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

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04518969
• Other study ID #: BrugmannUH 1066
• Status: Completed
• Phase: N/A
• Start date: May 3, 2020
• Est. completion date: September 16, 2021

Study information

• Verified date: March 2022
• Source: Brugmann University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 16, 2021
• Est. primary completion date: September 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

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.

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Dr David DE BELS

Country where clinical trial is conducted

Belgium, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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). pii: e01753-18. doi: 10.1128/mBio.01753-18. — View Citation

Hawchar F, László I, Öveges N, Trásy 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. — View Citation

Honore PM, Hoste E, Molnár 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmelé 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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 to 5
Secondary	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.	Day 28 and Day 90
Secondary	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]	Day 1 to 5
Secondary	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]	Day 1 to 5
Secondary	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]	Day 1 to 5
Secondary	PaO2/FiO2 ratio	Evaluation of PaO2/FiO2 ratio evolution during ICU stay	Up to 90 days