NCT05092698

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
110

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started May 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2020

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

October 22, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 25, 2021

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2021

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2022

Completed
Last Updated

March 7, 2022

Status Verified

November 1, 2021

Enrollment Period

1.7 years

First QC Date

October 22, 2021

Last Update Submit

February 18, 2022

Conditions

SARS-CoV2 Infection

Keywords

severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)coronavirus disease 2019 (COVID-19)severe and extremely severe diseaseVitamin Dcholecalciferol

Outcome Measures

Primary Outcomes (21)

  • Đ¡omplete blood count

    Đ¡omplete blood count

    Change from baseline on day 5 during ICU treatment

  • Đ¡omplete blood count dynamics 1

    Đ¡omplete blood count

    Change from baseline on day 10 during ICU treatment

  • Đ¡omplete blood count dynamics 2

    Đ¡omplete blood count

    Change from baseline on day 15 during ICU treatment

  • Đ¡omplete blood count dynamics 3

    Đ¡omplete blood count

    Change from baseline on day 21 during ICU treatment

  • C-reactive protein

    Concentration of C-reactive protein

    Change from baseline on day 5 during ICU treatment

  • C-reactive protein 1

    Concentration of C-reactive protein

    Change from baseline on day 10 during ICU treatment

  • C-reactive protein 2

    Concentration of C-reactive protein

    Change from baseline on day 15 during ICU treatment

  • C-reactive protein 3

    Concentration of C-reactive protein

    Change from baseline on day 21 during ICU treatment

  • Von Willebrand factor antigen

    Concentration of Von Willebrand factor antigen

    Change from baseline on day 7 during ICU treatment

  • Thrombotic complications

    Arterial or venous thrombotic complications

    60 days

  • Immunogram

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

    Change from baseline on day 7 during ICU treatment

  • Proinflammatory marker

    Concentration of D-dimer

    Change from baseline on day 5 during ICU treatment

  • Proinflammatory marker 1

    Concentration of D-dimer

    on day 10 during ICU treatment

  • Proinflammatory marker 2

    Concentration of D-dimer

    on day 15 during ICU treatment

  • Proinflammatory marker 3

    Concentration of D-dimer

    on day 21 during ICU treatment

  • inflammatory marker

    Concentration of Interleukin-6

    Change from baseline on day 5 during ICU treatment

  • inflammatory marker 1

    Concentration of Interleukin-6

    Change from baseline on day 10 during ICU treatment

  • inflammatory marker 2

    Concentration of Interleukin-6

    Change from baseline on day 15 during ICU treatment

  • inflammatory marker 3

    Concentration of Interleukin-6

    Change from baseline on day 21 during ICU treatment

  • Infection marker

    Concentration of Procalcitonin

    Change from baseline on day 5 during ICU treatment

  • Infection marker 1

    Concentration of Procalcitonin

    Change from baseline on day 10 during ICU treatment

Secondary Outcomes (6)

  • Mortality

    60 days

  • Mechanical ventilation duration

    30 days

  • Non-invasive Mechanical ventilation duration

    30 days

  • Length of stay in the ICU

    60 days

  • Length of stay in the hospital

    60 days

  • +1 more secondary outcomes

Study Arms (2)

Vit_D_suppl

ACTIVE COMPARATOR

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.

Dietary Supplement: Vitamin D (cholecalciferol)

Vit_D_placebo

PLACEBO COMPARATOR

Patients 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.

Dietary Supplement: Herbal oil

Interventions

Vitamin D (cholecalciferol)DIETARY_SUPPLEMENT

Patients will receive 60,000 IU of cholecalciferol dissolved in 45 ml herbal oil orally or via feeding tube after serum Vitamin D concentrations measurement followed by the same dose of cholecalciferol weekly and 5,000 IU of cholecalciferol (two drops) daily until discharge or death.

Vit_D_suppl
Herbal oilDIETARY_SUPPLEMENT

Patients will receive 45 ml of herbal oil orally or via feeding tube after serum Vitamin D concentrations measurement followed by the same dose of pure herbal oil weekly and two drops of herbal oil daily until discharge or death.

Also known as: Placebo
Vit_D_placebo

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • all patients with COVID-19 admitted to the ICU with vitamin D deficiency \[25-hydroxyvitamin D (25(OH)D) ≤ 30 ng/ml\]

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Federal Research Clinical Center of Federal Medical & Biological Agency

Moscow, 115682, Russia

Location

Related Publications (5)

  • 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.

    PMID: 33774074BACKGROUND

  • 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.

    PMID: 33982128BACKGROUND

  • 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.

    PMID: 32109013BACKGROUND

  • 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.

    PMID: 24196349BACKGROUND

  • 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.

    PMID: 36329227DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

CholestenesCholestanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSterolsVitamin DSecosteroidsMembrane LipidsLipids

Study Officials

  • Tatiana V Klypa, ScD

    Federal Research Clinical Center of Federal Medical & Biological Agency

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 22, 2021

First Posted

October 25, 2021

Study Start

May 1, 2020

Primary Completion

December 31, 2021

Study Completion

January 31, 2022

Last Updated

March 7, 2022

Record last verified: 2021-11

Locations

RU(1)