Comparison of two doses of vitamin D3 in critically ill patients undergoing continuous renal replacement therapy (NephroD): study protocol for a single-blinded, multicenter, parallel group randomized controlled trial.

Background: ICU patients are particularly susceptible to vitamin D3 deficiencies. This can be due to the severity of their underlying disease, the type of treatment they are on, and malnutrition before and inadequate nutrition during the hospitalization preceding ICU admission as well as advanced age. Literature provides no guidance on how to supplement vitamin D3 in severely deficient patients who are undergoing continuous renal replacement therapy (CRRT). Most serum 25(OH)D3 is bound with vitamin D binding protein in a complex whose molecular weight is 10 kDa. This means it can be removed during CRRT via convection mechanism. Critically ill patients undergoing CRRT can therefore be particularly prone to develop severe vitamin D3 deficiency.

Methods: As the trial design, a randomized controlled, single blinded, multicenter, parallel group approach was chosen to compare a single administration of 750,000 IU of vitamin D3 via the enteral or oral route in ICU patients with severe vitamin D3 deficiency (measured serum 25(OH)D3 levels ≤ 12.5 ng/ml) undergoing CRRT with a single administration of 500,000 IU of vitamin D3. The trial will be performed in up to five university hospitals in Poland. The primary outcome is the percentage of patients that achieved serum 25(OH)D3 levels ≥ 30 ng/ml on days 3 and 7 following vitamin D3 administration. Assuming a drop-out rate of approximately 10%, the number of recruited patients should be 138.

Discussion: Considering the potential pathophysiological mechanisms underlying hypovitaminosis D in critically ill patients under CRRT, it seems conceivable that these patients will require greater supplementation doses to correct severe deficiency. The study is meant to help answer the question whether increasing the supplementation dose by 50% will ensure a more effective replenishment of vitamin D3 in critically ill patients undergoing CRRT.

Trial Registration: ClinicalTrials.gov Identifier: NCT05657678, registered: December 12 2022, https://clinicaltrials.gov/study/NCT05657678?cond=NCT05657678&rank=1 .