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

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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Sepsis, Severe
• Intervention / Treatment: Device: oXiris blood purification set

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood Purification; 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; 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.
No Intervention: Conventional Treatment; Patients will receive standard care, including resuscitation and treatment according to current guidelines for septic shock.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): July 17, 2020
• Study Completion (Actual): August 20, 2020

Study Registration Dates

• First Submitted: June 2, 2019
• First Submitted That Met QC Criteria: June 2, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: septic shock; critical care; prognosis; cytokine storm; hemofiltration; endotoxin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 201808098DIPC

Drug and device information, study documents

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