Clinical trial NCT06602245: Clearance of Antibacterial Agents During Hemoperfusion in Patients With Sepsis
Official title: Multicenter Observational Prospective Open Pilot Study of Changes in the Total Clearance of Antibacterial Agents During Hemoperfusion Using Efferon LPS in Patients With Sepsis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sepsis
Septic Shock
Keywords: Sepsis
Septic shock
Antibiotic clearance
Hemoperfusion
Extracorporeal therapy
Lipopolysaccharide sorption
Lead sponsor: Efferon JSC
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The expected number of study subjects is 30 adult patients with sepsis and/or septic shock (presumably of Gramnegative aetiology and any localisation).

It is planned to recruit :

* 10 patients receiving meropenem
* 10 patients receiving vancomycin
* 10 patients receiving linezolid. Patients may receive more than one of these antibiotics at the same time, in which case they will be included in several subpopulations of the study.

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).

Eligibility criteria: 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\&amp;amp;#39;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.

Primary outcomes:
measure: Adsorption clearance of antibacterial drugs by the Efferon LPS
timeFrame: During hemoperfusion with Efferon LPS
Secondary outcomes:
measure: Total clearance of antibacterial drugs during haemoperfusion with the Efferon LPS
timeFrame: During hemoperfusion with Efferon LPS
measure: Contribution of adsorption clearance to the total clearance of antibacterial drugs
timeFrame: During hemoperfusion with Efferon LPS
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: N. V. Sklifosovsky Moscow Research Institute of Emergency
city: Moscow
country: Russian Federation
facility: N.I. Pirogov City Clinical Hospital No. 1
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
city: Perm
country: Russian Federation
facility: Perm regional clinical hospital
Study officials:
affiliation: N. V. Sklifosovsky Moscow Research Institute of Emergency, Moscow, Russia
name: Sergey Rey, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: