Early Vitamin D3 Supplementation for Critically Ill Patients

Official title

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

Overview

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.

Interventions

• Dietary supplement Vitamin D3
  Dose of vitamin D3 depends on participant's serum 25(OH)D levels, with one sample bottle contains 72,000 IU of vitamin D3; Intervention starts on ICU day 3 with a frequency of 1 ampule every 3 hours and is completed within the following 48 hours
• Dietary supplement Medium Chain Triglycerides (MCT)
  Dose of MCT depends on participant's serum 25(OH)D levels, with one sample bottle contains 5 cc. of MCT; Intervention starts on ICU day 3 with a frequency of 1 ampule every 3 hours and is completed within the following 48 hours

Primary outcome measures

• 30-day mortality rate [Time frame: 30 days]

Secondary outcome measures (7)

• 30-day mortality rate of patients who survives >7 days [Time frame: 30 days]
• Length of ICU stay for surviving patients [Time frame: 30 days]
• Length of hospital stay for surviving patients [Time frame: 30 days]
• 30-day mortality based on serum 25(OH)D levels on day 7 [Time frame: 30 days]
• 30-day mortality based on serum 25(OH)D levels on day 30 [Time frame: 30 days]
• 30-day mortality based on APACHE II scores at ICU 24 hours [Time frame: 30 days]
• Correlation of 25(OH)D increment after vitamin D supplement and body weight [Time frame: 7 days]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Identifiers

NCT: NCT05937789 · 202305074RIPC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗