AzTrials
AzTrials

Covid19NCT04518969

Determination of the Hemoadsorption Impact as Adjunctive Treatment Upon the Support Therapy of COVID-19

A study testing CytoSorb in people with Covid19, run by Dr David DE BELS at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A) Comparing the % of change in each clearances of pro-, and anti-inflammatory mediators (cytokine, chemokines and complement) in the COVID-19 patients treated with CytoSorb as compared to the same patient population who do not receive blood purification treatment. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Covid19
What is being tested?
CytoSorb
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteBelgium
Study dates
3 May 2020to 16 Sep 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult intensive care patient admit in acute respiratory distress needing intubation with suspicion of under the CT Scan of Covid 19 confirmed by positive antigen or PCR technology-Patient COVID type L (Criteria Gattinoni -CT Scan )

Who cannot join

  • Patient COVID type H ( Gattinoni's Criteria -CT Scan )
  • Patient's refusal or refusal of his legal representative
  • HIV + AIDS
  • Short life Expectancy
  • Patients over 80 years of age.
  • Patients under ECMO or ECCO2R
  • Immunosuppression (steroids, chemotherapy…)
  • Cancer

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • CHU Brugmann

    Brussels, 1020

Other trials in Belgium

About this study

Official title: Comparing the Cytokine Clearances of Pro-, and Anti-inflammatory Mediators, Chemokines and Complement in the COVID-19 Patients Treated With CytoSorb as Compared to the Same Patient Population Who do Not Receive Blood Purification Treatment

  1. Comparing the % of change in each clearances of pro-, and anti-inflammatory mediators (cytokine, chemokines and complement) in the COVID-19 patients treated with CytoSorb as compared to the same patient population who do not receive blood purification treatment.
  2. Testing the Cytokinetic model by measuring cytokines in the blood stream and in the BAL to see if you can create a reverse gradient allowing a massive passage of leucocyte from the blood toward the infected lungs.
Read the detailed description

Coronavirus disease-19 (COVID-19) has emerged as a serious pandemic recently, with high mortality especially in those patients who went on to develop acute respiratory failure (around 50%), and especially in those who also developed acute kidney injury (AKI) (80%). Extracorporeal cytokine removal has been recommended by international expert. Two technical approaches have been studied one from Jafron® HA380 (Jafron Biomedical, Zhuhai, Chine) and Cytosorb® (Cytosorbents Corporation, NJ, USA). Basically, it is a single -use sorbent technology that can be used together with an hemofiltration circuit in CVVHD mode only. The cartridge is made of adsorptive porous polymeric beats that represent all together an active surface of 60,000 square meters.The cut-off of these cartridge is about 60,000 daltons and all the cytokines smaller can easily removed by the cartridge especially in the blood stream. The elimination percentage goes from 4 to 30 % with the CytoSorb® and remain steady for the first 6 to 12 hours. The full elimination from the blood stream vary amongst cytokines. It is about 28 % for IL-6- (p = 0.006) and somewhat less for TNF-alpha (8,5%, p = 0.13). Currently, there is no available randomized controlled trial that assess morbidity and mortality in ARDS secondary to COVID infections. There is one pilot study looking at 20 patients with early (<24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrine>10 μg/min, procalcitonin (PCT) > 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. This was the first trial to investigate the effects of early extracorporeal cytokine adsorption treatment in septic shock applied without renal replacement therapy. It was found to be safe with significant effects on norepinephrine requirements, PCT and Big-endothelin-1 concentrations compared to controls.

Actually, other studies are only case report series upon other pulmonary infections than COVID 19.The sorbent chose is the CytoSorb ® it is easier to install, has a CEE approval and his temporally approval by the FDA for the time of the pandemic.

The features of acute hypoxemic respiratory failure in COVID-19 show two fundamentally different phenotypes. One is the L-type: Low elastance; Low ventilation-to-perfusion ratio; Low lung weight; Low lung recruitability. The H-type is characterized by the opposite features. The latter is more similar to the classical ARDS and being investigated by several studies. However, little is known about pathogenesis of the L-type, which can cause hypoxemia to the same degree as the H-type. Even the pathophysiology is yet to be discovered, however, vasoplegia is considered one of the major factors leading to severe right-to-left shunt.

It is postulated that cytokines , chemokines play a crucial role in the pathogenesis, but it has not been investigated yet. Therefore we have chosen the clearance of these substances as our primary endpoint. Usually, CytoSorb is attached to a CRRT circuit which has to run in a CVVHD mode only. In some circumstances CytoSorb might be attached to the ECMO device. In addition to cytokines complements may also play a major role in the pathophysiology of the COVID 19. Therefore, we decided to investigate whether early treatment with blood purification could exert any effects on the cytokine and complement profile and oxygenation in these patients. Testing the Cytokinetic model by measuring cytokines in the blood stream and in the BAL to see if you can create a reverse gradient allowing a massive passage of leucocyte from the blood toward the infected lungs.

Conditions
Covid19
Being tested
CytoSorb
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CytoSorbDevice

    Also called CRRT

    CRRT with CytoSorb.Nevertheless , patients will be uniquely in CVVHD mode in order to measure only the CytoSorb Effect.

    First 24 h : the CytoSorb should be changed after 12 h as we forecast a huge cytokine storm in the first 24 hours.

    After the initial 24 h, cartridge change will occur every 24 hours up a maximum of 96 h in total in the inflammation storm persist.

Study groups in NCT04518969
Study groupRoleWhat they receive
ControlNo interventionStandard medical therapy (ie: control group) : Adult intensive care patient admit in acute respiratory distress needing intubation with suspicion of under the CT Scan of Covid 19 confirmed by positive antigen or PCR technology N =12 -Mechanical ventilation, prone position if needed,fluid challenge if needed , vasopressors if needed, inotropic support in needed……
CytosorbExperimentalCytoSorb therapy (ie: study group): Adult intensive care patient admit in acute respiratory distress needing intubation with suspicion of under the CT Scan of Covid 19 confirmed by positive antigen or PCR technology N =12 -Mechanical ventilation, prone position if needed,fluid challenge if needed , vasopressors if needed, inotropic support in needed…… Plus patients will be on CRRT with CytoSorb.Nevertheless , patients will be uniquely in CVVHD mode in order to measure only the CytoSorb Effect. First 24 h : the CytoSorb should be changed after 12 h as we forecast a huge cytokine storm in the first 24 hours. After the initial 24 h, cartridge change will occur every 24 hours up a maximum of 96 h in total in the inflammation storm persist.
Receives: Device: CytoSorb

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. comparing % of change in cytokine's clearances of pro et anti -inflammatory types

    comparing the % of change in cytokine's clearances of pro et anti -inflammatory types, as well chemokines and complement pathway between a control population and a treated population with sorbent technology.

    Measured: Day 1 to 5

Secondary outcomes (5)
  1. Evaluation of the impact upon the survival rate at 28 and 90 days.

    Evaluation of the impact upon the survival rate at 28 and 90 days.Beside mortality, morbidity will be evaluate (free ventilatory days, ICU length of stay, shock free days , need of ECMO and secondary bacterial infections.

    Measured: Day 28 and Day 90

  2. Chemokine kinetics

    Chemokine kinetics over time and compared to the control group Chemkine kinetics between blood and lung [time frame at day 1,3 and 5]

    Measured: Day 1 to 5

  3. Cytokine kinetics

    Cytokine kinetics in COVID critically ill patients over time and compared to the control group. [Time Frame: Day 1 to 5] Cytokine kinetics over time and compared to the control group. Chemkine kinetics between blood and lung [time frame at day 1,3 and 5]

    Measured: Day 1 to 5

  4. Complement pathway kinetics

    Complement pathway kinetics in COVID critically ill patients. [Time Frame: Day 1 to 5] Complement pathway kinetics over time and compared to the control group Complement pathway kinetics between blood and lung [time frame at day 1,3 and 5]

    Measured: Day 1 to 5

  5. PaO2/FiO2 ratio

    Evaluation of PaO2/FiO2 ratio evolution during ICU stay

    Measured: Up to 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2020
  2. Study start3 May 2020
  3. Primary completion16 Sep 2021
  4. Study completion16 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Pilot randomized controlled study
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04518969
Sponsor's protocol ID
BrugmannUH 1066
Status last verified
Mar 2022
First submitted
25 Apr 2020
Last updated
4 Mar 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The Novel Coronavirus 2019 epidemic and kidneys. Kidney Int. 2020 May;97(5):824-828. doi: 10.1016/j.kint.2020.03.001. Epub 2020 Mar 7. No abstract available.

    PubMed 32204907
  • Ronco C, Navalesi P, Vincent JL. Coronavirus epidemic: preparing for extracorporeal organ support in intensive care. Lancet Respir Med. 2020 Mar;8(3):240-241. doi: 10.1016/S2213-2600(20)30060-6. Epub 2020 Feb 6. No abstract available.

    PubMed 32035509
  • Kellum JA, Venkataraman R, Powner D, Elder M, Hergenroeder G, Carter M. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans. Crit Care Med. 2008 Jan;36(1):268-72. doi: 10.1097/01.CCM.0000291646.34815.BB.

    PubMed 18090355
  • Hawchar F, Laszlo I, Oveges N, Trasy D, Ondrik Z, Molnar Z. Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study. J Crit Care. 2019 Feb;49:172-178. doi: 10.1016/j.jcrc.2018.11.003. Epub 2018 Nov 10.

    PubMed 30448517
  • Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. No abstract available.

    PubMed 32291463
  • Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation. 2002 Jul 30;106(5):562-8. doi: 10.1161/01.cir.0000023891.80661.ad.

    PubMed 12147537
  • Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC; GenIMS Investigators. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007 Aug 13-27;167(15):1655-63. doi: 10.1001/archinte.167.15.1655.

    PubMed 17698689
  • Honore PM, Hoste E, Molnar Z, Jacobs R, Joannes-Boyau O, Malbrain MLNG, Forni LG. Cytokine removal in human septic shock: Where are we and where are we going? Ann Intensive Care. 2019 May 14;9(1):56. doi: 10.1186/s13613-019-0530-y.

    PubMed 31089920
  • Cavaillon JM, Munoz C, Fitting C, Misset B, Carlet J. Circulating cytokines: the tip of the iceberg? Circ Shock. 1992 Oct;38(2):145-52.

    PubMed 1423923
  • Akil A, Ziegeler S, Reichelt J, Rehers S, Abdalla O, Semik M, Fischer S. Combined Use of CytoSorb and ECMO in Patients with Severe Pneumogenic Sepsis. Thorac Cardiovasc Surg. 2021 Apr;69(3):246-251. doi: 10.1055/s-0040-1708479. Epub 2020 Apr 6.

    PubMed 32252114
  • Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS. Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. mBio. 2018 Oct 9;9(5):e01753-18. doi: 10.1128/mBio.01753-18.

    PubMed 30301856
  • Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmele T, Singbartl K, Federspiel WJ, Clermont G, Kellum JA. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012 Feb;81(4):363-9. doi: 10.1038/ki.2011.320. Epub 2011 Sep 14.

    PubMed 21918497

Questions about this trial

What is this clinical trial studying?

A study testing CytoSorb in people with Covid19, run by Dr David DE BELS at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

comparing % of change in cytokine's clearances of pro et anti -inflammatory types (time frame: Day 1 to 5). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04518969, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in