Effects of Endotoxin Absorption and Cytokine Removal Hemofilter on Severe Septic Shock

Study Overview
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Brief Summary
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In recent years, many studies have pointed out that bacterial toxin and cytokine storm are the main causes of shock and multiple organ failure in patients with sepsis. Endotoxin is the main vehicle for systemic inflammatory reaction caused by gram-negative bacteria which induce sepsis. Endotoxin binds to Toll- Like receptor 4 (TLR4) trigger a cytokine storm. The amount of endotoxin is associated with shock, insufficient intestinal perfusion, and poor prognosis. Therefore, clinicians try to use various methods to antagonize the action of endotoxin, which can reduce the cytokine storm and inflammatory response to improve the prognosis of sepsis. Continuous venous venous hemofiltration plays a role in blood purification in septic shock. With different hemofiltration filters, it has different effects. By removing the inflammatory mediators caused by bacterial toxins and cytokines, shock can be improved. The study plans to receive patients with septic shock and use a hemofiltration filter that adsorbs endotoxin and removes cytokines (oXiris, Baxter Healthcare) to perform continuous venous venous hemofiltration in addition to basic septic shock resuscitation. The effect on the concentration of cytokines in the blood, the infusion dose of inotropics, the fluid balances, and the degree of organ damage was evaluated. It is hoped that the results of this pilot study can lead us to subsequent randomized clinical trials to explore whether this filter can improve the prognosis of septic shock patients.

Official Title
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Effects of Endotoxin Absorption and Cytokine Removal Hemofilter on Patients With Severe Septic Shock

Conditions
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Sepsis, Severe, Septic Shock

Intervention / Treatment
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* Device: oXiris blood purification set


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet all criteria (A+B+C): A) Identified infection source under adequate treatment B) Sepsis (the sequential organ failure assessment score rise 2 points or more) C) Severe septic shock (serum lactate > 2 mmol/L; need continuous norepinephrine infusion to maintain adequate blood pressure, of which dosage is > 0.2 mcg/kg/min for more than 1 hour or >0.1 mcg/kg/min for more than 3 hours ) Exclusion Criteria: Onset of severe septic shock more than 24 hours Received continuous renal replacement therapy within 24 hours before enrollment Serum white blood cell count count < 1000 cells/μL or Platelet count < 50000 cells/μL History of allergy to heparin Received cardiopulmonary resuscitation within 4 weeks before enrollment ICU admission due to severe septic shock within 2 months Patients or Family had chosen palliative care and signed an agreement to deny aggressive treatment Pregnancy APACHE II Score > 30 at enrollment Non-native speakers

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Purification<br>Patients will receive resuscitation and treatment according to current guidelines for septic shock. In addition to standard care, the patients will receive continuous venovenous hemofiltration and adsorption with oXiris blood purification set. | Device: oXiris blood purification set<br>* Continuous venovenous hemofiltration and adsorption (CVVHA) with oXiris filter for up to 72 hours if required. The filter will be replaced every 24 hours. The setting of CVVHA is as follows: blood flow rate 200 mL/min, replacement fluid rate 2000 mL/hr, pre-dilution 50% and post-dilution 50%. If continuous renal replacement therapy is indicated after 72 hours, conventional hemofiltration filters will be used.<br>|
| No Intervention: Conventional Treatment<br>Patients will receive standard care, including resuscitation and treatment according to current guidelines for septic shock. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of serum interleukin-6 level | Comparison to enrollment or between 2 groups | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of serum interleukin-6 level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum interleukin-6 level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of serum interleukin-1β level | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of serum interleukin-1β level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum interleukin-1β level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of serum interleukin-10 level | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of serum interleukin-10 level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum interleukin-10 level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of serum procalcitonin level | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of serum procalcitonin level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum procalcitonin level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of mean arterial pressure | Comparison to enrollment | 24 hours | 
| Difference of mean arterial pressure | Comparison to enrollment | 48 hours | 
| Difference of mean arterial pressure | Comparison to enrollment | 72 hours | 
| Difference of cardiac output | Comparison to enrollment | 24 hours | 
| Difference of cardiac output | Comparison to enrollment | 48 hours | 
| Difference of cardiac output | Comparison to enrollment | 72 hours | 
| Difference of norepinephrine infusion rate | Comparison to enrollment | 24 hours | 
| Difference of norepinephrine infusion rate | Comparison to enrollment | 48 hours | 
| Difference of norepinephrine infusion rate | Comparison to enrollment | 72 hours | 
| Difference of the sequential organ failure assessment score | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of the sequential organ failure assessment score | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of the sequential organ failure assessment score | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of serum endocan level | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of serum endocan level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum endocan level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of serum diamine oxidase level | Comparison to enrollment or between 2 groups | 24 hours | 
| Difference of serum diamine oxidase level | Comparison to enrollment or between 2 groups | 48 hours | 
| Difference of serum diamine oxidase level | Comparison to enrollment or between 2 groups | 72 hours | 
| Difference of daily IV fluids | Comparison between 2 groups | 24 hours | 
| Difference of daily IV fluids | Comparison between 2 groups | 48 hours | 
| Difference of daily IV fluids | Comparison between 2 groups | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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critical care, septic shock, hemofiltration, endotoxin, cytokine storm, prognosis