E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infants with febrile UTI at higher risk for renal scar development based on PCT values ≥ 1 ng/mL
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Bambini con IVU febbrile ad alto rischio di sviluppare cicatrici sulla base di livelli di PCT ≥ 1 ng/mL
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E.1.1.1 | Medical condition in easily understood language |
Infants with febrile Urinary tract infections at higher risk for renal scar development based on PCT values
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Bambini con infezione febbrile delle vie urinarie a più alto rischio di sviluppare esiti cicatriziali renali secondo i livelli di procalcitonina
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
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 |
To determine the usefulness of steroid therapy (adjunctive to standard antibiotic treatment) in reducing renal scar development in infants with first febrile UTI, at higher risk based on PCT values ≥ 1 ng/mL, measured at the time of initial evaluation
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Determinare l’utilità della terapia steroidea (aggiuntiva alla terapia antibiotica standard)nel ridurre lo sviluppo di cicatrici renali nei bambini con prima IVU febbrile, a più alto rischio sulla base di valori di PCT ≥ 1 ng/mL, misurata in occasione della valutazione iniziale
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E.2.2 | Secondary objectives of the trial |
To evaluate if the usefulness of adjunctive steroid therapy is greater in children with higher PCT values.
To evaluate the safety and acceptability of treatment.
To evaluate whether a metabolic profile exists predictive of scar development and/or associated with a positive response to Dexamethasone.
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Valutare se l’utilità della terapia steroidea aggiuntiva è maggiore nei bambini con valori elevati di PCT.
Valutare la sicurezza e l’accettabilità della terapia steroidea.
Individuare la presenza nelle urine di un profilo metabolico predittivo di sviluppo di scar renali e/o di risposta positiva alla terapia steroidea
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Infants and children aged 2 months to 2 years with a first episode of presumed UTI based on fever; positive urinalysis (two concordant consecutive test results), with white cell counts ≥25/uL, =+1 with dipstick and/or positive nitrites; and a PCT value >1 ng/mL measured at the time of first evaluation.
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Bambini di età 2 mesi-2 anni con un primo episodio di presunta IVU definita in base alla presenza di febbre, esame urine positivo (2 risultati concordanti su campioni consecutivi) ed una PCT≥1 ng/mL alla valutazione iniziale
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E.4 | Principal exclusion criteria |
Antibiotic therapy in the 48 hours prior to evaluation; known underlying renal disease or urinary tract abnormalities; history of previous UTI and UTI recurrence before DMSA scan performance at 6 months for detection of renal scars; prematurity (<36 weeeks); immunodeficiencies; contraindications for use of steroids
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Terapia antibiotica nelle 48 ore precedenti alla valutazione; patologie renali od anomalie del tratto urinario note; precedenti episodi di IVU o ricorrenza di IVU prima della scintigrafia renale statica programmata a 6 mesi dalla valutazione iniziale per l’identificazione degli esiti cicatriziali a distanza; storia di prematurità (<36 settimane); stati di immunodeficienza congenita o acquisita; malattie che a giudizio del medico costituiscono controindicazioni alla terapia steroidea.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the development of renal scars as identified by DMSA scan at 6 months after diagnosis of first febrile UTI.
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L’endpoint primario è lo sviluppo di cicatrici renali a distanza identificate tramite scintigrafia renale statica a 6 mesi dalla diagnosi di primo episodio di IVU febbrile
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Secondary endpoints include evaluation of adjunctive steroid therapy effectiveness in the subgroup of children with higher PCT values, in terms of renal scar development 2. Assessment of safety and acceptability of treatment, in terms of the rate of discontinuation of treatment and the incidence of side effects.
3.A further secondary endpoint will be the characterization of metabolic profiles associated with the development of renal scars and/or with the response to steroid therapy.
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1.L’endpoint secondario include la valutazione dell’efficacia della terapia steroidea aggiuntiva nel sottogruppo di pazienti con livelli più elevati di PCT, in termini di sviluppo di cicatrici renali
2.La valutazione della sicurezza e dell’accettabilità del trattamento steroideo in termini di percentuale di sospensione prematura della terapia ed incidenza di effetti collaterali.
3.Un ulteriore endpoint secondario sarà l’individuazione di un profilo metabolomico nelle urine predittivo dello sviluppo di scar e/o di risposta alla terapia steroidea.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 6 months
2. 1 week
3. 36 months |
1. 6 mesi
2. 1 settimana
3. 36 mesi |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 |
solo terapia antibiotica standard |
only standard antibiotic therapy |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 36 |
E.8.9.1 | In the Member State concerned days | |