Clinical trial NCT05092698: The Efficacy of Vitamin D Supplementation in Patients With Severe and Extremely Severe COVID-19
Official title: The Efficacy of Vitamin D Supplementation in Patients With Severe and Extremely Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: SARS-CoV2 Infection
Keywords: severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)
coronavirus disease 2019 (COVID-19)
severe and extremely severe disease
Vitamin D
cholecalciferol
Lead sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
Sponsor class: OTHER_GOV
First posted: 2021-10-25
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Сomplete blood count
timeFrame: Change from baseline on day 5 during ICU treatment
measure: Сomplete blood count dynamics 1
timeFrame: Change from baseline on day 10 during ICU treatment
measure: Сomplete blood count dynamics 2
timeFrame: Change from baseline on day 15 during ICU treatment
measure: Сomplete blood count dynamics 3
timeFrame: Change from baseline on day 21 during ICU treatment
measure: C-reactive protein
timeFrame: Change from baseline on day 5 during ICU treatment
measure: C-reactive protein 1
timeFrame: Change from baseline on day 10 during ICU treatment
measure: C-reactive protein 2
timeFrame: Change from baseline on day 15 during ICU treatment
measure: C-reactive protein 3
timeFrame: Change from baseline on day 21 during ICU treatment
measure: Von Willebrand factor antigen
timeFrame: Change from baseline on day 7 during ICU treatment
measure: Thrombotic complications
timeFrame: 60 days
measure: Immunogram
timeFrame: Change from baseline on day 7 during ICU treatment
measure: Proinflammatory marker
timeFrame: Change from baseline on day 5 during ICU treatment
measure: Proinflammatory marker 1
timeFrame: on day 10 during ICU treatment
measure: Proinflammatory marker 2
timeFrame: on day 15 during ICU treatment
measure: Proinflammatory marker 3
timeFrame: on day 21 during ICU treatment
measure: inflammatory marker
timeFrame: Change from baseline on day 5 during ICU treatment
measure: inflammatory marker 1
timeFrame: Change from baseline on day 10 during ICU treatment
measure: inflammatory marker 2
timeFrame: Change from baseline on day 15 during ICU treatment
measure: inflammatory marker 3
timeFrame: Change from baseline on day 21 during ICU treatment
measure: Infection marker
timeFrame: Change from baseline on day 5 during ICU treatment
measure: Infection marker 1
timeFrame: Change from baseline on day 10 during ICU treatment
Secondary outcomes:
measure: Mortality
timeFrame: 60 days
measure: Mechanical ventilation duration
timeFrame: 30 days
measure: Non-invasive Mechanical ventilation duration
timeFrame: 30 days
measure: Length of stay in the ICU
timeFrame: 60 days
measure: Length of stay in the hospital
timeFrame: 60 days
measure: Infection complications
timeFrame: 60 day
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal Research Clinical Center of Federal Medical & Biological Agency
Study officials:
affiliation: Federal Research Clinical Center of Federal Medical & Biological Agency
name: Tatiana V Klypa, ScD
role: STUDY_CHAIR
References:
citation: Bassatne A, Basbous M, Chakhtoura M, El Zein O, Rahme M, El-Hajj Fuleihan G. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism. 2021 Jun;119:154753. doi: 10.1016/j.metabol.2021.154753. Epub 2021 Mar 24.
citation: Bychinin MV, Klypa TV, Mandel IA, Andreichenko SA, Baklaushev VP, Yusubalieva GM, Kolyshkina NA, Troitsky AV. Low Circulating Vitamin D in Intensive Care Unit-Admitted COVID-19 Patients as a Predictor of Negative Outcomes. J Nutr. 2021 Aug 7;151(8):2199-2205. doi: 10.1093/jn/nxab107.
citation: Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
citation: Kong J, Zhu X, Shi Y, Liu T, Chen Y, Bhan I, Zhao Q, Thadhani R, Li YC. VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system. Mol Endocrinol. 2013 Dec;27(12):2116-25. doi: 10.1210/me.2013-1146. Epub 2013 Nov 6.
citation: Bychinin MV, Klypa TV, Mandel IA, Yusubalieva GM, Baklaushev VP, Kolyshkina NA, Troitsky AV. Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU. Sci Rep. 2022 Nov 3;12(1):18604. doi: 10.1038/s41598-022-22045-y.