Evaluation of Two Dosage Regimens of Colecalciferol in Critically Ill Patients with Vitamin D3 Deficiency Undergoing Continuous Renal Replacement Therapy

The primary objective of this study is to evaluate and compare the effect of two different supplementation doses of **vitamin D3** (25 (OH) D3) - 500,000 IU and 750,000 IU on the serum concentration of 25 (OH) D3. This is administered once enterally, either through a gastric tube or orally, in ICU patients with severe vitamin D3 deficiency undergoing continuous renal replacement therapy. The clinical relevance of this objective lies in addressing the deficiency of vitamin D3, which is critical for patients in intensive care units, particularly those undergoing continuous renal replacement therapy, as it may impact their recovery and overall health outcomes.

Secondary objectives include:

• Assessment and comparison of the effect of two different doses of vitamin D3 supplementation on mortality in ICU patients undergoing continuous renal replacement therapy.
• Assessment and comparison of the effect on the duration of ICU treatment in these patients.
• Assessment and comparison of the effect on the sepsis-related organ failure (SOFA) scale.
• Assessment and comparison of the effect on the duration of catecholamine supply.
• Evaluation of the correlation between the duration of continuous renal replacement therapy (CRRT) in hours from the moment of investigational medicinal product administration until the start of visit 4 and the serum vitamin D concentration in both treatment arms.
• Evaluation of the correlation between total gastric residual volume (GVR) in milliliters from the investigational medicinal product administration until the start of visit 4 and the serum vitamin D concentration in both treatment arms.

The clinical trial focuses on patients with **Vitamin D3 deficiency** undergoing continuous renal replacement therapy (CRRT). The study population includes both male and female subjects aged 18 years and older. Participants are ICU patients with severe vitamin D3 deficiency, specifically those with a serum concentration of 25(OH)D3 ≤12.5 ng/ml. The trial does not involve a vulnerable population. The selection criteria include patients with an organ failure score (SOFA) of at least 5 and those with properly managed enteral nutrition. The sponsor has not provided the total number of participants. The trial population was selected based on the presence of indications for CRRT, such as acute kidney injury, hyperkalemia, metabolic acidosis, pulmonary edema, and complications of uremia. Lifestyle considerations such as diet and physical activity are not specified. The study aims to evaluate the effect of two different doses of vitamin D3 supplementation on serum concentration levels in this specific patient group.

The clinical trial is designed to evaluate the efficacy of two different doses of **vitamin D3** in critically ill patients with severe vitamin D3 deficiency undergoing continuous renal replacement therapy (CRRT). This study is a randomized, double-blind, controlled trial, aiming to compare the effects of 500,000 IU and 750,000 IU doses of vitamin D3 on serum concentration levels. The trial is expected to run from November 18, 2022, to November 21, 2025, with participant involvement lasting up to 90 days post-administration.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, organ failure score, and serum vitamin D3 levels. Following successful screening, participants will be randomized to receive one of the two doses of vitamin D3 administered enterally. Follow-up visits will occur on days 3 and 7 post-administration to measure primary endpoints, including the percentage of patients achieving serum vitamin D3 levels of ≥30 ng/mL. Secondary endpoints will be assessed, such as mortality rates on days 28 and 90, duration of ICU treatment, and safety assessments for potential toxic serum vitamin D3 concentrations.

The end-of-study visit will occur on day 90, where final assessments will be conducted. Participants may be withdrawn from the study if they experience adverse events, fail to comply with study procedures, or withdraw consent. The trial's design ensures rigorous monitoring and data collection to evaluate the safety and efficacy of vitamin D3 supplementation in this patient population.

The clinical trial involves the administration of **Devikap**, an experimental medication containing the active substance **colecalciferol**. This medication is formulated as **oral drops, solution** and is produced by Zakłady Farmaceutyczne Polpharma S.A. The trial aims to evaluate the efficacy of two different doses of vitamin D3 in critically ill patients undergoing continuous renal replacement therapy. The medication is administered enterally, either through a gastric tube or orally, with a single dose of either 500,000 IU or 750,000 IU. The maximum daily and total dose is 750,000 IU, and the treatment period is limited to one day. The route of administration is gastroenteral use, ensuring direct delivery to the gastrointestinal tract.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the study protocol. The trial focuses solely on the administration of the experimental medication, Devikap, to assess its impact on serum concentrations of 25 (OH) D3 in patients with severe vitamin D3 deficiency. Participant compliance with the dosing schedule is monitored to ensure accurate assessment of the medication's efficacy. The trial does not involve any pediatric formulations or orphan drug designations.

Efficacy in the clinical trial titled "Efficacy comparison of two doses of vitamin D3 in critically ill patients undergoing continuous renal replacement therapy - NephroD" will be assessed using both primary and secondary endpoints. The primary endpoint is the percentage of patients achieving serum levels of **25(OH)D3** ≥30 ng/mL on days 3 and 7 following vitamin D3 administration. Secondary endpoints include the number of patients who died on days 28 and 90 post-administration, the duration of treatment in the ICU, the Sequential Organ Failure Assessment (SOFA) score on days 3 and 7, the duration of catecholamine supply, the duration of continuous renal replacement therapy (CRRT) in hours from investigational medicinal product (IMP) administration until the start of visit 4, and the total gastric residual volume in milliliters from IMP administration until the start of visit 3.

Safety assessments will also be conducted, focusing on the percentage of patients who achieve toxic serum vitamin D3 concentrations (25(OH)D3 ≥150 ng/mL) and those with serum total calcium concentrations >11 mg/dL on days 3 and 7. These efficacy and safety parameters will be measured and collected at specified time points using laboratory tests conducted by the local laboratory of the participating hospital. The trial aims to evaluate and compare the effects of two different doses of vitamin D3, specifically 500,000 IU and 750,000 IU, administered enterally to ICU patients with severe vitamin D3 deficiency undergoing continuous renal replacement therapy.