Aim

To conduct a large international randomised controlled trial to determine if treatment with a high dose of vitamin D improves patient outcomes and is cost-effective, in comparison to the placebo in severely vitamin D deficient (VDD) critically ill patients admitted to an intensive care unit (ICU).

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Total number of participants

The target population is adult critically ill patients (≥18 years) admitted to ICU with severe VDD (25(OH)D ≤12ng/ml (30nmol/L)). Total sample size of international trial n=2,400 of whom 25% will be recruited in the UK (sample size in UK n=600).

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Outcome Measures

Primary outcomes:

• All-cause mortality at 28 days after randomisation

Secondary outcomes:

• 90 day and 1-year mortality
• ICU and hospital mortality
• Hospital and ICU length of stay (starting at day 0, ending at discharge from the trial site or day 90 or mortality, whatever occurs first)
• Change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment score (SOFA), number of organ failures (0-6; defined as > 2 SOFA points in each of the 6 categories)
• Hospital and ICU readmission until day 90
• Discharge destination (home, rehabilitation, other hospital)
• Katz Activities of Daily Life at day 90
• Self-reported infections requiring antibiotics until day 90
• Health-related quality of life (EQ-5D-3L) at 90 days and 1 year
• Disability assessment (WHO-DAS 2.0) at 90 days and 1 year
• Secondary health care utilisation in the first year (ICU and hospital length of stay, readmissions and utilisation of hospital and community care resources after hospital discharge 1 year after randomisation), from Hospital Episode Statistics, civil registry data held by NHS Digital and patient questionnaires
• Health economics analysis
o Cost effectiveness of screening for and treating VDD in critical illness
o Cost per quality-adjusted life year gained 1 year after randomisation and at end of life

Feasibility outcomes:

• Health related quality of life (proxy EQ-5D-3L and proxy WHODAS 2.0) at randomisation (day 0)

Safety outcomes:

• Hypercalcaemia at day 5 (48 hours tolerance)/during ICU stay
• Self-reported falls, fractures until day 90
• New episodes of kidney stones