E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
urinary tract infections |
infezioni delle vie urinarie |
|
E.1.1.1 | Medical condition in easily understood language |
urinary tract infections |
infezioni delle vie urinarie |
|
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 | 10046849 |
E.1.2 | Term | UTI symptoms |
E.1.2 | System Organ Class | 100000004862 |
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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 investigate the non-inferiority of IV fosfomycin compared to the best available therapy according to current clinical practice/choice |
Indagare la non inferiorità della fosfomicina IV rispetto alla migliore terapia disponibile secondo la pratica/scelta clinica corrente. |
|
E.2.2 | Secondary objectives of the trial |
i) to describe the MIC distribution of isolates against all the study drugs by gold standard methods (i.e. agar dilution for fosfomycin and broth microdilution for alternative drugs) and investigate their correlation with clinical outcome; ii) to describe the main mechanisms of cephalosporin resistance in the isolates obtained from the blood cultures of patients with bacteremic cUTI by whole genome sequencing (WGS) and analyze their correlation with clinical outcome iii) to investigate the impact of PK/PD target attainment with clinical outcome; iv) to evaluate changes in the gut microbiota in patients with cUTIs and to compare the impact of each type of antibiotic therapy on the gut microbiota. Fecal microbial DNA will be extracted and subsequently analyzed by sequencing of the V3-V4 regions of the 16S ribosomal RNA gene. |
i) descrivere la distribuzione della MIC degli isolati rispetto a tutti i farmaci in studio secondo il gold standard e indagare la loro correlazione con l’esito clinico; ii) descrivere i principali meccanismi di resistenza alle cefalosporine negli isolati ottenuti dalle emocolture di pazienti con infezione delle vie urinarie complicate (cUTI) batteriemiche mediante sequenziamento dell'intero genoma e analizzare la loro correlazione con l’esito clinico; iii) indagare l'impatto del raggiungimento dell'obiettivo farmacocinetico/farmacodinamico con l'esito clinico; iv) valutare i cambiamenti del microbiota intestinale nei pazienti con cUTIs e confrontare l'impatto di ciascun tipo di terapia antibiotica sul microbiota stesso. Il DNA microbico fecale sarà estratto e successivamente analizzato mediante sequenziamento delle regioni V3-V4 del gene dell'RNA ribosomiale 16S. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
cUTI, in adult patients, defined as the presence of signs or symptoms, pyuria, and growth of cephalosporin-non-susceptible, fosfomycin susceptible Enterobacterales in urine (a positive urine culture of 105 colony-forming units (CFU)/ml). |
cUTI, in pazienti adulti, definita come la presenza di segni o sintomi, piuria e crescita di cefalosporine non sensibili, Enterobacterales sensibili alla fosfomicina nelle urine (un'urinocoltura positiva di 105 unità formanti colonia (CFU)/ml). |
|
E.4 | Principal exclusion criteria |
- Hemodynamical instability in the last 24 hours - Alternative source of infection explaining the fever according to physician’s judgement - Prostatitis, orchitis, or epididymitis - Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy prior to EOT) - pregnancy and/or breastfeeding |
- Instabilità emodinamica nelle ultime 24 ore - Fonte alternativa di infezione che spieghi la febbre secondo il giudizio del medico - Prostatite, orchite o epididimite - Chirurgia del tratto urinario nei 7 giorni precedenti alla randomizzazione o intervento chirurgico del tratto urinario pianificato - gravidanza e/o allattamento |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Response (CR) defined as clinical and microbiological cure (CMC) at 5 to 7 days after finalization of treatment (test of cure, TOC) |
Risposta clinica (CR) definita come cura clinica e microbiologica (CMC) da 5 a 7 giorni dopo la conclusione del trattamento (test di cura, TOC) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
5 to 7 days after finalization of treatment |
da 5 a 7 giorni dopo il termine del trattamento |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Information not present in EudraCT |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |