VITdAL@ICU - Correction of Vitamin D Deficiency in Critically Ill Patients (VITdAL@ICU)

Correction of Vitamin D Deficiency in Critically Ill Patients: a Randomized, Double-blind, Placebo-controlled Trial ("VITDAL@ICU")

Study hypothesis:

High-dose vitamin D leads to a shorter hospital stay in critically ill patients

Vitamin D deficient patients will be randomized to receive either 540,000 IU cholecalciferol or placebo.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Vitamin D Deficiency
• Intervention / Treatment: Drug: Placebo; Drug: Cholecalciferol

Detailed Description

Inclusion criteria

• Age ≥18 years
• expected ICU stay ≥48 hours
• vitamin D deficiency: 25(OH)D ≤ 20 ng/ml
• feasibility of study drug application via nasogastric tube in cases where oral food intake is not possible

Exclusion criteria

• moribund patient expected to die within 24 hours
• hypercalcaemia (total calcium >2.65 OR ion. calcium >1.35 mmol/l)
• severely impaired gastrointestinal motility (ileus, residual gastric volume > 400 ml)
• known history of recent kidney stones (≤ 1 year)
• known granulomatous diseases (tuberculosis, sarcoidosis)
• pregnancy

Primary endpoint

• hospital stay (hours; starting from ICU admission) Secondary endpoints
• percentage of patients with 25(OH)D ≥ 30 ng/ml at day 7
• serum calcium; phosphorus; 25(OH)D; 1,25(OH)D; PTH; osteocalcin; bALP; TRAP; urinary calcium

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• expected ICU stay ≥48 hours
• vitamin D deficiency: 25(OH)D ≤ 20 ng/ml
• feasibility of study drug application via nasogastric tube in cases where oral food intake is not possible

Exclusion Criteria:

• moribund patient expected to die within 24 hours
• hypercalcaemia (total calcium >2.65 OR ion. calcium >1.35 mmol/l)
• severely impaired gastrointestinal motility (ileus, residual gastric volume > 400 ml)
• known history of recent kidney stones (≤ 1 year)
• known granulomatous diseases (tuberculosis, sarcoidosis)
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo; Other Names: herbal oil
Experimental: Cholecalciferol	Drug: Cholecalciferol; loading dose of 540,000 IU of cholecalciferol via feeding tube or orally, then 5 monthly doses of 90,000 IU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	The length of hospital stay will be compared between the two groups (starting from application of the study medication; end is defined as death of the patient or hospital discharge) Survivors and non-survivors will also be analysed separately. Stay in rehabilitation facilities will not be counted.	maximum 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25(OH)D levels	serum 25(OH)D levels will be measured on day 0, 3 and 7	maximum 6 months
calcium levels	serum calcium levels will be measured on day 0, 3 and 7	maximum 6 months
length of ICU stay starting from application of study medication		until patient's death or referral to another ward
duration of mechanical ventilation	duration of mechanical ventilation including CPAP/mask ventilation	starting from application of study medication
hospital mortality, 28-day mortality, 6 month-mortality		maximum 6 months

Collaborators and Investigators

• Sponsor: Harald Dobnig, MD
• Investigators: Principal Investigator: Harald Dobnig, MD, Medical University of Graz, Austria

Publications and helpful links

General Publications

• Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically ill patients. N Engl J Med. 2009 Apr 30;360(18):1912-4. doi: 10.1056/NEJMc0809996. No abstract available. Erratum In: N Engl J Med. 2011 May 12;364(19):1882.
• Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med. 2012 Jan;40(1):63-72. doi: 10.1097/CCM.0b013e31822d74f3.
• Amrein K, Venkatesh B. Vitamin D and the critically ill patient. Curr Opin Clin Nutr Metab Care. 2012 Mar;15(2):188-93. doi: 10.1097/MCO.0b013e32834f0027.
• Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D. Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Med. 2010 Sep;36(9):1609-11. doi: 10.1007/s00134-010-1875-8. Epub 2010 Apr 7. No abstract available.
• Amrein K, Zajic P, Schnedl C, Waltensdorfer A, Fruhwald S, Holl A, Purkart T, Wunsch G, Valentin T, Grisold A, Stojakovic T, Amrein S, Pieber TR, Dobnig H. Vitamin D status and its association with season, hospital and sepsis mortality in critical illness. Crit Care. 2014 Mar 24;18(2):R47. doi: 10.1186/cc13790.
• Lee P, Nair P, Eisman JA, Center JR. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality? Intensive Care Med. 2009 Dec;35(12):2028-32. doi: 10.1007/s00134-009-1642-x. Epub 2009 Sep 15.
• Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, Luque de Castro MD, Pavon RG, Quesada Gomez JM. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):452-5. doi: 10.1016/j.jsbmb.2010.03.078. Epub 2010 Apr 21.
• Krishnan A, Ochola J, Mundy J, Jones M, Kruger P, Duncan E, Venkatesh B. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care. 2010;14(6):R216. doi: 10.1186/cc9341. Epub 2010 Nov 26.
• Amrein K, Schnedl C, Berghold A, Pieber TR, Dobnig H. Correction of vitamin D deficiency in critically ill patients - VITdAL@ICU study protocol of a double-blind, placebo-controlled randomized clinical trial. BMC Endocr Disord. 2012 Nov 7;12:27. doi: 10.1186/1472-6823-12-27.
• Schwetz V, Schnedl C, Urbanic-Purkart T, Trummer C, Dimai HP, Fahrleitner-Pammer A, Putz-Bankuti C, Christopher KB, Obermayer-Pietsch B, Pieber TR, Dobnig H, Amrein K. Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study. Osteoporos Int. 2017 Dec;28(12):3347-3354. doi: 10.1007/s00198-017-4190-1. Epub 2017 Aug 25.
• Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, Urbanic Purkart T, Waltensdorfer A, Munch A, Warnkross H, Stojakovic T, Bisping E, Toller W, Smolle KH, Berghold A, Pieber TR, Dobnig H. 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. JAMA. 2014 Oct 15;312(15):1520-30. doi: 10.1001/jama.2014.13204. Erratum In: JAMA. 2014 Nov 12;312(18):1932.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 24, 2010
• First Posted (Estimate): May 25, 2010

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 23, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Critical Illness; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: VITdAL@ICU - 19022010