High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial

Multicentre randomized controlled clinical trial conducted in 17 hospitals in four provinces of Argentina from August 2020 to June 2021. Hospitalized adults with confirmed mild-to-moderate COVID-19 and risk factors for progression were enrolled; in the vitamin D3 arm, the mean age was 59.8 years and 44.3% were women.

Participants in the active arm received a single oral dose of vitamin D3 500,000 IU as five 100,000 IU soft gel capsules, administered as soon as possible after randomization, versus matching placebo. For the vitamin D3 group, 115 participants were randomized in a 1:1 trial.

High-dose vitamin D3 did not prevent respiratory deterioration or improve clinical outcomes compared with placebo. The primary outcome, change in rSOFA from baseline to day 7, was 0.0 (0.0-1.0) in both groups, with a between-group difference of 0.00 (-0.18 to 0.15; p = 0.825). Other key outcomes were also null, including change in SpO2 (-1.0 vs -1.0; p = 0.952), length of stay (6.0 vs 6.0 days; p = 0.632), ICU admission (7.8% vs 10.7%; RR 0.73, 0.32 to 1.70; p = 0.622), and in-hospital death (4.3% vs 1.9%; RR 2.24, 0.44 to 11.29; p = 0.451). Serious adverse events occurred in 14.8% of the vitamin D3 group and 11.7% of placebo, with no clear efficacy signal across prespecified subgroups.

The trial tested only a single very high dose, so it does not address repeated dosing or other regimens. Event rates were low for several clinical endpoints, limiting power for harder outcomes such as mechanical ventilation and death. Generalizability may be limited to hospitalized adults with mild-to-moderate COVID-19 in Argentine hospitals, and baseline 25-hydroxyvitamin D was not clearly deficient in the active arm (32.5 ng/mL, IQR 27.2-44.2).