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Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study

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 preclinica...

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Autores principales: van Groenendael, Roger, Beunders, Remi, Hemelaar, Pleun, Hofland, Jan, Morshuis, Wim J., van der Hoeven, Johannes G., Gerretsen, Jelle, Wensvoort, Gert, Kooistra, Emma J., Claassen, Wout J., Waanders, Denise, Lamberts, Maud G. A., Buijsse, Leonie S. E., Kox, Matthijs, van Eijk, Lucas T., Pickkers, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043513/
https://www.ncbi.nlm.nih.gov/pubmed/33591006
http://dx.doi.org/10.1097/CCM.0000000000004847
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author van Groenendael, Roger
Beunders, Remi
Hemelaar, Pleun
Hofland, Jan
Morshuis, Wim J.
van der Hoeven, Johannes G.
Gerretsen, Jelle
Wensvoort, Gert
Kooistra, Emma J.
Claassen, Wout J.
Waanders, Denise
Lamberts, Maud G. A.
Buijsse, Leonie S. E.
Kox, Matthijs
van Eijk, Lucas T.
Pickkers, Peter
author_facet van Groenendael, Roger
Beunders, Remi
Hemelaar, Pleun
Hofland, Jan
Morshuis, Wim J.
van der Hoeven, Johannes G.
Gerretsen, Jelle
Wensvoort, Gert
Kooistra, Emma J.
Claassen, Wout J.
Waanders, Denise
Lamberts, Maud G. A.
Buijsse, Leonie S. E.
Kox, Matthijs
van Eijk, Lucas T.
Pickkers, Peter
author_sort van Groenendael, Roger
collection PubMed
description 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 × 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 rate(iohexol) measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m(2); 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 m(2); 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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spelling pubmed-80435132021-04-19 Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study van Groenendael, Roger Beunders, Remi Hemelaar, Pleun Hofland, Jan Morshuis, Wim J. van der Hoeven, Johannes G. Gerretsen, Jelle Wensvoort, Gert Kooistra, Emma J. Claassen, Wout J. Waanders, Denise Lamberts, Maud G. A. Buijsse, Leonie S. E. Kox, Matthijs van Eijk, Lucas T. Pickkers, Peter Crit Care Med Clinical Investigations 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 × 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 rate(iohexol) measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m(2); 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 m(2); 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. Lippincott Williams & Wilkins 2021-04-15 2021-05 /pmc/articles/PMC8043513/ /pubmed/33591006 http://dx.doi.org/10.1097/CCM.0000000000004847 Text en 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. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Clinical Investigations
van Groenendael, Roger
Beunders, Remi
Hemelaar, Pleun
Hofland, Jan
Morshuis, Wim J.
van der Hoeven, Johannes G.
Gerretsen, Jelle
Wensvoort, Gert
Kooistra, Emma J.
Claassen, Wout J.
Waanders, Denise
Lamberts, Maud G. A.
Buijsse, Leonie S. E.
Kox, Matthijs
van Eijk, Lucas T.
Pickkers, Peter
Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title_full Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title_fullStr Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title_full_unstemmed Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title_short Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study
title_sort safety and efficacy of human chorionic gonadotropin hormone-derivative ea-230 in cardiac surgery patients: a randomized double-blind placebo-controlled study
topic Clinical Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043513/
https://www.ncbi.nlm.nih.gov/pubmed/33591006
http://dx.doi.org/10.1097/CCM.0000000000004847
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