Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency The VITdAL-ICU Randomized Clinical Trial

IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE To investigate whether a vitamin D-3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (<= 20 ng/mL) assigned to receive either vitamin D-3 (n = 249) or a placebo (n = 243). INTERVENTIONS Vitamin D-3 or placebo was given orally or via nasogastric tube once at a dose of 540 000 IU followed by monthly maintenance doses of 90 000 IU for 5 months. MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (<= 12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS A total of 475 patients were included in the final analysis (237 in the vitamin D-3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D-3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3%[95% CI, 22.6%-34.5%] for vitamin D-3 vs 35.3%[95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0%[95% CI, 29.0%-41.5%] for vitamin D-3 vs 42.9%[95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D-3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6%[95% CI, 19.9%-38.6%]) for vitamin D-3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7%[95% CI, 25.4%-45.0%] for vitamin D-3 vs 50.0%[95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D-3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. Copyright 2014 American Medical Association. All rights reserved.