Vitamin D3 Supplementation in Critically Ill Patients Undergoing CRRT (NephroD)

Efficacy Comparison of Two Doses of Vitamin D3 in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

Patients hospitalized in intensive care units (ICU) 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, malnutrition before and inadequate nutrition during the hospitalisation preceding ICU admission, as well as advanced age. It has also been established that plasma levels of 25(OH)D3 tend to systematically decrease during ICU treatment. Therapeutic interventions administered in ICU settings such as fluid resuscitation or extracorporeal therapies can cause additional vitamin D3 deficiencies. The incidence of deficiency in critically ill patients can reach up to 90%, and even 30% of ICU patients can have undetectable plasma levels. It is impossible to replenish vitamin D3 levels in critically ill patients with traditional enteral and parenteral nutrition treatment regimens, because nutritional products contain too little of the vitamin. Vitamin D3 deficiency in critically ill patients has been associated with acute kidney injury, acute respiratory failure, sepsis, septic shock and increased all-cause ICU mortality. Despite that, assessment of plasma 25(OH)D3 levels is not a routine practice in ICUs. In view of the prevalence of vitamin D3 deficiencies in ICU patients, rapid replenishment of this deficiency with an increased supplementation dose should be considered as a potential means to improve prognosis in this patient population. The current standard therapy is the administration of 500,000 IU of vitamin D3 via the enteral route in ICU patients with severe deficiency (recommended by ESPEN). The NephroD study is meant to help answer the question whether increasing the standard ICU supplementation dose of vitamin D3 by 50% will ensure a more effective replenishment of this vitamin in critically ill patients undergoing CRRT.

Study Overview

• Status: Recruiting
• Conditions: Vitamin D3 Deficiency
• Intervention / Treatment: Drug: Vitamin D3 - 750 000 IU; Drug: Vitamin D3 - 500 000 IU

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tomasz Czarnik, MD, PhD; Phone Number: 0048669906333; Email: tczarnik@mac.com

Study Locations

• Poland
  • Krakow, Poland
    • Recruiting
    • 5 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ
    • Contact: Wojciech Szczeklik, MD, PhD
  • Lublin, Poland
    • Recruiting
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
    • Contact: Pawel Piwowarczyk, MD, PhD
  • Zabrze, Poland, 41-800
    • Recruiting
    • Samodzielny Publiczny Szpital Kliniczny nr 1 Śląski Uniwersytet Medyczny w Katowicach
    • Contact: Szymon Bialka, MD, PhD
  • Opolskie
    • Opole, Opolskie, Poland, 45-401
      • Recruiting
      • Uniwersytecki Szpital Kliniczny w Opolu
      • Contact: Ryszard Gawda, MD, PhD; Email: onetime@wp.pl
      • Contact: Tomasz Czarnik, MD, PhD; Email: tczarnik@mac.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Presence of the following indications for initiation of CRRT with CVVHDF or CVVHF (acc. to KDIGO, Clinical Practice Guideline for Acute Kidney Injury):

   • replacement of kidney function in acute kidney injury
   • hyperkalaemia
   • metabolic acidosis
   • pulmonary oedema
   • uraemic complications (bleeding disorder, pericarditis)
   • hypervolaemia
   • support of renal function (volume control, regulation of acid-base and electrolyte status)
2. Sequential Organ Failure Assessment (SOFA) score of minimum 5 points at enrolment
3. Age of >18 years
4. Plasma 25(OH)D3 levels ≤12.5 ng/ml as measured by the local laboratory of a participating hospital
5. Properly managed enteral nutrition regardless of dosing

Exclusion Criteria:

1. Acute or advanced chronic liver failure (estimated on the basis of the clinical picture and biochemical markers: plasma bilirubin, plasma AST and ALT, high plasma AST/ALT ratio, glycaemia, INR)
2. Hypercalcaemia (total calcium concentration >11 mg/dl)
3. Any parathyroid disorder
4. End stage renal disease according to the KDIGO classification
5. Patients undergoing plasmapheresis, extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide removal (ECCO2R)
6. Patients who, in the opinion of the investigator, are not expected to survive 72 hours since enrolment
7. A history of nephrolithiasis or de novo nephrolithiasis
8. Patient qualified to a protocol for the avoidance of futile therapy
9. Pregnancy
10. Sarcoidosis
11. Risk of impaired intestinal absorption caused by the critical illness, associated with impaired peristalsis and delayed gastric emptying, constipation, diarrhoea, shock-induced intestinal hypoperfusion, hyperhydration with resulting intestinal oedema following fluid resuscitation, intestinal flora disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional Arm; a single administration of 750,000 IU of vitamin D3 via the enteral route (through a gastric tube) in ICU patients with severe vitamin D3 deficiency (measured plasma 25(OH)D3 levels ≤12.5 ng/ml) undergoing continuous renal replacement therapy with CVVHDF or CVVHF	Drug: Vitamin D3 - 750 000 IU; a single administration of 750,000 IU of vitamin D3
Active Comparator: Control Arm; a single administration of 500,000 IU of vitamin D3 via the enteral route (through a gastric tube) in ICU patients with severe vitamin D3 deficiency (measured plasma 25(OH)D3 levels ≤12.5 ng/ml) undergoing continuous renal replacement therapy with CVVHDF or CVVHF	Drug: Vitamin D3 - 500 000 IU; a single administration of 500,000 IU of vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supplementation	To evaluate and compare the effects of two different supplementation doses of vitamin D3 (25(OH)D3) - 500,000 IU or 750,000 IU administered as one enteral dose - on plasma levels of 25(OH)D3 in ICU patients undergoing continuous renal replacement therapy and diagnosed with severe vitamin D3 deficiency	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	To evaluate and compare the effects of two different supplementation doses of vitamin D3 on mortality in ICU patients undergoing continuous renal replacement therapy	90 days
ICU treatment duration	To evaluate and compare the effects of two different supplementation doses of vitamin D3 on ICU treatment duration in patients undergoing continuous renal replacement therapy	90 days
SOFA	To evaluate and compare the effects of two different supplementation doses of vitamin D3 on Sequential Organ Failure Assessment (SOFA) scores in ICU patients undergoing continuous renal replacement therapy	90 days
Catecholamines	To evaluate and compare the effects of two different supplementation doses of vitamin D3 on the duration of catecholamine administration in ICU patients undergoing continuous renal replacement therapy	90 days
CRRT	To evaluate the relationship between the length of CRRT use in hours from the time of study drug administration to the beginning of visit 4 and serum vitamin D3 levels in both study arms	7 days
GRV	To assess the relationship between total gastric residual volume (GRV) in millilitres from the time of study drug administration to the date of the beginning of visit 3 and serum vitamin D3 levels in both study arms	7 days

Collaborators and Investigators

• Sponsor: Uniwersytecki Szpital Kliniczny w Opolu
• Investigators: Principal Investigator: Tomasz Czarnik, MD, PhD, Uniwersytecki Szpital Kliniczny w Opolu

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 21, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: intensive care; supplementation; vitamin D; continuous renal replacement therapy; severe deficiency
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: NephroD_2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No