Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Importance The efficacy of vitamin D3supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective To investigate the effect of a single high dose of vitamin D3on hospital length of stay in patients with COVID-19. Design, Setting, and Participants This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3(n = 120) or placebo (n = 120). Main Outcomes and Measures The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3(7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rankP = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39];P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, –4.1% to 9.2%];P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, –5.2% [95% CI, –15.1% to 4.7%];P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, –6.8% [95% CI, –15.1% to 1.2%];P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7];P  Conclusions and Relevance Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3for treatment of moderate to severe COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04449718