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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04910893
Other study ID # Cytosorb
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date November 27, 2014
Est. completion date December 31, 2018

Study information

Verified date June 2021
Source University of Zurich
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 48
Est. completion date December 31, 2018
Est. primary completion date August 24, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Device:
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.
Other:
Standard of Care
Standard intensive care of patients suffering septic shock

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
University of Zurich CytoSorbents Europe GmbH

References & Publications (8)

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).

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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

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. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary Cumulative intensive care mortality at 30 days Intensive care mortality assessment at day 30 between groups 30 days post fulfillment of inclusion criteria
Secondary Change in C-reactive protein levels over time Change in C-reactive protein levels, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in Procalcitonin levels over time Change in Procalcitonin levels, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in SOFA Score over time Change in SOFA Score, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in arterial lactate levels over time Change in arterial lactate levels, 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
Secondary Change in cardiac index over time Change in cardiac 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
Secondary Change in Extra Vascular Lung Water Index over time Change in Extra Vascular Lung Water Index, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in daily Infused Volume over time Change in daily Infused Volume, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in PaO2/ FiO2 Ratio over time Change in PaO2/ FiO2 Ratio, 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
Secondary Change in Serum Albumin levels over time Change in Serum Albumin levels, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
Secondary Change in Bilirubin levels over time Change in Bilirubin levels, stratified by groups, over the initial 72 hours ensuing fulfillment of inclusion criteria Mixed Model Assessment at timepoints 0, 24, 48, 72 hours
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