Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: the UK arm of an international multi-centre, placebo-controlled, Phase III double-blind trial
Vitamin D deficiency
Once randomised into the trial, the patient will receive either: 1. Intervention: A single loading high-dose oral/enteral vitamin D3 (540,000IU cholecalciferol, Oleovit™, Fresenius Kabi, Austria, dissolved in 37.5 ml of medium-chain triglycerides – MCT) followed by 4000 IU daily (10 drops) for 90 days. 2. Control: Placebo, identical regime of loading dose of 37.5 ml MCT (Fresenius Kabi, Austria) followed by MCT (10 drops) daily for 90 days.
1. Patients ≥18 years 2. Anticipated ICU stay ≥48 hours 3. Admission to ICU ≤72 hours before screening for VDD 4. Severe VDD (25(OH)D ≤12 ng/ml [30 nmol/l]) using either the hospital's clinical laboratory or rapid bedside testing after ICU admission
1. Severe gastrointestinal dysfunction (>400 ml nasogastric tube residual volume)/unable to receive trial medication 2. Not expected to survive initial 48 hours of admission or treatment withdrawal imminent within 24 hours 3. Patient with DNAR (Do Not Attempt Resuscitation) orders in place 4. Hypercalcemia (>2.65 mmol/l corrected calcium and/or >1.35 mmol/l ionized calcium at screening) 5. Known kidney stones within the last 12 months 6. Known active tuberculosis within the last 12 months 7. Known sarcoidosis within the last 12 months 8. Women of childbearing age who have tested positive for pregnancy or who are lactating 9. Known hypersensitivity to the trial drug or excipient 10. Medical team deem it not suitable to include patient 11. Known prisoners in the custody of HM Prison and Probation services