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The Efficacy of Vitamin D Supplementation in Patients With Severe and Extremely Severe COVID-19

Not Applicable
Completed
Conditions
SARS-CoV2 Infection
Interventions
Dietary Supplement: Vitamin D (cholecalciferol)
Dietary Supplement: Herbal oil
Registration Number
NCT05092698
Lead Sponsor
Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Brief Summary

Despite the successful treatment of patients with moderate coronavirus disease 2019 (COVID-19), outcomes for patients with severe disease remain unsatisfactory. In this category of patients, the course of the disease is complicated by the development of acute respiratory distress syndrome (ARDS) and the need for mechanical ventilation in the intensive care unit (ICU). Mortality in this category of patients reaches 85%. The lack of effective treatment for COVID-19 has prompted scientists to look for new strategies to reduce the incidence and severity of COVID-19, disease progression, and mortality.

Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation.

A number of experimental studies have shown that stimulation of vitamin D receptors can improve the course of ARDS due to inhibition of the hyperimmune inflammatory response, regulation of the renin-angiotensin system, modulation of neutrophil activity, maintenance of the integrity of the pulmonary epithelial barrier and stimulation of epithelial repair, as well as by reducing hypercoagulation.

Several studies on ICU patients have reported that low vitamin D (25(OH)D) concentrations are associated with a higher risk of negative outcomes such as death, organ failure, prolonged mechanical ventilation, a higher rate of ventilation-associated pneumonia, and sepsis.

While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions.

Detailed Description

The aim of the study is to evaluate the efficacy of vitamin D (cholecalciferol) supplementation in patients with severe and extremely severe disease caused by the SARS-CoV-2 virus, admitted to an ICU of the COVID-center on the first day and in dynamics until discharge from the hospital or death. Patients with vitamin D deficiency \[25-hydroxyvitamin D (25(OH)D) ≤ 30 ng/ml\] will be randomized to two groups: 1 - patients will receive 60,000 IU of cholecalciferol supplementation; 2 - patients will receive matched placebo.

The demographic and clinical data will be collected. Laboratory data (hemoglobin, lymphocytes, neutrophil to lymphocyte ratio, D-dimer level, Interleukin-6, procalcitonin, ferritin, glucose level, high-sensitive troponin Т, vitamin D level (25(OH)D), acid-base balance, signs of a secondary bacterial infection, immunogram, Von Willebrand factor antigen and Instrumental data (CT-scan, Electrocardiography, echocardiography, arterial and venous ultrasound investigation) will be analysed. The frequency of complications, duration of mechanical ventilation, length of stay in the ICU and in the hospital, and mortality will be evaluated.

This study is single-centre prospective randomized placebo-controlled trial.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
110
Inclusion Criteria
  • all patients with COVID-19 admitted to the ICU with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤ 30 ng/ml]
Exclusion Criteria
  • less than 24 hours in ICU by any reason
  • chronic decompensated disease with extrapulmonary organ dysfunction (tumour progression, liver cirrhosis, congestive heart failure) with a life expectancy of less than 48 hours
  • atonic coma
  • allergic reaction on cholecalciferol or herbal oil

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vit_D_supplVitamin D (cholecalciferol)Patients will receive 60,000 IU of cholecalciferol dissolved in 45 ml herbal oil orally or via feeding tube weekly followed by 5,000 IU of cholecalciferol (two drops) daily until discharge or death.
Vit_D_placeboHerbal oilPatients will receive 45 ml of herbal oil orally or via feeding tube followed by 45 ml of herbal oil weekly followed by two drops of herbal oil daily until discharge or death.
Primary Outcome Measures
NameTimeMethod
Сomplete blood count dynamics 2Change from baseline on day 15 during ICU treatment

Сomplete blood count

Сomplete blood count dynamics 3Change from baseline on day 21 during ICU treatment

Сomplete blood count

C-reactive protein 2Change from baseline on day 15 during ICU treatment

Concentration of C-reactive protein

Von Willebrand factor antigenChange from baseline on day 7 during ICU treatment

Concentration of Von Willebrand factor antigen

Thrombotic complications60 days

Arterial or venous thrombotic complications

Сomplete blood countChange from baseline on day 5 during ICU treatment

Сomplete blood count

Сomplete blood count dynamics 1Change from baseline on day 10 during ICU treatment

Сomplete blood count

C-reactive proteinChange from baseline on day 5 during ICU treatment

Concentration of C-reactive protein

Proinflammatory marker 1on day 10 during ICU treatment

Concentration of D-dimer

inflammatory marker 1Change from baseline on day 10 during ICU treatment

Concentration of Interleukin-6

inflammatory marker 2Change from baseline on day 15 during ICU treatment

Concentration of Interleukin-6

Infection marker 1Change from baseline on day 10 during ICU treatment

Concentration of Procalcitonin

C-reactive protein 1Change from baseline on day 10 during ICU treatment

Concentration of C-reactive protein

C-reactive protein 3Change from baseline on day 21 during ICU treatment

Concentration of C-reactive protein

ImmunogramChange from baseline on day 7 during ICU treatment

The amount of NKT cells (CD3+CD56+CD16+), NK cells (CD3-CD56+CD16+)

inflammatory markerChange from baseline on day 5 during ICU treatment

Concentration of Interleukin-6

Proinflammatory markerChange from baseline on day 5 during ICU treatment

Concentration of D-dimer

Proinflammatory marker 2on day 15 during ICU treatment

Concentration of D-dimer

Proinflammatory marker 3on day 21 during ICU treatment

Concentration of D-dimer

inflammatory marker 3Change from baseline on day 21 during ICU treatment

Concentration of Interleukin-6

Infection markerChange from baseline on day 5 during ICU treatment

Concentration of Procalcitonin

Secondary Outcome Measures
NameTimeMethod
Mortality60 days

The dead and survived patients ratio

Length of stay in the ICU60 days

The amount of day of ICU treatment

Infection complications60 day

The amount of Infection complications

Length of stay in the hospital60 days

The amount of day of hospital treatment

Mechanical ventilation duration30 days

The amount of mechanical ventilation days

Non-invasive Mechanical ventilation duration30 days

The amount of Non-invasive mechanical ventilation days

Trial Locations

Locations (1)

Federal Research Clinical Center of Federal Medical & Biological Agency

🇷🇺

Moscow, Russian Federation

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