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

Groenendael, Roger van; Beunders, Remi; Hemelaar, Pleun; Hofland, Jan; Morshuis, Wim J.; Hoeven, Johannes G. van der; Gerretsen, Jelle; Wensvoort, Gert; Kooistra, Emma J.; Claassen, Wout; Waanders, Denise; Lamberts, Maud G. A.; Buijsse, Leonie S. E.; Kox, Matthijs; Eijk, Lucas T. van; Pickkers, Peter

doi:10.1097/ccm.0000000000004847

Cited by 10 publications

(3 citation statements)

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“…Moreover, in several of these studies, CytoSorb therapy was applied as a single treatment of six hours per day (9, 10), and it is therefore plausible that the majority of cytokines were produced outside this therapeutic window. This might also explain why CytoSorb therapy applied during cardiopulmonary bypass did not affect plasma concentrations of IL-6 in 37 cardiac surgery patients (11), as cytokine concentrations are known to peak several hours after termination of CPB in these patients (11,20), and CytoSorb therapy in this particular study was ceased at the end of CPB (11). Given the pronounced effect on plasma cytokine concentrations in the present work, it appears plausible that these studies might have yielded different results if patient groups with a more pronounced cytokine response were selected and received more prolonged or continuous hemoadsorption treatments.…”

Section: Discussionmentioning

confidence: 99%

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

et al. 2023

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Background The CytoSorb hemoadsorption device has been demonstrated to be capable of clearing inflammatory cytokines, but has not yet been shown to attenuate plasma cytokine concentrations. We investigated the effects of CytoSorb hemoperfusion on plasma levels of various cytokines using the repeated human experimental endotoxemia model, a highly standardized and reproducible human in vivo model of systemic inflammation and immunological tolerance induced by administration of bacterial lipopolysaccharide (LPS). Methods Twenty-four healthy male volunteers (age 18–35) were intravenously challenged with LPS (a bolus of 1 ng/kg followed by continuous infusion of 0.5 ng/kg/hr for three hours) twice: on day 0 to quantify the initial cytokine response and on day 7 to quantify the degree of endotoxin tolerance. Subjects either received CytoSorb hemoperfusion during the first LPS challenge (CytoSorb group), or no intervention (control group). Plasma cytokine concentrations and clearance rates were determined serially. This study was registered at ClinicalTrials.gov (NCT04643639, date of registration November 24th 2020). Results LPS administration led to a profound increase in plasma cytokine concentrations during both LPS challenge days. Compared to the control group, significantly lower plasma levels of tumor necrosis factor (TNF, − 58%, p < 0.0001), interleukin (IL)-6 ( − 71%, p = 0.003), IL-8 ( − 48%, p = 0.02) and IL-10 ( − 26%, p = 0.03) were observed in the CytoSorb group during the first LPS challenge. No differences in cytokine responses were observed during the second LPS challenge. Conclusions CytoSorb hemoperfusion effectively attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo, whereas it does not affect long-term immune function. Therefore, CytoSorb therapy may be of benefit in conditions characterized by excessive cytokine release.

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Section: Discussionmentioning

confidence: 99%

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

et al. 2023

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“…First, timing and duration of CytoSorb therapy is of paramount importance (2). For instance, several previous studies have demonstrated that cytokine concentrations in cardiac surgery patients start to increase only several hours postoperatively (3, 4). Nonetheless, nine of ten studies in cardiac surgery patients in this meta-analysis applied CytoSorb therapy exclusively during cardiopulmonary bypass, when there are no circulating cytokines to clear.…”

Section: To the Editormentioning

confidence: 99%

Effect of CytoSorb on Interleukin-6

Waalders,

Jansen,

Pickkers

2024

Critical Care Medicine

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“…EA-230 was also found to confer survival benefits in animals with abdominal sepsis [119]. Furthermore, EA-230 demonstrated excellent safety and tolerability in healthy volunteers participating in Phase I clinical trials [120]. IMX-942, a synthetic IDR peptide designed based on the sequence of IDR-1, first entered Phase I clinical trial in 2009 [116].…”

Section: Innate Defense Regulator (Idr) Peptidesmentioning

confidence: 99%

Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

Zang

Zhou

et al. 2022

J Nanobiotechnol

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Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.

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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

Abstract: Supplemental Digital Content is available in the text.

Cited by 10 publications

References 49 publications

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

Effect of CytoSorb on Interleukin-6

Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

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