Vitamin D Supplementation and Clinical Improvement in COVID-19
Primary Purpose
COVID-19
Status
Completed
Phase
Not Applicable
Locations
Indonesia
Study Type
Interventional
Intervention
Vitamin D3 10000 IU
Vitamin D3 1000 IU
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Vitamin D, Hematology parameter, COVID-19, PCR Conversion, D-Dimer, Clinical Recovery
Eligibility Criteria
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
Sites / Locations
- Wahidin Sudirohusodo General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
High Dose Vitamin D3
Low Dose Vitamin D3
Arm Description
A chewing tablet of 5000 IU of vitamin D3 is given twice daily, orally in the morning and evening for two weeks
A chewing tablet of 1000 IU of vitamin D3 is given once daily, orally in the morning for two weeks
Outcomes
Primary Outcome Measures
Clinical Recovery Time
Defined as the time where the clinical symptoms resolve completely (including cough and other symptoms of pneumonia)
Length of Stay
Defined as the duration of receiving hospital care
PCR Conversion time
Defined as the duration of the time to obtain negative result on PCR
Platelet to Lymphocyte Ratio / PLR in blood
Defined as the ratio of platelet divided by lymphocyte value. A value of >180 indicates worse prognosis
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
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
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
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05126602
Brief Title
Vitamin D Supplementation and Clinical Improvement in COVID-19
Official Title
Vitamin D Supplementation and Changes of Hematology Parameter, Coagulation Profile, and Clinical Improvement Among COVID-19 Patients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
September 30, 2021 (Actual)
Study Completion Date
November 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Bumi Herman
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Vitamin D, Hematology parameter, COVID-19, PCR Conversion, D-Dimer, Clinical Recovery
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigatorOutcomes Assessor
Masking Description
Masking for participants is conducted by preparing a similar chewing tablet (appearance including the color and taste). The care provider will not aware as the tablet has been unpacked. Outcome assessors are unaware of the allocation and only statistician knows the allocation
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High Dose Vitamin D3
Arm Type
Experimental
Arm Description
A chewing tablet of 5000 IU of vitamin D3 is given twice daily, orally in the morning and evening for two weeks
Arm Title
Low Dose Vitamin D3
Arm Type
Active Comparator
Arm Description
A chewing tablet of 1000 IU of vitamin D3 is given once daily, orally in the morning for two weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3 10000 IU
Other Intervention Name(s)
Hi-D Cholecalciferol 5000
Intervention Description
Tablet of 5000 IU of vitamin D3 given twice daily
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3 1000 IU
Other Intervention Name(s)
Hi-D Cholecalciferol 1000
Intervention Description
Tablet of 1000 IU of vitamin D3 given once daily
Primary Outcome Measure Information:
Title
Clinical Recovery Time
Description
Defined as the time where the clinical symptoms resolve completely (including cough and other symptoms of pneumonia)
Time Frame
from baseline to the time when the symptoms disappear, assessed for up to 3 months
Title
Length of Stay
Description
Defined as the duration of receiving hospital care
Time Frame
from the admission time to the time of hospital discharge, assessed for up to 3 months
Title
PCR Conversion time
Description
Defined as the duration of the time to obtain negative result on PCR
Time Frame
from the time of diagnosis until proven negative in PCR test, assessed for up to 3 months
Title
Platelet to Lymphocyte Ratio / PLR in blood
Description
Defined as the ratio of platelet divided by lymphocyte value. A value of >180 indicates worse prognosis
Time Frame
Changes of PLR value from baseline to one week
Title
Total Lymphocyte Count (TLC) in blood
Description
Defined as the ratio of platelet divided by lymphocyte value. A value of less 2000 cell/ mm3 defined as depletion and indicates worse prognosis
Time Frame
Changes of TLC value from baseline to one week
Title
Neutrophil-Lymphocyte Ratio (NLR) in blood
Description
Defined as the ratio of Neutrophil divided by lymphocyte value. A value of less than 3.13 indicates worse prognosis
Time Frame
Changes of TLC value from baseline to one week
Title
D-Dimer
Description
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
Time Frame
Changes of D-dimer value from baseline to one week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sisca Agustia, MD
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Amirah Faisal, MD
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zahratul Fajri
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nurpudji Taslim, Prof
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Suryani Armyn, Prof
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haerani Rasyid, Prof
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Agussalim Bukhari, Prof
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Irawaty Djaharuddin, Prof
Organizational Affiliation
Hasanuddin University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wahidin Sudirohusodo General Hospital
City
Makassar
State/Province
South Sulawesi
ZIP/Postal Code
76124
Country
Indonesia
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No data sharing will be done
Citations:
PubMed Identifier
32605780
Citation
Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020 Oct;13(10):1373-1380. doi: 10.1016/j.jiph.2020.06.021. Epub 2020 Jun 20.
Results Reference
background
PubMed Identifier
32880651
Citation
Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2020 Sep 1;3(9):e2019722. doi: 10.1001/jamanetworkopen.2020.19722.
Results Reference
background
PubMed Identifier
32304994
Citation
Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol. 2020 Jul;84:106504. doi: 10.1016/j.intimp.2020.106504. Epub 2020 Apr 13.
Results Reference
background
PubMed Identifier
32665858
Citation
Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z, Chen X, Chen S, Yu K, Huang Z, Hu B. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care. 2020 Jul 10;8:49. doi: 10.1186/s40560-020-00466-z. eCollection 2020.
Results Reference
background
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Vitamin D Supplementation and Clinical Improvement in COVID-19
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