Spironolactone and Dexamethasone in Patients Hospitalized With COVID-19 (SPIDEX-II)

Chita State Regional Clinical Hospital Number 1

Status and phase: Unknown; Phase 3

Conditions: Pneumonia, Viral; Coronavirus Infection

Treatments: Drug: Standard-of-care SARS-CoV-2 treatment; Drug: Spironolactone + Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT04826822

SPII_1789461

Details and patient eligibility

About

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.

Enrollment: 440 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

440 participants in 2 patient groups

Treatment

Experimental group

Description:

After randomisation (Day 1): Spironolactone \[100 mg 1x/day\] + dexamethasone \[2 mg 2x/day, 12/12h\] Days 2-12\*: Spironolactone \[50 mg 2x/day, 12/12h\] + dexamethasone \[2 mg 2x/day, 12/12h\] Days 13-20: Spironolactone \[25 mg 2x/day, 12/12h\] Days 21-28: Spironolactone \[25 mg 1x/day\] Standard treatment is according to the treatment protocol for 2019-nCoV infection. \*In case of cortisol levels above 100 nmol/L on days 3 and 4, the dexamethasone dose should be increased to 3 mg in the morning and in the evening (total 6 mg per day).

Treatment:

Drug: Spironolactone + Dexamethasone

Control

Active Comparator group

Description:

Patients receiving standard-of-care treatment for SARS-CoV-2 infection as regulated by the relevant guidelines of the Ministry of Healthcare of the Russian Federation

Treatment:

Drug: Standard-of-care SARS-CoV-2 treatment