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

Sponsor

Prof. Dr. Jörg Leuppi (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04525820

Collaborator

(none)

Enrollment

Locations

Arms

11.5

Anticipated Duration (Months)

Patients Per Site

3.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Vitamin D Deficiency Corona Virus Infection ARDS Coronavirus SARS-CoV Infection	Drug: Single high dose vitamin D Drug: Placebo Drug: Treatment as usual vitamin D	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 TAUone 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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 15, 2020

Actual Primary Completion Date :

Aug 30, 2021

Anticipated Study Completion Date :

Nov 30, 2021

Arms and Interventions

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: Placebo Patient receives a single dose of a placebo solution Other Names: Oily placebo solution 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

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: Placebo

Patient receives a single dose of a placebo solution

Other Names:

Oily placebo solution

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

Outcome Measures

Primary Outcome Measures

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

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
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
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

Other Outcome Measures

Complications due to COVID-19 [During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)]
We assess every other complications which occurs due to COVID-19
Blood pressure (BP) [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)]
The BP will be assessed daily in mmHg
Heart rate [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)]
The heart rate will be assessed daily in bpm
Peripheral oxygen saturation (SpO2) [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)]
The SpO2 will be assessed daily in %
Percentage of patients who require oxygen [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)]
Requirement for oxygen will be assessed daily (yes/no) if yes how many liters per minute
Breathing frequency [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)]
Breathing frequence will be assessed daily in breaths per minute
Glasgow Coma Scale (GCS) [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.
Percentage of patients are smokers, former smokers or lifelong non-smokers [Assessing of the smoking Status at Basleine]
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
Current Symptoms [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)]
Assessed in No/ Mild/ Moderate /Severe
Temperature [Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)]
Temperature will be assessed daily in degrees celsius

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,