HOPE-Sepsis: Hemoadsorption Therapy for Sepsis

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and is associated with substantial morbidity and mortality in critically ill patients. Elevated circulating inflammatory mediators, including interleukin-6 (IL-6), are associated with disease severity and adverse clinical outcomes. Hemoadsorption is an extracorporeal blood purification approach in which whole blood passes through an adsorption cartridge to reduce circulating inflammatory mediators. Unlike plasma adsorption techniques, plasma separation is not required.

This single-center, prospective, single-arm study will enroll 30 adult patients with sepsis at Zhongshan Hospital, Fudan University. After screening and written informed consent, eligible participants will undergo baseline clinical assessment followed by hemoadsorption therapy using the CA330 Cytokine Adsorption Column. Blood samples will be collected at three prespecified time points: baseline before initiation of hemoadsorption (T0), immediately after completion of hemoadsorption (T1), and approximately 24 hours after completion of hemoadsorption (T2). IL-6 and other inflammatory biomarkers will be assessed at T0, T1, and T2. Exploratory TMT-based quantitative proteomics will be performed on plasma samples collected at T0 and T1 to characterize acute treatment-associated molecular changes.

Continuous renal replacement therapy (CRRT) and other organ-supportive treatments will be initiated according to routine clinical indications and standard ICU practice. CRRT is not required for study eligibility and, when used, will be recorded as concomitant therapy. Other treatments, including antimicrobial therapy, fluid resuscitation, vasopressors, mechanical ventilation, and additional organ support, will be provided according to the patient's clinical condition.

The primary outcome is the immediate change in plasma IL-6 concentration from the pre-hemoadsorption baseline (T0) to immediately after completion of hemoadsorption (T1). Secondary outcomes include the sustained change in IL-6 at approximately 24 hours (T2), changes in plasma proteomic profiles and other inflammatory biomarkers, Sequential Organ Failure Assessment (SOFA) scores, hemodynamic parameters, renal replacement therapy use, ventilator-free days, 28-day and 90-day all-cause mortality, ICU mortality, ICU length of stay, and hospital length of stay. Safety events associated with hemoadsorption, including bleeding, infection, and hypotension, will also be recorded.

The planned sample size is 30 participants. The sample size was determined based on an expected 30% within-participant reduction in IL-6 after hemoadsorption, with a two-sided alpha of 0.05 and statistical power of 80%, while allowing for participant dropout, specimen quality issues, and variability in IL-6 levels among patients with sepsis.

Within-participant changes in continuous variables will be assessed using paired statistical methods, including paired t-tests or Wilcoxon signed-rank tests, as appropriate. Plasma proteomic data will be analyzed to identify treatment-associated protein changes and associated biological pathways using pathway enrichment and protein-interaction analyses. Relationships between proteomic changes and clinical parameters will be explored using correlation analyses.

Participants will be followed during the index hospitalization and through Day 90 after enrollment. All-cause mortality will be assessed at Day 28 and Day 90.