+ Direct Access

The VITDALIZE Study

Q&A

What?

VITDALIZE is a multicentre, placebo-controlled double-blind phase III randomised clinical trial to examine the effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency.

Why?

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, 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 multicentre studies.

To date, only 7 interventions (e.g. noninvasive ventilation, pronepositioning…) have demonstrated a mortality benefit for ICU patients in multicentre trials. If proven to be beneficial, vitamin D treatment in critically ill patients could be immediately implemented worldwide.

When?

Data collection is set to begin in late 2017.

Recruitment phase: 2-3years (ideally 12-18 months recruiting)

Follow-up: 12 months
Maximum 2400 patients (1200 per group) 1 interim analysis after 1200 patients The sample size is based on an anticipated 5% absolute mortality reduction assuming an overall 28-mortality of 25% in the placebo group.

What data is required?

Screening:

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
  • DNR order/imminent death
  • hypercalcemia
  • known recent nephrolithiasis (occurrence in previous 12 months), active tuberculosis or sarcoidosis
  • pregnancy/lactation
  • other ongoing intervention trial
  • not deemed appropriate by study team/physician
  • co-enrollment may be possible after discussion with the respective investigators

Primary outcome(s): 28-day mortality

Secondary outcome(s): 

  • 90-day and 1-year mortality
  • ICU mortality
  • Hospital and ICU readmission
  • Hospital and ICU length of stay
  • Infections 90d
  • Hypercalcemia
  • Falls, fractures
  • SF 12
  • Hand grip strength

Methodology:

Investigator-initiated, non-commercial, multicentre double-blind phase III RCT: high dose oral vitamin D3 vs. placebo dosing: 540,000 IU of oral (or enteral) vitamin D 3 followed by 4000 IU of vitamin D3 daily for the entire active study period (90 days).

Intervention:

Cholecalciferol versus placebo: Day 0: One single bolus loading dose 540,000 IU of oral (or enteral) vitamin D3 followed by 4000 IU of vitamin D3 daily for the entire active study period (90 days) versus placebo.

Do I need IRB approval?

Yes. You will need to check with your local ethical committee and/ or with your national coordinator if any.

How is the data that is collected managed?

All data is annonymised and cannot be linked to individual subjects. The data is stored securely and all procedures regarding data management will comply with EU directive on data protection 95/46/EC.

Who owns and can access the collected data? 

Each site investigator is responsible for his own data and may request an export of his data after the database is locked. The request should be addressed to the Principal Investigator.

Is there any financial compensation?

No. Participation in the trial is completely voluntary.

What about authorship? 

Results from the trial will be published by the VITDALIZE nominated writing Committee. Investigators will be acknowledged as collaborators in the authorship of the paper and as such, listed in PubMed.

How do I participate?

Contact Principal Investigator:
Karin Amrein, MD, MSc, Associate Professor
Medical University of Graz, Austria
karin.amrein@medunigraz.at

Any further Questions?

Contact: Guy FRANCOIS / Sherihane BENSEMMANE – research@esicm.org

Principal Investigator:
Karin Amrein, MD, MSc, Associate Professor
Medical University of Graz, Austria
karin.amrein@medunigraz.at

Documents

  • Protocol: available upon request from the Principal Investigator (see above)