Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
SourceCritical Care Medicine, 49, 5, (2021), pp. 790-803
Article / Letter to editor
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Cardio Thoracic Surgery
Primary and Community Care
Critical Care Medicine
SubjectRadboudumc 0: Other Research RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 16: Vascular damage RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences
OBJECTIVES: To 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. DESIGN: Double-blinded, placebo-controlled, randomized study. SETTING: Collaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands. PATIENTS: One hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery. INTERVENTIONS: Ninety mg/kg/hr EA-230 or placebo administered during surgery. MEASUREMENTS AND MAIN RESULTS: During the study, no safety concerns emerged. EA-230 did not modulate interleukin-6 plasma concentrations (area under the curve 2,730 pg/mL x hr [1,968-3,760] vs 2,680 pg/mL x 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. CONCLUSIONS: EA-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.
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