Effects of Early Vitamin D3 Supplementation on Clinical Outcomes for Critically Ill Patients

Study Overview
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Brief Summary
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There are no clear international guidelines for dosing vitamin D based on deficiency severity. Therefore, a new clinical trial is needed to evaluate the benefits of early vitamin D supplementation in maintaining sufficient levels for critically ill patients. Our group conducted a multicenter clinical trial in Taiwan focusing on vitamin D and critically ill patientsWe will enroll 240 patients with low calcidiol levels and provide varying supplementation doses to maintain their serum calcidiol levels ≥ 30 ng/mL within 30 days of ICU admission. The results will serve as a valuable reference for intensivists when formulating appropriate vitamin D treatment strategy to maximize clinical benefits for critically ill patients.

Detailed Description
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Recent studies have highlighted a prevalent vitamin D deficiency in critically ill patients, ranging from 26% to 82%. These patients experience longer ICU stays, higher medical expenses, and increased sepsis-related mortality. Our group conducted a multicenter clinical trial in Taiwan focusing on vitamin D and critically ill patients. In the first phase, the epidemiological investigation found significantly lower serum calcidiol levels of approximately 20.9 ng/mL compared to the normal range of 30-60 ng/mL in ICU patients. The second phase, a randomized control study, preliminarily demonstrated that supplementing 576,000 IU of vitamin D3 in critically ill patients with serum calcidiol levels below 20 ng/mL significantly reduced the risk of multidrug resistant bacterial infections within 30 days. An Austrian trial also showed that adequate vitamin D supplementation lowered in-hospital mortality in severely deficient patients. The importance of vitamin D supplementation for critically ill patients with vitamin D deficiency is evident, as their clinical prognosis is closely related to achieving adequate serum calcidiol levels. However, there are no clear international guidelines for dosing vitamin D based on deficiency severity. Therefore, a new clinical trial is needed to evaluate the benefits of early vitamin D supplementation in maintaining sufficient levels for critically ill patients. We will enroll 240 patients with low calcidiol levels and provide varying supplementation doses to maintain their serum calcidiol levels ≥ 30 ng/mL within 30 days of ICU admission. The results will serve as a valuable reference for intensivists when formulating appropriate vitamin D treatment strategy to maximize clinical benefits for critically ill patients

Official Title
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Effects of Early Vitamin D3 Supplementation on Clinical Outcomes for Critically Ill Patients

Conditions
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Vitamin D Deficiency, Critical Illness

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Dietary Supplement: Medium Chain Triglycerides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18-year-old critically ill patient. Admission to ICU < 24 hours. APACHE II at 24 hours of admission to ICU ranged from 20-39 points. The basic blood calcifediol concentration within 24 hours of admission to the intensive care unit is < 20 ng/mL. Intensive care physician expects patient to stay in ICU for ≥ 72 hours. Exclusion Criteria: Hypercalcemia (total calcium ion concentration in blood > 2.6 mmol/L). Disorders affecting serum calcifediol concentration, calcium metabolism, or bone metabolism (eg, parathyroid disease, rickets, or severe cirrhosis [Child C]). Have received high-dose vitamin D3 therapy (> 2000 IU per day or ≥ 10,000 IU in a single dose) within four weeks. Admitted to the intensive care unit with a diagnosis of new coronary pneumonia (COVID-19). Organ transplant patients. Have had tuberculosis, sarcoidosis or kidney stones within a year. Kidney dialysis, continuous renal replacement therapy (Continuous Renal Replacement Therapy, CRRT), acute kidney injury (Acute kidney injury, AKI). Body weight <45 kg or >90 kg. Has been admitted to an intensive care unit within three months. Patients and family members who do not speak their native language. Pregnant women.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control1<br>Enteral supplement 8 ampoules Medium Chain Triglycerides if serum calcifediol level is 15-19.9 ng/mL. | Dietary Supplement: Medium Chain Triglycerides<br>* 1ampoule Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>* Other names: MCT;|
| Placebo Comparator: Control2<br>Enteral supplement 10 ampoules Medium Chain Triglycerides if serum calcifediol level is 12-14.9 ng/mL. | Dietary Supplement: Medium Chain Triglycerides<br>* 1ampoule Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>* Other names: MCT;|
| Placebo Comparator: Control3<br>Enteral supplement 12 ampoules Medium Chain Triglycerides if serum calcifediol level below 12 ng/mL | Dietary Supplement: Medium Chain Triglycerides<br>* 1ampoule Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>* Other names: MCT;|
| Experimental: Vitamin D1<br>Enteral supplement 8 ampoules vitamin D(576000IU) if serum calcifediol level is 15-19.9 ng/mL. | Dietary Supplement: Vitamin D<br>* 1ampoule (72000IU) Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>|
| Experimental: Vitamin D2<br>Enteral supplement 10 ampoules vitamin D(720000IU) if serum calcifediol level is 12-14.9 ng/mL. | Dietary Supplement: Vitamin D<br>* 1ampoule (72000IU) Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>|
| Experimental: Vitamin D3<br>Enteral supplement 12 ampoules vitamin D(864000IU) if serum calcifediol level below 12 ng/mL | Dietary Supplement: Vitamin D<br>* 1ampoule (72000IU) Q3H on ICU day 3 Number of Cycles: until progression or subject develops severe diarrhea (greater than 1000 grams) associated with vitamin D supplementation for two consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality within 30 days | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, calcidiol levels, critically ill