Clinical Research Directory

Hamoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation

Sponsor: Moscow Multidisciplinary Clinical Center "Kommunarka"

Summary

The study will include patients aged 18 to 80 years with a verified diagnosis of septic shock according to SEPSIS 3 criteria, diagnosed within 12 hours, and a SOFA score of 9 or more. The minimum waiting time after diagnosis of septic shock and initiation of basic therapy before inclusion of the patient in the study therapy is 4 hours. In addition to Standard of Care (SOC), blood purification, including hemoadsorption, will be used. The choice of procedure will be based on the EAA (Endotoxin Activity Assay) result: * for an EAA level of 0.6-0.9, selective lipopolysaccharide (LPS) adsorption with duration from 2 to 10 hours; * for an EAA level less than 0.6, inflammatory mediator adsorption with duration from 6 to 12 hours. The choice of a specific adsorbers within the LPS and inflammatory mediator sorption group will be based on randomization. The use of LPS adsorption is planned based on randomization: Toramyxin R-20 or Efferon LPS. The use of inflammatory mediator adsorption is planned based on randomization: Jafron (HA 330) or CytoSorb. Every patient 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 patients (Efferon LPS in 19 patients and Toramyxin in 19 patients), two procedures per patient. Inflammatory mediator adsorption will be performed in 38 patients (Jafron HA 330 in 19 patients and CytoSorb in 19 patients), two procedures per patient. 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 patients 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 patients per group. Therefore, a minimum of 17 patients per group (34 patients 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 patients in total for LPS+ 38 patients in total for Inflammatory mediators adsorption. 76 patients in total).

Official title: Hamoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation. A Pilot Multicenter Randomized Controlled Trial

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