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

Not Applicable

Completed

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

• Registration Number: NCT04525820
• Lead Sponsor: Prof. Dr. Jörg Leuppi

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-08-17
• Study First Submitted QC: 2020-08-24
• Study First Posted: 2020-08-25
• Study Start: 2020-12-15
• Primary Completion: 2021-08-30
• Study Completion: 2021-11-30
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High Dose Vitamin D	Single 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
High Dose Vitamin D	Treatment as usual 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
Placebo	Placebo	Patient will receive a single dose of placebo, orally administered and then treatment as usual (daily 800 IU of vitamin D, orally administered)
Placebo	Treatment as usual vitamin D	Patient will receive a single dose of placebo, orally administered and then treatment as usual (daily 800 IU of vitamin D, orally administered)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Need of intensive care	Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)	Did the patient need a intensive care treatment during the hospitalization (yes/no)
Lenght of the Intensive Care Treatment	Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)	Day of admission to ICU until discharge or fatality
Development of vitamin D levels	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)	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.
Development of sepsis	During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)	percentage of patients developing a sepsis
Overall mortality	During the length of hospitalisation (mean duration is between 14 and 22 days for Patients with COVID-19)	Percentage of patient died during hospitalization

Trial Locations

Locations (2)

Cantonal Hospital Baselland Liestal; 🇨🇭 Liestal, BL, Switzerland

Cantonal Hospital St. Gallen; 🇨🇭 Saint Gallen, SG, Switzerland