Clinical Outcomes of High Dose Vitamin D Versus Standard Dose in COVID-19 Egyptian Patients

Study Overview
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Brief Summary
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Vitamin D is a secosteroid hormone which may have beneficial role in reducing COVID-19 adverse outcomes by first regulating the renin angiotensin system (RAS). Recent studies on animal in which acute respiratory distress syndrome (ARDS) was induced, showed that vitamin D lead to pulmonary permeability reduction by modulating RAS activity as well as the expression of the angiotensin-2 converting enzyme (ACE2). During COVID-19, downregulation of ACE2 leads to cytokine storm in the host, causing ARDS. In contrast, an experimental study conducted on mice in which ARDS was induced chemically, revealed that vitamin D admiration contributed to mRNA and ACE2 proteins levels improvement, ADRS milder symptoms as well as less lung damage. Additionally, vitamin D had shown antiviral effects on several previous studies, that though to be exerted either by antimicrobial peptides induction which subsequently had direct antiviral action or through immunomodulatory and anti-inflammatory effects. In addition, vitamin D stabilizes physical barriers which prevent viruses from reaching tissues susceptible to infection. Finally, previous studies demonstrated that hypovitaminosis D is accompanied by various comorbidities including diabetes mellitus, hypertension, chronic cardiovascular and respiratory diseases, and cancers, all medical conditions that are considered risk factors of COVID-19 infection deterioration and even high mortality rate. The objective of this study is to evaluate whether supplementation with high-dose vitamin D improves the prognosis of patients diagnosed with COVID-19 compared to a standard dose of vitamin D.

Official Title
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Clinical Outcomes of High Dose Vitamin D Versus Standard Dose in COVID-19 Egyptian Patients

Conditions
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Covid19, Corona Virus Infection, Cytokine Storm, Vitamin D Deficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 years. COVID-19 hospitalized patients with pneumonia confirmed by chest X-ray or CT scan. RT-PCR Confirmed infection with COVID-19 or strongly suspected infection with pending confirmation studies. Presence of acute respiratory distress syndrome (ARDS). Having either peripheral capillary oxygen saturation (SpO2) ≤ 94% ambient air, or a partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio ≤ 300 mmHg. Exclusion Criteria: Vitamin D supplementation in the previous month. Contraindication for vitamin D supplementation: active granulomatosis (sarcoidosis, tuberculosis, lymphoma), history of calcic lithiasis, known hypervitaminosis D or hypercalcemia, known intolerance to vitamin D. Organ failure requiring admission to a resuscitation or high dependency unit. Pregnant women. Participation in another simultaneous clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Moderate and severe patients who were infected with SARS-CoV-2 and who were already receiving treatment with standard dose vitamin D in addition to standard COVID-19 management. | |
| Group 2<br>Moderate and severe patients who were infected with SARS-CoV-2 and who were already receiving treatment with high dose vitamin Din addition to standard COVID-19 management. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospitalization | Length of hospital stay | Two weeks | 
| In-hospital mortality | Death during hospitalization | Two weeks | 
| Clinical status improvement using six category ordinal scale | Change in six category ordinal scale. The categories were defined as follows: 1) patient discharged, 2) hospitalization not requiring supplemental oxygen, 3) hospitalization requiring supplemental low-flow oxygen, 4) hospitalization requiring high-flow supplemental oxygen, 5) hospitalization requiring invasive mechanical ventilation, 6) death. | Two weeks | 
| Change in gas exchange | Difference between ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, and before discharge | Two weeks | 
| Time to increase in oxygenation | Time to increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lactate dehydrogenase (LDH) levels | Change in levels of Lactate dehydrogenase (LDH) between baseline and before discharge | Two weeks | 
| Change in C-reactive protein (CRP) levels | Change in levels of C-reactive protein (CRP) between baseline and before discharge | Two weeks | 
| Change in serum ferritin levels | Change in levels of serum ferritin between baseline and before discharge | Two weeks | 
| Occurrence of secondary infection | Occurrence of sepsis | Two weeks | 
| Occurrence of at least one severe adverse event | Any serious or severe adverse event that might happens during hospital stay | Two weeks | 
| Need for mechanical ventilator or intensive care unit (ICU) support | Admission to ICU or usage of mechanical ventilator | Two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Cytokine Storm, Vitamin D