Clinical Trials Register

Summary
EudraCT Number:	2011-002823-16
Sponsor's Protocol Code Number:	02-2011
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-07
Trial results	View 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-002823-16

A.3

Full title of the trial

Effects of Vitamin D in patients affected by heart failure

Effetti della vitamina D in pazienti affetti da scompenso cardiaco

A.3.1

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

A.4.1

Sponsor's protocol code number

02-2011

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	A.O. UNIVERSITARIA INTEGRATA DI VERONA
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	Fondi Reparto Medicina C
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 Ospedaliera Universitaria Integrata Verona
B.5.2	Functional name of contact point	Reparto di Medicina C
B.5.3	Address:
B.5.3.1	Street Address	P.le L.A. Scuro, 10 (Borgo Roma)
B.5.3.2	Town/ city	Verona
B.5.3.3	Post code	37134
B.5.3.4	Country	Italy
B.5.4	Telephone number	045.8124414
B.5.5	Fax number	045.8027465
B.5.6	E-mail	pietro.delva@univr.it

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*IM OS 6F 1ML 100000UI/M
D.2.1.1.2	Name of the Marketing Authorisation holder	ABIOGEN PHARMA SpA
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 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	VITAMIN D NOS
D.3.9.1	CAS number	8000055643
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100000
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.IMP: 2
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*IM OS 2F 1ML 300000UI/M
D.2.1.1.2	Name of the Marketing Authorisation holder	ABIOGEN PHARMA SpA
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 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	VITAMIN D NOS
D.3.9.1	CAS number	8000055643
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300000
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 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 is a condition that occurs when the heart loses its normal ability to pump blood to maintain vital body functions and, therefore, works with lower efficiency. Several studies have shown that deficiency of vitamin D would delete the renin gene, regulate the myocytes growth and facilitate ventricular hypertrophy, favoring cardiovascular damage and the incidence of heart failure.

Lo scompenso cardiaco è una condizione che si ha quando il cuore perde la sua normale capacità di pompare sangue per mantenere le funzioni vitali dell'organismo e, quindi, lavora con sempre minore efficienza. Vari studi hanno dimostrato che la carenza di vit D sopprimerebbe il gene della renina, regolerebbe la crescita dei miocardiociti e favorirebbe l’ipertrofia ventricolare, favorendo danno cardiovascolare e l’incidenza di scompenso cardiaco.

E.1.1.1

Medical condition in easily understood language

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	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10007541
E.1.2	Term	Cardiac disorders
E.1.2	System Organ Class	10007541 - Cardiac 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 confirm the relationship between low serum levels of vitamin D and increased incidence of heart failure argued by the literature.

Confermare i dati in letteratura circa la relazione fra livelli sierici bassi di vitamina D e aumentata incidenza di scompenso cardiaco.

E.2.2

Secondary objectives of the trial

To verify the effectiveness of the additional therapy with vitamin D, proofing an improvement of cardiac contractility indices by an echocardiographic study and a reduction of cardiac fibrosis.

Verificare l’efficacia della terapia supplementativa con Vitamina D, dimostrando un miglioramento degli indici di contrattilità cardiaca tramite studio ecocardiografico e un’eventuale riduzione della fibrosi cardiaca.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Written informed consent signed by the patient or by a legally acceptable representative; -Men and women between the ages of 40 and 85 years; -Patients affected by chronic heart failure (Framingham criteria), not in the acute phase, in NYHA class I-II-III-IV secondary to a hypertensive ischemic heart disease or an idiopathic dilated cardiomyopathy, and with echocardiographic assessment of both systolic heart failure (left ventricular ejection fraction ≤ 50%) and heart failure with preserved systolic function (ejection fraction equal or > 45%, evidence of abnormal left ventricular relaxation); -Nutritional deficiency of Vitamin D (VIT D < 30 ng/mL and > 10 ng/mL).

-Firma del consenso informato da parte del paziente o di un suo rappresentante legalmente riconosciuto; -Uomini e donne con età compresa fra 40 e 85 anni; -Pazienti con scompenso cardiaco cronico (secondo criteri di Framingham), non in fase acuta, in classe NYHA I-II-III-IV secondario a cardiopatia ischemica, ipertensiva o miocardiopatia dilatativa idiopatica e valutazione ecocardiografica sia di scompenso sistolico (frazione di eiezione ventricolare sinistra ≤ 50%) che di scompenso a funzione sistolica conservata (frazione di eiezione maggiore o uguale al 45%, evidenza di anormale rilassamento ventricolare sinistro); -Carenza nutrizionale di Vitamina D ( VIT D < 30 ng/mL e > 10 ng/mL).

E.4

Principal exclusion criteria

-unstable angina; -recent myocardial infarction (within the 6 months prior to enrollment) -cardiogenic shock or hypotension (systolic pressure <100 mm Hg) -uncontrolled hypertension (SBP> 180, DBP> 110); -severe liver disease -severe renal impairment (creatinine> 2mg/dl); -infectious or chronic inflammatory disease; -active cancer or haematological disease; -recent blood transfusion (within 30 days); -abuse of alcohol or drugs in the last year; -severe osteoporosis requiring treatment with bisphosphonates and / or vitamin D; -intake of vitamin D within the 3 months prior to enrollment.

-angina instabile; -infarto miocardico recente (nei 6 mesi antecedenti l’arruolamento), -shock cardiogeno o ipotensione (pressione sistolica < 100 mm Hg), -ipertensione non controllata (PAS>180, PAD>110); -malattia epatica severa; -insufficienza renale severa (creatinina > 2mg/dl); -malattia infettiva o infiammatoria cronica; -neoplasia o malattia ematologia attiva; -recente trasfusione di sangue (entro i 30 giorni); -abuso di alcol o sostanze stupefacenti negli ultimi 1 anno; -grave osteoporosi che necessita di trattamento con bifosfonati e/o vitamina D; -assunzione di vitamina D nei 3 mesi antecedenti l’arruolamento.

E.5 End points

E.5.1

Primary end point(s)

EF (ejection fraction) % (B-mode measurement) measured by echocardiogram

FE (frazione di eiezione) % (misurazione in B mode) misurato tramite ecocardiogramma

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

1.wall thickness (IVS and PW) in mm (M-mode measurement) left ventricular mass index calculated by: 0.832* [(Dd+IVSd+PWd)3 – Dd3] + 0.6g (Dd is the left ventricular telediastolic diameter, IVS is the interventricular septum thickness, PWd is the diastolic posterior wall thickness) 2.Parameters of relaxation (E/A ratio) 3.DT in mm/sec 4.Serum carboxy-terminal propeptide of procollagen type I

1.spessore parietale ( SIV e PP) in mm (misurazione in M Mode) Indice di massa espresso come: 0.832* [(DTd+SIVd+PPd)3- DTd3*] + 0.6g (dove DTd è il diametro telediastolico del ventricolo sinistro, SIVd è lo spessore del setto interventricolare e PPd quello della parete posteriore in diastole) 2.Parametri di rilasciamento E/A 3.TD in mm/sec 4.Propeptide C terminale del collagene tipo I nel siero

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

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

Number of subjects for this age range:

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)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

The treatment with vitamin D could continue even after the end of the study because patients are vitamin D deficient.

Il trattamento con Vitamina D potrebbe continuare anche al termine dello studio essendo i pazienti carenti di Vitamina D.

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

2011-07-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-20

P. End of Trial
P.	End of Trial Status	Completed

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