Vitamin D Supplementation in Intensive Care Unit Patients

Study Overview
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Brief Summary
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A randomized controlled trial is designed to investigate the safety and clinical efficacy of a mega dose of VD in patients admitted in intensive care unit (ICU). Patients will be randomly allocated to receive 400,000 IU of VD3 or placebo. They will be followed up until ICU discharge or death or the 15th day of ICU stay. Adverse events that occur during ICU stay is collected. Primary outcome is intensive care unit-acquired infection (ICU-AI), and secondary outcomes are septic shock, organ failure, and ICU-mortality. Plasma 25-hydroxyvitamin D is assessed at baseline and at the end of follow-up. Cox regression models will be applied to test how VD supplementation affects adverse outcomes while adjusting for confounders.

Detailed Description
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The randomized controlled trial aimed to investigate the safety and clinical efficacy of a single mega dose of vitamin D (VD) in patients admitted at intensive care unit (ICU). Study participants: VD deficient ICU patients Criteria of inclusion, patients: newly admitted (within 24 hours) over eighteen, able to receive medication orally or through nasogastric tube expected to stay more than 72 hours in ICU. Criteria for non-inclusion and exclusion, patients: lack of patient's or relatives' consent expected short life or ICU stay (<48 hours) sepsis at admission kidney, liver or intestinal disease hypercalcemia (total calcium>10.6 mg/dL) history of a disorder associated with hypercalcemia (cancer, tuberculosis, sarcoidosis, hyperparathyroidism, nephrolithiasis) treatment with immunotherapy or vitamin supplements within one year pregnant or breastfeeding women discharge from ICU or death within 72 hours of admission Study protocol Patients will undergo physical examination with calculation of acute physiology and chronic assessment II (APACHE II) and sequential organ failure assessment (SOFA) scores. They will be randomly assigned to either VD or placebo group after stratification on gender, age and APACHE II: VD group, 170 patients will receive a single dose of 400,000 IU of VD3 orally or through nasogastric tube Placebo group, 170 patients will receive distilled water orally or through nasogastric tube. The patients will followed up until ICU discharge or death or the 15th day of ICU stay, whichever occurs first and adverse events that occurred during ICU stay were collected. Primary outcome: intensive care unit-acquired infection (ICU-AI), defined as an infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU. Secondary outcomes: urinary calcium:creatinine ratio as surrogate for VD toxicity, septic shock, organ failure, ICU-mortality. Plasma 25-hydroxyvitamin D (25-OHD) will be assessed at baseline and the end of follow-up using immunoassay. Cox regression models will be applied to test how VD supplementation affects adverse events and ICU-mortality while adjusting for confounders. Hypothesis. Recovering an adequate VD status might reduce poor outcome, especially infectious outcomes in ICU patients.

Official Title
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Effect of a Single Mega-dose of Vitamin D3 Supplementation on Clinical Course in Non-deficient Patients Admitted in Intensive Care Unit

Conditions
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Dietary Supplements, Intensive Care Unit, Vitamin D Deficiency, Vitamin D Toxicity

Intervention / Treatment
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* Dietary Supplement: Vitamin D supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly admitted (within 24 hours) over eighteen, able to receive medication orally or through nasogastric tube expected to stay more than 72 hours in ICU given consent Exclusion Criteria: lack of patient's or relatives' consent expected short life or ICU stay (<48 hours) sepsis at admission kidney, liver or intestinal disease hypercalcemia (total calcium>10.6 mg/dL) history of a disorder associated with hypercalcemia (i.e., cancer, tuberculosis, sarcoidosis, hyperparathyroidism, nephrolithiasis) treatment with immunotherapy or vitamin supplements within one year pregnant or breastfeeding women discharge from ICU or death within 72 hours of admission

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D group<br>170 patients receiving a single dose of 400,000 IU of VD3 (2 vials of 200,000 IU VD3; B.O.N., BOUCHARA RECORDATI) orally or through a nasogastric tube | Dietary Supplement: Vitamin D supplementation<br>* Patients are randomized to receive vitamin D or placebo and followed up for 15 days at maximum to investigate the safety and clinical efficacy of the supplements<br>|
| Sham Comparator: Placebo group<br>170 patients receiving distilled water (2 vials of 1 ml distilled water) orally or through a nasogastric tube | Dietary Supplement: Vitamin D supplementation<br>* Patients are randomized to receive vitamin D or placebo and followed up for 15 days at maximum to investigate the safety and clinical efficacy of the supplements<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of intensive care unit-acquired infection (ICU-AI) | Infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU, which occur during the ICU stay. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urinary calcium:creatinine ratio | used as a surrogate for VD toxicity | 15 days | 
| Rate of septic shock | persisting hypotension requiring vasopressors to maintain a mean arterial pressure of<65 mm Hg and a serum lactate level >2 mmol/L despite adequate volume resuscitation . | 15 days | 
| Rate of organ failure | acute change in sequential organ failure assessment (SOFA) score of 2 points or greater secondary to infection | 15 days | 
| Rate of ICU-mortality | Death within the ICU | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Critically ill, Intensive care unit, Vitamin D deficiencies