Clinical trial NCT04525820: High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Center Study
Official title: High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Center Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Vitamin D Deficiency
Corona Virus Infection
ARDS
Coronavirus
SARS-CoV Infection
Keywords: Covid19
Vitamin D Deficiency
ARDS
Corona Virus
High dose vitamin D
Lead sponsor: Cantonal Hosptal, Baselland
Sponsor class: OTHER
First posted: 2020-08-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Length of hospitalization
timeFrame: Administration to Discharge from hospital care (mean duration is between 14 and 22 days for Patients with COVID 19)
Secondary outcomes:
measure: Need of intensive care
timeFrame: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Lenght of the Intensive Care Treatment
timeFrame: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Overall mortality
timeFrame: During the length of hospitalisation (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Development of vitamin D levels
timeFrame: 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)
measure: Development of sepsis
timeFrame: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)
Other outcomes:
measure: Complications due to COVID-19
timeFrame: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Blood pressure (BP)
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Heart rate
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)
measure: Peripheral oxygen saturation (SpO2)
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
measure: Percentage of patients who require oxygen
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
measure: Breathing frequency
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
measure: Glasgow Coma Scale (GCS)
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
measure: Percentage of patients are smokers, former smokers or lifelong non-smokers
timeFrame: Assessing of the smoking Status at Basleine
measure: Current Symptoms
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
measure: Temperature
timeFrame: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
Locations:
city: Liestal
country: Switzerland
facility: Cantonal Hospital Baselland Liestal
state: BL
city: Saint Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
state: SG
Study officials:
affiliation: Cantonal Hosptal, Baselland
name: Jörg D Leuppi, Professor
role: STUDY_DIRECTOR
References:
citation: 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.