Clinical trial NCT01130181: VITdAL@ICU - Correction of Vitamin D Deficiency in Critically Ill Patients
Official title: Correction of Vitamin D Deficiency in Critically Ill Patients: a Randomized, Double-blind, Placebo-controlled Trial ("VITDAL@ICU")
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Critical Illness
Vitamin D Deficiency
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2010-05-25
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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 outcomes:
measure: Length of hospital stay
timeFrame: maximum 6 months
Secondary outcomes:
measure: 25(OH)D levels
timeFrame: maximum 6 months
measure: calcium levels
timeFrame: maximum 6 months
measure: length of ICU stay starting from application of study medication
timeFrame: until patient's death or referral to another ward
measure: duration of mechanical ventilation
timeFrame: starting from application of study medication
measure: hospital mortality, 28-day mortality, 6 month-mortality
timeFrame: maximum 6 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
affiliation: Medical University of Graz, Austria
name: Harald Dobnig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.