Early Vitamin D3 Supplementation for Critically Ill Patients

Not Applicable

Recruiting

• Conditions: Vitamin D Deficiency; Critical Illness
• Interventions: Dietary Supplement: Vitamin D3; Dietary Supplement: Medium Chain Triglycerides (MCT)

• Registration Number: NCT05937789
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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. The investigators conducted a multicenter clinical trial in Taiwan focusing on vitamin D and critically ill patients. 240 patients with low calcidiol levels will be enrolled and be provided varying supplementation doses to maintain their serum calcidiol levels ≥ 30 ng/mL within 30 days of ICU admission. The serum levels of calcidiol and PTH will be measured on Day 0, Day 7, Day 14 and Day 30 before and after vitamin D supplementation. 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

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. The investigators 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. The investigators 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 serum levels of calcidiol and PTH will be measured on Day 0, Day 7, Day 14 and Day 30 before and after vitamin D supplementation. 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.

Study Timeline

• Study First Submitted: 2023-06-30
• Study First Submitted QC: 2023-06-30
• Study First Posted: 2023-07-10
• Study Start: 2024-01-22
• Status Verified: 2024-07
• Last Update Submitted: 2024-08-14
• Last Update Posted: 2024-08-16
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• ≥18-year-old critically ill patient.
• ICU admission < 24 hours.
• Baseline 25(OH)D levels within 24 hours of ICU admission < 20 ng/mL.
• Expected ICU length of stay ≥ 72 hours.

Exclusion Criteria

• Hypercalcemia (ie. total serum calcium levels > 2.6 mmol/L).
• Disorders affecting serum 25(OH)D levels, calcium metabolism, or bone metabolism (eg, parathyroid disease, rickets, or severe cirrhosis [Child C]).
• Having received high-dose vitamin D3 therapy (ie. > 2,000 IU daily or a single dose of ≥ 10,000 IU) within the past four weeks.
• Active COVID-19 at ICU admission.
• Organ transplant.
• Having had tuberculosis, sarcoidosis or kidney stones within the past year.
• Having renal dialysis, continuous kidney replacement therapy (CKRT), acute kidney injury (AKI).
• Having ICU admission within the past three months.
• Non-native-speaking patients and their families
• Pregnant women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin D1	Vitamin D3	Participants with serum 25(OH)D levels of 15-19.9 ng/mL, receiving vitamin D3 of 576,000 IU supplement
Control3	Medium Chain Triglycerides (MCT)	Participants with serum 25(OH)D levels below 12 ng/mL, receiving 60 cc. MCT supplement.
Control1	Medium Chain Triglycerides (MCT)	Participants with serum 25(OH)D levels of 15-19.9 ng/mL, receiving 40 cc. medium-chain triglyceride (MCT) supplement.
Vitamin D2	Vitamin D3	Participants with serum 25(OH)D levels of 12-14.9 ng/mL, receiving vitamin D3 of 720,000 IU supplement
Control2	Medium Chain Triglycerides (MCT)	Participants with serum 25(OH)D levels of 12-14.9 ng/mL, receiving 50 cc. MCT supplement.
Vitamin D3	Vitamin D3	Participants with serum 25(OH)D levels below 12 ng/mL, receiving vitamin D3 of 864,000 IU supplement

Primary Outcome Measures

Name	Time	Method
30-day mortality rate	30 days	30-day mortality rate after intervention with the study samples.

Secondary Outcome Measures

Name	Time	Method
30-day mortality rate of patients who survives >7 days	30 days	30-day mortality rate of patients who survives \>7 days after intervention with the study. samples
30-day mortality based on APACHE II scores at ICU 24 hours	30 days	Comparison of 30-day mortality between the three groups based on 24-hour APACHE II scores: \<20, 20-39, and ≥39.
30-day mortality based on serum 25(OH)D levels on day 7	30 days	Comparison of 30-day mortality between the two treatment groups based on serum 25(OH)D levels on day 7: ≥ 30 ng/mL vs. \< 30 ng/mL.
30-day mortality based on serum 25(OH)D levels on day 30	30 days	Comparison of 30-day mortality between the two treatment groups based on serum 25(OH)D levels on day 30: ≥ 30 ng/mL vs. \< 30 ng/mL.
Length of ICU stay for surviving patients	30 days	Length of ICU stay for surviving patients.
Length of hospital stay for surviving patients	30 days	Length of hospital stay for surviving patients.
Correlation of 25(OH)D increment after vitamin D supplement and body weight	7 days	Correlation between 25(OH)D levels and body weight on day 7 after supplementation in the treatment group.

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan