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

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

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

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.

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.

one group receives a single high dose of vitamin D in addition to treatment as usual (TAU) the other group receives a single dose of placebo in addition to TAU

The blinding is performed by the hospital pharmacy of the university hospital of Basel. They will provide us with packed and labeled study medication and placebo. They will provide us with medication packages for each patient which includes either high dose vitamin D and the standard medication or the placebo and the standard medication.

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

Patient will receive a single dose of placebo, orally administered and then treatment as usual (daily 800 IU of vitamin D, orally administered)

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

Both groups receive the treatment as usual after the single high dose or the placebo which will be 800 IU per day

Administration to Discharge from hospital care (mean duration is between 14 and 22 days for Patients with COVID 19)

During the length of hospitalisation (mean duration 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.

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)

During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

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)

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

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

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,

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.