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 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 D

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 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.
• 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.

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; Enteral supplement with 8 ampules of medium chain triglycerides for participants with serum calcifediol levels of 15-19.9 ng/mL.	Dietary supplement: Medium Chain Triglycerides (MCT); One ampule of study sample 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; Enteral supplement 10 of medium chain triglycerides for participants with serum calcifediol levels of 12-14.9 ng/mL.	Dietary supplement: Medium Chain Triglycerides (MCT); One ampule of study sample 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; Enteral supplement 12 of medium chain triglycerides for participants with serum calcifediol levels below 12 ng/mL.	Dietary supplement: Medium Chain Triglycerides (MCT); One ampule of study sample 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; Enteral supplement 8 ampules vitamin D for participants with serum calcifediol levels of 15-19.9 ng/mL.	Dietary supplement: Vitamin D; One ampule of study sample contains 72,000 IU of vitamin D; 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; Enteral supplement 10 ampules vitamin D for participants with serum calcifediol levels of 12-14.9 ng/mL.	Dietary supplement: Vitamin D; One ampule of study sample contains 72,000 IU of vitamin D; 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; Enteral supplement 12 ampules vitamin D for participants with serum calcifediol levels below 12 ng/mL.	Dietary supplement: Vitamin D; One ampule of study sample contains 72,000 IU of vitamin D; 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
Mortality within 30 days	Mortality within 30 days	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality of patients who survived >7 days	30-day mortality of patients who survived >7 days	30 days
Number of days that participants do not need to stay in the intensive care unit (ICU-free day) within 30 days	Number of days that participants do not need to stay in the intensive care unit (ICU-free day) within 30 days	30 days
Number of days that surviving patients stayed in the ICU	Number of days that surviving patients stayed in the ICU	30 days
Number of days of hospitalization for surviving patients	Number of days of hospitalization for surviving patients	30 days
The difference in 30-day mortality between the two groups with serum calcifediol ≥ 30 ng/mL and < 30 ng/mL on the seventh day of the treatment group.	The difference in 30-day mortality between the two groups with serum calcifediol ≥ 30 ng/mL and < 30 ng/mL on the seventh day of the treatment group.	30 days
The difference in 30-day mortality between the two groups with serum calcifediol ≥ 30 ng/mL and < 30 ng/mL on day 30 of the treatment group.	The difference in 30-day mortality between the two groups with serum calcifediol ≥ 30 ng/mL and < 30 ng/mL on day 30 of the treatment group.	30 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): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: June 1, 2023

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; Vitamin D
• 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