Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation

Every participant will receive 2 adsorption procedures. The second procedure will be initiated no later than 24 hours after the initiation of the first procedure.

LPS adsorption will be performed in 38 participants (Efferon LPS in 19 participants and Toramyxin in 19 participants), two procedures per participant.

Inflammatory mediator adsorption will be performed in 38 participants (Jafron HA 330 in 19 participants and CytoSorb in 19 participants), two procedures per participant.

Sample size calculations were performed separately for each treatment cohort. For the endotoxemia cohort (EAA level of 0.6-0.9), this randomized trial is designed to compare Efferron LPS and Toraymyxin with respect to change in SOFA score at 72 hours.

At present, no universally accepted minimal clinically important difference (MCID) has been established for the SOFA score in participants with septic shock. Therefore, the assumed treatment effect was derived from published evidence and expert clinical judgment.

In the EUPHAS trial, polymyxin B hemoperfusion was associated with a mean reduction in SOFA score of approximately 3.4 points at 72 hours, whereas minimal change was observed in the control group. Similarly, the LASSO study demonstrated substantial improvement in organ dysfunction following endotoxin adsorption therapy.

For the inflammatory mediator adsorption cohort (EAA level less than 0.6), this randomized trial is designed to compare CytoSorb and Jafron HA 330 with respect to change in SOFA score at 72 hours.

In the retrospective study Mehta et al., CytoSorb hemoperfusion was associated with a mean reduction in SOFA score of approximately 2.0 points after treatment in survival group. Similarly, the case series Onuk et al. demonstrated substantial improvement in organ dysfunction following inflammatory adsorption therapy with Jafron HA 330 with a mean reduction in SOFA score of approximately 3.5 points at 72 hours.

A between-group difference of 2.5 SOFA points was considered clinically meaningful for both Endotoxin hemoadsorption and inflammatory mediators hemoadsorption because it represents a substantial proportion of the treatment effect observed in previous hemoperfusion studies and corresponds to a clinically relevant difference in the degree of organ dysfunction improvement.

The sample size for both groups (LPS and inflammatory mediator adsorption) was calculated based on the following assumption: the primary endpoint was the change in SOFA score at 72 hours (ΔSOFA); the expected between-group difference - 2.5 points on the SOFA score; standard deviation of ΔSOFA - 2.5 points; equal allocation ratio (1:1); two-sided significance level (α) of 0.05; statistical power of 80%.

Sample size estimation was performed in R using the power.t.test() function. The calculation yielded a required sample size of 16.7 participants per group. Therefore, a minimum of 17 participants per group (34 participants in total) is required to achieve the planned statistical power.

To account for an anticipated 10% dropout rate, the final sample size will be 19 patients per group (38 participants in total for LPS+ 38 participants in total for Inflammatory mediators adsorption. 76 participants in total).

• Vasoactive Inotropic Score (VIS) dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Norepinephrine dose dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Hemodynamic index dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Horowitz index dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Lactate level dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Total bilirubin level dynamics [Срок оценки: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Indirect bilirubin level dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Direct bilirubin level dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Ferritin level dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• Procalcitonin (PCT) level dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• C- reactive protein (CRP) level dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]
• NLR (neutrophil-to-lymphocyte ratio) dynamics [Срок оценки: Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation]