Trial of Vitamin D to Reduce Risk and Severity of COVID-19 and Other Acute Respiratory Infections

Study Overview
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Brief Summary
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CORONAVIT is an open-label, phase 3, randomised clinical trial testing whether implementation of a test-and-treat approach to correction of sub-optimal vitamin D status results in reduced risk and/or severity of COVID-19 and other acute respiratory infections.

Official Title
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Phase 3 Randomised Controlled Trial of Vitamin D Supplementation to Reduce Risk and Severity of COVID-19 and Other Acute Respiratory Infections in the UK Population

Conditions
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Covid19, Acute Respiratory Tract Infection

Intervention / Treatment
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* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: UK resident Age ≥16 years Gives informed consent to participate Exclusion criteria: taking digoxin, alfacalcidol, calcitriol, dihydrotachysterol or paricalcitol known diagnosis of sarcoidosis, primary hyperparathyroidism, renal stones or renal failure requiring dialysis known allergy to any ingredient in the study capsules (vitamin D, olive oil, caramel, gelatine or glycerol) pregnancy

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Standard of care (national recommendation of 400 IU/day vitamin D) | |
| Experimental: Intervention: Lower-dose vitamin D<br>Offer of a daily dose of 800 IU (20 micrograms) cholecalciferol to individuals with 25-hydroxyvitamin D level <75 nmol/L | Dietary Supplement: Vitamin D<br>* Capsules containing 800 IU (20 micrograms) or 3,200 IU (80 micrograms) cholecalciferol<br>|
| Experimental: Intervention: Higher-dose vitamin D<br>Offer of a daily dose of 3200 IU (80 micrograms) cholecalciferol to individuals with 25-hydroxyvitamin D level <75 nmol/L | Dietary Supplement: Vitamin D<br>* Capsules containing 800 IU (20 micrograms) or 3,200 IU (80 micrograms) cholecalciferol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants experiencing at least one doctor-diagnosed or laboratory-confirmed acute respiratory infection of any cause. |  | Over 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants developing PCR- or antigen test-positive COVID-19 | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants who are prescribed one or more courses of antibiotic treatment for acute respiratory infection | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants with asthma who experience one or more exacerbations of asthma requiring treatment with oral corticosteroids and/or requiring hospital treatment | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants with COPD who experience one or more exacerbations of COPD requiring treatment with oral corticosteroids and/or antibiotics, and/or requiring hospital treatment | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants who have had PCR-, antigen test- or antibody test-confirmed SARS-CoV-2 infection who report symptoms of COVID-19 lasting more than 4 weeks after onset | Secondary efficacy outcome | Over 6 months | 
| Mean MRC dyspnoea score at the end of the study in people who have had PCR-, antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset | Secondary efficacy outcome | 6 months | 
| Mean FACIT Fatigue Scale score at the end of the study in people with antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset | Secondary efficacy outcome | 6 months | 
| Mean COVID-19 Recovery Questionnaire score at the end of the study in people who have had antigen test- or antibody test-confirmed SARS-CoV-2 infection and who report symptoms of COVID-19 lasting more than 4 weeks after onset | Secondary efficacy outcome | 6 months | 
| Proportion of participants who experience one or more acute respiratory infections requiring hospitalisation | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants who experience COVID-19 requiring hospitalisation | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants hospitalised for COVID-19 requiring ventilatory support | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants dying of any cause during participation in the trial | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants dying of acute respiratory infection during participation in the trial | Secondary efficacy outcome | Over 6 months | 
| Proportion of participants dying of COVID-19 during participation in the trial | Secondary efficacy outcome | Over 6 months | 
| Mean end-study 25(OH)D concentration (sub-set of participants having end-study tests of vitamin D status) | Secondary efficacy outcome | 6 months | 
| Proportion of participants experiencing known hypercalcaemia | Secondary safety outcome | Over 6 months | 
| Proportion of participants experiencing a probable or definite adverse reaction to vitamin D supplementation | Secondary safety outcome | Over 6 months | 
| Proportion of participants experiencing a serious adverse event of any cause | Secondary safety outcome | Over 6 months | 
| Proportion of SARS-CoV-2 vaccinated participants with antibodies to SARS-CoV-2 spike protein | Secondary efficacy outcome | Over 6 months | 
| Median titre of antibodies to SARS-CoV-2 spike protein in SARS-CoV-2 vaccinated participants | Secondary efficacy outcome | Over 6 months | 
| Proportion of SARS-CoV-2 vaccinated participants with antigen-specific T cell responses to SARS-CoV-2 spike protein (sub-set of participants) | Secondary efficacy outcome | Over 6 months | 
| Frequency of antigen-specific T cells reacting to SARS-CoV-2 spike protein in SARS-CoV-2 vaccinated participants (sub-set of participants) | Secondary efficacy outcome | Over 6 months |