Clinical Trials Register

Summary
EudraCT Number:	2021-006789-19
Sponsor's Protocol Code Number:	NephroD_2021
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-02-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-006789-19

A.3

Full title of the trial

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

Porównanie skuteczności dwóch dawek witaminy D3 u pacjentów krytycznie chorych poddanych ciągłej terapii nerkozastępczej – NephroD

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

Porównanie skuteczności dwóch dawek witaminy D3 u pacjentów krytycznie chorych poddanych ciągłej terapii nerkozastępczej – NephroD

A.3.2

Name or abbreviated title of the trial where available

NephroD

A.4.1

Sponsor's protocol code number

NephroD_2021

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	USK w Opolu
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ABM, konkurs na działalność badawczo-rozwojową w zakresie niekomercyjnych badań klinicznych ABM/2020/1
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	USK w Opolu
B.5.2	Functional name of contact point	Tomasz Czarnik
B.5.3	Address:
B.5.3.1	Street Address	Al. Wincentego Witosa 26
B.5.3.2	Town/ city	Opole
B.5.3.3	Post code	45-401
B.5.3.4	Country	Poland
B.5.4	Telephone number	0048669 906 333
B.5.5	Fax number	00487745 20 303
B.5.6	E-mail	tomasz.czarnik@usk.opole.pl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Devikap 15 000 IU/ml, płyn doustny
D.2.1.1.2	Name of the Marketing Authorisation holder	Zakłady Farmaceutyczne POLPHARMA S.A
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Devikap
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral use Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Colecalciferol
D.3.9.1	CAS number	67-97-0
D.3.9.4	EV Substance Code	SUB06794MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Vitamin D3 deficiency

niedobór witaminy D3

E.1.1.1

Medical condition in easily understood language

Vitamin D3 deficiency

niedobór witaminy D3

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10047626
E.1.2	Term	Vitamin D deficiency
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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 (through a gastric tuber or orally) in ICU patients with severe vitamin D3 deficiency undergoing continuous renal replacement therapy.

E.2.2

Secondary objectives of the trial

- 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,
*the duration of ICU treatment in patients undergoing continuous renal replacement therapy,
*the sepsis-related organ failure (SOFA) scale in ICU patients undergoing continuous renal replacement therapy,
*the duration of catecholamine supply in ICU patients undergoing continuous renal replacement therapy.
- 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.
- 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.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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.

E.4

Principal exclusion criteria

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.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Will be formally summarized upon completion of the study

E.5.2

Secondary end point(s)

- Number of patients who died on day 28 and day 90 after administration of vitamin D3 preparation.
- Duration of treatment in the ICU of patients receiving vitamin D3 preparation.
- SOFA score on day 3 and day 7 in patients receiving vitamin D3 preparation.
- Duration of catecholamine supply in patients receiving vitamin D3.
- The CRRT duration in hours from the investigational medicinal product administration until the visit 4 start.
- Total gastric residual volume in milliliters from the investigational medicinal product administration until the visit 3 start.

Safety Assessment Endpoints:
- Percentage of patients who achieved toxic serum vitamin D3 concentrations (25(OH)D3 ≥150 ng/mL) on Days 3 and 7.
- Percentage of patients who achieved a serum total calcium concentration (>11 mg/dL) on Days 3 and 7.

E.5.2.1

Timepoint(s) of evaluation of this end point

Will be formally summarized upon completion of the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

The same IMP given to the patient at a different dose

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS (Last Visit Last Subject)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

138

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

138

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-02-11.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Unconscious patients

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

138

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

138

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-19

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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