The Effects of a Polyethyleneimine-coated Membrane (oXiris™) for Hemofiltration Versus Polymyxin B- Immobilized Fibre Column (Toraymyxin™) for Hemoperfusion on Endotoxin Activity and Inflammatory Conditions in Septic Shock- A Randomized Controlled Pilot Study (ENDoX-study)

The Effects of a Polyethyleneimine-coated Membrane (oXiris™) for Hemofiltration Versus Polymyxin B- Immobilized Fibre Column (Toraymyxin™) for Hemoperfusion on Endotoxin Activity and Inflammatory Conditions in Septic Shock- A Randomized Controlled Pilot Study

Septic shock has a high mortality risk despite the availability of various treatments. Endotoxin, that is present in the cell walls of gram-negative bacteria, is a potent trigger of innate immunity. Endotoxin leads to an activation of a cascade with an overwhelming systemic overflow of pro- and anti- inflammatory mediators at the early phase of sepsis with generalized vascular endothelial damage, tissue injury and multi-organ failure.

Extracorporeal blood purification therapies aim to reduce the circulating level of endotoxin. Different extracorporeal blood purification systems are available. The oXiris™ device comprises a surface treated AN69 membrane capable to adsorb a large spectrum of plasma cytokines, such as IL-6 and HMGB1 protein. The positively charged inner surface of the membrane allows absorbing negatively charged bacterial products such as endotoxin. From an historical perspective, filters containing AN69-based membranes have been the most commonly used products for CRRT in the management of critically ill patients and a substantial volume of published data exist.

Another extracorporeal endotoxin removal therapy is the hemoperfusion with ToraymyxinTM (PMX) filter, which is a cartridge selectively removing blood endotoxin. PMX is composed of polymyxin B covalently bonded to polystyrene-derivative fibres. It is well known that the polarity of the polymyxin B antibiotic binds endotoxin and has bactericidal activity. Therefore, the rationale underlying extracorporeal therapy with PMX is to remove circulating endotoxin by adsorption.

• Trial with medical device

Study Overview

• Status: Completed
• Conditions: Patients in Septic Shock
• Intervention / Treatment: Device: oXiris™ filter; Device: Toraymyxin Filter; Device: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland

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: • Patients with septic shock, defined as 30ml/kg of i.v. fluid administered within a period of 6 hours after initiation of vasopressor therapy with a vasopressor index =3, and at least one of the following criteria: metabolic acidosis, neurologic dysfunction, renal dysfunction, or acute hepatic dysfunction

• Male and Female patients =18 years
• Endotoxin levels =0.6 IU EAA (measured at ICU admission and repeated 24 hours later in case the initial value is =0.4 and <0.6)

Exclusion criteria: • Endotoxin levels <0.6 IU EAA

• Pregnancy or breast feeding
• Neutropenia (circulating neutrophils <500/µl)
• Pre-existing immune deficiencies or immune-suppressive therapy, especially corticosteroids
• Use of Vasopressin (Pitressin?)
• Organ transplantation within the last 12 months
• Terminally ill patients classified as "do not resuscitate"
• History of sensitivity to polymyxin B or to anticoagulant (heparin) HIT or allergy to heparin
• Need for extracorporeal membrane oxygenation (ECMO)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oXiris™ filter	Device: oXiris™ filter
Experimental: Toraymyxin Filter	Device: Toraymyxin Filter
Other: Standard of Care; Standard of Care CRRT if necessary	Device: Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measurement of the endotoxin activity 72 hours after treatment initiation	72 hours

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Marco Maggiorini, Prof MD, University Hospital Zurich, University Hospital Zurich, Medical intensive care unit

Publications and helpful links

General Publications

• Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9:CD013330. doi: 10.1002/14651858.CD013330.pub2. Review.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: August 30, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 24, 2013

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: ENDoX_CH012