Covid19
Conditions
Keywords
SARS-CoV-2, cytokine storm, Interleukin 6, hypercoagulability, Fibrinogen, D-dimer
Brief summary
Several studies have suggested a potential clinical benefit of controlling hyper inflammation triggered by SARS-CoV-2/COVID-19. Blood purification, the removal of excessive proinflammatory mediators may control disease progression and support clinical recovery. For this purpose, COVID-19 patients might benefit from treatment with AN69ST hemofilter based extracorporeal blood purification.
Detailed description
COVID-19 disease progression is associated with dysregulated immunity, commonly referred to as cytokine storm, in particular, aberrant Interleukin (IL) 6 levels that promote numerous pathological downstream effects. Hyperinflammation is a well-established trigger of multiorgan failure, for example, acute kidney injury. Moreover, recent reports point to a link between hyper inflammation and COVID-19 induced coagulopathy as a result of increased production of clotting factors by the liver. Despite several lines of evidence pointing to a potential clinical benefit of controlling hyperinflammation triggered by COVID-19, management of COVID-19 remains mostly supportive built around continuous respiratory support. To this end, considering the underlying immunological character of COVID-19 disease and the high risk of SARS-CoV-2 hyperinflammation to trigger ARDS, hypercoagulability and Acute Kidney Injury (AKI) this study aims to monitor selected biochemical, immunological and coagulation parameters in combination with radiological imaging to guide clinical practice and to tailor therapy consisting of 1) early initiation of blood purification using the oXiris® (AN69ST) filter, 2) systemic heparinisation and 3) respiratory support
Interventions
DEVICEExtracorporeal blood purification using the oXiris® (AN69ST) hemofilter
Admitted patients will receive at least 1 cycle of extracorporeal blood purification using the oXiris® (AN69ST) hemofilter (Baxter, IL, USA). The number of cycles of blood purification is determined based on multiple biochemical, immunological, coagulation parameters, radiological imaging and overall clinical condition. The patient is connected to the Prismaflex® oXiris® system via a double lumen catheter placed in the femoral vein or vena subclavia. Flow rates will be maintained as follow; effluent dose 35 mL/Kg/h, dialysate 14 - 16 mL/Kg/h, blood 150 mL/min, replacement 16 -18 mL/Kg/h; patient fluid removal is tailored to the individual's volume status, ≈ 100 - 250 mL/h. The oXiris® extracorporeal and organ support modality will be chosen according to the patient's kidney function; continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) or slow continuous ultrafiltration (SCUF).
Sponsors
Zan Mitrev Clinic
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Confirmed COVID-19 disease: * RT-PCR * Atypical Pneumonia; X-Ray and/or Computed Tomography * ≥ 1 oXiris® blood purification cycle
Exclusion criteria
* Pregnancy * Heart failure; severe systolic dysfunction, left ventricular ejection fraction \< 25% requiring urgent surgery * Aortic Aneurysms, dissection or rupture requiring urgent surgery * Recent Myocardial Infarction; cardiovascular disease patients requiring urgent surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ICU length of stay after admission (days) | An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first) | Duration of intensive care will be determined in relation to the number of blood purification cycles Patients will be followed for the duration of ICU stay. |
| Changes in inflammatory markers; C-Reactive Protein (CRP) (mg/L) | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Systemic levels of proinflammatory mediators are measured as a marker for disease severity. Measurement points: at admission, before and after a blood purification cycle and before discharge. |
| Changes in thrombocyte counts (10^3 counts/microL) | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Systemic levels of thrombocytes are measured as a marker for disease severity. Measurement points: at admission, before and after a blood purification cycle and before discharge. |
| Changes in the coagulation marker Fibrinogen (g/L) | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Coagulation markers will be followed to assess the effect of systemic heparinisation, Measurement points, at admission, before and after a blood purification cycle and before discharge |
| Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL) | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Systemic levels of IL-6, IL-8 and TNF-α are evaluated to assess the effect of blood purification. Measurement points: at admission, before and after a blood purification cycle and before discharge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the coagulation marker D-Dimers (ng/mL) | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Coagulation markers will be followed to assess the effect of systemic heparinisation, Measurement points, at admission, before and after a blood purification cycle and before discharge |
| Changes in the Activation Clotting Time (seconds). | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Coagulation markers will be followed to assess the effect of systemic heparinisation, Measurement points, at admission, before and after a blood purification cycle and before discharge |
| Changes in Neutrophil-to-Lymphocyte Ratio | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | Systemic levels of proinflammatory mediators are measured as a marker for disease severity. Measurement points: at admission, before and after a blood purification cycle and before discharge. |
Countries
North Macedonia
Outcome results
None listed