Clinical trial NCT04915963: Vitamin D Supplementation in Intensive Care Unit Patients
Official title: Effect of a Single Mega-dose of Vitamin D3 Supplementation on Clinical Course in Non-deficient Patients Admitted in Intensive Care Unit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dietary Supplements
Intensive Care Unit
Vitamin D Deficiency
Vitamin D Toxicity
Keywords: Critically ill
Intensive care unit
Vitamin D deficiencies
Lead sponsor: Association Tunisienne d'Etude & de Recherche sur l'Athérosclérose
Sponsor class: OTHER
Collaborators: name: Faculty of Medicine of Tunis
name: Rabta University Hospital
First posted: 2021-06-07
Enrollment: 340
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of intensive care unit-acquired infection (ICU-AI)
timeFrame: 15 days
Secondary outcomes:
measure: urinary calcium:creatinine ratio
timeFrame: 15 days
measure: Rate of septic shock
timeFrame: 15 days
measure: Rate of organ failure
timeFrame: 15 days
measure: Rate of ICU-mortality
timeFrame: 15 days
Other outcomes:
Locations:
Study officials:
affiliation: Rabta University Hospital
name: Moncef Feki, Professor
role: STUDY_DIRECTOR
References:
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