High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Center Study (VitCov)

The world is currently facing a pandemic with the coronavirus (SARS-CoV-2) which leads to the disease of COVID-19. Risk factors for a poor outcome of COVID-19 have so far been identified as older age and co-morbidity including chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD) and current smoking status. Previous studies found, that vitamin D deficiency is more prevalent among patients with these risk factors. There are observational studies reporting independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection.

Vitamin D substitution in patients with COVID-19 who show a vitamin D deficiency should therefore be investigated for efficacy and safety.

The study is designed as a randomized, placebo-controlled, double blind study. The objective of the study is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with a single high dose of vitamin D compared to standard treatment only.

Study Overview

• Status: Completed
• Conditions: Covid19; Vitamin D Deficiency; Corona Virus Infection; ARDS; SARS-CoV Infection; Coronavirus
• Intervention / Treatment: Drug: Single high dose vitamin D; Drug: Treatment as usual vitamin D; Drug: Placebo

Detailed Description

The world is currently experiencing a coronavirus (SARS-CoV-2) pandemic. The disease caused by infection with this virus is known as COVID-19. Risk factors for a poor outcome of COVID-19 have so far been found to include, older age and co-morbidity including chronic respiratory conditions and current smoking status. Previous studies found, that vitamin D deficiency is more prevalent among patients with these risk factors.

There are observational studies reporting independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection. 25-hydroxyvitamin D supports induction of antimicrobial peptides in response to both viral and bacterial stimuli suggesting a potential mechanism by which vitamin D inducible protection against respiratory pathogens might be mediated. The clear functions of vitamin D in the immune system are difficult to define because the immune response is not a static process. The vitamin-D-receptor, which has also been detected in immunological cells, suggests that vitamin D can regulate some processes related to immunity. A further argument which supports a potential antiviral activity of vitamin D is the modulation of the inflammatory response. The release of pro-inflammatory cytokines by the influenza virus appeared to correlate with the severity of illness. The use of vitamin D as a prophylactic for influenza has shown promise in prevention of illness and reduction of secondary asthma in children. Inadequate vitamin D status is associated with susceptibility to upper respiratory infections in patients with chronic obstructive pulmonary disease (COPD). In the ViDiCo-trial vitamin D supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD. A further study retrospectively examined data from 108 patients with acute respiratory distress syndrome (ARDS) for whom a vitamin D status was available at the time of diagnosis revealed that over 95% of these patients had vitamin D deficiency. When examined according to quarterly of serum 25- hydroxyvitamin D, a consistent inverse relationship between serum 25-hydroxyvitamin D and length of hospital and ICU stay among survivors was observed. Vitamin D substitution in patients with COVID-19 who show a vitamin D deficiency should therefore be investigated for efficacy and safety.

For this purpose the investigators designed a randomized, placebo controlled double blind trial to test the hypothesis hypothesis that a single high dose of vitamin D in addition to standard treatment improves the recovery period positively in patients with COVID-19 and vitamin D deficiency compared to standard treatment only. That means, that the time of recovery is shorter in the single high dose vitamin D group relative to standard treatment group only.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • BL
    • Liestal, BL, Switzerland, 4410
      • Cantonal Hospital Baselland Liestal
  • SG
    • Saint Gallen, SG, Switzerland, 9001
      • Cantonal Hospital St. Gallen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Hospitalized Patient
• Ongoing COVID-19 infection
• Vitamin D deficiency defined as a serum 25-hydroxyvitamin D concentration ≤ 50nmol/l( ≤20ng/ml)
• > 18 years of age

Exclusion Criteria:

• Known hypersensitivity to one of the used products of vitamin D or indigents in the drug's composition
• Active malignancy
• Hypercalcemia
• Granulomatous disease such as sarcoidosis
• History of renal stones within the past year
• Pregnancy/breastfeeding, as evaluated through screening,
• Previous enrollment into the current study,
• Enrollment of the investigator, his/her family members, employees and other dependent persons,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Dose Vitamin D; Patient will receive a single high dose of vitamin D (140'000) in addition to daily 800 IU of vitamin D. The medication be administered orally	Drug: Single high dose vitamin D; Patient receives either one dose orally of 140'000 IU (7 ml) of this drug once as an intervention treatment additionally to TAU or the patient receives 7 ml of the placebo Solution (7 ml) in addition to TAU; Other Names: VITAMIN D3 oil 500 IU/drop; Drug: Treatment as usual vitamin D; Both groups receive the treatment as usual after the single high dose or the placebo which will be 800 IU per day; Other Names: Vitamin D3 solution 4000 IU/ml
PLACEBO_COMPARATOR: Placebo; Patient will receive a single dose of placebo, orally administered and then treatment as usual (daily 800 IU of vitamin D, orally administered)	Drug: Treatment as usual vitamin D; Both groups receive the treatment as usual after the single high dose or the placebo which will be 800 IU per day; Other Names: Vitamin D3 solution 4000 IU/ml; Drug: Placebo; Patient receives a single dose of a placebo solution; Other Names: Oily placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospitalization	Overall duration of the hospitalization from day of admission until the day of discharge or fatality	Administration to Discharge from hospital care (mean duration is between 14 and 22 days for Patients with COVID 19)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need of intensive care	Did the patient need a intensive care treatment during the hospitalization (yes/no)	Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
Lenght of the Intensive Care Treatment	Day of admission to ICU until discharge or fatality	Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
Overall mortality	Percentage of patient died during hospitalization	During the length of hospitalisation (mean duration is between 14 and 22 days for Patients with COVID-19)
Development of vitamin D levels	percentage of patients with 25-hydroxyvitamin D > 50nmol/L (>20ng/mL) at day 7 - The values of calcium, phosphorus, 24-hydroxyvitamin D, 1.25-dihydroxyvitamin D, parathyroid hormone.	Day 1 (Baseline) and Day 7 after the first administration of the high dose vitamin D or the placebo and at discharge (mean hospital stay is between 14 and 22 days for Patients with COVID-19)
Development of sepsis	percentage of patients developing a sepsis	During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications due to COVID-19	We assess every other complications which occurs due to COVID-19	During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)
Blood pressure (BP)	The BP will be assessed daily in mmHg	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
Heart rate	The heart rate will be assessed daily in bpm	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
Peripheral oxygen saturation (SpO2)	The SpO2 will be assessed daily in %	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Percentage of patients who require oxygen	Requirement for oxygen will be assessed daily (yes/no) if yes how many liters per minute	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Breathing frequency	Breathing frequence will be assessed daily in breaths per minute	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Glasgow Coma Scale (GCS)	GCS will be assessed daily 3 to 15 points. It describes the extent of impaired consciousness. 15 points means no impairment, 3 points means severe impairment of consciousness.	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Percentage of patients are smokers, former smokers or lifelong non-smokers	Assessing the history of smoking in pack years (PY). the assessment will be made with the following options for answering Current smoker: Smoking for how many years? Cigarettes per day? Former smoker, how many years smoked? How many cigarettes per day Life-long non-smoker	Assessing of the smoking Status at Basleine
Current Symptoms	Assessed in No/ Mild/ Moderate /Severe	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Temperature	Temperature will be assessed daily in degrees celsius	Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

Collaborators and Investigators

• Sponsor: Prof. Dr. Jörg Leuppi
• Investigators: Study Director: Jörg D Leuppi, Professor, Cantonal Hosptal, Baselland

Publications and helpful links

General Publications

• Jaun F, Boesing M, Luthi-Corridori G, Abig K, Makhdoomi A, Bloch N, Lins C, Raess A, Grillmayr V, Haas P, Schuetz P, Gabutti L, Muser J, Leuppi-Taegtmeyer AB, Giezendanner S, Brandle M, Leuppi JD. High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study-VitCov Trial. Trials. 2022 Feb 4;23(1):114. doi: 10.1186/s13063-022-06016-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2020
• Primary Completion (ACTUAL): August 30, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (ACTUAL): August 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Covid19; ARDS; Vitamin D Deficiency; Corona Virus; High dose vitamin D
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Pharmaceutical Solutions; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2020-01401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No