Mineralocorticoid Receptor Antagonist and Pulmonary Fibrosis in COVID-19.

Study Overview
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Brief Summary
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In December 2019 SARS-CoV-2 virus appeared in the world, mainly appearing as an acute infection of the lower respiratory tract. In March 2020, the World Health Organization (WHO) announced a pandemic in relation to the disease caused by the SARS-CoV-2 virus, known as COronaVIrus Disease 2019 (COVID-19). Since then, the efforts of scientists from around the world have focused on finding the right treatment and vaccine for the new disease. COVID-19 has spread rapidly in a few months, affecting patients in all ages. The disease has a varied course, patients can be 80% asymptomatic, but many develop respiratory failure, complicated by sepsis and ultimately death. One of the possible complications associated with COVID-19 lung involvement is pulmonary fibrosis, leading to chronic breathing difficulties and prolonged disability. No specific mechanisms leading to this phenomenon have been identified in COVID-19, but some information is derived from previous studies on the SARS and MERS epidemic. There have been several reports that the use of spironolactone may be important in preventing pulmonary fibrosis. The aim of the study is to evaluate the effectiveness of intravenous form of mineralocorticoid receptor antagonist canrenoate potassium (an aldosterone antagonist of the spirolactone group) in the treatment of COVID-19-associated pulmonary fibrosis based on the mechanisms of the immune response.

Official Title
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The Use of a Mineralocorticoid Receptor Antagonist (Spironolactone) in the Treatment of Pulmonary Fibrosis Associated With SARS-CoV-2 Infection

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Canrenoate Potassium
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both sexes, 18-90 years of age. Patient requiring oxygen therapy, SpO2 <94%. Confirmed COVID-19 infection. At least one risk factor for increased mortality in the course of COVID-19: currently published in the literature e.g. smoking, hypertension, diabetes, cardiovascular disease. Documented informed consent according to ICH-GCP and national regulations. Exclusion Criteria: Chronic bronchitis, emphysema, interstitial lung disease, or other history of lung disease. Contraindications to the use of spironolactone. Hypersensitivity to spironolactone or any of the excipients. Pregnant patients (pregnancy test will be performed in every patient of reproductive age) and during lactation. Patients with mental illness or dementia who are unable to give informed consent to the examination. ARDS caused by another viral infection (SARS-CoV-2 negative). ARDS from other causes/trauma. Ionic disorders: hyperkalemia, hyponatraemia. Adrenal crisis. Acute and chronic renal failure, creatinine clearance less than 30 ml/min. Anuria. Porphyria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canrenoate potassium<br>Administration of 200 mg of potassium Canrenoate potassium dissolved in 100 ml of 0.9% sodium chloride intravenously twice a day for 7 days. | Drug: Canrenoate Potassium<br>* Intervention: 200 mg of Canrenoate potassium in 100 ml 0,9% NaCl, intravenously twice a day for 7 days.<br>* Other names: Investigational Product;|
| Placebo Comparator: Placebo<br>Administration of 100 ml of 0.9% sodium chloride intravenously twice a day for 7 days. | Drug: Normal Saline<br>* Placebo: 100 ml 0,9% NaCl, intravenously twice a day for 7 days.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation | Duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy | 30 days | 
| Passive oxygen therapy | Duration of passive oxygen therapy | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU LOS | Intensive Care Unit length of stay (LOS). | 30 days | 
| Hospital LOS | Total hospital length of stay (LOS). | 90 days | 
| Chest CT | Assessment of the dynamics of recovery of changes in chest CT at 3 months. | 90 days | 
| Lung ultrasound_7 | Assessment of the dynamics of recovery of changes in lung ultrasound at 7 days. | 7 days | 
| Lung ultrasound_30 | Assessment of the dynamics of recovery of changes in lung ultrasound at 30 days. | 30 days | 
| Mortality_30 | Assessment of mortality at 30 days. | 30 days | 
| Mortality_90 | Assessment of mortality at 90 days. | 90 days | 
| IL-1β level change. | Evaluation of the degree of change of the level of pro-inflammatory cytokine IL-1β. | 7 days | 
| IL-2 level change. | Evaluation of the degree of change of the level of pro-inflammatory cytokine IL-2. | 7 days | 
| IL-6 level change. | Evaluation of the degree of change of the level of pro-inflammatory cytokine IL-6. | 7 days | 
| IL-33 level change. | Evaluation of the degree of change of the level of pro-inflammatory cytokine IL-33. | 7 days | 
| TNFα level change. | Evaluation of the degree of change of the level of pro-inflammatory cytokine TNFα. | 7 days | 
| 6MWT | Six minute walk test. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrosis, COVID-19, spironolactone, pneumonia, SARS-CoV-2, potassium canrenoate