Clinical Trials Register

Summary
EudraCT Number:	2014-004592-23
Sponsor's Protocol Code Number:	DLIFE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-05-21
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-004592-23

A.3

Full title of the trial

Phase IV randomized, double blind, placebo-controlled study: role of hypovitaminosis D in heart failure and possible advantages of cholecalciferol (Vit D) administration

Studio di fase IV randomizzato, controllato con placebo, in doppio cieco a due bracci paralleli: ruolo dell’ipovitaminosi D nello scompenso cardiaco e possibili vantaggi della somministrazione di colecalciferolo (vitamina D3)

A.3.1

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

Role of vitamin D administration in heart failure patients

Ruolo della somministrazione di vitamina D sul cuore

A.3.2

Name or abbreviated title of the trial where available

DLIFE

A.4.1

Sponsor's protocol code number

DLIFE

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	AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
B.1.3.4	Country	Italy
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	Azienda Farmaceutica: ABIOGEN PHARMA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
B.5.2	Functional name of contact point	U.O.ENDOCRINOLOGIA 2
B.5.3	Address:
B.5.3.1	Street Address	VIA PARADISA 2
B.5.3.2	Town/ city	PISA
B.5.3.3	Post code	56100
B.5.3.4	Country	Italy
B.5.4	Telephone number	050995001
B.5.5	Fax number	050995878
B.5.6	E-mail	claudio.marcocci@med.unipi

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	DIBASE - 10.000 UI/ML GOCCE ORALI, SOLUZIONE FLACONE CON GONTACOCCE 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ABIOGEN PHARMA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLECALCIFEROLO
D.3.9.1	CAS number	67-97-0
D.3.9.3	Other descriptive name	COLECALCIFEROLO
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	10.000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral drops, solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HEART FAILURE

SCOMPENSO CARDIACO

E.1.1.1

Medical condition in easily understood language

Heart failure occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the needs of the body.

L'insufficienza cardiaca si verifica quando il cuore non riesce a pompare sufficiente per mantenere il flusso di sangue per soddisfare le esigenze del corpo.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10011949
E.1.2	Term	Decompensation cardiac
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of cardiopulmonary test (CPET) paramethers improvement, after cholecalciferol administration with standard doses, for 6 months, in patients with heart failure (NHYA II and III)

Valutazione del miglioramento dei parametri del cardiopolmonare (CPET), in particolare del consumo di ossigeno al picco, dopo adeguata supplementazione con dosi standard di colecalciferolo nei pazienti in classe III e II NHYA dopo 6 mesi di trattamento

E.2.2

Secondary objectives of the trial

- Correlation between CPET paramethers and 25OHvitamin D basal levels, in heart failure patients
- Assessment of clinical improvement of patients with heart failure after cholecalciferol (vitamin D) administration for 6 months
- Assessment of improvements in heart failure outcome biomarkers, after cholecalciferol (vitamin D) administration for 6 months

- Valutazione della correlazione tra i parametri del test cardiopolmonare (CPET), in particolare il consumo di ossigeno, ed i livelli di 25OHvitamina D basali, nell’ipotesi che livelli più bassi di 25OHD si associno ad una peggiore performance al CPET.
- Andamento clinico del paziente con scompenso cardiaco (valutabile mediante anamnesi, esame obiettivo e test di autovalutazione come da routine clinica) dopo supplementazione con dosi standard di colecalciferolo dopo 6 mesi di trattamento.
- Andamento dei parametri ecocardiografici, ECG e biochimici di scompenso cardiaco (NT-proBNP, catecolammine plasmatiche, aldosterone, renina diretta, elettroliti, funzione renale) routinariamente indagati nella valutazione basale e nel follow-up dei pazienti con scompenso cardiaco, dopo supplementazione con dosi standard di colecalciferolo dopo 6 mesi trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients who belong to the Service of Cardiology at Fondazione Toscana G. Monasterio
- Diagnosis of heart failure (NYHA class II-III)
- Optimized heart failure therapy according to clinical practice
- Medical conditions stable without change of heart medicine for at least 3 months
- Capacity / ability to perform the CPET
- Age> 18 years
- Sex female and male
- Signing of the informed consent

- Pazienti che afferiscono al Servizio di Cardiologia presso la Fondazione Toscana G. Monasterio
- Diagnosi di scompenso cardiaco (NYHA classe II–III)
- Terapia per lo scompenso cardiaca ottimizzata secondo pratica clinica
- Condizioni mediche stabili senza modifica della terapia cardiologica da almeno 3 mesi
- Capacità/abilità ad eseguire il CPET
- Età >18 anni
- Sesso femminile e maschile
- Firma del consenso informato

E.4

Principal exclusion criteria

- BMI>30
- Primary or secondary to kidney failure Hyperparathyroidism
- Phospho-calcic metabolism alterations/diseases
- History of pulmonary embolism
- Moderate-to-severe aortic and mitral stenosis
- Pericardial disease
- Severe obstructive lung disease
- Exercise-induced angina and significant ECG alterations
- Incapacity
- Pregnancy, lactation
- Cholecalciferol or expients intolerance
- Hypercalcemia/hypercalciuria
- Kidney stones (nephrolithiasis/nephrocalcinosis)
- Chronic kidney failure
- Current therapy, or place within three months prior to the study, along with other vitamin D analogs
- Use of anticonvulsants or barbiturates.

• BMI>30
• Iperparatirodismo primario o secondario ad insufficienza renale
• Altre malattie del metabolismo fosfo-calcico
• Storia di embolia polmonare
• Stenosi moderata/severa aortica o mitralica
• pericardite
• BPCO severa
• Angina da sforzo e/o alterazioni significative del ECG
• Incapacità di intendere e di volere
• Gravidanza, allattamento
• Ipersensibilità al colecalciferolo o a uno qualsiasi degli eccipienti.
• Ipercalcemia, ipercalciuria
• Calcolosi renale (nefrolitiasi, nefrocalcinosi)
• Insufficienza renale
• Terapia in corso, o effettuata nei tre mesi precedenti lo studio, con altri analoghi della vitamina D.
• Uso di anticonvulsivanti o barbiturici.

E.5 End points

E.5.1

Primary end point(s)

Performance of the parameters of cardiopulmonary exercise testing (CPET) after 6 months of treatment. Instruments to be used: Cardiopulmonary exercise testing (CPET) performed as per routine clinical practice. The parameters used are mainly the assessment of metabolic response indices such as VO2 and VE / VCO2. Among the many parameters that can be evaluated with the CPET, the latter have been identified and validated in the literature as the best predictors of prognosis in heart failure.

Andamento dei parametri del test cardiopolmonare da sforzo (CPET) dopo 6 mesi di trattamento. Strumenti da utilizzare: test cardiopolmonare da sforzo (CPET) eseguito come da routinaria pratica clinica. I parametri utilizzati sono principalmente la valutazione degli indici di risposta metabolica quali VO2 e VE/VCO2. Tra i tanti parametri che è possibile valutare con il CPET, questi ultimi sono stati identificati e validati in letteratura come migliori predittori della prognosi nello scompenso cardiaco.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 month

6 mesi

E.5.2

Secondary end point(s)

1-Prevention of 25OHD deficiency and correction of the levels of 25OHD. Instruments to be used: 25OHD assay with mass spectrometry, a method of last generation that has already shown, in preliminary studies (see background), greater accuracy than conventional methods
2-Prevalence of hypovitaminosis D in the general population suffers from congestive heart failure and correlation with clinical and instrumental data.
3-Performance of clinical signs after 6 months of treatment. Instruments to be used: anamnesis, physical examination and general cardiology, self-assessment questionnaires.
4-Development of instrumental and biochemical parameters after 6 months of treatment. Tools to use: Dosage of hemoglobin, electrolytes, creatinine, glomerular filtration rate, renin directly, aldosterone, catecholamines, NT-proBNP, ECG, echocardiography (especially left ventricular volumes and systolic diastolic)

1-Prevenzione del deficit di 25OHD e correzione dei livelli di 25OHD. Strumenti da utilizzare: dosaggio 25OHD con spettrometria di massa, metodica di ultima generazione che ha già dimostrato, in studi preliminari (vedere background), una maggiore accuratezza rispetto ai metodi tradizionali
2-Prevalenza della ipovitaminosi D nella popolazione affetta da scompenso cardiaca e correlazione con i dati clinico-strumentali.
3-Andamento delle manifestazioni cliniche dopo 6 mesi di trattamento. Strumenti da utilizzare: raccolta anamnestica, esame obiettivo cardiologico e generale, questionari di autovalutazione.
4-Development of instrumental and biochemical parameters after 6 months of treatment. Tools to use: Dosage of hemoglobin, electrolytes, creatinine, glomerular filtration rate, renin directly, aldosterone, catecholamines, NT-proBNP, ECG, echocardiography (especially left ventricular volumes and systolic diastolic)

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3, 4- 6 month

1, 2, 3, 4- 6 mesi

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

Information not present in EudraCT

E.8.2.2

Placebo

E.8.2.3

Other

Information not present in EudraCT

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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 2015-05-21.

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

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Patients will continue with the programs therapeutic care that would perform regardless of participation in the study

I pazienti proseguiranno con i programmi teraputici assistenziali che effettuerebbero indipendentemente dalla partecipazione allo studio

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

2014-12-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-12

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials