E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute bacterial prostatitis due to multi-drug resistant Escherichia coli |
Prostatitis aguda bacteriana por Escherichia coli multirresistente |
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E.1.1.1 | Medical condition in easily understood language |
Acute prostatitis |
Prostatitis aguda |
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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 assess clinical and microbiological cure in patients with acute bacterial prostatitis due to multi-drug resistant Escherichia coli treated with oral fosfomycin-trometamol |
Determinar la eficacia del tratamiento secuencial con fosfomicina-trometamol (FT) por vía oral de las prostatitis agudas por E. coli multiresistente (MR) con sensibilidad in vitro a la fosfomicina en pacientes con estabilidad clínica y que hayan recibido entre 2 y 5 días de antibioterapia previa con un antimicrobiano con actividad in vitro. |
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E.2.2 | Secondary objectives of the trial |
- Assessment of use of carbapenems. - Assessment of length of stay. - Pharmacokinetic study. |
- Determinar, comparando con una cohorte histórica, el uso de carbapenémicos en DDD por episodio de ITU.
- Determinar, comparando con una cohorte histórica, la duración del ingreso hospitalario o ingreso en régimen de hospitalización a domicilio.
- Estudiar la farmacocinética de la FT por vía oral a través de la determinación de niveles en sangre. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male adult patients (18 years of age or older) with acute prostatitis due to multi-drug resistant (MDR) Escherichia coli susceptible to fosfomycin.
Diagnosis of prostatitis requires prostatic-specific antigen (PSA) elevation> 4 μg/L and the presence of at least one microbiological criterion and two clinical criteria among the following:
Microbiological criteria (at least 1):
Urine culture with >100,000 cfu/mL of MDR E. coli with MIC to fosfomycin <=32 mg/L. Positive blood culture by MDR E. coli with MIC to fosfomycin <32 mg/L, with clinical data of sepsis without another evident or probable origin of bacteremia more than the urinary and presence of pyuria (≥10 leukocytes / mm3 or positive leukocyte esterase in urine strip). Clinical criteria (at least 2):
Presence of any symptoms of the lower urinary tract:
Irritative symptoms: urgency, urinary frequency, dysuria or tenesmus. Obstructive symptoms: difficulty in voiding onset, decreased calibre, post-void residue or acute urinary retention) Spontaneous perineal pain or during urination.
Pain referred to the suprapubic, perineal, lumbosacral, scrotal, penile or inner thigh areas. Enlarged, increased temperature and painful prostate on the digital rectal examination. History of prostatic disease (prostate neoplasm, benign prostatic hypertrophy) and:
History of recent manipulation of the urinary tract. Recent history (<7 days) of transrectal prostate biopsy. Decrease in the level of consciousness in elderly patients (> 70 years) with no other apparent cause. |
Varones adultos (18 años o más) con prostatitis aguda bacteriana, febril, por E. coli mutlirresistente sensible a fosfomicina (ver definiciones más adelante). El diagnóstico de prostatitis requiere la elevación del PSA > 4 μg/L y la presencia de al menos un criterio microbiológico y dos criterios clínicos entre los siguientes:
Criterios microbiológicos (al menos 1): (1) Urinocultivo con más de 100.000 ufc/mL de E. coli multirresistente con CMI a la fosfomicina < =32 mg/L. (2) Hemocultivo positivo por E. coli multirresistente con CMI a la fosfomicina < 32 mg/L, con datos clínicos de sepsis sin otro origen evidente o probable de la bacteriemia más que el urinario y presencia de piuria (≥10 leucocitos/mm3 o esterasa leucocitaria positiva en tira de orina). Criterios clínicos (al menos 2): 1. Presencia de algún síntoma del tracto urinario inferior: - Síntomas irritativos: urgencia miccional, polaquiuria, disuria o tenesmo. - Síntomas obstructivos: dificultad de inicio miccional, calibre disminuido, residuo postmiccional o retención aguda de orina) 2. Dolor perineal espontáneo o a la micción. - Dolor referido a área suprapúbica, perineal, lumbosacra, escrotal, peneana o cara interna de muslos. - Tacto rectal con próstata agrandada, aumentada de Tª y dolorosa. 3. Antecedentes de enfermedad prostática (neoplasia de próstata, hipertrofia benigna de próstata) y: - Historia de manipulación reciente de la vía urinaria. - Antecedente reciente (<7 días) de biopsia prostática transrectal. - Disminución del nivel de consciencia en pacientes ancianos (> 70 años) sin otra causa aparente. |
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E.4 | Principal exclusion criteria |
- Allergy or known intolerance to fosfomycin. - Polymicrobial bacteria or urine culture. - Clinical criteria of acute pyelonephritis (fist-positive renal percussion, obstruction of the urinary tract, abscess renal). - Anatomical alterations of the urinary tract. - Urinary infections associated with urinary catheters. - Undrained prostatic abscess. - Another concomitant infection. - Patients who have not reached clinical stability after 5 days of parenteral treatment. - Patients with septic shock at the time of randomization. - Polycystic kidney disease. - History of chronic prostatitis. - Immunosuppressed patients (kidney transplant, liver cirrhosis, patients on renal replacement therapy, chronic treatment with corticosteroids, which receive active chemotherapy, use of anti-TNF) - Terminal situation or estimated life expectancy of less than 90 days or in purely palliative treatment of their base disease. - Patients who are participating in another clinical trial with active treatment. - MIC to fosfomycin superior to that established by the inclusion criteria of the study. - Patients who refuse to give consent to participate in the study. |
- Alergia o intolerancia conocida a la fosfomicina. - Bacteriemia o urocultivo polimicrobianos - Criterios clínicos de pielonefritis aguda (puño-percusión renal positiva, obstrucción de la vía urinaria, absceso renal). - Alteraciones anatómicas de las vías urinarias - Infecciones urinarias asociadas a catéteres urinarios. - Absceso prostático no drenado. - Otra infección concomitante. - Pacientes que no hayan alcanzado la estabilidad clínica después de 5 días de tratamiento parenteral. - Pacientes con shock séptico en el momento de la aleatorización. - Poliquistosis renal. - Historia de prostatitis crónica. - Pacientes inmunodeprimidos (trasplantados renales, cirrosis hepática, pacientes en terapia de sustitución renal, tratamiento crónico con corticoides, que reciben quimioterapia activa, uso de antiTNF) - Situación terminal o esperanza de vida estimada inferior a 90 días o en tratamiento puramente paliativo de su enfermedad de base. - Pacientes que estén participando en otro ensayo clínico con tratamiento activo. - CMI a fosfomicina superior a la establecida por los criterios de inclusión del estudio. - Pacientes que rechacen dar el consentimiento para participar en el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Clinical cure will be assess by a clinical team as the resolution of all symptoms of prostatitis that were present at the time of diagnosis (fever, symptoms of the lower urinary tract (irritative sypmtoms: urgency, urinary frequency...) and perineal pain (spontaneous or during urination).
- Microbiological cure requires negative urine culture at days 5-7 after the EOT. |
- Curación clínica: resolución de todos los síntomas del paciente presentes en el momento del diagnóstico. Además, el paciente no debe presentar ninguno de los siguientes: fiebre, síntomas urinarios (disuria, polaquiuria, urgencia miccional) o dolor suprapúbico.
- Curación microbiológica: Se definirá como la obtención de un urinocultivo negativo a los 7 días (+/- 3 días) de finalización del tratamiento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Clinical cure: at the end of therapy (21 +/- 5 days).
- Microbiological cure: 7 days (+/- 3 days) after EoT. |
- Curación clínica: al final de tratamiento (FdT) 21 +/-5 días.
- Curación microbiológica: 7 días +/- 3 días de final de tratamiento. |
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E.5.2 | Secondary end point(s) |
- Carbapenemic DDD per 100 stays in the experimental group versus the control group.
- Length of hospital stay (days) in the experimental group versus the control group.
- Fosfomycin pharmacokinetic parameters ([Cmax], [Cmin], AUC, clearance, volume of distribution). |
- DDD de carbapenémicos por 100 estancias en el grupo experimental frente al grupo control.
- Duración de la estancia hospitalaria (días) en el grupo experimental frente al grupo control.
- Parámetros farmacocinéticos de fosfomicina ([Cmax], [Cmin], ABC, aclaramiento, volumen de distribución). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 6 months after the end of recruitment period. |
- 6 meses después de finalizar el reclutamiento. |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Grupo control: cohorte histórica retrospectiva |
Control group will be a retrospective historic cohort |
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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 | 4 |
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 | 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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LVLS (46-56 days after EoT of last patient recruited) |
Última visita del último paciente reclutado (46-56 días de FdT). |
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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 | |
E.8.9.1 | In the Member State concerned days | |