Clearance of Antibacterial Agents During Hemoperfusion in Patients With Sepsis

Recruiting

• Conditions: Sepsis; Septic Shock

• Registration Number: NCT06602245
• Lead Sponsor: Efferon JSC

Brief Summary

One of the significants health problems in the world is sepsis, with the number of cases reaching 20-30 million per year, according to the WHO. Numerous studies have shown that the use of extracorporeal methods improves outcomes in patients with septic shock. Safety parameters are particularly important in deciding whether to initiate such therapy in a patient. To date, numerous post-marketing observations and data from the published literature have shown no serious adverse hemoperfusion events, with the exception of occasional thrombocytopenia. However, the potential removal of life-saving drugs, such as antibiotics, by hemoperfusion in patients with sepsis remains poorly understood and requires special attention.

The main objective of this study is to evaluate the incremental increase in total clearance of antibacterial drugs during haemoperfusion using the Efferon LPS device in patients with sepsis.

Detailed Description

Sepsis is a major public health problem worldwide, with 20-30 million cases per year according to the WHO. Lipopolysaccharide adsorption is used for the rapid resolution of the severe symptom complex associated with sepsis and septic shock. To date, numerous post-approval observations and data from the published literature have shown no serious adverse hemoperfusion events, except for occasional thrombocytopenia. At the same time, it is very important in the treatment of sepsis to start antibacterial drugs as early as possible, and the effect of lipopolysaccharide and cytokine adsorption on the clearance of antibacterial drugs remains poorly understood.

Little is known about the effects of modern sorption devices on the pharmacokinetics of antimicrobial drugs. The results obtained in animals and reports of single patient studies, as well as the results of in vitro studies, cannot be extrapolated to the general population of sepsis patients receiving hemoperfusion for the underlying disease. The observations need to be confirmed in clinical trials in patients with sepsis and septic shock in order to develop appropriate recommendations for dose adjustment of the antibacterial drugs used.

The present study in patients with sepsis and/or septic shock is designed to determine the effect of lipopolysaccharide adsorption using the Efferon LPS device on the pharmacokinetics of several antimicrobial agents (meropenem, vancomycin and linezolid).

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-16
• Study First Submitted QC: 2024-09-16
• Study First Posted: 2024-09-19
• Study Start: 2024-10-21
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-14
• Primary Completion: 2025-09-30
• Study Completion: 2026-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patient weight greater than 40 kg.
• Diagnosis of sepsis and/or septic shock according to CEPSIS-3 criteria (2016), presumed (at time of enrolment) to be of Gram-negative aetiology, requiring, in the opinion of the investigator, isolated lipopolysaccharide hemoperfusion.

Exclusion Criteria

• Failure to obtain informed consent from the patient, family member or legal representative.
• Any patient condition requiring other methods of renal replacement therapy (e.g. hemodialysis, hemofiltration, hemodiafiltration).
• Pregnancy, breastfeeding period.
• General contraindications to extracorporeal treatments.
• Any other condition that, in the opinion of the investigator, would prevent the patient from being a suitable candidate for inclusion in the study (e.g. terminal chronic disease).
• Development of an adverse event, including a serious adverse event; individual intolerance to the investigational product, hypersensitivity to the components of the product due to which further participation in the study is not possible.
• Continued participation in the study is not, in the opinion of the investigator, in the best interests of the patient's health.
• The patient, in the opinion of the investigator, fails to comply with the requirements of the study procedures.
• The presence of protocol deviations that, in the opinion of the Sponsor and the investigator, require withdrawal of the participant from the study.
• A positive pregnancy test result at any time during the study.
• Use of any other methods of renal replacement therapy and extracorporeal hemocorrection during isolated hemoperfusion with the Efferon LPS device.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adsorption clearance of antibacterial drugs by the Efferon LPS	During hemoperfusion with Efferon LPS	Adsorption сlearance of antibacterial drugs by the Efferon LPS device, mL/min

Secondary Outcome Measures

Name	Time	Method
Total clearance of antibacterial drugs during haemoperfusion with the Efferon LPS	During hemoperfusion with Efferon LPS	Total clearance of antibacterial drugs (adsorption clearance + patient system clearance), mL/min
Contribution of adsorption clearance to the total clearance of antibacterial drugs	During hemoperfusion with Efferon LPS	Efferon LPS device adsorption clearance relative to total clearance, %

Trial Locations

Locations (4)

N. V. Sklifosovsky Moscow Research Institute of Emergency; 🇷🇺 Moscow, Russian Federation

Perm regional clinical hospital; 🇷🇺 Perm, Russian Federation

N.I. Pirogov City Clinical Hospital No. 1; 🇷🇺 Moscow, Russian Federation

Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko; 🇷🇺 Nizhny Novgorod, Russian Federation