Clinical Trials Register

Summary
EudraCT Number:	2019-002923-13
Sponsor's Protocol Code Number:	2535
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:	2020-10-22
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

2019-002923-13

A.3

Full title of the trial

Indication for the exougenous surfactant administration to treat neonatal respiratory distress syndrome in the preterm infant: a single-center randomized phase 4 trial based on the comparison of two levels of respiratory severity.

Indicazione alla somministrazione di surfactante esogeno per il trattamento della sindrome da distress respiratorio nel neonato pretermine: un trial monocentrico randomizzato di fase 4 di confronto tra due livelli di gravità respiratoria.

A.3.1

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

Comparison of two respiratory severity thresholds as indications for the administration of exogenous surfactant in preterm infants with respiratory disease.

Confronto di due livelli di gravità respiratoria come indicazione alla somministrazione di surfattante esogeno in neonati pretermine con malattia respiratoria.

A.3.2

Name or abbreviated title of the trial where available

respiratory severity and exogenous surfactant

gravità respiratoria e surfattante esogeno

A.4.1

Sponsor's protocol code number

2535

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 OSPEDALI RIUNITI DI ANCONA
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	AOU Ospedali Riuniti di Ancona
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 OSPEDALI RIUNITI DI ANCONA
B.5.2	Functional name of contact point	SEGRETERIA SOD NEONATOLOGIA
B.5.3	Address:
B.5.3.1	Street Address	Via Enrico Toti 4
B.5.3.2	Town/ city	Ancona
B.5.3.3	Post code	60123
B.5.3.4	Country	Italy
B.5.4	Telephone number	0715962045
B.5.5	Fax number	0715962440
B.5.6	E-mail	v.carnielli@staff.univpm.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	CUROSURF - 80 MG/ML SOSPENSIONE PER INSTILLAZIONE ENDOTRACHEOBRONCHIALE 2 FLACONCINI 1.5 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	CHIESI FARMACEUTICI 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.3.1	Product name	CUROSURF
D.3.2	Product code	[10122-510]
D.3.4	Pharmaceutical form	Endotracheopulmonary instillation, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Endotracheopulmonary use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	frazione fosfolipidica da polmone suino
D.3.9.1	CAS number	129069-19-8
D.3.9.2	Current sponsor code	CS-1
D.3.9.4	EV Substance Code	SUB22150
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	80
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
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

Neonatal respiratory distress syndrome (RDS)

Sindrome da distress respiratorio (RDS) del neonato.

E.1.1.1

Medical condition in easily understood language

Neonatal respiratory disease

Malattia respiratoria del neonato

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10038690
E.1.2	Term	Respiratory distress syndrome (neonatal)
E.1.2	System Organ Class	100000004855

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 the superior effectiveness of the respiratory severity level "CURO25" (FiO2>25%) compared to the respiratory severity level CURO35 (FiO2>35% - actual clinical practice in the study center) as indication for the exogenous surfactant administration in preterm infants with respiratory distress syndrome (RDS).

Valutare la superiorità di efficacia del livello di gravità respiratoria "CURO25", definito da una soglia di FiO2 del 25%, rispetto al livello di gravità respiratoria "CURO35", definito da una soglia di FiO2 del 35% (attuale pratica clinica), come indicazione al trattamento con surfactante esogeno nella sindrome da distress respiratorio (RDS) del neonato pretermine.

E.2.2

Secondary objectives of the trial

To evaluate the effects of two respiratory severity levels (CURO25 vs CURO35) as indications for the exogenous surfactant administration in preterm infants with respiratory distress syndrome (RDS) in terms of the incidence of neonatal complications, duration of in-hospital therapy and short-medium respiratory outcomes.

Valutare l'impatto del livello di gravità respiratoria CURO25 e CURO35 utilizzato come indicazione per il trattamento con surfactante esogeno nella RDS del neonato pretermine sull'incidenza delle principali complicanze neonatali, durata delle terapie e funzionalità polmonare a breve e medio termine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- gestational age between 24 and 32 weeks postmenstrual age;
- diagnosis of neonatal respiratory distress (RDS);
- need of invasive/non-invasive ventilatory support;
- written informed consent.

- età gestazionale alla nascita compresa tra 24 e 32 settimane;
- diagnosi di distress respiratorio neonatale (RDS);
- necessità di supporto ventilatorio non invasivo o invasivo;
- consenso informato firmato da genitore/i o tutore.

E.4

Principal exclusion criteria

- congenital malformations;
- genetic disorders;
- perinatal asphyxia;
- presence or concomitance of other diseases compatible with RDS.

- malformazioni congenite;
- anomali genetiche;
- asfissia perinatale;
- presenza o concomitanza di altre patologie compatibili con il quadro clinico di RDS
(polmonite connatale, wet lung, sindrome da inalazione di meconio.

E.5 End points

E.5.1

Primary end point(s)

Respiratory function defined as oxygen saturation/FiO2 ratio (SFR).

Funzionalità respiratoria polmonare definita dal rapporto tra la saturazione di ossigeno del paziente e frazione di ossigeno inspirata (SFR).

E.5.1.1

Timepoint(s) of evaluation of this end point

At day 3 of life.

Al 3° giorno di vita.

E.5.2

Secondary end point(s)

Duration of the oxygen therapy (days); Duration of the mechanical ventilation (days).; Late respiratory function defined as oxygen saturation/FiO2 ratio (SFR).; Silvermann score as secondary respiratory severity index.; Lung ultrasound score (LUS score) as secondary respiratory severity index.; Oxygenation index as an indicator of the intensity of ventilator support.; In-hospital death.; The incidence of neonatal complications: intraventricular hemorrhage (grade 3 and 4), periventricular leukomalacia, retinopathy of prematurity and bronchopulmonary dysplasia.; Duration of non-invasive positive pressure ventilation (CPAP - days).; Number of patients who received mechanical ventilation.

Durata di ossigeno terapia (giorni); Durata della ventilazione meccanica (giorni).; Funzionalità respiratoria polmonare tardiva definita dal rapporto tra la saturazione di ossigeno del paziente e frazione di ossigeno inspirata (SFR).; Punteggio di Silvermann come indicatore secondario di gravità respiratoria.; Punteggio di ecografia polmonare (punteggio di LUS) come indice secondario di gravità respiratoria.; Indice di ossigenazione come indicatore di intensità del supporto ventilatorio.; Morte intra-ospedaliera; Incidenza di complicazioni neonatali (emorragia intravetricolare di 3 e 4 grado, leucomalacia periventicolare, retinopatia del prematuro e displasia broncopolmonare).; Durata della ventilazione meccanica non invasiva a pressione positiva (CPAP - giorni).; Numero di pazienti sottoposti a ventilazione meccanica.

E.5.2.1

Timepoint(s) of evaluation of this end point

From the admission to 36 weeks of postmenstrual age or at the discharge if it occurs first.; From the admission to 36 weeks of postmenstrual age or at the discharge if it occurs first..; At day 7 and 28 of life, at 36 weeks of postmenstrual age or at the discharge if it occurs first, and at 1 year of corrected age.; At day 3, 7 and 28 of life and at 36 weeks of postmenstrual age or at the discharge if it occurs first.; At day 3, 7 and 28 of life and at 36 weeks of postmenstrual age or at the discharge if it occurs first.; At day 3, 7 and 28 of life and at 36 weeks of postmenstrual age or at the discharge if it occurs first.; From birth to discharge from the neonatal intensive care unit.; From birth to 36 weeks of postmenstrual age or at the discharge if it occurs first.; From the admission

Dal ricovero in reparto al compimento della 36° settimana di età gestazionale corretta o alla dimissione se precedente.; Dal ricovero in reparto al compimento della 36° settimana di età gestazionale corretta o alla dimissione se precedente.; Al giorno 7 e 28 di vita, a 36 settimane di età gestazionale corretta o alla dimissione se precedente, e a 1 anno di età corretta.; Al giorno 3, 7 e 28 di vita e a 36 settimane di età corretta o alla dimissione se
precedente.; Al giorno 3, 7 e 28 di vita e a 36 settimane di età corretta o alla dimissione se
precedente.; Al giorno 3, 7 e 28 di vita e a 36 settimane di età corretta o alla dimissione se precedente.; Dal ricovero alla dimissione dal reparto di terapia intensiva neonatale.; Dal ricovero a 36 settimane di età gestazionale o dimissione se pre

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

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

Yes

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

Stesso farmaco (IMP1), con stesso dosaggio, ma somministrato in base a una diverso livello di gravit

IMP1 will be used at the same dose but a different respiratory levels defined by the needed of suppl

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

Information not present in EudraCT

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

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

Yes

F.1.1.1

In Utero

F.1.1.2

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

Yes

F.1.1.2.1

Number of subjects for this age range:

200

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)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Neonates cannot directly give consent to participate at the study. Informed
consent will be obtain from parents or legal guardian.

Neonati incapaci di consenso autonomo alla partecipazione allo studio che sarà
per tale ragione richiesto ai genitori o tutore.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

200

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

nessuno

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

2021-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-15

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

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