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

Primary Purpose

Sepsis, Severe, Septic Shock

Status
Completed
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
oXiris blood purification set
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis, Severe focused on measuring critical care, septic shock, hemofiltration, endotoxin, cytokine storm, prognosis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Blood Purification

Conventional Treatment

Arm Description

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.

Patients will receive standard care, including resuscitation and treatment according to current guidelines for septic shock.

Outcomes

Primary Outcome Measures

Difference of serum interleukin-6 level
Comparison to enrollment or between 2 groups

Secondary Outcome Measures

Difference of serum interleukin-6 level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-6 level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-1β level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-1β level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-1β level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-10 level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-10 level
Comparison to enrollment or between 2 groups
Difference of serum interleukin-10 level
Comparison to enrollment or between 2 groups
Difference of serum procalcitonin level
Comparison to enrollment or between 2 groups
Difference of serum procalcitonin level
Comparison to enrollment or between 2 groups
Difference of serum procalcitonin level
Comparison to enrollment or between 2 groups
Difference of mean arterial pressure
Comparison to enrollment
Difference of mean arterial pressure
Comparison to enrollment
Difference of mean arterial pressure
Comparison to enrollment
Difference of cardiac output
Comparison to enrollment
Difference of cardiac output
Comparison to enrollment
Difference of cardiac output
Comparison to enrollment
Difference of norepinephrine infusion rate
Comparison to enrollment
Difference of norepinephrine infusion rate
Comparison to enrollment
Difference of norepinephrine infusion rate
Comparison to enrollment
Difference of the sequential organ failure assessment score
Comparison to enrollment or between 2 groups
Difference of the sequential organ failure assessment score
Comparison to enrollment or between 2 groups
Difference of the sequential organ failure assessment score
Comparison to enrollment or between 2 groups
Difference of serum endocan level
Comparison to enrollment or between 2 groups
Difference of serum endocan level
Comparison to enrollment or between 2 groups
Difference of serum endocan level
Comparison to enrollment or between 2 groups
Difference of serum diamine oxidase level
Comparison to enrollment or between 2 groups
Difference of serum diamine oxidase level
Comparison to enrollment or between 2 groups
Difference of serum diamine oxidase level
Comparison to enrollment or between 2 groups
Difference of daily IV fluids
Comparison between 2 groups
Difference of daily IV fluids
Comparison between 2 groups
Difference of daily IV fluids
Comparison between 2 groups

Full Information

First Posted
June 2, 2019
Last Updated
March 10, 2021
Sponsor
National Taiwan University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03974386
Brief Title
Effects of Endotoxin Absorption and Cytokine Removal Hemofilter on Severe Septic Shock
Official Title
Effects of Endotoxin Absorption and Cytokine Removal Hemofilter on Patients With Severe Septic Shock
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
July 1, 2019 (Actual)
Primary Completion Date
July 17, 2020 (Actual)
Study Completion Date
August 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Severe, Septic Shock
Keywords
critical care, septic shock, hemofiltration, endotoxin, cytokine storm, prognosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blood Purification
Arm Type
Experimental
Arm Description
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.
Arm Title
Conventional Treatment
Arm Type
No Intervention
Arm Description
Patients will receive standard care, including resuscitation and treatment according to current guidelines for septic shock.
Intervention Type
Device
Intervention Name(s)
oXiris blood purification set
Intervention Description
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.
Primary Outcome Measure Information:
Title
Difference of serum interleukin-6 level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Difference of serum interleukin-6 level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum interleukin-6 level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of serum interleukin-1β level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of serum interleukin-1β level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum interleukin-1β level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of serum interleukin-10 level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of serum interleukin-10 level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum interleukin-10 level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of serum procalcitonin level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of serum procalcitonin level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum procalcitonin level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of mean arterial pressure
Description
Comparison to enrollment
Time Frame
24 hours
Title
Difference of mean arterial pressure
Description
Comparison to enrollment
Time Frame
48 hours
Title
Difference of mean arterial pressure
Description
Comparison to enrollment
Time Frame
72 hours
Title
Difference of cardiac output
Description
Comparison to enrollment
Time Frame
24 hours
Title
Difference of cardiac output
Description
Comparison to enrollment
Time Frame
48 hours
Title
Difference of cardiac output
Description
Comparison to enrollment
Time Frame
72 hours
Title
Difference of norepinephrine infusion rate
Description
Comparison to enrollment
Time Frame
24 hours
Title
Difference of norepinephrine infusion rate
Description
Comparison to enrollment
Time Frame
48 hours
Title
Difference of norepinephrine infusion rate
Description
Comparison to enrollment
Time Frame
72 hours
Title
Difference of the sequential organ failure assessment score
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of the sequential organ failure assessment score
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of the sequential organ failure assessment score
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of serum endocan level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of serum endocan level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum endocan level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of serum diamine oxidase level
Description
Comparison to enrollment or between 2 groups
Time Frame
24 hours
Title
Difference of serum diamine oxidase level
Description
Comparison to enrollment or between 2 groups
Time Frame
48 hours
Title
Difference of serum diamine oxidase level
Description
Comparison to enrollment or between 2 groups
Time Frame
72 hours
Title
Difference of daily IV fluids
Description
Comparison between 2 groups
Time Frame
24 hours
Title
Difference of daily IV fluids
Description
Comparison between 2 groups
Time Frame
48 hours
Title
Difference of daily IV fluids
Description
Comparison between 2 groups
Time Frame
72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan

12. IPD Sharing Statement

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

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