title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01130181.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Amrein
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schnedl
authors.affiliation: Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Holl
authors.affiliation: Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Riedl
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Christopher
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pachler
authors.affiliation: Division of General Neurology, Department of Neurology, Medical University of Graz, Austria.
authors.forename: Tadeja
authors.initials: T
authors.lastname: Urbanic Purkart
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Waltensdorfer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Münch
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Helga
authors.initials: H
authors.lastname: Warnkross
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Egbert
authors.initials: E
authors.lastname: Bisping
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Toller
authors.affiliation: Medical Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Smolle
authors.affiliation: Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Berghold
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Austria10Schilddrüsen-Endokrinologie-Osteoporose Institut Dobnig GmbH, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
mesh_terms: D000368:Aged; D002762:Cholecalciferol / Q000627:therapeutic use*; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D014808:Vitamin D Deficiency / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D002762:Cholecalciferol