Clinical Trials Register

Summary
EudraCT Number:	2019-001941-41
Sponsor's Protocol Code Number:	RC10-18
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:	2021-05-24
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

2019-001941-41

A.3

Full title of the trial

Shortened antibiotic therapy for febrile urinary tract infections (UTI) in childhood: a multicentre randomized controlled trial

Terapia antibiotica breve nelle infezioni delle vie urinarie (IVU) febbrili del bambino: trial multicentrico controllato randomizzato

A.3.1

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

Shortened antibiotic therapy in urinary tract infections in childhood

Terapia antibiotica breve nelle infezioni delle vie urnarie febbrili nel bambino

A.3.2

Name or abbreviated title of the trial where available

Short UTI

Short IVU

A.4.1

Sponsor's protocol code number

RC10-18

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	IRCCS MATERNO INFANTILE BURLO GAROFOLO
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 della ricerca corrente dell'IRCCS Burlo Garofolo
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	IRCCS materno infantile Burlo Garofolo
B.5.2	Functional name of contact point	Ufficio Ricerca Clinica
B.5.3	Address:
B.5.3.1	Street Address	Via dell'Istria 65/1
B.5.3.2	Town/ city	TRIESTE
B.5.3.3	Post code	34137
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390403785418
B.5.5	Fax number	+390403785411
B.5.6	E-mail	sperimentazioni.cliniche@burlo.trieste.it

D. IMP Identification
D.IMP: 1
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	amoxicillina acido clavulanico
D.2.1.1.2	Name of the Marketing Authorisation holder	026141212
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	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.2	Product code	[037954043]
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.9.2	Current sponsor code	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.2.1.1.2	Name of the Marketing Authorisation holder	NA
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	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.9.2	Current sponsor code	AMOXICILLINA TRIIDRATO POTASSIO CLAVULANATO
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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

FEBRILE URINARY TRACT INFECTION

infezione febbrile delle vie urinarie

E.1.1.1

Medical condition in easily understood language

FEBRILE URINARY TRACT INFECTION

infezione delle vie urinarie associata a febbre

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10000822
E.1.2	Term	Acute kidney infection
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 if a five days oral course of amoxicillin and calvulanic acid is non-inferior to the standard ten-day regimen in the treatment of febrile urinary tract infections in children

Determinare la non inferiorità della terapia antibiotica con amoxicillina-acido clavulanico per 5 giorni rispetto al regime standard di 10 giorni previsto nel trattamento della pielonefrite acuta del bambino in termini di frequenza di recidiva di infezione, definita come la ricomparsa di segni e sintomi di pielonefrite a partire dal primo giorno dal termine della terapia antibiotica.

E.2.2

Secondary objectives of the trial

- to evaluate short-term clinical efficacy defined as the complete resolution of the signs and symptoms related to the infection at the end of the treatment whitout the need of additional or alternative antibiotic therapy
- to evaluate the presence of antibiotic-resistant or opportunistic strains in relapses

- Valutare il tasso di efficacia clinica a breve termine, definita come la completa risoluzione dei segni e sintomi di pielonefrite, senza necessità di terapia antibiotica supplementare o alternativa;
- Valutare l’emergenza di antibiotico-resistenze o di ceppi opportunisti nelle recidive.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- age from 3 months to 5 years
- clinical diagnosis of febrile urinary tract infection, defined by fever > or = 38 °C and positive result of urinalysis (nitrite and/or leukocyte esterase positivity) in two consecutive urine samples collected by bladder catheterization or clan catch

- Età compresa tra 3 mesi e 5 anni
- Sospetta pielonefrite acuta in base alla presenza dei criteri clinici (febbre > o = a 38°C) e positività dello stix urine per nitriti (indicatori di batteriuria) e/o dell’esterasi leucocitaria (indicatore di piuria) in due campioni consecutivi di urine raccolte da mitto intermedio o da cateterismo vescicale. L’esame al microscopio ottico potrà essere associato, quando possibile, a rinforzo del sospetto

E.4

Principal exclusion criteria

- "Complicated" febrile urinary tract infection (septic appearance, repeated vomiting with the impossibility to take the antibiotic by mouth, moderate severe-dehydration with the need for intravenous antibiotic therapy)
- Presence of an inserted urinary catheter
- Immunodeficiency
- Hypersensitivity to the active substance or other beta-lactam antibiotics
- Any Antibiotic treatment received in the previous 15 days.
- Presence of other chronic, uncontrolled medical condition
- Neurological bladder
- Phenylketonuria or glucose-galactose malabsorption
- Intestinal malabsorption
- Need for hospitalization
- poor compliance.

- Pielonefrite “complicata” (aspetto settico, vomito, disidratazione di grado moderato severo con necessità di terapia antibiotica endovenosa)
- Presenza di catetere urinario inserito
- Immunodeficienza
- Ipersensibilità al principio attivo o ad altra penicillina
- Trattamento antibiotico in atto o nei precedenti 15 giorni.
- Presenza di altra condizione medica di base, non controllata.
- Vescica neurologica
- Fenilchetonuria o malassorbimento glucosio-galattosio
- Malassorbimento intestinale
- Previsione di scarsa compliance

E.5 End points

E.5.1

Primary end point(s)

Rate of infection recurrence after the discontinuance of antibiotic therapy

Esito primario dello studio è la frequenza di recidiva, definita come ricomparsa di segni e sintomi suggestivi di pielonefrite, in accordo alle Raccomandazioni della Società Italiana di Nefrologia Pediatrica (febbre >38°C e positività dello stix urine per nitriti e/o esterasi leucocitaria), a partire dal primo giorno dalla sospensione della terapia antibiotica.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days after the end of the treatment

30 giorni dal termine della terapia

E.5.2

Secondary end point(s)

- short term clinical efficacy at the end of the treatment cycle, defined as the complete resolution of the signs and symptoms related to pyelonephritis during treatment, without the need for additional or alternative antibiotic therapy, evaluated at the first follow-up;; - occurrance of adverse events (nausea, diarrhea, headache); - the emergence of antibiotic resistance or opportunistic strains, defined as the presence of positive urine (nitrite and / or leukocyte esterase) and positive urine culture for a single type of bacterium, resistant to amoxicillin-clavulanic acid. It will be evaluated only in suspected relapses through the execution of urine and urine culture.

- la guarigione clinica al termine del ciclo di trattamento, definita come la completa risoluzione dei segni e sintomi correlati alla pielonefrite durante il trattamento, senza necessità di terapia antibiotica supplementare o alternativa, valutata al primo follow-up;; - la comparsa di eventi avversi (nausea, diarrea, cefalea); - l’emergenza di antibiotico-resistenze o di ceppi opportunisti, definita come presenza di urine positive (nitriti e/o esterasi leucocitaria) ed urinocoltura positiva per un singolo tipo di batterio, resistente ad amoxicillina-acido clavulanico. Verrà valutata solo nelle sospette recidive attraverso l’esecuzione di esame urine ed urinocoltura.

E.5.2.1

Timepoint(s) of evaluation of this end point

5 days after the end of the treatment; 5 days after the end of the treatment; 30 days after the end of the treatment

a 5 giorni dal termine della terapia; a 5 giorni dalla fine del trattamento; a 30 giorni dalla fine della terapia

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

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

Yes

E.6.13.1

Other scope of the trial description

non inferiority of the duration of the treatment

non inferiorità della durata del trattamento

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

stesso farmaco altra durata terapia

the same active principle but different duration of the therapy

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

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

Number of subjects for this age range:

260

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

260

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

Pediatric patients

Pazienti pediatrici

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

520

F.4.2

For a multinational trial

F.4.2.1

In the EEA

520

F.4.2.2

In the whole clinical trial

520

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)

Patients will undergo clinical evaluation on day 5 and day 30 from conclusion of antibiotic regimen independently from the treatment arm

I pazienti verranno rivalutati in regime ambulatoriale a 5 e a 30 giorni dal termine della terapia indipendentemente dal braccio

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

2020-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-12-31

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