The VITDALIZE Study: Effect of High-dose Vitamin D3 on 28-day Mortality in Adult Critically Ill Patients (VITDALIZE)
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| ClinicalTrials.gov Identifier: NCT03188796 |
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Recruitment Status :
Recruiting
First Posted : June 15, 2017
Last Update Posted : May 15, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Critical Illness Vitamin D Deficiency Covid19 | Drug: Cholecalciferol Drug: Placebo | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 2400 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | October 10, 2017 |
| Estimated Primary Completion Date : | December 2024 |
| Estimated Study Completion Date : | March 2025 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
oral/enteral loading dose of 37.5 ml MCT followed by 10 drops daily for 90 days
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Drug: Placebo
oral/enteral loading dose of 37.5 ml MCT followed by 10 drops daily for 90 days |
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Experimental: High Dose Vitamin D3
oral/enteral pharmacological dose of cholecalciferol (vitamin D3) - total dose 900,000
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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 Name: Vitamin D3 |
- 28-day mortality [ Time Frame: 28 days ]all-cause mortality
- Hospital Length of stay [ Time Frame: 90 days ]Length of stay in days
- Hypercalcemia at day 5 [ Time Frame: Day 5 - 48 hours tolerance ]
- Hospital readmissions [ Time Frame: 90 days ]Number of readmissions
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| Ages Eligible for Study: | 18 Years to 100 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03188796
| Contact: Karin Amrein, MD, MSc | +43 316 385 ext 82383 | karin.amrein@medunigraz.at | |
| Contact: Astrid Friedel | +43 316 385 ext 72061 | astrid.friedel@medunigraz.at |
| Austria | |
| LKH Enzenbach | Recruiting |
| Enzenbach, Austria | |
| Contact: Otmar Schindler | |
| LKH Feldbach | Recruiting |
| Feldbach, Austria | |
| Contact: Norbert Watzinger | |
| Medical University of Graz | Recruiting |
| Graz, Austria | |
| Contact: Karin Amrein, MD, MSc | |
| Klinikum am Wörthersee | Recruiting |
| Klagenfurt, Austria | |
| Contact: Rudolf Likar, MD | |
| LKH Hochsteiermark Standort Leoben | Recruiting |
| Leoben, Austria | |
| Contact: Viktor Wutzl | |
| Barmherzige Schwestern | Recruiting |
| Linz, Austria | |
| Contact: Johann Reisinger, MD | |
| Kepler Universitätsklinikum Linz | Recruiting |
| Linz, Austria | |
| Contact: Jens Meier | |
| Krankenhaus Schwarzach | Recruiting |
| Schwarzach Im Pongau, Austria | |
| Contact: Franz Wimmer, MD | |
| Barmherzige Brüder | Recruiting |
| Vienna, Austria | |
| Contact: Rene Schmutz, MD | |
| Medical University of Vienna | Recruiting |
| Vienna, Austria | |
| Contact: Peter Schellongowski, MD | |
| LKH Villach | Not yet recruiting |
| Villach, Austria | |
| Contact: Ernst Trampitsch | |
| Kaiser Franz Josef Spital Wien | Recruiting |
| Wien, Austria | |
| Contact: Sabine Schmaldienst | |
| Belgium | |
| Erasme Hospital | Recruiting |
| Brussel, Belgium | |
| Contact: Jean-Charles Preiser | |
| CHU de Charleroi | Recruiting |
| Charleroi, Belgium | |
| Contact: Maxime van Cutsem | |
| CHR Citadelle | Recruiting |
| Liège, Belgium | |
| Contact: Vincent Fraipont | |
| CHU Ambroise Pare | Recruiting |
| Mons, Belgium | |
| Contact: Alain D´hondt | |
| Principal Investigator: | Karin Amrein, MD, MSc | Medical University of Graz |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Medical University of Graz |
| ClinicalTrials.gov Identifier: | NCT03188796 |
| Other Study ID Numbers: |
VITDALIZE 1.0 |
| First Posted: | June 15, 2017 Key Record Dates |
| Last Update Posted: | May 15, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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vitamin D critical care COVID-19 |
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COVID-19 Vitamin D Deficiency Critical Illness Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases |
Disease Attributes Pathologic Processes Avitaminosis Deficiency Diseases Malnutrition Nutrition Disorders Vitamin D Cholecalciferol Vitamins Micronutrients Physiological Effects of Drugs Bone Density Conservation Agents Calcium-Regulating Hormones and Agents |