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Original Investigation
Caring for the Critically Ill Patient
October 15, 2014

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

Author Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria
  • 2Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria
  • 3Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, Austria
  • 4Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • 5Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Austria
  • 6Division of General Neurology, Department of Neurology, Medical University of Graz, Austria
  • 7Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
  • 8Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria
  • 9Medical Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Austria
  • 10Schilddrüsen-Endokrinologie-Osteoporose Institut Dobnig GmbH, Graz, Austria
JAMA. 2014;312(15):1520-1530. doi:10.1001/jama.2014.13204
Abstract

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 D3 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 D3 (n = 249) or a placebo (n = 243).

Interventions  Vitamin D3 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 D3 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 D3 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 D3 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 D3 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 D3 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 D3 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 D3 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 D3 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.

Trial Registration  clinicaltrials.gov Identifier: NCT01130181

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