Clinical trial NCT05126602: 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
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Keywords: Vitamin D
Hematology parameter
COVID-19
PCR Conversion
D-Dimer
Clinical Recovery
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
First posted: 2021-11-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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

1. Descriptive statistics
2. Repeated measures ANOVA
3. a Linear mixed model or generalized estimated equation will be applied to adjust the variables in the baseline

Eligibility criteria: 1. Inclusion Criteria:

   1. Belongs to moderate case
   2. Diagnosed using PCR test
   3. Showing a vitamin D deficiency (\<30 ng/dL).
2. Exclusion Criteria

   1. Pregnant or doing breastfeeding
   2. Patient under specific medication (Tuberculosis, or HIV, or malignancy) or undergo hemodialysis
   3. Receive vitamin D supplementation prior to allocation.
   4. Tested negative less than 5 days after receiving vitamin D
   5. Creatinine \>2,0 mg/dL
   6. Blood Calcium \>10,5 mg/dL.
   7. Ventilated
   8. Hypersensitive to vitamin D
   9. Consistent desaturation \<85% with oxygen supplementation and require High-Flow Nasal Cannula (HFNC)/Extracorporeal membrane Oxygenation (ECMO) via a ventilator.
   10. Refuse to attend blood examination for follow up

Primary outcomes:
measure: Clinical Recovery Time
timeFrame: from baseline to the time when the symptoms disappear, assessed for up to 3 months
measure: Length of Stay
timeFrame: from the admission time to the time of hospital discharge, assessed for up to 3 months
measure: PCR Conversion time
timeFrame: from the time of diagnosis until proven negative in PCR test, assessed for up to 3 months
measure: Platelet to Lymphocyte Ratio / PLR in blood
timeFrame: Changes of PLR value from baseline to one week
measure: Total Lymphocyte Count (TLC) in blood
timeFrame: Changes of TLC value from baseline to one week
measure: Neutrophil-Lymphocyte Ratio (NLR) in blood
timeFrame: Changes of TLC value from baseline to one week
measure: D-Dimer
timeFrame: Changes of D-dimer value from baseline to one week
Secondary outcomes:
Other outcomes:
Locations:
city: Makassar
country: Indonesia
facility: Wahidin Sudirohusodo General Hospital
state: South Sulawesi
Study officials:
affiliation: Hasanuddin University
name: Sisca Agustia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Amirah Faisal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Zahratul Fajri
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Nurpudji Taslim, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Suryani Armyn, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Haerani Rasyid, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Agussalim Bukhari, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Irawaty Djaharuddin, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.