Efficacy of Polymyxin B Hemoperfusion on Severe Sepsis Secondary to Pneumonia or Urinary Tract Infection

Study Overview
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Brief Summary
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Toraymyxin is an extracorporeal hemoperfusion cartridge containing Polymyxin B-immobilized fiber column designed to reduce blood endotoxin levels in sepsis. Meta-analysis of randomized trials showed that polymyxin B hemoperfusion significantly reduced the mortality of severe sepsis; however, the evidence was mainly contributed by the studies of abdominal sepsis. The data about using polymyxin B hemoperfusion to treat non-abdominal sepsis remain very limited. Investigators designed a clinical trial to evaluate the efficacy of polymyxin B hemoperfusion on treating non-abdominal severe sepsis. The study hypothesis is that removal of endotoxin by polymyxin B hemoperfusion in patients with pneumonia or urinary tract infection (UTI)-related severe sepsis will attenuate sepsis associated microcirculation failure and result in early reversal of shock and less extent of end-organ damage.

Official Title
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Efficacy of Polymyxin B Hemoperfusion on Severe Sepsis Secondary to Pneumonia or Urinary Tract Infection: A Single-arm Clinical Trial

Conditions
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Sepsis

Intervention / Treatment
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* Device: Toraymyxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with septic shock defined by the third international consensus definitions for sepsis and septic shock Newly diagnosed pneumonia or urinary tract infection (UTI) defined as the following: 2-1. Pneumonia is defined by a new infiltrate on chest radiograph and the presence of one or several of the following signs or symptoms: cough, sputum production, dyspnea, core body temperature ≥ 38.0°C, auscultatory findings of abnormal breath sounds and rales and leukocyte count > 10000 or < 4000/L. 2-2. UTI is defined by at least one clinical symptom (core body temperature ≥38.0°C, urinary urgency, polyuria, dysuria, suprapubic pain, flank pain, costovertebral angle tenderness, nausea and vomiting) and one urinary criterion (pyuria >20 leukocytes/μL). Hyperlactatemia (>2 mmol/L) Endotoxin activity assay (EAA) ≥ 0.5 units. Exclusion Criteria: Shock persisted >12 hours before screening Mechanical ventilation >21 days Uncontrolled hemorrhage Thrombocytopenia (platelet count < 30,000 cells/mm3) Leukopenia (leukocyte count < 1500 cells/mm3) Suspected allergy to polymyxin Females with pregnancy Terminal cancer or organ failure with life expectancy less than 30 days

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Usual care with two sessions of 2-hour hemoperfusion with Toraymyxin in 24 hours apart | Device: Toraymyxin<br>* Toraymyxin is an extracorporeal hemoperfusion device designed to reduce blood endotoxin levels in sepsis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reversal of sepsis-associated circulatory failure | Comparison of the proportion of subjects free from vasopressor on Day 7 between the intervention group and historical control group. | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate clearance of survived subjects | Comparison of lactate clearance between the intervention group and historical control group. Lactate clearance = (initial lactate level - subsequent lactate level) / (initial lactate level) | Day 3 | 
| Change of endotoxin levels (Endotoxin Activity Assay) | Change of endotoxin levels after the intervention | Day 3 | 
| Change of Sequential Organ Failure Assessment (SOFA) score | Comparison of SOFA score between the intervention group and historical control group. | Day 7 | 
| Vasopressor-free days | Comparison of vasopressor-free days in 7 days between the intervention group and historical control group. | 7 days | 
| 28-day all-cause mortality | Comparison of 28-day all-cause mortality between the intervention group and historical control group. | 28 days | 
| Catheter-related complications | Comparison of the proportion of the cases with catheter-related complications between the intervention group and historical control group. | 3 days | 
| Thrombocytopenia (<25,000/μL) | Comparison of the proportion of the cases with thrombocytopenia (<25,000/μL) between the intervention group and historical control group. | 3 days | 
| Cases with major bleeding needed transfusion with packed red blood cells > 2 units/day | Comparison of the proportion of the cases with major bleeding between the intervention group and historical control group. | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polymyxin B, Pneumonia, Sepsis, Urinary tract infection