Clinical Trials Register

Summary
EudraCT Number:	2009-012575-10
Sponsor's Protocol Code Number:	CH/2007/2661
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2022-01-18
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

2009-012575-10

A.3

Full title of the trial

Trial of Optimal Therapy for Pseudomonas Eradication in Cystic Fibrosis

Studio di terapia ottimale per l’eradicazione di Pseudomonas in fibrosi cistica.

A.3.1

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

Trial of Therapy for the first pulmonary infection by Pseudomonas aeruginosa in Cystic Fibrosis.

Studio della terapia per la prima infezione polmonare da Pseudomonas aeruginosa in fibrosi cistica.

A.3.2

Name or abbreviated title of the trial where available

TORPEDO-FC

A.4.1

Sponsor's protocol code number

CH/2007/2661

A.5.4

Other Identifiers

Name:

TORPEDO-FC

Number:

ch/2007/2661

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	UNIVERSITY OF LIVERPOOL
B.1.3.4	Country	United Kingdom
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	University of Liverpool
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Istituto Giannina Gaslini
B.5.2	Functional name of contact point	UOSD Epidemiologia, Biostatistica e
B.5.3	Address:
B.5.3.1	Street Address	Via Gaslini 5
B.5.3.2	Town/ city	Genova
B.5.3.3	Post code	16133
B.5.3.4	Country	Italy
B.5.4	Telephone number	01056363462
B.5.5	Fax number	0108981116
B.5.6	E-mail	comitatoetico@ospedale-gaslini.ge.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	TOTTIZIM - 1 G/10 ML POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE PER USO ENDOVENOSO 1 FLACONCINO POLVERE + 1 FIALA SOLVENTE 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	SO.SE.PHARM S.R.L. SOCIETA' DI SERVIZIO PER L'INDUSTRIA FARMACEUTICA ED AFFINI
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	Powder for solution for infusion
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.3.8	INN - Proposed INN	CEFTAZIDIMA PENTAIDRATO
D.3.9.1	CAS number	72558-82-8
D.3.9.2	Current sponsor code	ceftazidima
D.3.9.3	Other descriptive name	ceftazidime
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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.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	BRAMICIL - 100 MG/ 2 ML SOLUZIONE INIETTABILE 10 FIALE DA 2 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	FISIOPHARMA S.R.L.
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	Tobramicina
D.3.2	Product code	tobramicina
D.3.4	Pharmaceutical form	Suspension 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.3.8	INN - Proposed INN	TOBRAMICINA SOLFATO
D.3.9.1	CAS number	32986-56-4
D.3.9.2	Current sponsor code	Tobramicina
D.3.9.3	Other descriptive name	Tobramicyn
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	CIPROXIN - 500 MG COMPRESSE RIVESTITE 14 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER 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	Ciprofloxacina
D.3.4	Pharmaceutical form	Modified-release tablet
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	CIPROFLOXACINA CLORIDRATO
D.3.9.1	CAS number	85721-33-1
D.3.9.2	Current sponsor code	ciprofloxacina
D.3.9.3	Other descriptive name	ciprofloxacin
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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

First Pseudomonas aeruginosa infection in patients with cystic fibrosis

Prima infezione da Pseudomonas Aeruginosa in pazienti con fibrosi cistica

E.1.1.1

Medical condition in easily understood language

First Pulmonary infection in patients with cystic fibrosis

Prima infezione polmonare nei pazienti con fibrosi cistica

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10021860
E.1.2	Term	Infection Pseudomonas aeruginosa
E.1.2	System Organ Class	100000004862

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 assess whether fourteen days intravenous ceftazidime with tobramycin is superior to three months (12 weeks)* oral ciprofloxacin. Both treatment regimes will be in conjunction with three months (12 weeks)* nebulised colistin.

Valutare se quattordici giorni di terapia con ceftazidime e tobramicina per via endovenosa sia più efficace di tre mesi (12 settimane) di terapia con ciprofloxacina orale. Entrambi i trattamenti saranno in associazione con tre mesi (12 settimane) di colistina nebulizzata.

E.2.2

Secondary objectives of the trial

To remain infection free through to 15 months after the start of allocated treatment.

Mantenimento nel tempo della eradicazione da Pseudomonas

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosis of cystic fibrosis
2. Children over the age of 28 days, older children and adult CF participants are all eligible with no upper age limitation.
3. Competent adults should provide fully informed written consent to participate in the trial
4. Minors should have proxy consent by the parent or legal guardian and should provide assent where applicable to participate in the trial
5. The participant should have isolated P. aeruginosa and should be either:
a. P. aeruginosa -naïve (i.e. has never previously isolated P. aeruginosa) or
b. P. aeruginosa -free (i.e. any cough or sputum samples within the previous year (365 days) should be P. aeruginosa free)
6. The participant should be able to commence treatment no later than 21 days from the date of a P. aeruginosa positive microbiology report.

1. Diagnosi di FC
2. Bambini sopra i 28 giorni di età, bambini più grandi e adulti FC partecipanti sono tutti eleggibili, senza limitazioni di età superiore.
3. Adulti competenti dovranno fornire consenso scritto pienamente informato al fine di partecipare allo studio.
4. I minori devono avere il consenso/delega da parte del genitore o del tutore legale e dovranno eventualmente fornire assenso di partecipazione al trial.
5. Deve essere isolato P. aeruginosa dalla coltura espettorato del paziente. Egli dovrà essere o:
a. P. aeruginosa-naÏve (cioè mai isolato precedentemente P. aeruginosa) oppure
b. P. aeruginosa-free (cioè i campioni di espettorato/espettorazione indotta entro l'anno precedente (365 giorni) devono essere liberi da P. aeruginosa).
6. Il partecipante deve essere in grado di iniziare il trattamento entro e non oltre 21 giorni dalla data di un campione microbiologico positivo per P. aeruginosa.

E.4

Principal exclusion criteria

1. Antibiotic resistance of the current P. aeruginosa sample to any of: ciprofloxacin, ceftazidime, tobramycin or colistin reported by local microbiology laboratory lab
2. Known participant hypersensitivity to either ciprofloxacin, ceftazidime, tobramycin or colistin
3. Other known contraindications to any of ciprofloxacin, ceftazidime, tobramycin or colistin, including previous aminoglycoside hearing or renal damage
4. Participant receiving P. aeruginosa suppressing treatment, in particular nebulised colistin or tobramycin, or oral ciprofloxacin for the previous nine calendar months. Please note, short courses of oral ciprofloxacin or intravenous antibiotics (with an anti-pseudomonal spectrum of action) are not an exclusion unless they are given to treat proven infections with P. aeruginosa
5. Treatment with other anti-pseudomonal nebuliser
6. Pregnant and nursing mothers (women of child bearing age will be counselled on the risks of becoming pregnant during the trial and will be offered a pregnancy test)
7. Previous randomisation in TORPEDO-CF study
8. Previous participation in another related intervention trial within four weeks of taking part in TORPEDO-CF

1.Resistenza del campione di P. aeruginosa isolato ai seguenti antibiotici: ciprofloxacina, ceftazidime, tobramicina o colistina, segnalata dal laboratorio locale di microbiologia.
2. Nota ipersensibilità del paziente a qualunque antibiotico tra ciprofloxacina, ceftazidime, tobramicina o colistina.
3. Altre controindicazioni note a qualsiasi antibiotico tra ciprofloxacina, ceftazidime, tobramicina compresa precedente udienza di aminoglicosidi o danno renale.
4. Pazienti che abbiano ricevuto un trattamento eradicante per P. aeruginosa (in particolare colistina nebulizzata o tobramicina o ciprofloxacina orale) nei 9 mesi precedenti. Brevi cicli di ciprofloxacina orale o antibiotici per via endovenosa (con uno spettro di azione anti-pseudomonas) non sono criterio di esclusione a meno che non siano indicati per infezioni accertate da P. aeruginosa.
5. Trattamento con altri farmaci anti-pseudomonas per via inalatoria.
6. Donne incinte o che allattano (donne in età fertile saranno informate sui rischi di una gravidanza sopravvenuta durante lo studio e sarà loro offerto un test di gravidanza).
7. Randomizzazione precedente nel trial TORPEDO-CF.
8. Partecipazione precedente ad un altro studio entro quattro settimane dalla partecipazione a TORPEDO-CF

E.5 End points

E.5.1

Primary end point(s)

Successful eradication of P. aeruginosa infection three months after allocated treatment has started, remaining infection free through to 15 months after the start of allocated treatment.

Il successo dell’eradicazione dell’infezione da P. aeruginosa verrà valutato a tre mesi dall’inizio del trattamento assegnato, restando liberi dall’infezione per 15 mesi dall’inizio del trattamento assegnato.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 months

3 mesi

E.5.2

Secondary end point(s)

Time to recurrence of original P. aeruginosa infection; Re-infection with a different genotype of P. aeruginosa; Lung function - FEV1 , FVC, FEF25-75; O2 saturation; Growth and nutritional status – height, weight and body mass index; Number of pulmonary exacerbations; Admission to hospital; Quality of life (CFQ); Adverse events; Other sputum/cough Microbiology (Methicillin resistant Staphylococcus aureus (MRSA), Burkholderia cepacia complex, Aspergillus, Candida Infection); Cost per patient (from NHS perspective)

tempo di ricorrenza della prima infezione di P.aeruginosa; Re-infezione con un diverso genotipo di P. aeruginosa ; Funzione polmonare - FEV1 , FVC, FEF 25-75 ; Saturazione dell'ossigeno; Crescita e stato nutrizionale – altezza, peso e indice di massa corporea ; Numero di esacerbazioni polmonari ; RicoverI in ospedale ; Qualità della vita (CFQ) ; Eventi avversi; Altri isolamenti microbiologici nei campioni di espettorato/espettorazione indotta (Staphylococcus aureus Meticillino resistente (MRSA), Burkholderia cepacia complex, Aspergillus, infezione da Candida) ; Costo per paziente (da NHS prospettiva)

E.5.2.1

Timepoint(s) of evaluation of this end point

every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months; every 3 months

ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 mesi; ogni 3 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

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

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)

Yes

E.8.2.2

Placebo

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1