NCT04910893

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Nov 2014

Longer than P75 for not_applicable

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 27, 2014

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 24, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2018

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

May 27, 2021

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 2, 2021

Completed
Last Updated

June 10, 2021

Status Verified

June 1, 2021

Enrollment Period

3.7 years

First QC Date

May 27, 2021

Last Update Submit

June 7, 2021

Conditions

Septic ShockCytokine Storm

Keywords

Septic ShockCytokine AdsorptionHemadsorptionextracorporeal removal

Outcome Measures

Primary Outcomes (3)

  • Change in circulating Interleukin-6 levels over time

    Change in circulating Interleukin-6 levels, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria

    Mixed Model Assessment at timepoints 0, 24, 48, 72 hours

  • Change in Vasopressor requirements over time

    Change in the Vasopressor Dependency Index, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria

    Mixed Model Assessment at timepoints 0, 2, 4, 8, 12 , 24, 48, 72 hours

  • Cumulative intensive care mortality at 30 days

    Intensive care mortality assessment at day 30 between groups

    30 days post fulfillment of inclusion criteria

Secondary Outcomes (10)

  • Change in C-reactive protein levels over time

    Mixed Model Assessment at timepoints 0, 24, 48, 72 hours

  • Change in Procalcitonin levels over time

    Mixed Model Assessment at timepoints 0, 24, 48, 72 hours

  • Change in SOFA Score over time

    Mixed Model Assessment at timepoints 0, 24, 48, 72 hours

  • Change in arterial lactate levels over time

    Mixed Model Assessment at timepoints 0, 2, 4, 8, 12 , 24, 48, 72 hours

  • Change in cardiac index over time

    Mixed Model Assessment at timepoints 0, 2, 4, 8, 12 , 24, 48, 72 hours

  • +5 more secondary outcomes

Study Arms (2)

Cytokine Adsorption Arm

EXPERIMENTAL

Intervention with CytoSorb

Device: Cytokine Adsorption

Historical Comparison

OTHER

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

Other: Standard of Care

Interventions

Cytokine AdsorptionDEVICE

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.

Also known as: CytoSorb
Cytokine Adsorption Arm
Standard of CareOTHER

Standard intensive care of patients suffering septic shock

Historical Comparison

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients diagnosed septic shock in the 24 hours ensuing diagnosis:
  • (I) severe, refractory septic shock defined as:
  • an acute SOFA score increase ≥2 points consequent to a presumed or proven infection
  • volume resuscitation of at least 30ml/kg in the last 24 hours
  • a Vasopressor Dependency Index11 (VPI) above or equal to 3
  • 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.

You may not qualify if:

  • Contraindication on ethical grounds
  • child bearing or breastfeeding women
  • terminal patients
  • human immunodeficiency virus with a CD4 cell count \<0.2 106/l
  • allergy to Polystyrene/ Divinylbenzene, Polycarbonate, Polypropylene, Silicon or Polyester
  • need for extra-corporeal membrane oxygenation
  • no given consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (8)

  • Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med. 2008 Jul;26(6):711-5. doi: 10.1016/j.ajem.2007.10.031.

    PMID: 18606328BACKGROUND

  • Taniguchi T. Cytokine adsorbing columns. Contrib Nephrol. 2010;166:134-141. doi: 10.1159/000314863. Epub 2010 May 7.

    PMID: 20473001BACKGROUND

  • 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.

    PMID: 28979423BACKGROUND

  • Rimmele T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care. 2011;15(1):205. doi: 10.1186/cc9411. Epub 2011 Feb 16.

    PMID: 21371356BACKGROUND

  • Reiter K, Bordoni V, Dall'Olio G, Ricatti MG, Soli M, Ruperti S, Soffiati G, Galloni E, D'Intini V, Bellomo R, Ronco C. In vitro removal of therapeutic drugs with a novel adsorbent system. Blood Purif. 2002;20(4):380-8. doi: 10.1159/000063108.

    PMID: 12169849BACKGROUND

  • 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.

    PMID: 15090965BACKGROUND

  • 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.

    PMID: 18434884BACKGROUND

  • D Schädler, C Porzelius, A Jörres, G Marx, A Meier-Hellmann, C Putensen, M Quintel, C Spies, C Engel, NWeiler, M Kuhlmann. A multicenter randomized controlled study of an extracorporeal cytokine hemoadsorption device in septic patients. Critical Care 2013, 17(Suppl 2):P62 (19 March 2013).

    BACKGROUND

MeSH Terms

Conditions

Shock, SepticCytokine Release Syndrome

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

SepsisInfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShock

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Study Officials

  • Marco Maggiorini, MD

    Medizinische Intensivstation D-HOER 27, UniversitatsSpital Zürich

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Prospective interventional study with comparative matched septic shock cohort
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2021

First Posted

June 2, 2021

Study Start

November 27, 2014

Primary Completion

August 24, 2018

Study Completion

December 31, 2018

Last Updated

June 10, 2021

Record last verified: 2021-06

Data Sharing

IPD Sharing
Will not share