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)

NCT ID: NCT01948778

Last Updated: 2019-07-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2019-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

oXiris™ filter

oXiris™ filter

Group Type: EXPERIMENTAL

oXiris™ filter

Intervention Type: DEVICE

Toraymyxin Filter

Toraymyxin Filter

Group Type: EXPERIMENTAL

Toraymyxin Filter

Intervention Type: DEVICE

Standard of Care

Standard of Care CRRT if necessary

Group Type: OTHER

Standard of Care

Intervention Type: DEVICE

Interventions

oXiris™ filter

Intervention Type: DEVICE

Toraymyxin Filter

Intervention Type: DEVICE

Standard of Care

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Maggiorini, Prof MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 38095800 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34519356 (View on PubMed)

Other Identifiers

ENDoX_CH012

Identifier Type: -

Identifier Source: org_study_id