Extracorporeal cfDNA Removal in Septic Shock Patients With Elevated DNA Levels

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

• 28-day mortality rate [Срок оценки: Day 28]
• Duration of ICU stay [Срок оценки: Up to 28 days (or through hospital discharge)]
• Number of ventilator-free days [Срок оценки: Up to 28 days]
• Number of renal replacement therapy (RRT)-free days [Срок оценки: Up to 28 days]
• SOFA score [Срок оценки: at baseline, 24, 48, and 72 hours post-hemosorption]
• Changes in oxygenation index [Срок оценки: at baseline, 24, 48, and 72 hours post-hemosorption]
• Change from baseline in Vasoactive-Inotropic Score (VIS) [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption]
• Change from baseline in inflammatory and tissue injury biomarkers [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption.]
• Change from baseline in hematological parameters [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption]
• Change from baseline in bilirubin levels [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption]
• Change from baseline in blood lactate levels [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption]
• Change from baseline in coagulation parameters and thromboelastography (TEG) indices [Срок оценки: Baseline, 24, 48, and 72 hours post-hemosorption]