SPIDEX-II: Spironolactone and Dexamethasone in Patients Hospitalized With COVID-19
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment 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). |
Drug: Spironolactone + Dexamethasone
Low doses of orally administered spironolactone and dexamethasone
|
| Active Comparator: Control 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 |
Drug: Standard-of-care SARS-CoV-2 treatment
Standard-of-care SARS-CoV-2 treatment administered according to the local guidelines
|
Outcome Measures
Primary Outcome Measures
- Evaluation of the clinical status [Day 14 post-randomization]
Clinical status at day 14 post-randomization defined by a 6-point ordinal scale score (6 being the worst score)
Secondary Outcome Measures
- 28-day all-cause mortality [28 days post-randomization]
All-cause mortality at 28 days post-randomization
- Oxygen-free days [28 days post-randomization]
The number of days without oxygen support of any type
- Ventilator-free days [28 days post-randomization]
The number of days without invasive mechanical ventilation
- Invasive mechanical ventilation [28 days post-randomization]
The number of patients requiring invasive mechanical ventilation during hospitalization and the number of days spent on newly-administered invasive mechanical ventilation
- Time to discharge [28 days post-randomization]
The number of days from hospitalization to discharge
- Length of ICU stay [28 days post-randomization]
The number of days spent in the intensive care unit
- New ICU admission [28 days post-randomization]
The number of patients requiring transfer to ICU and the number of days spent in the ICU post-transfer
- Long-COVID development [60 and 90 days post-admission]
The number of patients with signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis (Post-COVID-19 syndrome as defined by the relevant NICE guidance)
- Evaluation of the clinical status [Day 7 post-randomization]
Clinical status at day 7 post-randomization defined by a 6-point ordinal scale score (6 being the worst score)
Other Outcome Measures
- Adverse events [28 days post-randomization]
Incidence of adverse events related to the use of the investigational products
- Laboratory abnormalities [28 days post-randomization]
Occurrence of laboratory hematimetric parameters, creatinine, d-dimer, c-reactive protein
- Change in classic cough score [28 days post-randomization]
Change in classic cough score measured daily in hospitalized patients
- Radiological abnormalities [28 days post-randomization]
Occurrence of viral pneumonia-associated changes on sequential chest CT scans in hospitalized patients
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 years or above;
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Signed informed consent;
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PCR-confirmed diagnosis of SARS-CoV-2 infection
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Presenting with moderate-to-severe disease (scores 4-6 on WHO ordinal scale)
Exclusion Criteria:
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Women of childbearing age without a negative urine pregnancy test, currently pregnant or breastfeeding women;
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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)
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Participating in another clinical trial
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Severe electrolyte imbalance (hyperkalemia > 5.0 mmol/l, hyponatremia < 120 mmol/l)
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Hypersensitivity or contraindications to the study drugs (spironolactone and dexamethasone)
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Renal dialysis
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Severe uncontrolled diabetes mellitus
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Patient receiving one of the following medications that cannot be substituted over the trial duration: ACE inhibitors, amiloride, eplerenone, cortisone acetate, potassium canrenoate, triamterene
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chita State Regional Clinical Hospital Number 1 | Chita | Russian Federation | 672039 |
Sponsors and Collaborators
- Chita State Regional Clinical Hospital Number 1
Investigators
- Principal Investigator: Sergey Lukyanov, MD, Chita State Regional Clinical Hospital Number 1
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SPII_1789461