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)

NCT01948778 | Completed

• 1 other identifier: ENDoX_CH012
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Patients in Septic Shock

Outcome Measures

Primary Outcomes (1)

• Measurement of the endotoxin activity 72 hours after treatment initiation

  72 hours

Study Arms (3)

oXiris™ filter

EXPERIMENTAL

oXiris™ filter

Device: oXiris™ filter

Toraymyxin Filter

EXPERIMENTAL

Toraymyxin Filter

Device: Toraymyxin Filter

Standard of Care

OTHER

Standard of Care CRRT if necessary

Device: Standard of Care

Interventions

oXiris™ filter DEVICE

oXiris™ filter

Toraymyxin Filter DEVICE

Toraymyxin Filter

Standard of Care DEVICE

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Unknown Facility

Zurich, Switzerland

Location

Related Publications (2)

• Wendel-Garcia PD, Eberle B, Kleinert EM, Hilty MP, Blumenthal S, Spanaus K, Fodor P, Maggiorini M. Effects of enhanced adsorption haemofiltration versus haemoadsorption in severe, refractory septic shock with high levels of endotoxemia: the ENDoX bicentric, randomized, controlled trial. Ann Intensive Care. 2023 Dec 14;13(1):127. doi: 10.1186/s13613-023-01224-8.

  PMID: 38095800 DERIVED

• 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(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.

  PMID: 34519356 DERIVED

Study Officials

• Marco Maggiorini, Prof MD

  University Hospital Zurich, University Hospital Zurich, Medical intensive care unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: September 24, 2013
• Study Start: August 1, 2013
• Primary Completion: May 1, 2019
• Study Completion: July 1, 2019
• Last Updated: July 5, 2019

Record last verified: 2019-06

Locations

CH (1)