Determination of the Hemoadsorption Impact as Adjunctive Treatment Upon the Support Therapy of COVID-19
Condition: Covid19
MeSH terms: COVID-19
Study type: Interventional

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.
    

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.
    

Intervention name(s): CytoSorb
Intervention type(s): Device
Intervention description(s): 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 intervention name(s): CRRT
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Pilot randomized controlled study
Masking: None (Open Label)
Primary purpose: Treatment