Standard Medical Therapy according to local protocols based on the current international 'Surviving Sepsis Campaign' guidelines.

Arterial blood concentrations of glypican-1, heparan sulfate, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin/CD62E), and soluble P-selectin (sP-selectin) will be measured in ng/mL. For each biomarker, the change from baseline (T0) will be calculated at each post-baseline assessment. Results will be reported separately for each biomarker; no composite score will be calculated.

Arterial blood concentrations of monocyte chemoattractant protein-1/C-C motif chemokine ligand 2 (MCP-1/CCL2) and vascular endothelial growth factor (VEGF) will be measured in pg/mL. For each biomarker, the change from baseline (T0) will be calculated at each post-baseline assessment. Results will be reported separately for each biomarker; no composite score will be calculated.

Expression of miR-126, miR-92a, miR-155, miR-21, and miR-23a will be measured in arterial blood samples by quantitative reverse-transcription polymerase chain reaction and reported as quantification cycle (Cq) values. For each microRNA, change from baseline at each post-baseline time point will be calculated as the Cq value at that time point minus the corresponding Cq value at baseline (T0). Results will be analyzed and reported separately for each microRNA; no composite or aggregated microRNA score will be calculated. Hemolyzed samples will be excluded from the microRNA analyses.

Arterial lactate concentration will be measured in arterial blood samples and reported in mmol/L. at each post-baseline time point will be calculated as the arterial lactate concentration at that time point minus the arterial lactate concentration at baseline (T0). Changes at each time point will be reported separately.

Procalcitonin (PCT) concentration will be measured in arterial blood samples and reported in ng/mL. For each participant, change from baseline at each post-baseline time point will be calculated as the PCT concentration at that time point minus the PCT concentration at baseline (T0). Changes at each time point will be reported separately.

C-reactive protein (CRP) concentration will be measured in arterial blood samples and reported in mg/L. For each participant, change from baseline at each post-baseline time point will be calculated as the CRP concentration at that time point minus the CRP concentration at baseline (T0). Changes at each time point will be reported separately.

White blood cell count (WBC) will be measured in arterial blood samples and reported in G/L. For each participant, change from baseline at each post-baseline time point will be calculated as the WBC count at that time point minus the WBC count at baseline (T0). Changes at each time point will be reported separately.

Ferritin concentration will be measured in arterial blood samples and reported in ng/mL. For each participant, change from baseline at each post-baseline time point will be calculated as the ferritin concentration at that time point minus the ferritin concentration at baseline (T0). Changes at each time point will be reported separately.

Tumor necrosis factor alpha (TNF-α) concentration will be measured in arterial blood samples and reported in pg/mL. For each participant, change from baseline at each post-baseline time point will be calculated as the TNF-α concentration at that time point minus the TNF-α concentration at baseline (T0). Changes at each time point will be reported separately.

Interleukin-1 beta (IL-1β) concentration will be measured in arterial blood samples and reported in pg/mL. For each participant, change from baseline at each post-baseline time point will be calculated as the IL-1β concentration at that time point minus the IL-1β concentration at baseline (T0). Changes at each time point will be reported separately.

Interleukin-8 (IL-8) concentration will be measured in arterial blood samples and reported in pg/mL. For each participant, change from baseline at each post-baseline time point will be calculated as the IL-8 concentration at that time point minus the IL-8 concentration at baseline (T0). Changes at each time point will be reported separately.

Extravascular Lung Water Index willl be measured using invasive hemodynamic monitoring and reported in ml/kg. Change from baseline at each post-baseline time point will be calculated as the EVLWI at that time point minus the EVLWI at baseline

The Vasoactive-Inotropic Score (VIS) quantifies the amount of cardiovascular support a patient receives through vasoactive and inotropic medications. The VIS is calculated as: VIS = dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10 × vasopressin (U/kg/min) at each time point. Higher score indicates worse outcome. VIS at each post-baseline time point will be calculated as the VIS at that time point minus the VIS at baseline (T0). Changes at each time point will be reported separately.

Daily fluid balance will be calculated for each 24-hour period as total fluid intake minus total fluid output. Negative values indicate that fluid output exceeded fluid intake during the corresponding 24-hour period. Daily fluid balance will be reported in mL at each assessment day.

Time to first negative daily fluid balance will be calculated as the time from T0 to the end of the first 24-hour assessment period during which total fluid output exceeds total fluid intake, corresponding to a daily fluid balance of less than zero. Time will be reported in days. Participants who do not achieve a negative daily fluid balance by Day 28 will be censored at Day 28.

Cumulative fluid balance will be calculated as the sum of fluid intake minus fluid output from T0 through each assessment time point. Negative values indicate that cumulative fluid output exceeded cumulative fluid intake since T0. Cumulative fluid balance will be reported in mL at each assessment day.

Time to first negative cumulative fluid balance will be calculated as the time from T0 to the first assessment at which cumulative fluid output since T0 exceeds cumulative fluid intake since T0, corresponding to a cumulative fluid balance of less than zero. Time will be reported in days. Participants who do not achieve a negative cumulative fluid balance by Day 28 will be censored at Day 28.

Vasopressor-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from vasopressor treatment. A day will be counted as vasopressor-free only when no vasopressor is administered during that day. The possible range is 0 to 28 days, with higher values indicating more days alive without vasopressor support.

Mechanical ventilation-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from mechanical ventilation. A day will be counted as ventilation-free only when no mechanical ventilation is provided during that day. The possible range is 0 to 28 days, with higher values indicating more days alive without mechanical ventilatory support.

Continuous renal replacement therapy (CRRT)-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from CRRT. A day will be counted as CRRT-free only when no CRRT is administered during that day. The possible range is 0 to 28 days, with higher values indicating more days alive without CRRT.

Intensive Care Unit (ICU) length of stay will be calculated as the elapsed time in days from ICU admission to ICU discharge or death in the ICU, whichever occurs first. Participants who remain in the ICU on Day 28 will be censored at Day 28.

ICU survival, hospital survival, and 28-day survival will be recorded separately as alive/deceased status at ICU discharge, hospital discharge, and Day 28 after randomization. Results will be reported as proportions of participants surviving at each time point.

Adverse events, serious adverse events, and device deficiencies will be recorded from baseline through Day 28. Events will be summarized by incidence, event type, severity, relationship to the study device or procedure, outcome, and seriousness.