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.
Level 2 - randomized trial
Individual double-blind randomized placebo-controlled trial.
PubMed 33595634 · doi:10.1001/jama.2020.26848
What was done
In a multicenter, double-blind, randomized, placebo-controlled trial across two sites in São Paulo, Brazil, 240 hospitalized patients with moderate to severe COVID-19 were randomized 1:1 to receive a single oral dose of 200,000 IU of vitamin D3 (n = 120) or placebo (n = 120). The primary outcome was hospital length of stay from randomization to discharge. Prespecified secondary outcomes included in-hospital mortality, ICU admission, mechanical ventilation requirement, and serum 25-hydroxyvitamin D levels.
What was found
A total of 237 patients were analyzed (mean age 56.2 years, 43.9% women, baseline mean 25-hydroxyvitamin D 20.9 ng/mL). Median hospital length of stay was 7.0 days (IQR 4.0–10.0) in the vitamin D3 group versus 7.0 days (IQR 5.0–13.0) in the placebo group (unadjusted HR for discharge 1.07; 95% CI, 0.82–1.39; P = .62). There were no significant differences in in-hospital mortality (7.6% vs 5.1%; difference 2.5% [95% CI, -4.1% to 9.2%]; P = .43), ICU admissions (16.0% vs 21.2%; difference -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or mechanical ventilation requirement (7.6% vs 14.4%; difference -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Serum 25-hydroxyvitamin D levels increased significantly in the vitamin D3 group compared with placebo (44.4 ng/mL vs 19.8 ng/mL; difference 24.1 ng/mL [95% CI, 19.5–28.7]; P < .001).
Why it matters
This randomized trial provides rigorous evidence that a single high-dose vitamin D3 intervention does not improve clinical outcomes or shorten hospital stay in patients already hospitalized with moderate to severe COVID-19.
Limits
The study evaluated a single high bolus dose administered late in the disease course among hospitalized patients, meaning it cannot assess daily maintenance dosing or pre-infection prophylaxis. The sample size was powered to detect differences in length of stay rather than lower-frequency endpoints like mortality or mechanical ventilation. The trial was conducted at only two centers within a single metropolitan area.
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- supports A Brazilian clinical study in COVID-19 patients found that a single bolus dose of 200,000 IU of vitamin D showed no significant clinical effect.