Effect of Extracorporeal Adsorption of Plasma Neutrophil Extracellular Traps (NET) in Sepsis

Study Overview
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Brief Summary
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This open non-randomized controlled single center study investigates to what extent the removal of circulating Neutrophil Extracellular Traps (NETs) from blood by NucleoCapture device has a positive effect on the treatment of patients with sepsis and sepsis-associated AKI (SA-AKI).

Detailed Description
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The term sepsis refers to a clinical syndrome in which a dysregulation of the host's inflammatory reaction to infection leads to a life-threatening of organ dysfunctions. Sepsis and septic shock are major causes of death in intensive care units worldwide. Sepsis remains the most important cause of AKI in the intensive care unit (ICU) with 15%-20% of patients with sepsis-associated AKI (SA-AKI) prescribed RRT . In addition to association with short term mortality, AKI is also linked to the later development of CKD, ESRD, and long-term increased risk of death NETosis is a unique form of neutrophil cell death that is characterized by the release of neutrophil extracellular traps (NETs) composed of DNA web-like structures decorated with highly cytotoxic protein components. Release of NETs leads to bystander tissue damage (including the kidneys) and drives a fatal course of disease in sepsis patients. The plasmapheresis is a medical procedure, where pathogenic components are being removed from the blood by adsorbers outside the body in an extracorporeal circulation. For removal of the pathogenic substances the plasma is separated from the blood to pass the adsorber. The purified plasma is merged with the solid blood components thereafter and returned to the patient. The NucleoCapture device provide highly selective removal of neutrophil extracellular traps from human blood during plasmapheresis procedure.

Official Title
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Safety and Efficacy Assessment of NucleoCapture Selective DNA Adsorber in Humans

Conditions
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Sepsis, Sepsis-associated AKI

Intervention / Treatment
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* Device: NucleoCapture device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 and ≤ 75 years of age. Meet the clinical criteria of sepsis according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)) Written informed consent Exclusion Criteria: A terminal state Active bleeding or uncontrolled acute massive bleeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with NucleoCapture device<br>Device: 100 ml NucleoCapture selective DNA adsorber. Treatment with NucleoCapture in one arm. | Device: NucleoCapture device<br>* Device: 100 ml NucleoCapture selective DNA adsorber. Treatment with NucleoCapture in one arm<br>* Other names: NucleoCapture selective DNA adsorber;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute kidney injury (AKI) | Incidence of acute kidney injury (AKI) in accordance with Kidney Disease Improving Global Outcomes (KDIGO) definitions for AKI | from [start of treatment] through 28 days after | 
| Severity of acute kidney injury (AKI) | Severity of acute kidney injury (AKI) in accordance with KDIGO definitions for AKI | from [start of treatment] through 28 days after | 
| Rate of AKI transition to the more severe stage (for patients with AKI at baseline). | Rate of worsening of acute kidney injury (AKI) in accordance with KDIGO AKI classification (Changing stages from 1 to 2, from 2 to 3). | from [start of treatment] through 28 days after | 
| Serum creatinine change over time | Change of creatinine in serum over time for each patient and in average in group | from [start of treatment] through 28 days after | 
| Serum urea change over time | Change of urea in serum over time for each patient and in average in group | from [start of treatment] through 28 days after | 
| Urine output change | Change of urine output over time for each patient and in average in group | from [start of treatment] through 28 days after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Mortality for any reasons for each patient and in average in group | from [start of treatment] through 28 days after | 
| SOFA scores change | Change in SOFA scores over time for each patient and in average in group | from [start of treatment] through 28 days after | 
| qSOFA scores change | Change in qSOFA scores over time for each patient and in average in group | from [start of treatment] through 28 days after |