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

National Taiwan University Hospital1 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Sepsis

Interventions

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with septic shock defined by the third international consensus definitions for sepsis and septic shock 2. 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). 3. Hyperlactatemia (\>2 mmol/L) 4. Endotoxin activity assay (EAA) ≥ 0.5 units. Exclusion Criteria: 1. Shock persisted \>12 hours before screening 2. Mechanical ventilation \>21 days 3. Uncontrolled hemorrhage 4. Thrombocytopenia (platelet count \< 30,000 cells/mm3) 5. Leukopenia (leukocyte count \< 1500 cells/mm3) 6. Suspected allergy to polymyxin 7. Females with pregnancy 8. Terminal cancer or organ failure with life expectancy less than 30 days

Outcomes

Primary Outcomes

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.

Time frame: Day 7

Secondary Outcomes

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)

Time frame: Day 3

Change of endotoxin levels (Endotoxin Activity Assay)

Change of endotoxin levels after the intervention

Time frame: Day 3

Change of Sequential Organ Failure Assessment (SOFA) score

Comparison of SOFA score between the intervention group and historical control group.

Time frame: Day 7

Vasopressor-free days

Comparison of vasopressor-free days in 7 days between the intervention group and historical control group.

Time frame: 7 days

28-day all-cause mortality

Comparison of 28-day all-cause mortality between the intervention group and historical control group.

Time frame: 28 days

Catheter-related complications

Comparison of the proportion of the cases with catheter-related complications between the intervention group and historical control group.

Time frame: 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.

Time frame: 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.

Time frame: 3 days

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes