Is Bio-adrenomedullin (Bio-ADM) a Prognostic Factor in Patients With COVID-19 Treated in the ICU?

Study Overview
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Brief Summary
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This is prospective, observational study using point of care test to determine bio-ADM whole blood concentrations and its predictive value in patients with COVID-19 treated in the ICU.

Detailed Description
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About 5% of all patients infected with the SARS-CoV-2 virus require treatment in the ICU. The main reason for admission to the ICU is acute hypoxemic respiratory failure, which in most cases is associated with the need for mechanical ventilation. The progression of lung damage affects not only alveoli but also endothelium of the pulmonary vessels. Occurring endotheliopathy is caused by direct infection with SARS-CoV-2 virus and activation of the immune system leading to an increased inflammatory reaction. Damage to the endothelium barrier with concomitant cytokine storm lead to activation of the coagulation system and formation of microthrombotic events in the vascular bed, resulting in thromboembolic complications and development of multiorgan failure. The reflection of the above pathophysiological phenomena in laboratory tests is a significant increase in the concentration of D-dimers. At present, no specific markers of endotheliopathy in patients with SARS-CoV-2 are known. Adrenomedullin (ADM) is a peptide hormone that plays a key role in regulating the function of the endothelium, by modulating its integrity and permeability, it also has an effect on the vascular muscle, leading to vasodilation. Recently, the role of ADM has been intensively studied, including in sepsis. Several studies have confirmed an association between elevated ADM levels and poor prognosis in sepsis and septic shock. In these studies, measurements of various adrenomedullin precursors and free, biologically active adrenomedullin (bio-adrenomedullin, bio-ADM) were performed. The role of bio-ADM in the course of COVID -19 remains unclear. The aim of the study is to determine the baseline concentration of bio-ADM and to determine the dynamic of the concentration changes in three measurements in patients with COVID-19 during ICU treatment. Additional measurement of bio-ADM will be performed as standard monitoring in patients suspected of septic complications of the course of COVID-19.

Official Title
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Is Bio-adrenomedullin (Bio-ADM) a Prognostic Factor in Patients With COVID-19 Treated in the ICU?

Conditions
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Covid19

Intervention / Treatment
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* Device: IB10 sphingotest® bio-ADM® apparatus (Sphingotec GmbH, Hennigsdorf, Germany)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years polymerase chain reaction (PCR) confirmed COVID-19 severe stage of pneumonia caused by SARS-CoV-2 requiring oxygen therapy informed consent to participate in the study Exclusion Criteria: qualification to palliative care life expectancy < 48 h mechanical ventilation at the beginning of the hospitalization transfer from other ICU pregnancy

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

| Intervention/Treatment |
| --- |
|Device: IB10 sphingotest® bio-ADM® apparatus (Sphingotec GmbH, Hennigsdorf, Germany)|Point of care assessment of bio-adrenomedullin concentration will be performed using the IB10 sphingotest® bio-ADM® apparatus (Sphingotec GmbH, Hennigsdorf, Germany) on the 1,3,5-day ICU stay in COVID-19 patients. The method used is a double monoclonal sandwich immunoassay to measure the concentration of C-terminal amidated, biologically active adrenomedullin (bio-ADM) in whole blood. Additional measurement of bio-ADM will be performed as standard monitoring in patients suspected of septic complications of the course of COVID-19.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 28-day mortality will be assessed | 28-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequential Organ Failure Assessment (SOFA) Score and its changes over time | Occurrence of multiorgan failure expressed in SOFA scores | 28-days | 
| Need for catecholamines | Need for catecholamines (drug, highest/lowest dose, duration) | 28-days | 
| Need for renal replacement therapy | Need for renal replacement therapy (duration) | 28-days | 
| Need for mechanical ventilation | Need for mechanical ventilation (duration) | 28-days | 
| Changes of partial pressure of oxygen in arterial blood (PaO2) / fraction of inspired oxygen (FiO2) during treatment in ICU | PaO2/FiO2 | 28-days | 
| Changes in D-dimer | Changes in D-dimer (in ng/ml) | 28-days | 
| Changes in blood lactate levels | Changes in blood lactate levels (in mg/dl) | 28-days | 
| Changes C reactive protein (CRP) | Changes CRP (in mg/l) | 28-days | 
| Changes in procalcitonin levels | Changes in procalcitonin levels (in ng/ml) | 28-days | 
| Changes in creatinine levels | Changes in creatinine levels (in mg/dl) | 28-days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bio-adrenomedullin, point of care, sepsis