Extracorporeal Blood Purification as a Treatment Modality for COVID-19

Study Overview
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Brief Summary
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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
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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

Official Title
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Clinical Efficacy and Safety of Extracorporeal Blood Purification to Control Hyperinflammation and Hypercoagulability in COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 patients admitted to the ICU<br>COVID-19 patients will be treated with the Prismaflex® oXiris® system in the ICU. Treatment will be initiated within 4 - 12 hours after admission upon establishing control of the haemostasis, ACT = Activated Coagulation Time of 180 seconds | Device: Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cytokine levels of Interleukin (IL) 6, IL-8 and Tumor Necrosis Factor-α (pg/mL) | 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 | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| Changes in inflammatory markers; C-Reactive Protein (CRP) (mg/L) | 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. | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| Changes in thrombocyte counts (10^3 counts/microL) | 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. | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| Changes in the coagulation marker Fibrinogen (g/L) | 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 | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| ICU length of stay after admission (days) | 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. | An expected average of 4 - 14 hospitalisation days or until hospital discharge (whichever comes first) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Neutrophil-to-Lymphocyte Ratio | 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. | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| Changes in the coagulation marker D-Dimers (ng/mL) | 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 | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 
| Changes in the Activation Clotting Time (seconds). | 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 | Hospitalisation window, day 0 until day 14 or until hospital discharge (whichever comes first) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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D-dimer, SARS-CoV-2, cytokine storm, Interleukin 6, hypercoagulability, Fibrinogen