Clinical trial NCT04912011: Mineralocorticoid Receptor Antagonist and Pulmonary Fibrosis in COVID-19.
Official title: The Use of a Mineralocorticoid Receptor Antagonist (Spironolactone) in the Treatment of Pulmonary Fibrosis Associated With SARS-CoV-2 Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: COVID-19 Pneumonia
Keywords: COVID-19
spironolactone
pneumonia
fibrosis
SARS-CoV-2
potassium canrenoate
Lead sponsor: Pomeranian Medical University Szczecin
Sponsor class: OTHER
First posted: 2021-06-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mechanical ventilation
timeFrame: 30 days
measure: Passive oxygen therapy
timeFrame: 30 days
Secondary outcomes:
measure: ICU LOS
timeFrame: 30 days
measure: Hospital LOS
timeFrame: 90 days
measure: Chest CT
timeFrame: 90 days
measure: Lung ultrasound_7
timeFrame: 7 days
measure: Lung ultrasound_30
timeFrame: 30 days
measure: Mortality_30
timeFrame: 30 days
measure: Mortality_90
timeFrame: 90 days
measure: IL-1β level change.
timeFrame: 7 days
measure: IL-2 level change.
timeFrame: 7 days
measure: IL-6 level change.
timeFrame: 7 days
measure: IL-33 level change.
timeFrame: 7 days
measure: TNFα level change.
timeFrame: 7 days
measure: 6MWT
timeFrame: 30 days
Other outcomes:
Locations:
city: Szczecin
country: Poland
facility: Pomeranian Medical University
Study officials:
affiliation: Pomeranian Medical University
name: Katarzyna L Kotfis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lechowicz K, Drozdzal S, Machaj F, Rosik J, Szostak B, Zegan-Baranska M, Biernawska J, Dabrowski W, Rotter I, Kotfis K. COVID-19: The Potential Treatment of Pulmonary Fibrosis Associated with SARS-CoV-2 Infection. J Clin Med. 2020 Jun 19;9(6):1917. doi: 10.3390/jcm9061917.
citation: Kotfis K, Lechowicz K, Drozdzal S, Niedzwiedzka-Rystwej P, Wojdacz TK, Grywalska E, Biernawska J, Wisniewska M, Parczewski M. COVID-19-The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection. Pharmaceuticals (Basel). 2021 Jan 17;14(1):71. doi: 10.3390/ph14010071.