Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.

Randomized, placebo-controlled trial in critically ill adults with vitamin D deficiency enrolled within 12 hours of the decision to admit to the ICU. The vitamin D group had 690 randomized participants, with 538 in the primary-analysis population and 531 in the 90-day mortality analysis.

A single enteral dose of vitamin D3 540,000 IU was given within 2 hours of randomization, administered orally or through a nasogastric or orogastric tube in liquid form. The comparison group received matched placebo.

Early high-dose enteral vitamin D3 did not improve survival or other major clinical outcomes in critically ill, vitamin D-deficient patients. Ninety-day mortality was 23.5% (125 of 531) with vitamin D3 versus 20.6% (109 of 528) with placebo, a difference of 2.9 percentage points (95% CI, -2.1 to 7.9; P = 0.26). In the screened-deficient population, 90-day mortality was also not significantly different: 23.3% (159 of 681) versus 20.9% (137 of 656), difference 2.5 percentage points (95% CI, -2.0 to 6.9; P = 0.28). Secondary outcomes, including mortality to day 28, hospital mortality to day 90, length of stay, ventilator-free days, and EQ-5D-5L change, were not significantly different. Vitamin D deficiency was rapidly corrected, but no clinical benefit was observed and safety findings were similar between groups.

The trial was stopped for futility, limiting the chance to detect smaller benefits. It was conducted in a heterogeneous ICU population and tested a single early bolus dose, so results may not generalize to other dosing strategies or less acute populations. Prespecified subgroup analyses did not identify benefit.