• Roger van Groenendael, Remi Beunders, Pleun Hemelaar, Jan Hofland, Wim J Morshuis, Johannes G van der Hoeven, Jelle Gerretsen, Gert Wensvoort, Emma J Kooistra, Wout J Claassen, Denise Waanders, Maud G A Lamberts, Leonie S E Buijsse, Matthijs Kox, Lucas T van Eijk, and Peter Pickkers.
• Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
• Crit. Care Med. 2021 May 1; 49 (5): 790803790-803.

ObjectivesTo determine the safety and efficacy of human chorionic gonadotropin hormone-derivative EA-230 in cardiac surgery patients. Cardiac surgery induces systemic inflammation and may impair renal function, affecting patient outcome. EA-230 exerted immunomodulatory and renoprotective effects in preclinical models and was safe and showed efficacy in phase I and II human studies.DesignDouble-blinded, placebo-controlled, randomized study.SettingCollaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands.PatientsOne hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery.InterventionsNinety mg/kg/hr EA-230 or placebo administered during surgery.Measurements And Main ResultsDuring the study, no safety concerns emerged. EA-230 did not modulate interleukin-6 plasma concentrations (area under the curve 2,730 pg/mL × hr [1,968-3,760] vs 2,680 pg/mL × hr [2,090-3,570] for EA-230 and placebo group, respectively; p = 0.80). Glomerular filtration rate increased following surgery (mean ± sem increase in the EA-230 vs placebo groups: glomerular filtration rateiohexol measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m2; p = 0.13 and estimated glomerular filtration rate with the Modification of Diet in Renal Disease equation using creatinine: 6 ± 1 vs 2 ± 1 mL/min/1.73 m2; p = 0.01). The "injury" stage of the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria for acute kidney injury was 7% in the EA-230 group versus 18% in the placebo group (p = 0.07). In addition, EA-230-treated patients had a less positive fluid balance compared with placebo-treated patients (217 ± 108 vs 605 ± 103 mL; p = 0.01), while the use of vasoactive agents was similar in both groups (p = 0.39). Finally, hospital length of stay was shorter in EA-230 treated patients (8 d [7-11] vs 10 d [8-12]; p = 0.001). Efficacy results were more pronounced in patients that had longer duration of surgery and thus longer duration of study drug infusion.ConclusionsEA-230 was safe in patients undergoing on-pump cardiac surgery. It did not modulate interleukin-6 plasma concentrations but appeared to exert beneficial renal and cardiovascular effects and shortened in-hospital length of stay.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.

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