10.1186/s13054-019-2573-8
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 mu g/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.
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页数:10
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