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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Acute Respiratory Tract Infection
• Intervention / Treatment: Dietary supplement: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 6200
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • County (optional)
    • London, County (optional), United Kingdom, E1 2AB
      • Queen Mary University of London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. UK resident
2. Age ≥16 years
3. Gives informed consent to participate

Exclusion criteria:

1. taking digoxin, alfacalcidol, calcitriol, dihydrotachysterol or paricalcitol
2. known diagnosis of sarcoidosis, primary hyperparathyroidism, renal stones or renal failure requiring dialysis
3. known allergy to any ingredient in the study capsules (vitamin D, olive oil, caramel, gelatine or glycerol)
4. pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard of care (national recommendation of 400 IU/day vitamin D)
Experimental: Intervention: Lower-dose vitamin D; 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; Capsules containing 800 IU (20 micrograms) or 3,200 IU (80 micrograms) cholecalciferol
Experimental: Intervention: Higher-dose vitamin D; 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; Capsules containing 800 IU (20 micrograms) or 3,200 IU (80 micrograms) cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: Barts & The London NHS Trust; Pharma Nord; Fischer Family Trust; The AIM Foundation; Synergy Biologics Ltd; Cytoplan Ltd

Publications and helpful links

General Publications

• Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR. Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). BMJ. 2022 Sep 7;378:e071230. doi: 10.1136/bmj-2022-071230.

Helpful Links

• Pre-print

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2020
• Primary Completion (Actual): June 17, 2021
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases; Respiratory Tract Infections; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: 289515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified IPD will be shared with other researchers subject to terms of Data Transfer Agreement and IRB approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No