Efficacy comparison of two doses of vitamin D3 in critically ill patients undergoing continuous renal replacement therapy - NephroD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uniwersytecki Szpital Kliniczny W Opolu

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

19 Dec 2022 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agencja Badań Medycznych (ABM)

External identifiers

EU CT number

2024-510834-42-00

EudraCT number

2021-006789-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

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 administered once enterally (througha gastric tuber or orally) in ICU patients with severe vitamin D3 deficiency undergoing continuous renal replacement therapy.

Secondary objectives 6

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

Conditions and MedDRA coding

Vitamin D3 deficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Presence of at least one of the following indications for implementation of CRRT by CVVHDF or CVVHF (Clinical Practice Guideline for Acute Kidney Injury): replacement of non-functioning kidney function when acute kidney injury occurs; hyperkalemia; metabolic acidosis; pulmonary edema; complications of uremia (hemorrhagic diathesis, pericarditis) - hypervolaemia; -Renal function support (control of goiter, acid-base, ion balance)
2. Organ failure score (SOFA) of at least 5 at the time of qualification for the study
3. Patient age >18 years
4. 25(OH)D3 serum concentration ≤12.5 ng/ml - test performed by the local laboratory of the participating hospital
5. Properly managed enteral nutrition (through a gastric tuber or orally) at any dose.

Exclusion criteria 11

1. Acute or advanced chronic liver failure (estimated by clinical presentation and biochemical markers: serum bilirubin, serum AST and ALT, high AST/ALT serum ratio, glycemia, INR value)
2. Hypercalcemia (total calcium >11 mg/dL or >2,7mmol/L)
3. Any parathyroid disease
4. KDIGO classification of end-stage renal disease
5. Patients undergoing plasmapheresis, extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide elimination (ECCO2R)
6. Patients who, in the opinion of the investigator, do not have a good chance of surviving the 72 hour period after study entry
7. History of kidney stones or de novo renal calculi
8. Patient eligible for futile therapy avoidance protocol
9. Pregnancy
10. Sarcoidosis
11. Risk of impaired intestinal absorption in critical illness associated with at least one of the mentioned: impaired intestinal motility and delayed gastric emptying, constipation, diarrhea, intestinal hypoperfusion in shock, intoxication with subsequent intestinal edema after fluid resuscitation, changes in the intestinal microbiome.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with 25(OH)D3 serum levels ≥30 ng/mL on days 3 and 7 after vitamin D3 administration.

Secondary endpoints 8

1. Number of patients who died on day 28 and 90 after administration of vitamin D3 preparation.
2. Duration of treatment in the ICU of patients receiving vitamin D3 preparation.
3. SOFA score on day 3 and 7 in patients receiving vitamin D3 preparation.
4. Duration of catecholamine supply in patients receiving vitamin D3.
5. The CRRT duration in hours from the IMP administration until the visit 4 start.
6. Total gastric residual volume in milliliters from the IMP administration until the visit 3 start.
7. Safety Assessment Endpoint: Percentage of patients who achieved toxic serum vitamin D3 concentrations (25(OH)D3 ≥150 ng/mL) on Days 3 and 7.
8. Safety Assessment Endpoint: Percentage of patients who achieved a serum total calcium concentration (>11 mg/dL) on Days 3 and 7.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uniwersytecki Szpital Kliniczny W Opolu

Sponsor organisation

Uniwersytecki Szpital Kliniczny W Opolu

Address

Al. Wincentego Witosa 26

City

Opole

Postcode

45-401

Country

Poland

Scientific contact point

Organisation

Uniwersytecki Szpital Kliniczny W Opolu

Contact name

USK w Opolu

Public contact point

Organisation

Uniwersytecki Szpital Kliniczny W Opolu

Contact name

USK w Opolu

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications