Extracorporeal cfDNA Removal in Septic Shock Patients With Elevated DNA Levels
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Extracorporeal therapy, Extracorporeal elimination of cfDNA using "Nucleocore".
- Who it may be relevant to
- Registry conditions: Sepsis. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Russia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Sepsis continues to be a major global health concern, characterized by high morbidity and 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 lipopolysaccharides 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 are 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.
Detailed description
Sepsis remains a critical challenge, associated with significant morbidity and mortality in modern healthcare. According to the latest definitions, sepsis is a clinical syndrome characterized by a dysregulated systemic response to infection that leads to organ failure. Recent breakthroughs in the pathophysiology of sepsis have identified key signaling molecules-including cytokines, toxins, and Damage-Associated Molecular Patterns (DAMPs)-that initiate and perpetuate this 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 modalities include non-selective hemoperfusion, which targets pro-inflammatory middle-molecular-weight proteins (10-60 kDa) such as Interleukin-1 (IL-1), Tumor Necrosis Factor-alpha (TNF-α), IL-2, IL-6, IL-8, IL-10, Interferon-gamma (IFN-γ), and complement proteins (e.g., CytoSorb and HA330 hemadsorption cartridges), and selective hemoperfusion, designed to eliminate Gram-negative bacterial lipopolysaccharides via affinity-binding fibers like Polymyxin B (e.g., Toraymyxin). A recent meta-analysis demonstrated that LPS-selective hemoperfusion significantly reduces mortality and endotoxin levels while stabilizing hemodynamic parameters. Furthermore, the EUPHRATES trial, the largest randomized controlled trial 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. TPE serves as an alternative adjunctive therapy that entails the complete separation and removal of the patient's plasma from cellular components, thereby eliminating cytokines and toxins. A recent EXCHANGE-1 study demonstrated that TPE is associated with a reduction in acute-phase proteins and improved hemodynamics in patients with septic shock. Thus, the clinical potential of TPE in sepsis treatment remains a subject of active investigation.
A prominent frontier in sepsis research focuses on the extracorporeal removal of cfDNA and NETs, which are now recognized as critical drivers of systemic inflammation. Excessive circulating cfDNA acts as a (DAMP, further activating immune cells and the endothelium through the Toll-like receptor 9 (TLR9) 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 injury (AKI) and acute lung injury (ALI). These mechanisms provide a robust pathophysiological framework for therapies targeting the extracorporeal elimination of cfDNA in septic shock. The Nucleocor plasma adsorption column pioneers a novel approach by targeting these circulating DNA-containing structures to halt the amplification of systemic inflammation. To date, there are no universally accepted guidelines for the extracorporeal elimination of DNA-containing structures-such as cfDNA and NETs-from the systemic circulation in sepsis and septic shock. This study will evaluate the efficacy and safety of extracorporeal therapy using the Nucleocor plasma adsorption column in patients with septic shock characterized by prognostically unfavorable elevations in cfDNA levels. Representing a world-first technology, the Nucleocor adsorber is uniquely designed for the selective removal of DNA-containing molecular structures from the bloodstream. Ultimately, this project aims to establish a standardized protocol for this extracorporeal therapy and generate the evidence base required for its subsequent inclusion in national clinical guidelines
Interventions
- 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: "Nucleocore" (NPO "Pokcard") 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 a
Primary outcome measures
- cfDNA following the completion of extracorporeal therapy [Time frame: at baseline and 72 hours post-hemosorption]
- Rate of septic shock resolution by Day 7 [Time frame: Up to Day 7]
Secondary outcome measures (12)
- 28-day mortality rate [Time frame: Day 28]
- Duration of ICU stay [Time frame: Up to 28 days (or through hospital discharge)]
- Number of ventilator-free days [Time frame: Up to 28 days]
- Number of renal replacement therapy (RRT)-free days [Time frame: Up to 28 days]
- SOFA score [Time frame: at baseline, 24, 48, and 72 hours post-hemosorption]
- Changes in oxygenation index [Time frame: at baseline, 24, 48, and 72 hours post-hemosorption]
- Change from baseline in Vasoactive-Inotropic Score (VIS) [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption]
- Change from baseline in inflammatory and tissue injury biomarkers [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption.]
- Change from baseline in hematological parameters [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption]
- Change from baseline in bilirubin levels [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption]
- Change from baseline in blood lactate levels [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption]
- Change from baseline in coagulation parameters and thromboelastography (TEG) indices [Time frame: Baseline, 24, 48, and 72 hours post-hemosorption]
Eligibility criteria
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).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
Russia · 1 center
- Moscow City Clinical Hospital named after S. S. Yudin — Moscow
Identifiers
NCT: NCT07657767 · № 0910-4/25