Efficacy and Safety of Hemoperfusion With Polymyxin B in Septic Shock Associated With Severe Endotoxemia in Cardiac Surgery Patients (РМХ vs SS) (РМХ vs SS)
Primary Purpose
Multiple Organ Dysfunction With Severe Endotoxemia
Status
Recruiting
Phase
Not Applicable
Locations
Russian Federation
Study Type
Interventional
Intervention
hemoperfusion with polymyxin B
Sponsored by
About this trial
This is an interventional prevention trial for Multiple Organ Dysfunction With Severe Endotoxemia focused on measuring test EAA, endotoxemia, hemoperfusion with Polymyxin B, cardiac syrgery
Eligibility Criteria
Inclusion Criteria:
- SOFA +2 points in comparison with the previous assessment; РСТ more than 2 ng / ml; CRP more than 150 ng / ml; norepinephrine infusion; intestinal paresis; positive data of blood culture; ЕАА more than 0,6
Exclusion Criteria:
- bleeding; heparin-induced thrombocytopenia
Sites / Locations
- Petrovsky National Reasearch Centre of SurgeryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
cardiac surgery patients with multiple organ dysfunction
cardiac surgery patients
Arm Description
hemoperfusion procedure with polymyxin B will be performed for 12 hours
without hemoperfusion with polymyxin B
Outcomes
Primary Outcome Measures
endotoxin activity level
frequency of cases of decrease in EAA below 0.6
vasopressor
frequency of discontinuation of vasopressor infusion
Secondary Outcome Measures
mortality
frequency
SOFA
dynamics on the SOFA scale
IL6/IL10
ratio
Full Information
NCT ID
NCT04920565
First Posted
June 8, 2021
Last Updated
September 27, 2022
Sponsor
Petrovsky National Research Centre of Surgery
1. Study Identification
Unique Protocol Identification Number
NCT04920565
Brief Title
Efficacy and Safety of Hemoperfusion With Polymyxin B in Septic Shock Associated With Severe Endotoxemia in Cardiac Surgery Patients (РМХ vs SS)
Acronym
РМХ vs SS
Official Title
Evalution of the Efficacy and Safety of Hemoperfusion Use With Polymyxin B un Patients With Severe Endotoxemia With Multiple Organ Dysfunction Syndrome After Complicated Operations With Cardiopulmonary Bypass
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Petrovsky National Research Centre of Surgery
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Sepsis is a state of multiple organ dysfunction caused by a generalized immune-inflammatory response of the body to an infectious agent, with pronounced heterogeneity and interchangeability of clinical and laboratory manifestations. Violation of autoregulation and multiple organ dysfunctions in case of not timely started and / or ineffective therapy lead to the development of multiple organ failure and thanatogenesis in 40-90% of cases. At the moment, there is no standardized approach to the treatment of the entire pool of sepsis patients. Pharmacological effects on receptors for interleukins and endotoxin, antibiotic therapy and immunoprotection do not allow taking the process under complete control. The pathogenesis and clinical diversity of manifestations dictates the need for a personalized approach based on identifying a group of patients with homogeneous characteristics and the course of the process, where one or another technique would have the greatest benefit. The choice of tactics for extracorporeal therapy should be based on early support of organ function and consistent elimination of high concentrations of trigger compounds (endotoxin, other metabolic products of microorganisms and products of cytolysis of a macroorganism), as well as aimed at minimizing the loss of proteins and immune complexes.
The aim of this clinical study was to assess the efficacy and safety of the selective adsorption of endotoxin in patients with severe multiple organ dysfunction after complicated cardiac surgery.
Detailed Description
PMX versus SS (polymyxin B versus septic shock) is a single-center, historic, randomized clinical trial to investigate the safety and efficacy of polymyxin B columns (PMX 20R, Toray) in adult patients with severe endotoxemia for the prevention and correction of septic shock after cardiac surgery. All patients must sign an informed consent prior to surgery. The study group will be represented by patients with severe multiple organ dysfunction (SOFA ≥5 points, PCT> 2 ng / ml; CRP> 150 ng / ml, vasopressor use, intestinal paresis and / or positive blood culture data) and endotoxin activity level on the test EAA is higher than 0.6. Patients by outcome will be divided into 2 groups according to the EAA test values: values from 0.6 to 0.89 (group A) and 0.9 and above (group B).
Due to the presence of renal failure in such patients, hemoperfusion will be performed in combination with the oXiris (Baxter) kit on the Prismaflex (Baxter) apparatus (PMX20R - 12 hours; oXiris - 72 hours). The effectiveness of PMX will be assessed based on the decrease in the EAA value below 0.6 12 hours after the end of the hemoperfusion session. If EAA2 is greater than 0.6 PMX will reconnect.
• For patients with a baseline EAA1 value greater than 0.9, PMX reuse is included in the study protocol and performed 12 hours after the first set is turned off. The EAA3 test runs 12 hours after the PMX2 is turned off.
The safety of hemoperfusion will be assessed based on the presence of side effects (progression of signs of hemodynamic impairment) during the procedure.
The control group will consist of 10 patients (historical randomization without endotoxemia assessment) with septic shock with multiple organ dysfunction (SOFA ≥5, use of vasopressors) using the Oxyris universal renal replacement therapy kit for 72 hours. The comparison group will be formed by the matching method.
Additionally, the following will be assessed: the length of stay in the intensive care unit, mortality on the 14th and 28th days after the operation.
It is also planned to assess the dynamics of changes in the immunological status (cellular and humoral immunity) and microbiota metabolism (the level of aromatic microbial metabolites) during hemoperfusion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Organ Dysfunction With Severe Endotoxemia
Keywords
test EAA, endotoxemia, hemoperfusion with Polymyxin B, cardiac syrgery
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
In 10 patients meeting three of the following criteria: SOFA ≥5 points, PCT> 2 ng / ml; CRP> 150 ng / ml, vasopressor use, intestinal paresis and / or positive blood culture data - as well as with an EAA level above 0.6, a hemoperfusion procedure with polymyxin B will be performed for 12 hours.
- with an initial EAA level of more than 0.9, 2 hemoperfusion procedures will be performed with a difference of 12 hours
Masking
None (Open Label)
Masking Description
Using the matching method, a control group of 10 patients (historical randomization without endotoxemia assessment) with multiple organ dysfunction (SOFA ≥5, use of vasopressors) will be formed using the Oxyris universal set for renal replacement therapy for 72 hours.
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
cardiac surgery patients with multiple organ dysfunction
Arm Type
Experimental
Arm Description
hemoperfusion procedure with polymyxin B will be performed for 12 hours
Arm Title
cardiac surgery patients
Arm Type
No Intervention
Arm Description
without hemoperfusion with polymyxin B
Intervention Type
Device
Intervention Name(s)
hemoperfusion with polymyxin B
Other Intervention Name(s)
PMX 20 R
Intervention Description
polymyxin B is covalently immobilized on polystyrene strands, selectively removes endotoxin and at the same time there is no leaching of the ligand, immobilization is carried out by electrostatic interaction and Vanderwals force
Primary Outcome Measure Information:
Title
endotoxin activity level
Description
frequency of cases of decrease in EAA below 0.6
Time Frame
12 hours after the end of the procedure
Title
vasopressor
Description
frequency of discontinuation of vasopressor infusion
Time Frame
6 hours after the start of the procedure
Secondary Outcome Measure Information:
Title
mortality
Description
frequency
Time Frame
14 and 28 day
Title
SOFA
Description
dynamics on the SOFA scale
Time Frame
24 hours after the end of the procedure
Title
IL6/IL10
Description
ratio
Time Frame
12, 24 hours after the end of the procedure
Other Pre-specified Outcome Measures:
Title
adverse events
Description
frequency
Time Frame
during the procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
SOFA +2 points in comparison with the previous assessment; РСТ more than 2 ng / ml; CRP more than 150 ng / ml; norepinephrine infusion; intestinal paresis; positive data of blood culture; ЕАА more than 0,6
Exclusion Criteria:
bleeding; heparin-induced thrombocytopenia
Facility Information:
Facility Name
Petrovsky National Reasearch Centre of Surgery
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MAXIM BABAEV, D.Sc.(medical)
Phone
89160269066
Email
maxbabaev@mail.ru
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Hemoperfusion With Polymyxin B in Septic Shock Associated With Severe Endotoxemia in Cardiac Surgery Patients (РМХ vs SS)
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