Hamoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation (HAdSS)

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Device: CytoSorb; Device: Jafron HA 330; Device: Toramyxin PMX 20R; Device: Efferon LPS

Detailed Description

Study Inclusion Algorithm

1. Diagnosis of septic shock.
2. SOFA score calculation.
3. Definition of inclusion/exclusion criteria.
4. Obtaining informed consent.
5. Determining EAA. Selecting the procedure modality (LPS adsorption/inflammatory mediator adsorption).
6. Database registration. Obtaining randomization data.
7. Selecting a specific device based on randomization.
8. Initial data collection.
9. Initiating the first procedure.

When a patient is enrolled in the study and is ready to begin the hemoadsorption procedure, the following parameters are assessed:

1. Dose of norepinephrine (mcg/kg/min).
2. Dose of alternative vasopressors: epinephrine (mcg/kg/min), dopamine (mcg/kg/min), phenylephrine (mcg/kg/min), dobutamine (mcg/kg/min), terlipressin (mcg/kg/min). VIS will be calculated.
3. Mean arterial pressure (MAP) based on invasive hemodynamic monitoring.
4. Fractional oxygen content (%).
5. Diuresis rate over 12 hours (ml/kg/hour).

Blood sampling:

1. Arterial blood acid-base balance:

   • Arterial blood lactate level (mmol/L).
   • PaO2- Partial pressure of oxygen in arterial blood (mmHg).

2. Blood chemistry panel:

   • Total bilirubin level (μmol/L).
   • Direct bilirubin level (μmol/L).
   • Indirect bilirubin level (μmol/L).
   • Procalcitonin level (ng/ml).
   • C-reactive protein (CRP) level (mg/L).
   • Creatinine level (μmol/L).
   • Ferritin level (μg/L).

3. Complete blood count White blood cell count

   • Absolute neutrophil count (cells/µL).
   • Absolute lymphocyte count (cells/µL).
   • Absolute platelet count (10.9 /L).
4. Blood collection for immunological testing (IL 6, IL 10, TNF).

Upon patient enrollment in the study, a description of the CRRT procedure parameters, dialysis membrane type, anticoagulation type, antibacterial agents, and suspected infectious agents is provided in the electronic patient record.

Data collection will occur at 24, 48, 72, and 120 hours from the start of the first hemoadsorption procedure.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aleksandr Burov, PHD; Phone Number: +79854215478; Email: Aleksander.bour@mail.ru

Study Locations

• Russia
  • Moscow, Russia
    • Petrovsky National Research Centre of Surgery
    • Contact: Maxim Babaev, MD, PHD; Phone Number: +79160269066; Email: maxbabaev@mail.ru
  • Moscow, Russia
    • Bakulev Scientific Center of Cardiovascular Surgery
    • Contact: Mikhail Yarustovskiy, MD, PHD; Phone Number: +79104194682; Email: mbyar@yandex.ru
  • Moscow, Russia
    • City clinical hospital named after S. S. Yudin, Moscow City Health
    • Contact: Nikolay Krotenko, PHD; Phone Number: +79268664976; Email: npkrotenko@gmail.com
  • Moscow, Russia
    • City Clinical Hospital No 52, Moscow, Russia
    • Contact: Rustam Iskhakov; Phone Number: +79265317813; Email: stamius@yandex.ru
  • Moscow, Russia
    • Moscow Multi-disciplinary Clinical Center "Kommunarka"
  • Moscow, Russia
    • Sklifosovsky Institute of Emergency Care
    • Contact: Sergei Rei, PHD; Phone Number: +79166001362; Email: reysi@sklif.mos.ru
  • Rostov-on-Don, Russia
    • National Medical Research Centre for Oncology Rostov-on-Don
    • Contact: Natalia Ushakova, MD, PHD; Phone Number: +79185533155; Email: ndu2000@rambler.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Septic shock according to SEPSIS-3 criteria
• Age: 18-80 years
• SOFA ≥9 points
• Diagnosis of septic shock established <12 hours ago
• Invasive hemodynamic monitoring
• Norepinephrine dose >0.2 mcg/kg/min

Exclusion Criteria:

• Absolute neutrophil count less than 500 cells/μL
• Pregnancy
• End-stage heart failure (NYHA stage IV)
• Pulmonary embolism with obstructive shock
• Ongoing bleeding
• Atonic coma
• More than 30 points on the MELD scale, class C on the Child-Pugh scale
• HIV infection
• Burns over 10% of the body surface area
• Patients with oncohematological diseases
• Patients with a recognized palliative status or the definition of "metastatic cancer"
• RRT using membranes with a high cutoff point and increased adsorption capacity within 72 hours from the initiation of the first hemoadsorption procedure
• Use of plasma exchange within 72 hours from the initiation of the first hemoadsorption procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inflammatory mediatiors adsorption with CytoSorb; Inflammatory mediatiors adsorption with EAA <0,6 with CytoSorb	Device: CytoSorb; Blood purification with Jafron HA 330
Active Comparator: Inflammatory mediatiors adsorption with Jafron HA 330; Inflammatory mediatiors adsorption with EAA <0,6 with Jafron HA 330	Device: Jafron HA 330; Blood purification with Jafron HA 330
Experimental: Endotoxin haemoadsorption with Toramyxin PMX 20R; Endotoxin haemoadsorption with EAA [0.6-0.9] with Toramyxin PMX 20R	Device: Toramyxin PMX 20R; Blood purification with Toramyxin PMX 20R
Active Comparator: Endotoxin haemoadsorption with Efferon LPS; Endotoxin haemoadsorption with EAA [0.6-0.9] with Efferon LPS	Device: Efferon LPS; Blood purification with Efferon LPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SOFA score	MODS dynamics majored by SOFA (sequential organ failure assessment) score	Assessed at 72 hours after hemoadsorption initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VIS dynamics	Vasoactive Inotropic Score (VIS) dynamics VIS = dopamine dose (mcg∕kg∕ min ) + dobutamine dose (mcg∕kg∕ min ) + 100 × epinephrine dose (mcg∕kg∕ min ) + 10 × milrinone dose (mcg∕kg∕ min ) + 10,000 × vasopressin dose (units∕kg∕ min ) + 100 × norepinephrine dose (mcg∕kg∕ min )	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
NE dose dynamics	Norepinephrine dose dynamics (mcg/kg/min)	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
MAP/VIS dynamics	Mean arterial pressure (MAP) to Vasoactive Inotropic Score (VIS) dynamics VIS = dopamine dose (mcg∕kg∕ min ) + dobutamine dose (mcg∕kg∕ min ) + 100 × epinephrine dose (mcg∕kg∕ min ) + 10 × milrinone dose (mcg∕kg∕ min ) + 10,000 × vasopressin dose (units∕kg∕ min ) + 100 × norepinephrine dose (mcg∕kg∕ min )	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
P/f ratio dynamics	Arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio (Horowitz index) dynamics	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
Lactate level dynamics	Lactate level dynamics (mmol/l)	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
Total bilirubin level dynamics	Total bilirubin level dynamics (mcmol/l)	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
Indirect bilirubin level dynamics	Indirect bilirubin level dynamics (mcmol/l)	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	Direct bilirubin level dynamics (mcmol/l)	Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
Ferritin level dynamics	Ferritin level dynamics (mcg/l)	Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
PCT level dynamics	Procalcitonin (PCT) level dynamics (ng/ml)	Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
CRP level dynamics	C- reactive protein (CRP) level dynamics (mg/l)	Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
NLR dynamics	NLR (neutrophil-to-lymphocyte ratio) dynamics	Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
PLR dynamics	PLR (Platelet-to-lymphocyte ratio) dynamics	Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation
TNF level dynamics	TNF (Tumor necrosis factor-alpha) level dynamics (pg/ml)	Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
IL 6 level dynamics	IL 6 (Interleukin 6) level dynamics (pg/ml)	Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
IL 10 level dynamics	IL 10 (Interleukin 10) level dynamics (pg/ml)	Time Frame: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation
28 - days mortality	28 - days mortality	Will be calculated for 28 days after hemoadsorption initiation
90 - days mortality	90 - days mortality	Will be calculated for 90 days after hemoadsorption initiation
SOFA dynamics	MODS dynamics majored by SOFA (sequential organ failure assessment) score	Assessed at 4 time points: before hemoadsorption initiatioin (baseline); at 24, 48 and 120 hours after hemoadsorption initiation
SOFA 2 dynamics	MODS dynamics majored by SOFA 2 (sequential organ failure assessment) score	Assessed at 5 time points: before hemoadsorption initiatioin (baseline); at 24, 48, 72 and 120 hours after hemoadsorption initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days	Ventilator-free days	Will be calculated for 28 days after hemoadsorption initiation
Vasopressor-free days	Vasopressor-free days	Will be calculated for 28 days after hemoadsorption initiation
Dialysis-free days	Dialysis-free days	Will be calculated for 28 days after hemoadsorption initiation
Hospital length of stay	Hospital length of stay	Will be calculated for 28 days after hemoadsorption initiation
ICU length of stay	Intensive care unit (ICU) length of stay	Will be calculated for 28 days after hemoadsorption initiation
AEs	The safety will be assessed by analysing the number of adverse events (AEs) where causal relationship with the intervention cannot be excluded, up until Day 28.	Serious AEs will be reported up to Day 28

Collaborators and Investigators

• Sponsor: Moscow Multidisciplinary Clinical Center "Kommunarka"
• Collaborators: Petrovsky National Research Centre of Surgery; Sklifosovsky Institute of Emergency Care; Bakulev Scientific Center of Cardiovascular Surgery; City clinical hospital named after S. S. Yudin, Moscow City Health; City Clinical Hospital No 52, Moscow, Russia; Rostov Regional Clinical Hospital
• Investigators: Study Director: Denis Protsenko, MD, PHD, Moscow Multi-disciplinary Clinical Center "Kommunarka"

Publications and helpful links

General Publications

• Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009 Jun 17;301(23):2445-52. doi: 10.1001/jama.2009.856.
• Onuk S, Akin AK, Sari A, Gundogan K, Baskol G, Dogru K, Sungur M. The Clinical and Laboratory Efficacy of HA 330 Treatment Combined with Continuous Renal Replacement Therapy in Septic Shock Patients: A Case Series. Blood Purif. 2023;52(2):140-147. doi: 10.1159/000528150. Epub 2023 Jan 12.
• Mehta Y, Mehta C, Kumar A, George JV, Gupta A, Nanda S, Kochhar G, Raizada A. Experience with hemoadsorption (CytoSorb(R)) in the management of septic shock patients. World J Crit Care Med. 2020 Jan 31;9(1):1-12. doi: 10.5492/wjccm.v9.i1.1. eCollection 2020 Jan 31.
• Rey S, Kulabukhov VM, Popov A, Nikitina O, Berdnikov G, Magomedov M, Kim T, Masolitin S, Ignatenko O, Krotenko N, Marysheva A, Chaus N, Ohinko L, Mendibaev M, Chumachenko A, Pisarev V. HEMOPERFUSION USING THE LPS-SELECTIVE MESOPOROUS POLYMERIC ADSORBENT IN SEPTIC SHOCK: A MULTICENTER RANDOMIZED CLINICAL TRIAL. Shock. 2023 Jun 1;59(6):846-854. doi: 10.1097/SHK.0000000000002121. Epub 2023 Apr 6.
• Klein DJ, Foster D, Walker PM, Bagshaw SM, Mekonnen H, Antonelli M. Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial. Intensive Care Med. 2018 Dec;44(12):2205-2212. doi: 10.1007/s00134-018-5463-7. Epub 2018 Nov 23.

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Septic shock; Endotoxemia; MODS; blood purification; hemoadsorption
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Bacteremia; Toxemia; Pathological Conditions, Signs and Symptoms; Shock, Septic; Multiple Organ Failure; Endotoxemia
• Other Study ID Numbers: HAdSS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in the primary publication (including baseline characteristics, blood purification parameters, hemodynamics and SOFA score dynamics, clinical outcomes) will be made publicly available to ensure absolute transparency and academic reproducibility.
• IPD Sharing Time Frame: Data will become available immediately following the official publication of the primary trial results, approximately at 12/2027.
• IPD Sharing Access Criteria: The dataset will be openly accessible to any researcher, clinician, or analyst interested in replicating the study findings, conducting systematic reviews, or performing secondary meta-analyses. The data will be hosted publicly, and no formal research proposal review or data use agreements are required for access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No