Extracorporeal cfDNA Removal in Septic Shock Patients With Elevated DNA Levels

Extracorporeal cfDNA Removal in Septic Shock Patients With Elevated DNA Levels.

modern medicine, associated with profound morbidity and high mortality rates. As a clinical syndrome characterized by a dysregulated systemic response to infection, its progression toward life-threatening organ dysfunction is driven by an array of signaling molecules. Extracorporeal therapy has emerged as a key adjunctive strategy for the targeted elimination of these inflammatory mediators. While current modalities - including non-selective cytokine adsorption, selective LPS-adsorption, and therapeutic plasma exchange (TPE) - have shown clinical benefits in specific patient cohorts, research into more precise interventions continues.

A new frontier focuses on the extracorporeal removal of cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), which recognized as pivotal drivers of systemic inflammation. This study evaluates the "Nucleocor" plasma adsorption column, a pioneering device designed for the selective removal of DNA-containing structures. By targeting septic shock patients with prognostically unfavorable cfDNA elevations, this research aims to establish standardized protocols and generate the evidence base necessary for integrating this novel therapy into national clinical guidelines.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Device: Extracorporeal therapy; Device: Extracorporeal elimination of cfDNA using "Nucleocore"

Detailed Description

Sepsis remains a critical problem with significant morbidity and mortality for a modern healthcare. According to the latest definitions, sepsis is a clinical syndrome defined by a systemic response to infection leading to organ failure. Recent breakthroughs in the pathophysiology of sepsis have identified key signaling molecules - including cytokines, toxins, and DAMPs - that initiate and perpetuate the dysregulated immune response. As an adjunctive treatment, extracorporeal therapy has emerged as an effective strategy for the targeted elimination of these mediators.

Current clinical and research methods include: non-selective hemoperfusion, which targets pro-inflammatory middle-molecular-weight proteins (10-60 kDa) such as s IL-1, TNF-α, IL-2, IL-6, IL-8, IL-10, IFN-γ and complement proteins (e.g., CytoSorb, HA330 hemadsorption cartridges); and selective hemoperfusion, designed to eliminate Gram-negative bacterial lipopolysaccharides (LPS) via affinity-binding fibers like Polymyxin B (e.g., Toraymyxin). A meta-analysis by Li et al. (2021), synthesizing data from 13 randomized controlled trials, demonstrated that LPS-selective hemoperfusion significantly reduces mortality and endotoxin levels while stabilizing hemodynamic parameters. The EUPHRATES trial, the largest RCT to date, demonstrated improvements in mean arterial pressure and 28-day survival exclusively within the subgroup of patients exhibiting endotoxin activity levels between 0.6 and 0.89.

Therapeutic Plasma Exchange (TPE) serves as an alternative adjunctive therapy that entails the complete separation and removal of the patient's plasma from cellular components, including cytokines and toxins. A recent EXCHANGE-1 study has demonstrated that TPE is associated with the reduction of acute-phase proteins and improved hemodynamics in patients with septic shock. The clinical potential of TPE in sepsis treatment remains a subject of active investigation.

A prominent frontier in sepsis research focuses on the novel approach extracorporeal removal of cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), which are now recognized as one more critical drivers of systemic inflammation. Excessive cell-free DNA (cfDNA) acts as DAMP, further activating immune cells and the endothelium through the TLR-9 (Toll-like receptor) signaling pathway. This process leads to cellular damage and microvascular thrombosis. Consequently, cfDNA serves as a primary driver of 'immunothrombosis' - a state of inflammation-induced hypercoagulation. Furthermore, cfDNA is implicated in the pathogenesis of sepsis-associated acute kidney and lung injury. These mechanisms provide a robust hypothetical framework for therapies targeting the extracorporeal elimination of cfDNA in septic shock.

Some hemoadsorption cartridges like 'Nucleocor' bind circulating histones to prevent them from triggering NETosis and systemic inflammation. To date, there are no universally accepted guidelines for the extracorporeal elimination of DNA-containing structures-such as cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs)-from the systemic circulation in sepsis and septic shock. This study will evaluate the efficacy and safety of extracorporeal therapy using 'Nucleocor' plasma adsorption columns in patients with septic shock characterized by prognostically unfavorable elevations in cfDNA levels. The 'Nucleocor' adsorption columns represent a unique, world-first device designed for the selective removal of DNA-containing molecular structures from the bloodstream. The project aims to establish a standardized protocol for this extracorporeal therapy and generate the evidence base required for its inclusion in national clinical guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sergey Savko; Phone Number: 89635156233; Email: d.t.d.savko@gmail.com
• Study Contact Backup: Name: Nikolai Krotenko, Cand. of Sci. (Med.); Email: npkrotenko@gmail.com

Study Locations

• Russia
  • Moscow, Russia
    • Moscow City Clinical Hospital named after S. S. Yudin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The age of patients is 18-65 years,
• Septic shock (Sepsis-3 criteria) with dependence on vasopressor and/ or sympathomimetic therapy (norepinephrine - more than 0.05 mcg / kg/min, adrenaline - more than 0.05 mcg / kg/min), persisting after correction of hypovolemia.
• concentration of cfDNA in the bloodstream is greater than its prognostically unfavorable level, determined by the fluorimetric method, or the presence of predictors of a prognostically unfavorable level of cfDNA: the concentration of mixed venous blood lactate is more than 1.9 mmol/l, the number of SOFA scores is more than 7

Exclusion Criteria:

• Clinical death after the onset of sepsis;
• An untreated surgical infection site;
• History of transfusion-related acute lung injury;
• Allergy to heparin, GIT in the anamnesis;
• Uncontrolled bleeding or a high risk of its occurrence,
• The presence of cardiovascular events within the last 2 months: AMI, stroke, PE, Severe congestive CHF;
• Severe chronic congestive heart failure;
• End-stage CKD;
• Chronic use of immunosuppressive therapy;
• HIV infection, Constant use of immunosuppressive therapy, severe granulocytopenia (WBC less than 500 cells /mm3),
• Development of acute cardiovascular insufficiency characterized by hypotension (BP system. less than 60 mmHg) and/or bradycardia (heart rate less than 40 min -1), refractory to adrenaline (bolus of more than 100 micrograms or infusion of more than 300 mcg/kg/min).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Baseline therapy; Baseline therapy Patients of group one received standard treatment according to Surviving Sepsis, according to the Clinical recommendations of the Ministry of Health of the Russian Federation - Sepsis (in adults)	Device: Extracorporeal therapy; Extracorporeal therapy - only in case of AKI - in HD/CVVHD format using standard polysulfone filters with a permeability of no more than 30 kDa
Other: Baseline therapy + Extracorporeal elimination of cfDNA; Baseline therapy + Extracorporeal elimination of cfDNA using "Nucleocore" (NPO "Pokcard")	Device: Extracorporeal therapy; Extracorporeal therapy - only in case of AKI - in HD/CVVHD format using standard polysulfone filters with a permeability of no more than 30 kDa; Device: Extracorporeal elimination of cfDNA using "Nucleocore"; Device: Efferon CT Extracorporeal cfDNA elimination will be performed according to the following protocol. Vascular access is established by inserting a 12 Fr, 200 mm catheter into the femoral vein. The procedures are conducted using the Spectra Optia system ("Exchange Set") with the following parameters: blood flow rate of 70-100 mL/min, plasma flow rate of 40-50 mL/min, and citrate anticoagulation (using a 4% sodium citrate solution) with an anticoagulant ratio of 1:20, in accordance with the Terumo "Plasmapheresis" procedure protocol. Monitoring of the patient's venous blood electrolytes and pH is performed hourly; hypocalcemia is managed via continuous infusion of a 10% calcium gluconate solution. Adsorption procedures for DNA-containing structures will be performed daily over two consecutive days, processing two total plasma volumes per session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cfDNA following the completion of extracorporeal therapy	Circulating cell-free DNA (cfDNA) levels in septic shock, measured via a fluorometric method (cobas® cfDNA Sample Preparation Kit), which enables the quantification of chromatin-containing molecular structures in the bloodstream	0-7 days
time to resolution of septic shock	Number of days to resolve the septic shock. A patient is given a value of 0 if they die before day 7 or are still remains in shock at day	0-7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation - Free Days	All days of life spent without mechanical ventilation. A patient is assigned a value of 0 if he or she dies before day 60 or continues to be on mechanical ventilation on day 60.	0-60 days
Duration of ICU stay	All days of life spent outside the intensive care unit within 60 days after inclusion in the study. A patient is given a value of 0 if they die before day 60 or are still receiving MV at day 60.	0-60 days
Changes in oxygenation index	The change in value of oxygenation index (Pa02 / Fi02) from baseline (hour 0) at the initiation of hemoperfusion to 48 hours post-treatment initiation. Oxygenation index (OI) is commonly used to assess the severity of hypoxic respiratory failure (HRF).	0-48 hours
SOFA score	Value of indicators on the Sequential Organ Failure Assessment (SOFA) Score. Each organ system received a score ranging from 0 (normal) to 4 (most abnormal), with a minimum SOFA score of 0 and a maximum SOFA score of 24. The change of SOFA score from baseline (hour 0) at the initiation of hemoperfusion to 48 hours post-treatment initiation.	0-48 hours

Collaborators and Investigators

• Sponsor: Sergey Savko

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: June 13, 2026
• First Submitted That Met QC Criteria: June 13, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 13, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: septic shock; sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic
• Other Study ID Numbers: № 0910-4/25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No