Clinical trial NCT04826822: Spironolactone and Dexamethasone in Patients Hospitalized With COVID-19
Official title: Spironolactone and Dexamethasone in Patients Hospitalized With Moderate-to-severe COVID-19 (SPIDEX-II): a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Coronavirus Infection
Pneumonia, Viral
Lead sponsor: Chita State Regional Clinical Hospital Number 1
Sponsor class: OTHER_GOV
First posted: 2021-04-01
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of the clinical status
timeFrame: Day 14 post-randomization
Secondary outcomes:
measure: 28-day all-cause mortality
timeFrame: 28 days post-randomization
measure: Oxygen-free days
timeFrame: 28 days post-randomization
measure: Ventilator-free days
timeFrame: 28 days post-randomization
measure: Invasive mechanical ventilation
timeFrame: 28 days post-randomization
measure: Time to discharge
timeFrame: 28 days post-randomization
measure: Length of ICU stay
timeFrame: 28 days post-randomization
measure: New ICU admission
timeFrame: 28 days post-randomization
measure: Long-COVID development
timeFrame: 60 and 90 days post-admission
measure: Evaluation of the clinical status
timeFrame: Day 7 post-randomization
Other outcomes:
measure: Adverse events
timeFrame: 28 days post-randomization
measure: Laboratory abnormalities
timeFrame: 28 days post-randomization
measure: Change in classic cough score
timeFrame: 28 days post-randomization
measure: Radiological abnormalities
timeFrame: 28 days post-randomization
Locations:
city: Chita
country: Russian Federation
facility: Chita State Regional Clinical Hospital Number 1
Study officials:
affiliation: Chita State Regional Clinical Hospital Number 1
name: Sergey Lukyanov, MD
role: PRINCIPAL_INVESTIGATOR
References: