E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
evaluation of the effectiveness of antimicrobial prophylaxis in infants with vesico-ureteral reflux grade III-V, started before the first symptomatic infection |
Valutazione dell’efficacia della profilassi antibiotica iniziata in lattanti con reflusso vescico-ureterale di III-V, iniziata prima dell’insorgenza della prima infezione urinaria sintomatica |
|
E.1.1.1 | Medical condition in easily understood language |
evaluation of the effectiveness of antimicrobial prophylaxis in infants with vesico-ureteral reflux grade III-V, started before the first symptomatic infection |
Valutazione dell’efficacia della profilassi antibiotica iniziata in lattanti con reflusso vescico-ureterale di III-V, iniziata prima dell’insorgenza della prima infezione urinaria sintomatica |
|
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 | 16.0 |
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 | No |
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 III-V, started before the first symptomatic infection. |
Valutazione dell’efficacia della profilassi antibiotica iniziata in lattanti con reflusso vescico-ureterale di III-V, iniziata prima dell’insorgenza della prima infezione urinaria sintomatica. |
|
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.
|
1. Valutazione del ruolo delle infezioni sintomatiche e febbrili delle vie urinarie nell’insorgenza e nella progressione del danno renale e nell’evoluzione della funzione renale.
2. Valutazione della storia naturale della funzione renale in pazienti pediatrici con anomalie congenite del rene o delle vie urinarie nei primi 5 anni di vita.
3. Valutazione dell’evoluzione naturale del reflusso vescico-ureterale durante i primi 5 anni di vita e della sua correlazione con l’insorgenza di Infezioni delle vie Urinarie, cicatrici renali o peggioramento della funzione renale.
4. Valutazione dell’ipotetica influenza di una terapia antibiotica somministrata nei primi mesi di vita sul Body Mass Index (BMI) valutato al 2° e al 5° anno di vita
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Age between 1 and 4 months b. Gestational age > 35 weeks c. Glomerular filtration rate (calculated according to Schwartz) > 15 ml/min/1.73 m2 at three months of age d. No previous symptomatic UTI e. Imaging Diagnostic work-up completed and presence of grade III to V vesico-ureteral reflux f. Informed consent of parents
|
a. Età compresa tra 1 e 4 mesi all’arruolamento. b. Eta gestazionale > 35 settimane. c. Filtrato glomerulare (GFR) calcolato secondo la formula di Schwartz > 15 ml/min/1.73 m2 a 3 mesi di età. d. Non precedenti Infezioni delle vie Urinarie Sintomatiche. e. Completamento del work-up radiologico di screening e presenza di reflusso vescico-ureterale di 3°-5° grado. f. Consenso informato firmato dai genitori. |
|
E.4 | Principal exclusion criteria |
a. Age <1 and >4 months b. Gestational age < 35 weeks c. Glomerular filtration rate (calculated according to Schwartz) < 15 ml/min/1.73 m2 at three months of age d. Patients with neurogenic bladder, myelomeningocele, uretero-pelvic junction and/or uretero-vescico junction obstruction, or other malformations leading to potential voiding disturbances, apart from urethral valves e. Patients with no or low grade reflux (grade I and II). f. Hypersensitivity to the all the utilized antimicrobial agent g. Children with serious clinical conditions which, according to the investigator, prevent them from being included in the study cohort. h. Use of experimental drugs in the month previous to the beginning of the study i. Children unable to follow the established protocol procedures or whose parents are unable to sign the informed consent.
|
a. Età <1 o >4 mesi. b. Età gestazionale < 35 weeks. c. Filtrato glomerulare (GFR) calcolato secondo la formula di Schwartz < 15 ml/min/1.73 m2 a 3 mesi di età. d. Pazienti con vescica neurologica, mielomeningocele, stenosi del giunto pielo-ureterale, ostruzione della giunzione uretero-vescicale, o altre malformazioni potenzialmente correlate all’insorgenza di disturbi minzionali, eccetto le valvole dell’uretra. e. Pazienti senza reflusso vescico-ureterale o con reflusso vescico-ureterale di 1°-2° grado. f. Ipersensibilità a tutti i principi attivi previsti dal protocollo g. Bambini in condizioni cliniche severe che, a parere dello sperimentatore, non permettano l’arruolamento nella coorte dello studio. h. L’uso di farmaci nel mese precedente l’arruolamento nello studio. i. Bambini non in grado di seguire le procedure stabilite dal protocollo o bambini con genitori incapaci di firmare il consenso informato.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
symptomatic urinary tract infection rate during the 24-month observation period.
|
tasso di infezioni sintomatiche delle vie urinarie durante i 24 mesi di trattamento/osservazione. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
number of febrile UTIs and of new renal scars (DMSA scan) at the 2 and 5 years follow-up in relation to the development of renal function (creatinine and Cystatin C plasma values, eGFR), hypertension (blood pressure >95th%ile per age, sex and height) and/or proteinuria (protein/creatinine), anatomical growth (renal length) of the kidneys at 2 and 5 years follow-up, evaluation of the natural course of renal function for hypo-dysplastic kidneys during the first 5 years of life |
Gli END POINT SECONDARI sono le infezioni urinarie febbrili, il numero di cicatrici renali alla scintigrafia con DMSA di controllo dopo 2 anni; l’evoluzione della funzionalità renale, l’ipertensione arteriosa e/o la proteinuria, la valutazione della storia naturale della funzione renale per i reni ipo-displasici durante i primi 5 anni di vita e la valutazione del Body Mass Index (BMI) a 2 e a 5 anni di età |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
nessun farmaco, solo sorveglianza clinica |
NO drug, normal clinical surveillance |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 | No |
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 |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Lithuania |
Poland |
Portugal |
Serbia |
Switzerland |
Turkey |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |