Vitamin D Supplementation and Clinical Improvement in COVID-19

Study Overview
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Brief Summary
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Background and objective Vitamin D is important as the interaction between vitamin D and its receptors at the immune cells stimulates innate and adaptive immunity. Deficiency in vitamin D is associated with increased susceptibility to infection and it is commonly found in Indonesia. Several studies indicate the potential of vitamin D supplementation against Coronavirus Disease 2019 (COVID-19), particularly in combating the proinflammatory situation as well as coagulopathy. This study aims to evaluate the supplementation of vitamin D in COVID 19 patients, particularly the changes in hematology parameters and other clinical parameters. Method A double-blind randomized clinical trial is conducted among moderate COVID 19 patients. High-dose of vitamin D is given orally in the intervention group, compared with a low dose of vitamin D. Hematology parameters, D Dimer, conversion time on Polymerase Chain Reaction (PCR) test, and clinical symptoms are assessed Hypothesis High Dose vitamin D shows a better hematology parameter, short PCR conversion time, and faster clinical recovery

Detailed Description
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Population: The COVID 19 patients admitted to hospital with moderate severity, defined as Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have an oxygen saturation (SpO2) ≥94% on room air at sea level. Methodology: A double-blind randomized clinical trial allocated with simple random sampling Intervention: 5000 International unit/ IU of vitamin D3 (Cholecalciferol) given orally twice daily (total 10000 IU per day) Comparison group: 1000 International unit/ IU of vitamin D3 (Cholecalciferol) given once daily Variables to be collected : The level of 25-hydroxyvitamin D in the blood D-Dimer Platelet-to-Lymphocyte Ratio (PLR) Total Lymphocyte Count (TLC) Neutrophil to Lymphocyte Ratio (NLR) Age Sex Comorbidities including chronic diseases Body Mass Index Handgrips Strength Anticoagulant administration Clinical Symptoms and days to recover Length of Stay Time to PCR conversion where the PCR is conducted every two days Sample size and recruitment Following the study in Saudi Arabia, the sample size was derived from the days to achieve recovery, where the group who received the 5000 D had an average recovery day of 6.2 ± 0.8. The intervention is expected to shorten the average recovery days up to 10%. Using the difference between the two means, the effect size derived from this result is 0.775. With 5% type 1 error and 90% power and equal allocation (1:1), the number needed for each group is 30 participants Participants are allocated consecutively according to the permutation of the simple random sampling. Proposed statistical analysis Descriptive statistics Repeated measures ANOVA a Linear mixed model or generalized estimated equation will be applied to adjust the variables in the baseline

Official Title
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Vitamin D Supplementation and Changes of Hematology Parameter, Coagulation Profile, and Clinical Improvement Among COVID-19 Patients

Conditions
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COVID-19

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 10000 IU
* Dietary Supplement: Vitamin D3 1000 IU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Belongs to moderate case Diagnosed using PCR test Showing a vitamin D deficiency (<30 ng/dL). Exclusion Criteria Pregnant or doing breastfeeding Patient under specific medication (Tuberculosis, or HIV, or malignancy) or undergo hemodialysis Receive vitamin D supplementation prior to allocation. Tested negative less than 5 days after receiving vitamin D Creatinine >2,0 mg/dL Blood Calcium >10,5 mg/dL. Ventilated Hypersensitive to vitamin D Consistent desaturation <85% with oxygen supplementation and require High-Flow Nasal Cannula (HFNC)/Extracorporeal membrane Oxygenation (ECMO) via a ventilator. Refuse to attend blood examination for follow up

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: Two arms trial will be conducted with one group receiving a high dose of vitamin D3 whereas comparison group receiving a low dose of vitamin D3
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Vitamin D3<br>A chewing tablet of 5000 IU of vitamin D3 is given twice daily, orally in the morning and evening for two weeks | Dietary Supplement: Vitamin D3 10000 IU<br>* Tablet of 5000 IU of vitamin D3 given twice daily<br>* Other names: Hi-D Cholecalciferol 5000;|
| Active Comparator: Low Dose Vitamin D3<br>A chewing tablet of 1000 IU of vitamin D3 is given once daily, orally in the morning for two weeks | Dietary Supplement: Vitamin D3 1000 IU<br>* Tablet of 1000 IU of vitamin D3 given once daily<br>* Other names: Hi-D Cholecalciferol 1000;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Recovery Time | Defined as the time where the clinical symptoms resolve completely (including cough and other symptoms of pneumonia) | from baseline to the time when the symptoms disappear, assessed for up to 3 months | 
| Length of Stay | Defined as the duration of receiving hospital care | from the admission time to the time of hospital discharge, assessed for up to 3 months | 
| PCR Conversion time | Defined as the duration of the time to obtain negative result on PCR | from the time of diagnosis until proven negative in PCR test, assessed for up to 3 months | 
| Platelet to Lymphocyte Ratio / PLR in blood | Defined as the ratio of platelet divided by lymphocyte value. A value of >180 indicates worse prognosis | Changes of PLR value from baseline to one week | 
| Total Lymphocyte Count (TLC) in blood | Defined as the ratio of platelet divided by lymphocyte value. A value of less 2000 cell/ mm3 defined as depletion and indicates worse prognosis | Changes of TLC value from baseline to one week | 
| Neutrophil-Lymphocyte Ratio (NLR) in blood | Defined as the ratio of Neutrophil divided by lymphocyte value. A value of less than 3.13 indicates worse prognosis | Changes of TLC value from baseline to one week | 
| D-Dimer | The D-dimer indicates the degree of fibrin degradation that is associated with blood clot breakage. A value of >500 ug/L indicates worse outcome | Changes of D-dimer value from baseline to one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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D-Dimer, Clinical Recovery, Vitamin D, Hematology parameter, COVID-19, PCR Conversion