Selenium as a Potential Treatment for Moderately-ill, Severely-ill, and Critically-ill COVID-19 Patients.

Study Overview
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Brief Summary
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Given its anti-viral, anti-oxidative, immune-enhancing, cytokine-modulating, and anticoagulant properties, the investigators hypothesize that Selenium infusion at supranutritional doses for moderately-ill, severely-ill, and critically-ill COVID-19 patients will prevent further clinical deterioration thus decreasing overall mortality and improving survival. To test this hypothesis, a prospective, single-center, phase II trial is proposed to assess the efficacy of Selenium in hospitalized adult patients with moderate, severe, and critical COVID-19 infections.

Detailed Description
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COVID-19 is a respiratory illness that is caused by the novel SARS-CoV-2. Illness severity can widely range from mild, moderate, severe featuring pneumonia, to critical. Despite ongoing extensive research to find a cure for COVID-19, there had been no proven, efficacious, and widely-available treatment for the disease. With the death toll rising in various parts of the US and the world, it is imperative that investigators work on determining new therapeutic modalities. This study relates to inpatient and critical care for COVID-19 patients. The role of Selenium (Se) as a trace element involved in many biological processes and reactions is well established in various organisms. Particularly, Selenium is known to have anti-viral, anti-oxidative, cytokine-modulating, immune-enhancing, and anticoagulant properties that might be beneficial in COVID-19 infections given the pathophysiological processes involved in the disease. Multiple preclinical and clinical studies have shed the light on the various effects exerted by Selenium in multiple inflammatory conditions including acute lung injury and acute respiratory distress syndrome, as well as viral infections including HIV and Influenza. The study team aims to explore the possible role of Selenium in mitigating the inflammatory processes involved in COVID-19 infections and hence its effect on disease progression and mortality. Patients with COVID-19 who exhibit the signs and symptoms of moderate or severe infection or are critically ill will receive Selenium infusion for 14 days. The working hypothesis of this trial is that selenium treatment would decrease the death rates and increase the rate of hospital discharges among hospitalized patients.

Official Title
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Selenium as a Potential Treatment for Moderately-ill, Severely-ill, and Critically-ill COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Drug: Selenium (as Selenious Acid)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (age ≥18) prior to performing study procedure. Aged ≥ 18 years. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization. Currently hospitalized. Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen on screening. Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19. Evidence of multiorgan failure. Mechanically ventilated for > 5 days. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN). Creatinine clearance < 50 mL/min.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized double-blinded, placebo-controlled Phase 2 clinical trial to assess the efficacy of Selenium in the treatment of moderately-ill, severely-ill, and critically ill COVID-19 patients. The patients will be randomized in a 1:1 ratio to receive standard of care plus a loading dose of Selenium followed by continuous infusion for a total of 14 days, or standard of care plus a Saline-based placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selenious Acid + Standard Of Care (SOC)<br>Participants who are moderately-ill, severely-ill, or critically ill will receive a Selenious Acid infusion of 2000µg on day 1 as a loading dose infusion, followed by a continuous infusion of Selenious Acid at a maintenance dose of 1000µg daily on days 2-14 together with continued Standard Of Care therapy. | Drug: Selenium (as Selenious Acid)<br>* Interventional arm participants will receive Selenium as Selenious Acid infusion plus the standard of care therapy.<br>* Other names: Selenious Acid (AMERICAN REGENT);|
| Active Comparator: Standard Of Care (SOC) + Placebo<br>Participants will receive a Saline-based placebo infusion of 2000µg on day 1 as a loading dose, followed by continuous infusion of a Saline-based placebo at a maintenance dose of 1000µg daily on days 2-14. Standard Of Care is to be determined according to patients' clinical picture and may include Dexamethasone, Azithromycin, Ceftriaxone, Remdesivir, Convalescent Plasma. | Other: Placebo<br>* Active comparator arm participants will receive the standard of care therapy plus a Saline-based placebo.<br>* Other names: Saline-based Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the ordinal scale | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. | Day 1 through Day 29 | 
| Rate of hospital discharges or deaths | Rate of patient discharge to home or other long-term care facilities, or death. | Study duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status using ordinal scale | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. | Day 1 through Day 29 | 
| Mean change in the ordinal scale | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. | Day 1 though Day 29 | 
| Time to an improvement of one category using an ordinal scale | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. | Day 1 though Day 29 | 
| Change in National Early Warning Score (NEWS) from baseline | The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. | Day 1 through Day 29 | 
| Cumulative incidence of serious adverse events (SAEs) | An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. | Day 1 through Day 29 | 
| Duration of hospitalization | Measured in days. | Day 1 though Day 29 | 
| Incidence of new oxygen use | Incidence of new oxygen use. | Day 1 though Day 29 | 
| Duration of new oxygen use | Measured in days. | Day 1 though Day 29 | 
| Incidence of new non-invasive ventilation or high flow oxygen use | Incidence of new non-invasive ventilation or high flow oxygen use. | Day 1 though Day 29 | 
| Duration of new non-invasive ventilation or high flow oxygen use | Measured in days. | Day 1 though Day 29 | 
| Incidence of new ventilator use | Incidence of new ventilator use. | Day 1 though Day 29 | 
| Duration of new ventilator use | Measured in days. | Day 1 though Day 29 | 
| Discontinuation or temporary suspension of investigational therapeutics | For any reason. | Day 1 through Day 14 | 
| Change from baseline in alanine transaminase (ALT) | Change from baseline in alanine transaminase (ALT). | Day 1 through Day 29 | 
| Change from baseline in aspartate transaminase (AST) | Change from baseline in aspartate transaminase (AST). | Day 1 through Day 29 | 
| Change from baseline in creatinine (Cr) | Change from baseline in creatinine (Cr). | Day 1 through Day 29 | 
| Change from baseline in glucose | Change from baseline in glucose. | Day 1 through Day 29 | 
| Change from baseline in hemoglobin | Change from baseline in hemoglobin. | Day 1 through Day 29 | 
| Change from baseline in platelets | Change from baseline in platelets. | Day 1 through Day 29 | 
| Change from baseline in prothrombin time | Change from baseline in prothrombin time. | Day 1 through Day 29 | 
| Change from baseline in total bilirubin | Change from baseline in total bilirubin. | Day 1 through Day 29 | 
| Change from baseline in white blood cell count (WBC) with differential | Change from baseline in white blood cell count (WBC) with differential. | Day 1 through Day 29 | 
| Change from baseline in interleukin-1 (IL-1) | Change from baseline in interleukin-1 (IL-1). | Day 1 through Day 29 | 
| Change from baseline in interleukin-6 (IL-6) | Change from baseline in interleukin-6 (IL-6). | Day 1 through Day 29 | 
| Change from baseline in tumor necrosis factor alpha (TNF-α) | Change from baseline in tumor necrosis factor alpha (TNF-α). | Day 1 through Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Pneumonia, Cytokine Storm, ARDS, Moderate COVID-19 Infections, Severe COVID-19 Infections, Critical COVID-19 Infections, Selenium