Clinical Trials Register

Summary
EudraCT Number:	2013-000309-21
Sponsor's Protocol Code Number:	PREDICT
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-01-28
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

Lithuania - SMCA

A.2

EudraCT number

2013-000309-21

A.3

Full title of the trial

PREDICT trial – antibiotic prophylaxis and renal damage in congenital abnormalities of the kidney and urinary tract

PREDICT – Antibakterinė profilaktika ir inkstų pažeidimas, esant įgimtoms inkstų ir šlapimo organų anomalijoms.

A.3.1

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

Antibiotic Prophylaxis and Renal Damage In Congenital abnormalities of
the kidney and urinary Tract.

Antibakterinė profilaktika ir inkstų pažeidimas esant įgimtoms inkstų ir šlapimo takų anomalijoms.

A.3.2

Name or abbreviated title of the trial where available

PREDICT trial

PREDICT studija

A.4.1

Sponsor's protocol code number

PREDICT

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	AOU di Bologna, Policlinico S.Orsola-Malpighi
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	Ministero della Salute, Project Code:RF-2010-2308451
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	AOU di Bologna, Policlinico S.Orsola-Malpighi
B.5.2	Functional name of contact point	G.Montini,S.S.Neforologia Pediatric
B.5.3	Address:
B.5.3.1	Street Address	Via Albertoni 15
B.5.3.2	Town/ city	Bologna
B.5.3.3	Post code	40138
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390516364617
B.5.5	Fax number	0039051636617
B.5.6	E-mail	giovanni.montini@aosp.bo.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	Nitrofurantoinum
D.2.1.1.2	Name of the Marketing Authorisation holder	JSC Olainfarm, Latvia
D.2.1.2	Country which granted the Marketing Authorisation	Lithuania
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	Furadonins
D.3.4	Pharmaceutical form	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	NITROFURANTOIN
D.3.9.1	CAS number	67-20-9
D.3.9.3	Other descriptive name	NITROFURANTOIN
D.3.9.4	EV Substance Code	SUB09326MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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.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	Trimetoprimum
D.2.1.1.2	Name of the Marketing Authorisation holder	Vitabalans Oy, Finland
D.2.1.2	Country which granted the Marketing Authorisation	Lithuania
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	Trimetop
D.3.4	Pharmaceutical form	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.3.9.1	CAS number	738-70-5
D.3.9.3	Other descriptive name	TRIMETHOPRIM
D.3.9.4	EV Substance Code	SUB11310MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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.IMP: 3
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	Biseptol
D.2.1.1.2	Name of the Marketing Authorisation holder	Medana Pharma SA, Poland
D.2.1.2	Country which granted the Marketing Authorisation	Lithuania
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	Biseptol
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	SULFAMETHOXAZOLE
D.3.9.1	CAS number	723-46-6
D.3.9.4	EV Substance Code	SUB10711MIG
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	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	738-70-5
D.3.9.3	Other descriptive name	TRIMETHOPRIM
D.3.9.4	EV Substance Code	SUB11310MIG
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	40
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

The influence of congenital abnormalities of the kidney and urinary tract for developing urinary tract infections.

Įgimtų inkstų ir šlapimo organų anomalijų – vezikoureterinio refliukso ir inkstų hipodisplazijos – įtaka šlapimo organų infekcijos išsivystymui.

E.1.1.1

Medical condition in easily understood language

Inborn urinary tract anomaly.

Įmita šlapimo takų anomalija.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10047371
E.1.2	Term	Vesicoureteral reflux
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is the evaluation of the effectiveness of
antimicrobial prophylaxis in infants with vesico-ureteral reflux grade IIIV,
started before the first symptomatic infection.

Įvertinti antibakterinio profilaktinio gydymo efektyvumą sumažinti šlapimo organų infekcijų skaičių, kai jis pradedamas kūdikiams, kuriems nustatytas III-V laipsnio vezikoureterinis refliuksas, iki pirmosios simptominės šlapimo organų infekcijos.

E.2.2

Secondary objectives of the trial

The secondary objectives are the evaluation of
1. the role of symptomatic and febrile UTIs on the appearance and
progression of kidney damage and development of renal function;
2. the natural history of renal function of paediatric patients with
congenital kidney or urinary tract anomalies during the first 5 years of
life;
3. the natural evolution of vesico-ureteral reflux during the first 5 years
of life and its correlation with UTIs, renal scars and impairment of renal
function;
4. the hypothetic role of prophylactic antibiotic therapy during the first
months of life on BMI at 2 and 5 years of age.

Įvertinti: simptominės ir febrilios šlapimo organų inkfekcijos reikšmę inkstų pažeidimo atsiradimui ir progresavimui ir inkstų funkcijos dinamikai; inkstų funkcijos dinamiką 5 metų laikotarpyje vaikams, kuriems yra įgimtos inkstų ir šlapimo organų anomalijos; vezikoureterinio refliukso evoliuciją 5 metų laikotarpyje ir jo ryšį su šlapimo organų infekcija, inkstų randais ir inkstų funkcijos blogėjimu; hipotetinę profilaktinės antibakterinės profilaktikos pirmais gyvenimo mėnesiais reikšmę kūno masės indeksui 2 ir 5 metų amžiaus vaikams.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

a. Age between 1 and 4 months (20 weeks) at enrolment.
b. Gestational age > 35 weeks.
c. Glomerular Filtration Rate (GFR) calculated using the Schwartz formula > 15 ml/min/1.73 m2 .
d. No previous symptomatic Urinary Tract Infections.
e. Complete instrumental screening work-up and presence of vesicoureteral reflux grade III to V.
f. Informed Consent form signed by the parents.

a. 1-4 mėn. (20 savaičių) amžius įtraukimo metu.
b. Gestacinis amžius ≥35 sav.
c. Glomerulų filtracijos greitis (paskaičiuotas pagal Schwartz formulę) > 15 ml/min/1.73 m2.
d. Anksčiau nebuvę simptominių ŠOI.
e. Atlikti vaizdiniai tyrimai ir nustatytas III-V laipsnio vezikoureterinis refliuksas.
f. Paisrašytas tėvų sutikimas.

E.4

Principal exclusion criteria

a. Age <1 or >4 months.
b. Gestational age < 35 weeks.
c. Glomerular Filtration Rate (GFR) calculated using the Schwartz formula < 15 ml/min/1.73 m2 at 3 months of age.
d. Patients with neurogenic bladder, myelomeningocele, pyeloureteral stenosis, ureterovesical junction obstruction or other malformations potentially related to the onset of micturition disorders, except ureteral valves.
e. Patients without vesicoureteral reflux or with vesicoureteral reflux grade I or II.
f. Hypersensitivity to all the active ingredients listed in the protocol.
g. Children whose clinical condition is so severe that, in the Investigator’s opinion, they cannot be included in the study cohort.
h. The use of experimental drugs during the month previous to enrolment.
i. Children who are not able to follow the procedures indicated in the protocol or children whose parents are unable to express consent.

a. Amžius <1 ir >4 mėn.
b. Gestacinis amžius < 35 sav.
c. Glomerulų filtracijos greitis (paskaičiuotas pagal Schwartz formulę) ≤ 15 ml/min/1.73 m2 trijų mėnesių amžiuje.
d. Pacientai su neurogenine šlapimo pūsle, mielomeningocele, uretero-pelvinės jungties ir/arba uretero-veziko jungties obstrukcija ar kitomis malformacijomis, sukeliančiomis galimus šlapinimosi sutrikimus, išskyrus šlaplės vožtuvus.
e. Pacientai, kuriems nenustatytas ar nustatytas mažo laipsnio (I ar II) VUR.
f. Padidėjęs jautrumas visiems skiriamiems antibakteriniams preparatams.
g. Vaikai, kurie tyrėjo nuomone dėl savo sunkios būklės yra netinkami studijai.
h. Vartojantys eksperimentinius vaistus mėnesį iki studijos pradžios.
i. Vaikai, kuriems negalima taikyti nustatyto protokolo ir kurių tėvai negali pasirašyti sutikimo formoje.

E.5 End points

E.5.1

Primary end point(s)

Evaluation of the efficacy of antibiotic prophylaxis in reducing the number of urinary tract infections when initiated before the onset of the first symptomatic first symptomatic urinary tract infection in infants with vesicoureteral reflux grade III to V.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months

24 mėnesiai

E.5.2

Secondary end point(s)

Evaluation of the role that symptomatic and febrile urinary tract infections play in the appearance and progression of renal damage and the evolution of renal function; evaluation of the natural history of renal function in paediatric patients with congenital abnormalities of the kidney and urinary tract during the first five years of life; evaluation of the natural evolution of vesicoureteral reflux during the first five years of life and its correlation with the onset of urinary tract infections, renal scars or a worsening of renal function; evaluation of the hypothetical influence of an antibiotic therapy administered during the first months of life on Body Mass Index evaluated at the 2nd and 5th year of life.

Įvertinti: 1. simptominės ir febrilios ŠOI reikšmę inkstų pažeidimo atsiradimui ir progresavimui ir inkstų funkcijos dinamikai; 2. inkstų funkcijos vystymosi dinamiką 5 metų laikotarpyje vaikams, kuriems yra įgimtos inkstų ir šlapimo organų anomalijos; 3. VUR evoliuciją 5 metų laikotarpyje ir jo ryšį su ŠOI, inkstų randais ir inkstų funkcijos blogėjimu; 4. hipotetinę profilaktinės antibakterinės profilaktikos pirmais gyvenimo mėnesiais reikšmę KMI 2 ir 5 m. amžiaus vaikams.

E.5.2.1

Timepoint(s) of evaluation of this end point

60 months

60 mėnesių

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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

Sekimo grupė, negaunanti jokio profilaktinio antibakterinio gydymo

NO drug, normal clinical surveillance

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

France

Italy

Portugal

Czech Republic

Germany

Hungary

Lithuania

Poland

Serbia

Switzerland

Turkey

United Kingdom

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

Paskutinis paskutinio tiriamojo vizitas.

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

436

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:

436

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

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Infants, Consent should be obtained by parents/tutor

Kūdikiai, bus gautas tėvų/globėjų sutikimas

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

300

F.4.2.2

In the whole clinical trial

436

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)

According to the clinical conditions will be guaranteed clinical care, and
eventualy therapeutic, more appropriate.

Priklausomai nuo klinikinės situacijos bus užtikrinta visa reikiama paciento priežiūra.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	ESCAPE group
G.4.3.4	Network Country	Germany

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-04-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-02-10

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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