Cytokine Adsorption in Severe, Refractory Septic Shock

NCT ID: NCT04910893

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-27
• Study Completion Date: 2018-12-31

Brief Summary

Septic shock and the underlying dysregulated inflammatory host-response remain a major contributor to mortality in critically ill patients. Cytokine adsorption represents an attractive approach to the treatment of septic shock. Nevertheless, its effect on circulating cytokine levels, as well as on the course of disease remains largely unassessed.

Detailed Description

Cytokine-release plays an important role in the physiology of immune response to pathologic influences by recruiting immune cells to the pathogenic loci, be they of infectious or of non-infectious nature. Once at the focus, the activated immune cells can in turn release more cytokines if a more extensive immune response is needed. This extremely important mechanism for the organism, can however become pathological if the positive feedback loop between immune cells and cytokines, for any reason, overshoots in form of a so called cytokine storm and substantial amounts of released cytokines gain a systemic influence. The acute complication of this immune over-reaction is a SIRS, which can critically escalate into a potentially lethal multiple organ dysfunction syndrome, thus requiring immediate intensive care treatment.

It is, having this framework in mind, the reason why the CytoSorb-Adsorber has been developed as a new therapeutic milestone. Essentially a haemoperfusion-filter, which through its layering with polymer beads (Divinylbenzene/ Polyvinylpyrrolidone) can adsorb cytokines as well as multiple inflammatory mediators and thus effectively remove them from the bloodstream, reducing their possible systemic influence and hence improving the outcome for patients being treated with it.

The CytoSorb-Adsorber is an already CE-approved product, which has demonstrated its capacity to significantly reduce cytokine-levels such as IL-6, IL-8, IL-10, TNFα, HMGB-1, IL-1ra in a variety of pre-clinical studies. As well as in a clinical randomised multicentre study, which tested the CytoSorb-Adsorber on a cohort of ALI/ ARDS and severely septic/ septically shocked patients. The results of the later study can be very positively assessed, first of all and most importantly showing, that no security concerns had to be had in regard to the haemoperfusion-filter, as no adverse-effects attributable to the device were found. And further, by proving an effect on systemic cytokine-levels in form of a significant reduction in IL-6, IL-8, MCP-1 and IL-1ra, as well as a reduction in mortality of those patients with high initial cytokine levels, effectively reducing the 60 day mortality rate from 60% to 17% in a pool of 14 patients.

With the intention to further elucidate the usefulness and clinical importance of this device this study proposes a prospective recruitment of patients in severe refractory septic shock to test the efficiency of this device.

Conditions

Septic Shock; Cytokine Storm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cytokine Adsorption Arm

Intervention with CytoSorb

Group Type: EXPERIMENTAL

Cytokine Adsorption

Intervention Type: DEVICE

Cytokine adsorption therapy will be provided continuously for 72 hours by means of the CytoSorb® (CytoSorbents Corporation, Monmouth Junction, USA) column, run in series to a veno-venous continuous hemodialysis system, which will be exchanged every 24 hours.

Historical Comparison

Patients extracted from a septic shock population treated at the same institution between 2010 and 2018 and matched to the intervention group.

Group Type: OTHER

Standard of Care

Intervention Type: OTHER

Standard intensive care of patients suffering septic shock

Interventions

Cytokine Adsorption

Cytokine adsorption therapy will be provided continuously for 72 hours by means of the CytoSorb® (CytoSorbents Corporation, Monmouth Junction, USA) column, run in series to a veno-venous continuous hemodialysis system, which will be exchanged every 24 hours.

Intervention Type: DEVICE

Standard of Care

Standard intensive care of patients suffering septic shock

Intervention Type: OTHER

Other Intervention Names

CytoSorb

Eligibility Criteria

Inclusion Criteria

Patients diagnosed septic shock in the 24 hours ensuing diagnosis:

(I) severe, refractory septic shock defined as:

1. an acute SOFA score increase ≥2 points consequent to a presumed or proven infection

2. volume resuscitation of at least 30ml/kg in the last 24 hours

3. a Vasopressor Dependency Index11 (VPI) above or equal to 3

4. a persistently elevated serum lactate level >2mmol/l (II) Interleukin-6 levels equal or above 1000 ng/l (III) were above 18 years of age.

Exclusion Criteria

1. Contraindication on ethical grounds

2. child bearing or breastfeeding women

3. terminal patients

4. human immunodeficiency virus with a CD4 cell count <0.2 106/l

5. allergy to Polystyrene/ Divinylbenzene, Polycarbonate, Polypropylene, Silicon or Polyester

6. need for extra-corporeal membrane oxygenation

7. no given consent.

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

Sponsors

CytoSorbents Europe GmbH

INDUSTRY

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Maggiorini, MD

Role: PRINCIPAL_INVESTIGATOR

Medizinische Intensivstation D-HOER 27, UniversitatsSpital Zürich

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Morris C, Gray L, Giovannelli M. Early report: The use of Cytosorb haemabsorption column as an adjunct in managing severe sepsis: initial experiences, review and recommendations. J Intensive Care Soc. 2015 Aug;16(3):257-264. doi: 10.1177/1751143715574855. Epub 2015 Mar 18.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 12169849 (View on PubMed)

Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004 Mar;32(3):801-5. doi: 10.1097/01.ccm.0000114997.39857.69.

Reference Type: BACKGROUND

PMID: 15090965 (View on PubMed)

Peng ZY, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med. 2008 May;36(5):1573-7. doi: 10.1097/CCM.0b013e318170b9a7.

Reference Type: BACKGROUND

PMID: 18434884 (View on PubMed)

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Reference Type: BACKGROUND

Other Identifiers

Cytosorb

Identifier Type: -

Identifier Source: org_study_id