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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronavirus Infection; Pneumonia, Viral
• Intervention / Treatment: Drug: Spironolactone + Dexamethasone; Drug: Standard-of-care SARS-CoV-2 treatment

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sergey Lukyanov, MD; Phone Number: +79242772971; Email: lukyanov-sergei@mail.ru

Study Locations

• Russian Federation
  • Chita, Russian Federation, 672039
    • Recruiting
    • Chita State Regional Clinical Hospital Number 1
    • Contact: Sergey Lukyanov, MD; Phone Number: +7 924 277-29-71; Email: lukyanov-sergei@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality	All-cause mortality at 28 days post-randomization	28 days post-randomization
Oxygen-free days	The number of days without oxygen support of any type	28 days post-randomization
Ventilator-free days	The number of days without invasive mechanical ventilation	28 days post-randomization
Invasive mechanical ventilation	The number of patients requiring invasive mechanical ventilation during hospitalization and the number of days spent on newly-administered invasive mechanical ventilation	28 days post-randomization
Time to discharge	The number of days from hospitalization to discharge	28 days post-randomization
Length of ICU stay	The number of days spent in the intensive care unit	28 days post-randomization
New ICU admission	The number of patients requiring transfer to ICU and the number of days spent in the ICU post-transfer	28 days post-randomization
Long-COVID development	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)	60 and 90 days post-admission
Evaluation of the clinical status	Clinical status at day 7 post-randomization defined by a 6-point ordinal scale score (6 being the worst score)	Day 7 post-randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence of adverse events related to the use of the investigational products	28 days post-randomization
Laboratory abnormalities	Occurrence of laboratory hematimetric parameters, creatinine, d-dimer, c-reactive protein	28 days post-randomization
Change in classic cough score	Change in classic cough score measured daily in hospitalized patients	28 days post-randomization
Radiological abnormalities	Occurrence of viral pneumonia-associated changes on sequential chest CT scans in hospitalized patients	28 days post-randomization

Collaborators and Investigators

• Sponsor: Chita State Regional Clinical Hospital Number 1
• Investigators: Principal Investigator: Sergey Lukyanov, MD, Chita State Regional Clinical Hospital Number 1

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Anticipated): July 8, 2021
• Study Completion (Anticipated): September 2, 2021

Study Registration Dates

• First Submitted: March 28, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Coronavirus Infections; Pneumonia, Viral; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Dexamethasone; Spironolactone
• Other Study ID Numbers: SPII_1789461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Sharing IPD would require material transfer agreement according to the local rules and regulations. The study protocol, statistical analysis plan, and the translated version of the informed consent form can be shared upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No