Clinical Trials Register

Summary
EudraCT Number:	2015-003881-96
Sponsor's Protocol Code Number:	EPAFC
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:	2020-11-05
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

2015-003881-96

A.3

Full title of the trial

Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing classic treatment protocols with classic treatment together with antibiotic treatment of upper airways.

Studio randomizzato multicentrico sull' eradicazione di Pseudomonas aeruginosa in pazienti con fibrosi cistica: confronto tra il trattamento eradicante classico e il trattamento classico associato con la terapia antibiotica delle alte vie respiratorie

A.3.1

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

Clinical study to assess two different Pseudomonas aeruginosa eradication protocols in patients with cystic ¿brosis

Studio clinico per confrontare due trattamenti per l’eradicazione di Pseudomonas aeruginosa in pazienti con fibrosi cistica

A.3.2

Name or abbreviated title of the trial where available

Clinical study to assess two different Pseudomonas aeruginosa eradication protocols in patients with

Studio clinico per la valutazione di due diversi protocolli di eradicazione di Pseudomonas aeruginos

A.4.1

Sponsor's protocol code number

EPAFC

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 MEYER
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	FONDAZIONE FIBROSI CISTICA ONLUS
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 MEYER
B.5.2	Functional name of contact point	FIBROSI CISTICA
B.5.3	Address:
B.5.3.1	Street Address	VIALE PIERACCINI 24
B.5.3.2	Town/ city	FIRENZE
B.5.3.3	Post code	50139
B.5.3.4	Country	Italy
B.5.4	Telephone number	0555662474
B.5.5	Fax number	0555662470
B.5.6	E-mail	giovanni.taccetti@meyer.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	COLIMICINA - 1000000 U/4 ML POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE PER USO INTRAMUSCOLARE1 FLACONCINO POLVERE + 1 FIALA SOLVENTE 4 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB 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.3.1	Product name	NA
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLISTIMETATO SODICO
D.3.9.1	CAS number	1264-72-8
D.3.9.2	Current sponsor code	COLISTINA
D.3.9.3	Other descriptive name	COLISTIN
D.3.9.4	EV Substance Code	SUB01429MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000
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	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	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

cystic fibrosis

fibrosi cistica

E.1.1.1

Medical condition in easily understood language

cystic fibrosis

fibrosi cistica

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of the classic protocol together with nasal lavage using colistin (arm B) versus the classic eradication protocol used up until now (arm A), in terms of eradication of P aeruginosa in the the lower airways of CF patients

Valutare l’efficacia del trattamento standard associato a lavaggi nasali con colistina (trattamento B) rispetto al solo trattamento standard (trattamento A) in termini di eradicazione dello P. aeruginosa a livello delle vie aeree inferiori.

E.2.2

Secondary objectives of the trial

- Evaluation of the efficacy of medical treatment B on P. aeruginosa eradication in the upper airways
- Evaluation of correlation between the presence of P. aeruginosa in the upper airways and successive lower respiratory infections
- Evaluation of the role of the microbiological status of the paranasal sinuses in the development of P. aeruginosa infection
- Evaluation of the evolution of P. aeruginosa adaptations in the respiratory

- Valutare l’efficacia del trattamento B a livello a livello delle vie aeree superiori
- Valutare la correlazione fra vie aeree superiori e inferiori in termini di presenza di P. aeruginosa
- Determinare lo status microbiologico dei seni paranasali al momento dell’isolamento di P. aeruginosa nelle vie aeree inferiori
- Valutare l’adattamento e l’evoluzione di P. aeruginosa nelle vie aeree di pazienti affetti da FC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- CF patients older than 4 years with initial (first or intermittent) P. aeruginosa infection of the lower airways. The infection is defined according to Leeds’ criteria.
- Patients who make regular (quarterly) visit and undergo regular (quarterly) microbiological follow-up
- No clinical signs or symptoms of respiratory exacerbation
- Informed Consent
- Female patients with reproductive potential must agree to use effective contraception during the study period

- Pazienti con diagnosi di FC di età superiore a 4 anni con iniziale (prima o intermittente) infezione da P.aeruginosa delle vie aeree inferiori, stabilita attraverso l’analisi dell’espettorato o tampone faringeo, secondo la classificazione di Leeds
- Pazienti che si presentano regolarmente alle 4 visite di controllo annuali durante le quali viene svolto il follow-up microbiologico
- Assenza di segni o sintomi di esacerbazione respiratoria
- Ottenimento del consenso informato
- Donne in età fertile che adottano appropriate misure anticoncezionali

E.4

Principal exclusion criteria

- Chronic infection by P. aeruginosa (according to the Leeds’ definition).
- Chronic infection by other non-fermentative Gram- negative bacteria.
- CF patients who, concurrently with P. aeruginosa infection, show evidence of respiratory exacerbation, which renders treatment with intravenous antibiotics indispensable.
- History of aminoglycoside, aztreonam lisine or colistin hypersensitivity.
- Adverse reaction to study antibiotics.
- History of hypersensitivity or adverse reaction to ciprofloxacin or other fluoroquinolones.
- History of persistent, unresolved hearing loss not associated with middle ear disease or an abnormal tympanogram.
- Abnormal kidney function at study entry (defined as a serum creatinine level more than 1.5 times the upper normal limit for the participant’s age).
- Abnormal liver function test results at study entry, defined as ALT and/ or AST levels more than twice the upper limit of the normal range.
- Use of any investigational drug within 30 days of study entry.
- Chronic macrolide use in the 3 months prior to study entry.
- Presence of a condition or abnormality that would compromise the participant’s safety or the quality of the study data, in the opinion of the investigator.
- Pregnancy
- Breastfeeding

- Infezione cronica da P.aeruginosa (secondo la definizione di Leeds)
- Infezione cronica da altri batteri non- fermentativi Gram-negativi
- Pazienti FC con infezione P. aeruginosa in atto che mostrano evidenza di esacerbazione respiratoria che rende necessario il trattamento con terapia antibiotica endovenosa
- Storia di ipersensibilità ad aminoglicosidici, aztreonam lisina o colistina
¿ Storia di reazioni avverse gravi agli antibiotici impiegati nello studio
- Storia di ipersensibilità o reazioni avverse alla ciprofloxacina o ad altri fluoroquinolonici.
- Storia di persistente perdita dell'udito non risolvibile associata a malattia dell'orecchio medio o ad un anormale timpanogramma.
- Funzione renale alterata all'ingresso dello studio, definita con livelli di creatinine serica 1.5 volte superiori al limite superiore della norma per l’età del paziente
- Funzione epatica alterata all'ingresso dello studio, definita con livelli di AST/ALT due volte superiori al limite della norma
- Utilizzo di un qualsiasi altro farmaco oggetto di studio 30 giorni dall'inizio dell'ingresso nello studio
- Uso cronico di macrolidi nei 3 mesi prima dell'ingresso nello studio
- Presenza di altra condizione di anormalità, a discrezionalità del ricercatore, che potrebbe compromettere la sicurezza del partecipante.
- Gravidanza presunta o accertata
- Donne in allattamento

E.5 End points

E.5.1

Primary end point(s)

- Difference between the 2 groups in terms of proportion of eradication of P. aeruginosa in the lower airways. Eradication is defined as at least 3 negative cultures performed over a period of 6 months.

- Differenza nella proporzione di eradicazione di P. aeruginosa dalle vie aeree inferiori nei due gruppi, definita sulla base di standard internazionali (3 esami colturali consecutivi, tampone faringeo o escreato, negativi per P. aeruginosa nell'arco di 6 mesi).

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

- proportion of eradication of P. aeruginosa in the upper airways. P. aeruginosa eradication is defined as at least 3 negative cultures performed over a period of 6 months.
- Proportion of patients with P. aeruginosa isolation from upper and lower respiratory tracts.
- P. aeruginosa isolation from upper respiratory tracts after the nasal colistin irrigations
- phenotypic and genotypic features of P. aeruginosa

- proporzione di pazienti con eradicazione di P. aeruginosa dalle vie aeree superiori definita sulla base di standard internazionali (3 esami colturali consecutivi, lavaggio nasale, negativi per P. aeruginosa nell'arco di 6 mesi)
- Proporzione di pazienti che presentano P. aeruginosa sia nelle vie aeree superiori (lavaggio nasale) che inferiori (escreato/tampone faringeo)
- Isolamento di P. aeruginosa dalle prime vie aeree dopo lavaggio nasale effettuato durante 3 visite di controllo ai pazienti di entrambi i gruppi
- genotipizzazione e fenotipizzazione di P. aeruginosa

E.5.2.1

Timepoint(s) of evaluation of this end point

All: 6 months
Phenotypic and genotypic features of P. aeruginosa: 24 months

Tutti: 6 mesi
Genotipizzazione e fenotipizzazione di P. aeruginosa: 24 mesi

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

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

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

Terapia standard per l'eradicazione di P. aeruginosa

Standard therapy for P. aeruginosa eradication

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

Information not present in EudraCT

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
Or in case interim analysis show highier efficacy of the experimental treatment

LVLS
Oppure se le interim analysis dimostrano una maggiore efficacia del trattamento in sperimentazione.

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)

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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

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

112

F.4.2

For a multinational trial

F.4.2.1

In the EEA

112

F.4.2.2

In the whole clinical trial

112

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)

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

2016-05-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-17

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

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