Abstract
OBJECTIVES: To determine the effect of vitamin D supplementation on disease progression and post-exposure prophylaxis for COVID-19 infection. We hypothesize that high-dose vitamin D3 supplementation will reduce risk of hospitalization/death among those with recently diagnosed COVID-19 infection and will reduce risk of COVID-19 infection among their close household contacts. METHODS: We report the rationale and design of a planned pragmatic, cluster randomized, double-blinded trial (N = 2700 in total nationwide), with 1500 newly diagnosed individuals with COVID-19 infection, together with up to one close household contact each (~1200 contacts), randomized to either vitamin D3 (loading dose, then 3200 IU/day) or placebo in a 1:1 ratio and a household cluster design. The study duration is 4 weeks. The primary outcome for newly diagnosed individuals is the occurrence of hospitalization and/or mortality. Key secondary outcomes include symptom severity scores among cases and changes in the infection (seroconversion) status for their close household contacts. Changes in vitamin D 25(OH)D levels will be assessed and their relation to study outcomes will be explored. CONCLUSIONS: The proposed pragmatic trial will allow parallel testing of vitamin D3 supplementation for early treatment and post-exposure prophylaxis of COVID-19. The household cluster design provides a cost-efficient approach to testing an intervention for reducing rates of hospitalization and/or mortality in newly diagnosed cases and preventing infection among their close household contacts.