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

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ClinicalTrials.gov Identifier: NCT04518969
Recruitment Status : Recruiting
First Posted : August 19, 2020
Last Update Posted : August 19, 2020
Sponsor:
Information provided by (Responsible Party):
Dr David DE BELS, Brugmann University Hospital

Brief 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.

B) 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.


Condition or disease Intervention/treatment Phase
Covid19 Device: CytoSorb Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pilot randomized controlled study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 3, 2020
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2020

Arm Intervention/treatment
No Intervention: Control
Standard 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……
Experimental: Cytosorb

CytoSorb 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.

Device: CytoSorb

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.

Other Name: CRRT




Primary Outcome Measures :
  1. comparing % of change in cytokine's clearances of pro et anti -inflammatory types [ Time Frame: Day 1 to 5 ]
    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.


Secondary Outcome Measures :
  1. Evaluation of the impact upon the survival rate at 28 and 90 days. [ Time Frame: Day 28 and Day 90 ]
    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.

  2. Chemokine kinetics [ Time Frame: Day 1 to 5 ]
    Chemokine kinetics over time and compared to the control group Chemkine kinetics between blood and lung [time frame at day 1,3 and 5]

  3. Cytokine kinetics [ Time Frame: Day 1 to 5 ]
    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]

  4. Complement pathway kinetics [ Time Frame: Day 1 to 5 ]
    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]

  5. PaO2/FiO2 ratio [ Time Frame: Up to 90 days ]
    Evaluation of PaO2/FiO2 ratio evolution during ICU stay



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- 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 )

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04518969


Contacts
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Contact: Patrick Honore, MD 0032/24773946 Patrick.Honore@CHU-Brugmann.be

Locations
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Belgium
CHU Brugmann Recruiting
Brussels, Belgium, 1020
Contact: Patrick Honoré, MD    0032/24773946    Patrick.Honore@CHU-Brugmann.be   
Principal Investigator: Patrick Honoré, MD         
Sponsors and Collaborators
Dr David DE BELS
Investigators
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Principal Investigator: Patrick Honore, MD CHU Brugmann
Publications:

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Responsible Party: Dr David DE BELS, Chairmn ICU, Brugmann University Hospital
ClinicalTrials.gov Identifier: NCT04518969    
Other Study ID Numbers: BrugmannUH 1066
First Posted: August 19, 2020    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No