Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06404424
Status:
COMPLETED
Last Update Posted:
2024-06-05
First Post:
2024-05-05
Brief Title:
Combined Hemoperfusion and Therapeutic Plasma Exchange for Treatment of Patients With Septic Shock
Sponsor:
Efferon JSC
Organization:
Efferon JSC
Study Overview
Official Title:
Consecutive Hemoperfusion and Therapeutic Plasma Exchange in Adult Patients With Septic Shock
Status:
COMPLETED
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Sepsis is a critical burden for a healthcare From 2000 to 2020 the number of publications and clinical studies on the topic of Sepsis and septic shock on the National Library of Medicine resource The National Center for Biotechnology Information has tripled Sepsis is a life-threatening condition that causes significant pathophysiological changes in the body Currently sepsis is understood as organ dysfunction caused by a dysregulatory response of the macroorganism to infection A special role in this process belongs to the innate and adaptive immune response
Despite the trend towards improving survival rates mortality in sepsis remains high - about 25 reaching 60 with the development of septic shock
Extracorporeal therapy as an adjuvant method of treatment has been used for more than 30 years but conducting large randomized studies confirming its effectiveness is associated with a complex of problems including the extreme heterogeneity of the population of patients with sepsis and septic shock different etiologies and complex pathogenesis non-identical pathophysiological pathways of the dominant organ dysfunction in specific time period and degree of its severity
Goal of the study is to evaluate safety and efficiency of combined hemoperfusion and therapeutic plasma exchange in adult patients with septic shock
Despite the trend towards improving survival rates mortality in sepsis remains high - about 25 reaching 60 with the development of septic shock
Extracorporeal therapy as an adjuvant method of treatment has been used for more than 30 years but conducting large randomized studies confirming its effectiveness is associated with a complex of problems including the extreme heterogeneity of the population of patients with sepsis and septic shock different etiologies and complex pathogenesis non-identical pathophysiological pathways of the dominant organ dysfunction in specific time period and degree of its severity
Goal of the study is to evaluate safety and efficiency of combined hemoperfusion and therapeutic plasma exchange in adult patients with septic shock
Detailed Description:
Sepsis is a critical burden for a healthcare From 2000 to 2020 the number of publications and clinical studies on the topic of Sepsis and septic shock on the National Library of Medicine resource The National Center for Biotechnology Information has tripled Sepsis is a life-threatening condition that causes significant pathophysiological changes in the body Currently sepsis is understood as organ dysfunction caused by a dysregulatory response of the macroorganism to infection A special role in this process belongs to the innate and adaptive immune response
Despite the trend towards improving survival rates mortality in sepsis remains high - about 25 reaching 60 with the development of septic shock
Modern understanding of the pathophysiology of sepsis allows us to identify several groups of molecules that are of significant interest as targets for targeted therapy Activation of Toll-like receptors of neurophils and macrophages by the so-called PAMPs pathogen-associated molecular patterns - extracellular bacterial DNA lipopolysaccharides flagellin lipoteichoic acid peptidoglycan leads to changes in the transcription of genes involved in the regulation of the inflammatory response cellular metabolism with a significant release of cytokinessuch as IL-1 TNF-α IL-2 IL-6 IL-8 IL-10 IFN-γ and complement proteins
Extracorporeal therapy as an adjuvant method of treatment has been used for more than 30 years but conducting large randomized studies confirming its effectiveness is associated with a complex of problems including the extreme heterogeneity of the population of patients with sepsis and septic shock different etiologies and complex pathogenesis non-identical pathophysiological pathways of the dominant organ dysfunction in specific time period and degree of its severity
The strategy of using separate methods for extracorporeal elimination of LPS and cytokines yielded controversial results with an obvious association of endotoxemia and high concentrations of inflammatory mediators with mortality and severity of organ failure
According to a meta-analysis of Li X et al 2021 which included 13 RCTs LPS-selective hemoperfusion was associated with a decrease in mortality concentration and activity level of endotoxin and improved hemodynamic parameters The EUPHAS 2 trial showed the effect of LPS elimination on improvement in hemodynamics oxygenation and survival but the nature of the data collection was retrospective there was no control group and the study population was highly heterogeneous in the source of infection and severity of the condition The largest RCT EUPHRATES also confirmed an increase in mean arterial pressure and 28-day survival but only in patients with endotoxin activity levels in the range of 06-089 The ABDOMIX study did not demonstrate an effect of endotoxin adsorption on mortality and was associated with a large number of technical difficulties during extracorporeal treatment that affected the outcome
The use of plasma exchange as an integral technique that allows one to simultaneously eliminate both high-molecular toxins and mediators and medium-sized factors seems justified from the point of view of pathogenesis Many studies have shown a correlation of high VWF levels and low ADAMTS-13 activity in sepsis with mortality disease severity and the intensity of both systemic inflammation and disseminated intravascular coagulation There are similar data for other molecules the normalization of which by plasma exchange can potentially improve outcome - high levels of NETs IgA IgG d-dimer PAI-1 C3 and C4 factors of the complement system and conversely low levels of plasminogen fibrinogen antithrombin III protein C are associated with increased mortality But there is relatively little research on plasma exchange
Thus blood purification techniques used for sepsis certainly have a therapeutic effect it is assumed that their combined use will enhance it which will potentially improve treatment results
The need to influence different classes of molecules weight kinetics volume of distribution of both the immune system and the hemostatic system determines the choice of methods of combined extracorporeal therapy
Despite the trend towards improving survival rates mortality in sepsis remains high - about 25 reaching 60 with the development of septic shock
Modern understanding of the pathophysiology of sepsis allows us to identify several groups of molecules that are of significant interest as targets for targeted therapy Activation of Toll-like receptors of neurophils and macrophages by the so-called PAMPs pathogen-associated molecular patterns - extracellular bacterial DNA lipopolysaccharides flagellin lipoteichoic acid peptidoglycan leads to changes in the transcription of genes involved in the regulation of the inflammatory response cellular metabolism with a significant release of cytokinessuch as IL-1 TNF-α IL-2 IL-6 IL-8 IL-10 IFN-γ and complement proteins
Extracorporeal therapy as an adjuvant method of treatment has been used for more than 30 years but conducting large randomized studies confirming its effectiveness is associated with a complex of problems including the extreme heterogeneity of the population of patients with sepsis and septic shock different etiologies and complex pathogenesis non-identical pathophysiological pathways of the dominant organ dysfunction in specific time period and degree of its severity
The strategy of using separate methods for extracorporeal elimination of LPS and cytokines yielded controversial results with an obvious association of endotoxemia and high concentrations of inflammatory mediators with mortality and severity of organ failure
According to a meta-analysis of Li X et al 2021 which included 13 RCTs LPS-selective hemoperfusion was associated with a decrease in mortality concentration and activity level of endotoxin and improved hemodynamic parameters The EUPHAS 2 trial showed the effect of LPS elimination on improvement in hemodynamics oxygenation and survival but the nature of the data collection was retrospective there was no control group and the study population was highly heterogeneous in the source of infection and severity of the condition The largest RCT EUPHRATES also confirmed an increase in mean arterial pressure and 28-day survival but only in patients with endotoxin activity levels in the range of 06-089 The ABDOMIX study did not demonstrate an effect of endotoxin adsorption on mortality and was associated with a large number of technical difficulties during extracorporeal treatment that affected the outcome
The use of plasma exchange as an integral technique that allows one to simultaneously eliminate both high-molecular toxins and mediators and medium-sized factors seems justified from the point of view of pathogenesis Many studies have shown a correlation of high VWF levels and low ADAMTS-13 activity in sepsis with mortality disease severity and the intensity of both systemic inflammation and disseminated intravascular coagulation There are similar data for other molecules the normalization of which by plasma exchange can potentially improve outcome - high levels of NETs IgA IgG d-dimer PAI-1 C3 and C4 factors of the complement system and conversely low levels of plasminogen fibrinogen antithrombin III protein C are associated with increased mortality But there is relatively little research on plasma exchange
Thus blood purification techniques used for sepsis certainly have a therapeutic effect it is assumed that their combined use will enhance it which will potentially improve treatment results
The need to influence different classes of molecules weight kinetics volume of distribution of both the immune system and the hemostatic system determines the choice of methods of combined extracorporeal therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None