Clinical Trials Register

Summary
EudraCT Number:	2012-004583-22
Sponsor's Protocol Code Number:	548.12
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:	2012-10-25
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-004583-22

A.3

Full title of the trial

Verification of the effectiveness of intravenous sildenafil compared to other pulmonary vasodilators used in the test vessel reactivity of pulmonary

Verifica dell'efficacia del sildenafil per via endovenosa rispetto agli altri agenti vasodilatatori polmonari utilizzati nel test di vaso reattivitÃƒÂ polmonare

A.3.1

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

Verification of the effectiveness of intravenous sildenafil compared to other pulmonary vasodilators used in the test vessel reactivity of pulmonary

Verifica dell’efficacia del sildenafil per via endovenosa rispetto agli altri agenti vasodilatatori polmonari utilizzati nel test di vaso reattività polmonare

A.3.2

Name or abbreviated title of the trial where available

Intravenous sildenafil in children

Sildenafil endovena in età pediatrica

A.4.1

Sponsor's protocol code number

548.12

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	OSPEDALE PEDIATRICO BAMBINO GESU' DI ROMA
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	Ospedale Pediatrico Bambino Gesù
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	Ospedale Pediatrico Bambino Gesù
B.5.2	Functional name of contact point	Cardiologia
B.5.3	Address:
B.5.3.1	Street Address	Piazza S.Onofrio 4
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00165
B.5.3.4	Country	Italy
B.5.4	Telephone number	06.6859. 2459
B.5.5	Fax number	06.6859.
B.5.6	E-mail	paolo.guccione@opbg.net

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	REVATIO*EV 1FL 20ML 0,8MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER ITALIA Srl
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	139755-83-
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	.35
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects in children with congenital heart disease surgery or not, with echocardiographic signs of pulmonary hypertension followed at the Pediatric Cardiology Centre of the Mediterranean or reported by other centers I and Level II.

Soggetti in età pediatrica affetti da cardiopatia congenita operata e non, con segni ecocardiografici di ipertensione polmonare seguiti presso il Centro Cardiologico Pediatrico del Mediterraneo o riferiti da altri centri di I e II livello.

E.1.1.1

Medical condition in easily understood language

Subjects in children with congenital heart disease surgery or not, with echocardiographic signs of pulmonary hypertension

Soggetti in età pediatrica affetti da cardiopatia congenita operata e non, con segni ecocardiografici di ipertensione polmonare.

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	10047065
E.1.2	Term	Vascular disorders
E.1.2	System Organ Class	10047065 - Vascular 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

assess the appropriateness, sensitivity and specificity of sildenafil ev in reducing pulmonary hypertension and its possible superiority in terms of results / costs / organizational aspects than nitric oxide during the execution of the test vessel pulmonary artery reactivity.

valutare l’appropriatezza, la sensibilità e la specificità del sildenafil e.v. nella riduzione dell’ipertensione polmonare e la sua eventuale superiorità in termini di risultati/costi/ aspetti organizzativi rispetto l’ossido di azoto durante l’esecuzione del test di vaso reattività polmonare.

E.2.2

Secondary objectives of the trial

reducing the invasiveness of the procedure, with less intubation / sedation, which is necessary for proper administration of nitric oxide, especially in adolescent patients;
- Significant reduction of costs;
- Assessing the effectiveness of all, useful prognostic sense and proper therapeutic management in the future.

riduzione dell’invasività della procedura; con minore ricorso all’intubazione/sedazione profonda, necessaria per una corretta somministrazione dell’ossido di azoto, soprattutto nei pazienti adolescenti;
- riduzione significativa dei costi;
- valutazione dell’efficacia in assoluto, utile in senso prognostico e per una corretta gestione terapeutica futura.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

subjects in children with congenital heart disease surgery or not, with echocardiographic signs of pulmonary hypertension followed at the Pediatric Cardiology Centre of the Mediterranean or reported by other centers I and Level II.

soggetti in età pediatrica affetti da cardiopatia congenita operata e non, con segni ecocardiografici di ipertensione polmonare seguiti presso il Centro Cardiologico Pediatrico del Mediterraneo o riferiti da altri centri di I e II livello.

E.4

Principal exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

assessment in cardiac patients with pulmonary hypertension tested for pulmonary vessel reactivity in absolute terms and compared the effectiveness of nitric oxide, sildenafil ev in determining improvement of:
- Blood pressure in the pulmonary artery;
- Pulmonary capillary pressure;
- Transpulmonary gradient;
- Flow rate (measured by the method of thermodilution or the Fick principle);
- Heating lung total arteriolar and venous capillaries.

valutare nei pazienti cardiopatici con ipertensione polmonare sottoposti a test di vaso reattività polmonare l’efficacia in assoluto e rispetto all’ossido di azoto, del sildenafil e.v. nel determinare miglioramento di:
- Pressione arteriosa in arteria polmonare;
- Pressione capillare polmonare;
- Gradiente transpolmonare;
- Portata cardiaca (valutata con la metodica della termodiluizione o principio di Fick);
- Resistenze polmonari totali, arteriolari e venocapillari.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

- Reducing the invasiveness of the procedure, with less intubation / sedation, which is necessary for proper administration of nitric oxide, especially in adolescent patients;
- Significant reduction of costs;
- Assessing the effectiveness of all, useful prognostic sense and proper therapeutic management in the future.

- riduzione dell’invasività della procedura; con minore ricorso all’intubazione/sedazione profonda, necessaria per una corretta somministrazione dell’ossido di azoto, soprattutto nei pazienti adolescenti;
- riduzione significativa dei costi;
- valutazione dell’efficacia in assoluto, utile in senso prognostico e per una corretta gestione terapeutica futura.

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

CROSS SECTIONAL

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

Information not present in EudraCT

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

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

Yes

F.1.1