Mineralocorticoid Receptor Antagonist and Pulmonary Fibrosis in COVID-19. (SpiroCOVID19)

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Canrenoate Potassium; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Katarzyna L Kotfis, MD, PhD; Phone Number: 0048602449202; Email: katarzyna.kotfis@pum.edu.pl

Study Locations

• Poland
  • Szczecin, Poland, 70-111
    • Recruiting
    • Pomeranian Medical University
    • Contact: Katarzyna L Kotfis, MD; Phone Number: 0048914661144; Email: katarzyna.kotfis@pum.edu.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pomeranian Medical University Szczecin
• Investigators: Principal Investigator: Katarzyna L Kotfis, MD, PhD, Pomeranian Medical University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; pneumonia; spironolactone; fibrosis; potassium canrenoate
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; Fibrosis; COVID-19; Pneumonia; Pulmonary Fibrosis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Canrenoic Acid
• Other Study ID Numbers: 0012/100/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No