Spironolactone and Dexamethasone in Patients Hospitalized With COVID-19

NCT04826822 | Unknown Phase 3 DMC

• 1 other identifier: SPII_1789461
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronavirus Infection; Pneumonia, Viral

Outcome Measures

Primary Outcomes (1)

• Evaluation of the clinical status

  Clinical status at day 14 post-randomization defined by a 6-point ordinal scale score (6 being the worst score)

  Day 14 post-randomization

Secondary Outcomes (9)

• 28-day all-cause mortality

  28 days post-randomization

• Oxygen-free days

  28 days post-randomization

• Ventilator-free days

  28 days post-randomization

• Invasive mechanical ventilation

  28 days post-randomization

• Time to discharge

  28 days post-randomization

Other Outcomes (4)

• Adverse events

  28 days post-randomization

• Laboratory abnormalities

  28 days post-randomization

• Change in classic cough score

  28 days post-randomization

Study Arms (2)

Treatment

EXPERIMENTAL

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

Control

ACTIVE COMPARATOR

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

Interventions

Spironolactone + Dexamethasone DRUG

Low doses of orally administered spironolactone and dexamethasone

Treatment

Standard-of-care SARS-CoV-2 treatment DRUG

Standard-of-care SARS-CoV-2 treatment administered according to the local guidelines

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Chita State Regional Clinical Hospital Number 1: lead

Study Sites (1)

Chita State Regional Clinical Hospital Number 1

Chita, 672039, Russia

RECRUITING

MeSH Terms

Conditions

Coronavirus Infections; Pneumonia, Viral

Interventions

Spironolactone; Dexamethasone

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated

Study Officials

• Sergey Lukyanov, MD

  Chita State Regional Clinical Hospital Number 1

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sergey Lukyanov, MD

CONTACT

+79242772971; lukyanov-sergei@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2021
• First Posted: April 1, 2021
• Study Start: February 24, 2021
• Primary Completion: July 8, 2021
• Study Completion: September 2, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)