Early Vitamin D3 Supplementation for Critically Ill Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: Medium Chain Triglycerides (MCT); Dietary supplement: Vitamin D3

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yin Yi Han, doctor; Phone Number: 886972651405; Email: noviahan@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Yin-Yi Han, doctor; Phone Number: 886972651405; Email: noviahan@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control1; Participants with serum 25(OH)D levels of 15-19.9 ng/mL, receiving 40 cc. medium-chain triglyceride (MCT) supplement.	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
Placebo Comparator: Control2; Participants with serum 25(OH)D levels of 12-14.9 ng/mL, receiving 50 cc. MCT supplement.	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
Placebo Comparator: Control3; Participants with serum 25(OH)D levels below 12 ng/mL, receiving 60 cc. MCT supplement.	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
Experimental: Vitamin D1; Participants with serum 25(OH)D levels of 15-19.9 ng/mL, receiving vitamin D3 of 576,000 IU supplement	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
Experimental: Vitamin D2; Participants with serum 25(OH)D levels of 12-14.9 ng/mL, receiving vitamin D3 of 720,000 IU supplement	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
Experimental: Vitamin D3; Participants with serum 25(OH)D levels below 12 ng/mL, receiving vitamin D3 of 864,000 IU supplement	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality rate	30-day mortality rate after intervention with the study samples.	30 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: critically ill; vitamin D; calcidiol levels
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Critical Illness; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 202305074RIPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No