Spironolactone and Dexamethasone in Patients Hospitalized With COVID-19

Spironolactone and Dexamethasone in Patients Hospitalized With Moderate-to-severe COVID-19 (SPIDEX-II): a Randomized Clinical Trial

The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a rapidly spreading infection of the respiratory tract. Most infected patients have either asymptomatic disease or mild symptoms. However, a proportion of patients, especially elderly men or patients with comorbidities, are at risk of developing acute respiratory distress syndrome (ARDS). ARDS, alongside clotting abnormalities, is known to be a major contributor to SARS-CoV-2-related mortality and admission to intensive care units, with evidenced effective preventative treatment options lacking. In this study, the investigators test a novel hypothesis that the use of a combination of spironolactone and dexamethasone at low doses will improve the clinical progression of the infection evaluated by the 6-point ordinal scale in patients with moderate and severe disease by blocking exocytosis of the Weibel-Palade bodies from endothelial cells.

Inclusion Criteria:

• Age 18 years or above;
• Signed informed consent;
• PCR-confirmed diagnosis of SARS-CoV-2 infection
• Presenting with moderate-to-severe disease (scores 4-6 on WHO ordinal scale)

Exclusion Criteria:

• Women of childbearing age without a negative urine pregnancy test, currently pregnant or breastfeeding women;
• Severe heart failure (NYHA4), severe renal failure (eGFR < 30 ml/min/1.73 m2), severe liver failure (ALT/AST ratio > 5 norms), severe anemia (haemoglobin < 30 g/l)
• Participating in another clinical trial
• Severe electrolyte imbalance (hyperkalemia > 5.0 mmol/l, hyponatremia < 120 mmol/l)
• Hypersensitivity or contraindications to the study drugs (spironolactone and dexamethasone)
• Renal dialysis
• Severe uncontrolled diabetes mellitus
• Patient receiving one of the following medications that cannot be substituted over the trial duration: ACE inhibitors, amiloride, eplerenone, cortisone acetate, potassium canrenoate, triamterene