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

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

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 Overview

• Status: Terminated
• Conditions: Sepsis
• Intervention / Treatment: Device: Toraymyxin

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Sheng-Yuan Ruan, MD, Natioanl Taiwan University Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): March 26, 2019
• Study Completion (Actual): March 26, 2019

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Pneumonia; Sepsis; Urinary tract infection; Polymyxin B
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Infections; Pneumonia; Urinary Tract Infections
• Other Study ID Numbers: 201411023RIPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided