CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19

Study Overview
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Brief Summary
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The 'CAPMYKCO' study is a randomized controlled, open-label, single center proof of concept trial. The aim of this study is to evaluate whether a CRP-apheresis in addition to the current standard therapy is intended to mitigate the severity of the disease course of SARS-CoV-2, especially with regard to tissue injury in the lungs, heart and kidneys and their consequences. CRP-apheresis should reduce the necessity and duration of non-invasive/invasive ventilation requirements compared to the control group. The influence of CRP-apheresis on the attenuation of pulmonary, myocardial and/or kidney tissue injury as well as the course of the COVID-19 disease will also be demonstrated by evaluating various biomarkers, several clinical scoring systems, and the duration of intensive care medical treatment.

Detailed Description
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The prognostic value of C-reactive protein (CRP) in assessing disease progression in COVID-19 is well known: The steeper the CRP rise in the days after infection and the higher the CRP concentration at hospitalization, the worse the prognosis. It is believed that CRP concentration not only reflects tissue damage but also causally contributes to the severity of the damage that occurs. CRP apheresis effectively limits CRP rise, which may lead to improved prognosis. CRP apheresis is a therapeutic hemapheresis procedure that selectively removes C-reactive protein from the patient's plasma. Other causal therapies for immediate selective reduction of CRP in the acute phase of disease are not currently available. In the planned 'CAPMYKCO' study, CRP-apheresis in addition to current standard COVID-19 therapy is expected to mitigate the severity of disease progression, particularly with regard to tissue injury in the lungs, the heart and/or the kidneys and their respective clinical consequences. CRP-apheresis treatment in COVID-19 patients should reduce the necessity and duration of non-invasive / invasive ventilation compared to the control group. The influence of CRP-apheresis on the course of the COVID-19 disease will also be demonstrated by evaluating different organ biomarkers and the duration of intensive medical treatment.

Official Title
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Randomized, Controlled, Proof-Of-Concept Trial of CRP-Apheresis for Attenuation of Pulmonary MYocardial and/or Kidney Injury in COvid-19

Conditions
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Covid19

Intervention / Treatment
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* Device: CRP-apheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed SARS CoV-2 infection (PCR-test) Oxygen therapy (maximum 'high-flow' therapy) CRP plasma concentration ≥ 50 mg/l and/or CRP increase ≥ 15 mg/l within 24 h after admission. Completed informed consent and written informed consent. Legal capacity Exclusion Criteria: Age < 18 years Pregnancy / lactation period Invasive, mechanical ventilation Extracorporeal membrane oxygenation (ECMO) Participation in other interventional trials Extracorporeal membrane oxygenation (ECMO) support Participation in other interventional trials

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CRP-apheresis<br>Patients randomized to this group will undergo apheresis treatments with treatments every 24 ± 12 h each lasting 4-7 hours, until the CRP value does not rise to ≥ 30 mg/l within 96 h after the last treatment | Device: CRP-apheresis<br>* The major advantages of depleting C-reactive protein by therapeutic apheresis are the selective removal of the damaging agent by the highly specific ligand and the good controllability of the procedure, since the plasma can be passed over the column as often as necessary to achieve the desired reduction. In addition, treatment can be interrupted or discontinued at any time.<br>* Other names: CRP-depletion;|
| No Intervention: Control<br>Patients randomized to this group will not undergo a apheresis treatments. They will be treated according to the current conventional treatment concept for covid-19 disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necessity and duration of non-invasive/ invasive ventilation | In the intervention group, a reduced necessity and duration of non-invasive/ invasive ventilation is expected. | through study completion, an average of 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of intensive care unit stay | In the intervention group, a shorter intensive care unit stay is expected. | through study completion, an average of 14 days | 
| Necessity of endotracheal intubation | In the intervention group, a reduced necessity of endotracheal intubation is expected. | through study completion, an average of 14 days | 
| Reduction of lung injury | In the intervention group, a reduced lung injury as reflected by peripheral oxygen saturation, oxygen supplementation, Horovitz index, lung injury score is expected. | through study completion, an average of 14 days | 
| Reduction of myocardial damage | In the intervention group, a reduced myocardial damage as reflected by hs troponin, creatin kinase, creatin kinase MB fraction is expected. | up to 10 days | 
| Reduction of kidney damage | In the intervention group, a reduced kidney damage as reflected by creatinine, glomerular filtration rate, onset of dialysis, CKD stadium is expected. | up to 10 days | 
| Improvement in general immune status | In the intervention group, an improved general immune status as reflected by CRP, fibrinogen, leukocytes, thrombocytes and lactate dehydrogenase is expected. | up to 10 days | 
| Cardiovascular, respiratory and renal SOFA score | In the intervention group, improvements in cardiovascular, respiratory and renal SOFA scores are expected. *(Vincent JL: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. In:Intensive Care Med 1996:22;707-10.) | through study completion, an average of 14 days | 
| Respiratory events | In the intervention group, a reduction of respiratory events (pulmonary embolism) is expected. | through study completion, an average of 14 days | 
| Myocardial events | In the intervention group, a reduction of cardial events (cardiac arrhythmias, myocardial infarction, cardiopulmonary resuscitation, low cardiac output syndrome (LCOS), operation, percutaneous coronary intervention (PCI), angina pectoris) is expected. | through study completion, an average of 14 days | 
| Renal events | In the intervention group, a reduction of renal events (onset of dialysis requirement, deterioration of renal function (CKD increase) is expected. | through study completion, an average of 14 days | 
| Safety of CRF apheresis | In the intervention group, the absence of serious incidents is expected. | through study completion, an average of 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRP-apheresis, COVID-19, SARS-CoV-2