Mineralocorticoid Receptor Antagonist and Pulmonary Fibrosis in COVID-19.

Phase 4

• Conditions: COVID-19 Pneumonia
• Interventions: Drug: Canrenoate Potassium; Drug: Normal Saline

• Registration Number: NCT04912011
• Lead Sponsor: Pomeranian Medical University Szczecin

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-01
• Status Verified: 2021-06
• Study First Submitted: 2021-06-01
• Study First Submitted QC: 2021-06-02
• Study First Posted: 2021-06-03
• Last Update Submitted: 2021-06-03
• Last Update Posted: 2021-06-08
• Primary Completion: 2021-08-31
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Patients of both sexes, 18-90 years of age.
2. Patient requiring oxygen therapy, SpO2 <94%.
3. Confirmed COVID-19 infection.
4. 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.
5. Documented informed consent according to ICH-GCP and national regulations.

Exclusion Criteria

1. Chronic bronchitis, emphysema, interstitial lung disease, or other history of lung disease.
2. Contraindications to the use of spironolactone.
3. Hypersensitivity to spironolactone or any of the excipients.
4. Pregnant patients (pregnancy test will be performed in every patient of reproductive age) and during lactation.
5. Patients with mental illness or dementia who are unable to give informed consent to the examination.
6. ARDS caused by another viral infection (SARS-CoV-2 negative).
7. ARDS from other causes/trauma.
8. Ionic disorders: hyperkalemia, hyponatraemia.
9. Adrenal crisis.
10. Acute and chronic renal failure, creatinine clearance less than 30 ml/min.
11. Anuria.
12. Porphyria.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Canrenoate potassium	Canrenoate Potassium	Administration of 200 mg of potassium Canrenoate potassium dissolved in 100 ml of 0.9% sodium chloride intravenously twice a day for 7 days.
Placebo	Normal Saline	Administration of 100 ml of 0.9% sodium chloride intravenously twice a day for 7 days.

Primary Outcome Measures

Name	Time	Method
Mechanical ventilation	30 days	Duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy
Passive oxygen therapy	30 days	Duration of passive oxygen therapy

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Pomeranian Medical University; 🇵🇱 Szczecin, Poland