Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.
What this study found
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,…
- Study & population
- Randomized, placebo-controlled trial in critically ill adults with vitamin D deficiency enrolled within 12 hours of the decision to admit to the ICU.
- Intervention
- 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.
- Key limitation
- The trial was stopped for futility, limiting the chance to detect smaller benefits.
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Open PDFOriginal abstract
BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).