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)

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Patients in Septic Shock

Intervention / Treatment
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* Device: oXiris™ filter
* Device: Toraymyxin Filter
* Device: Standard of Care


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oXiris™ filter<br>oXiris™ filter | Device: oXiris™ filter<br> <br> |
| Experimental: Toraymyxin Filter<br>Toraymyxin Filter | Device: Toraymyxin Filter<br> <br> |
| Other: Standard of Care<br>Standard of Care CRRT if necessary | Device: Standard of Care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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