Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study.
Journal
Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
pubmed:
17
2
2021
medline:
18
9
2021
entrez:
16
2
2021
Statut:
ppublish
Résumé
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. Double-blinded, placebo-controlled, randomized study. Collaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands. One hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery. Ninety mg/kg/hr EA-230 or placebo administered during surgery. 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 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. 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.
Identifiants
pubmed: 33591006
doi: 10.1097/CCM.0000000000004847
pii: 00003246-202105000-00008
pmc: PMC8043513
doi:
Substances chimiques
Cardiotonic Agents
0
Oligopeptides
0
alanyl-glutaminyl-glycyl-valine
0
Banques de données
ClinicalTrials.gov
['NCT03145220']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
790-803Informations de copyright
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.
Déclaration de conflit d'intérêts
The sponsor had no role in the study design, data collection, analysis, or reporting. Dr. Pickkers received consulting fees and travel reimbursements from EBI. Dr. Wensvoort received consulting fees and travel reimbursements from EBI and owned shares in EBI, and he disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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