The VITDALIZE Study: Effect of High-dose Vitamin D3 on 28-day Mortality in Adult Critically Ill Patients (VITDALIZE)

November 18, 2025 updated by: Medical University of Graz

The VITDALIZE Study: Effect of High-dose Vitamin D3 on 28-day Mortality in Adult Critically Ill Patients With Severe Vitamin D Deficiency: a Multicenter, Placebo-controlled Double-blind Phase III Randomized Controlled Trial (RCT)

In the VITdAL-ICU trial using a large oral dose of vitamin D3 in 480 adult critically ill patients, there was no benefit regarding the primary endpoint hospital length of stay. However, the predefined subgroup with severe vitamin D deficiency (25(OH)D ≤ 12ng/ml) had significantly lower 28-day mortality (36.3% placebo vs. 20.4% vitamin D group, hazard ratio (HR) 0.52 (0.30-0.89), number needed to treat = 6). Therefore, high-dose vitamin D3 in a population of severely vitamin D deficient critically ill patients is a promising and inexpensive intervention that requires confirmatory multicenter studies.

To date, only 7 interventions (e.g. noninvasive ventilation or prone positioning) have ever demonstrated mortality benefit for Intensive Care Unit (ICU) patients in multicenter trials. In case of benefit, vitamin D treatment in critically ill patients could be immediately implemented worldwide.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A very limited number of intervention trials, most including less than 30 patients, have been published. The only phase III study, our VITdAL-ICU study recruited from 2010 to 2012 and (n=475) did not find a difference in the primary endpoint "length of hospital stay" between placebo and high-dose vitamin D3. However, there was a non-significant absolute risk reduction in all-cause hospital mortality in the total population. The difference was larger (17.5%) and significant in the predefined subgroup of patients with severe vitamin D deficiency at baseline, see Kaplan Meier curve below (n=200, 28.6 vs 46.1%, p=0.01, 0.56 (0.35-0.90) ), corresponding to a number needed to treat of 6. (51) As this was only a secondary endpoint in the predefined subgroup with severe vitamin D deficiency, this finding is hypothesis generating and requires further study, leading to this application.

In our study, we were unable to identify a mechanism by which this benefit was achieved. Interestingly, looking at the causes of death, the vitamin D group seemed to benefit in every category.

The VITDALIZE study is a pragmatic, multicenter, placebo-controlled double-blind randomized controlled phase III trial in adult critically ill patients which will be conducted in academic and non-academic centers. The sponsor is the Medical University of Graz, Austria.

Subjects will be randomised in a 1:1 ratio to receive either of the two treatments:

Vitamin D: oral/enteral pharmacological dose of cholecalciferol (vitamin D3)

  • total dose 900,000
  • loading dose of 540,0000 (dissolved in 37.5 ml of medium chain triglycerides - MCT) followed by 4000 IU daily (10 drops) for the entire active study period (90 days)

Placebo: identical regime - loading dose of 37.5 ml MCT followed by 10 drops daily

This study uses a group sequential design, with one interim analysis when 50% of the planned enrolled patients in each arm (N=600 per arm) have completed their day 28 assessment by the independent data safety monitoring board. The enrollment of patients will continue while the interim analyses is performed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Austria
      • Enzenbach, Austria
        • Recruiting
        • LKH Enzenbach
        • Contact:
          • Otmar Schindler
      • Feldbach, Austria
        • Terminated
        • LKH Feldbach
      • Graz, Austria
        • Recruiting
        • Medical University of Graz
        • Contact:
          • Karin Amrein, MD, MSc
      • Klagenfurt, Austria
        • Recruiting
        • Klinikum am Wörthersee
        • Contact:
          • Rudolf Likar, MD
      • Leoben, Austria
        • Recruiting
        • LKH Hochsteiermark Standort Leoben
        • Contact:
          • Viktor Wutzl
      • Linz, Austria
        • Recruiting
        • Barmherzige Schwestern
        • Contact:
          • Johann Reisinger, MD
      • Linz, Austria
        • Recruiting
        • Kepler Universitätsklinikum Linz
        • Contact:
          • Jens Meier
      • Schwarzach im Pongau, Austria
        • Terminated
        • Krankenhaus Schwarzach
      • Vienna, Austria
        • Recruiting
        • Medical University of Vienna
        • Contact:
          • Peter Schellongowski, MD
      • Vienna, Austria
        • Recruiting
        • Barmherzige Brüder
        • Contact:
          • Rene Schmutz, MD
      • Vienna, Austria
        • Suspended
        • Kaiser Franz Josef Spital Wien
      • Villach, Austria
        • Recruiting
        • LKH Villach
        • Contact:
          • Christoph Widhalm
  • Belgium
      • Brussels, Belgium
        • Terminated
        • Erasme Hospital
      • Charleroi, Belgium
        • Terminated
        • CHU de Charleroi
      • Liège, Belgium
        • Terminated
        • CHR Citadelle
      • Mons, Belgium
        • Terminated
        • CHU Ambroise Pare
  • Germany
      • Würzburg, Germany
        • Recruiting
        • University Hospital Wuerzburg
        • Contact:
          • Patrick Meybohm, MD
  • United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • University of Birmingham
        • Contact:
          • Dhruv Parekh, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥18 years
  • Anticipated ICU stay ≥ 48 hours
  • Admission to ICU ≤ 72 hours before screening
  • Severe vitamin D deficiency (≤12 ng/ml or undetectable)

Exclusion Criteria:

  • Severe gastrointestinal dysfunction (> 400 ml residual volume)/unable to take study medication
  • Do not resuscitate (DNR) order/imminent death
  • hypercalcemia
  • known recent nephrolithiasis, active tuberculosis or sarcoidosis
  • pregnancy/lactation
  • not deemed appropriate by study team/physician

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
oral/enteral loading dose of 37.5 ml MCT followed by 10 drops daily for 90 days
Drug: Placebo
oral/enteral loading dose of 37.5 ml MCT followed by 10 drops daily for 90 days
Experimental: High Dose Vitamin D3

oral/enteral pharmacological dose of cholecalciferol (vitamin D3) - total dose 900,000

  • loading dose of 540,0000 (dissolved in 37.5 ml of medium chain triglycerides - MCT)
  • followed by 4000 IU daily (10 drops) for the entire active study period (90 days)
Drug: Cholecalciferol
oral/enteral loading dose of 37.5 ml MCT including 540,000 IU vitamin D3 followed by 10 drops daily (4000 IU) for 90 days
Other Names:
  • Vitamin D3

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
28-day mortality
Time Frame: 28 days
all-cause mortality
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital Length of stay
Time Frame: 90 days
Length of stay in days
90 days
Hypercalcemia at day 5
Time Frame: Day 5 - 48 hours tolerance
Day 5 - 48 hours tolerance
Hospital readmissions
Time Frame: 90 days
Number of readmissions
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Graz

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical University of Vienna
University Hospital, Essen
Goethe University
Guy's and St Thomas' NHS Foundation Trust
University Hospital, Bonn
University of Plymouth
Johannes Gutenberg University Mainz
Johannes Kepler University of Linz
Wuerzburg University Hospital
East Lancashire Hospitals NHS Trust
The Queen Elizabeth Hospital
Erasme University Hospital
Krankenhaus Barmherzige Schwestern Linz
Centre Hospitalier Régional de la Citadelle
Klinikum Klagenfurt am Wörthersee
Barmherzige Brüder Vienna
Centre Hospitalier Universitaire de Charleroi
Hospital Barmherzige Brüder St. Veit
Kages
KABEG Management
Centre Hospitalier Universitaire Mons
Royal Bolton Hospital NHS Foundation Trust
Heartlands Hospital
Royal Oldham Hospital
Great Western Hospital
Musgrove Park Hospital
Scunthorpe General Hospital
Nottingham University Hospitals
Royal Victoria Hospital, Belfast
Hospital Barmherzige Brüder Graz
Mid Yorkshire Teaching NHS Trust
University Hospital Kiel
Klinikum rechts der Isar der TUM
Landeskrankenhaus Villach

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Karin Amrein, MD, MSc, Medical University of Graz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 10, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VITDALIZE 1.0

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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