Fosfomycin Trometamol Compared With an Alternative Active Antibiotic as Step-down Therapy for the Treatment of Acute Pyelonephritis Due to Escherichia Coli in Elderly Women : a Randomized, Multicenter, Non-inferiority Trial (FOSFOLD)
Fosfomycine trométamol comparé à un Autre Traitement Antibiotique Actif en Relais Pour le Traitement Des pyélonéphrites aiguës à Escherichia Coli Chez Les Femmes âgées : Essai randomisé, Multicentrique de Non infériorité
Acute pyelonephritis (APN) is among the most common bacterial infections in older women. Oral step-down antibiotic therapy may potentially be associated with toxicity, particularly with fluoroquinolones or trimethoprim-sulfamethoxazole, espcially in geriatric patients. The emergence of resistant strains reduces the choice of oral step-down treatment, thereby increasing the risk of nosocomial complications related to intravenous access and prolonged hospitalization.
Fosfomycin trometamol (FT) has broad activity against Enterobacterales, including resistant strains. It has an excellent safety profile and moderate ecological impact, and has been used for several years to treat cystitis. Recent studies have demonstrated its efficacy as an oral step-down therapy for the treatment of E.coli APN in younger women. Its efficacy in a geriatric population remains to be demonstrated.
The primary objective is to demonstrate the non-inferiority, in terms of clinical cure, of FT compared with an alternative active antibiotic as step-down therapy for E. coli APN in older women.
FOSFOLD is a national, multicenter, randomised, comparative, phase 3, non-inferiority trial (1:1), open-label with two parallel treatment groups. After 3 or 4 days of appropriate empirical antibiotic therapy, women aged 75 or over with E.coli APN will be randomised to receive either 3g of FT once daily or an alternative antibiotic treatment in accordance with current french guidelines, for a total of 10 days.
The primary endpoint is clinical cure at Day 17, i.e. 10 days after completion of antibiotic therapy.
If non-inferiority of FT is confirmed, it could provide a new therapeutic approach for oral step-down therapy in the older patients with APN. Its favorable tolerability profile could help prevent common geriatric complications, such as delirium, falls and malnutrition. Ultimately, it could help prevent some of the iatrogenic functional decline associated with hospitalisation.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Jérôme Lambert, MD PhD
- Número de teléfono: +33 +33 1 42 49 97 42
- Correo electrónico: jerome.lambert@u-paris.fr
Copia de seguridad de contactos de estudio
- Nombre: Clara Pouchelon, MD
- Número de teléfono: +33 +33 1 40 36 73 67
- Correo electrónico: clara.pouchelon@ght-gpne.fr
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Female.
- Age ≥ 75 years.
- Body temperature ≥ 38°C on at least once during the 72 hours preceding diagnosis.
- At least one new symptom among the following : urinary urgency, dysuria, increased urinary frequency, gross hematuria, burning on urination, spontaneous of provoked flank or suprapubic pain or urinary incontinence.
- Positive urine culture collected before initiation of antibiotic therapy defined as : ≥ 10,000 leukocytes/mL and monomicrobial culture with Escherichia coli ≥ 103 CFU/mL and susceptibility to FT,the empirical antibiotic,and at least one alternative antibiotic (active and not contraindicated), administered either orally (fluoroquinolone, amoxicillin, amoxicillin-clavulanic acid, or trimethoprim-sulfamethoxazole or, in the absence of an oral alternative, intravenously.
- Ability to reveive oral medication
- Favorable clinical course after 3 or 4 days of effective empirical antibiotic therapy, defined as resolution of fever (temperature < 38°C) and regression or reduction in the intensity and/or frequency of the clinical sign(s) present at the time of APN diagnosis, without the occurrence of any new symptoms.
Exclusion Criteria:
- Presence of an infectious focus other than the urinary tract.
- Severe infection and/or initial infectious complications, including septic shock, requirement for an emergency upper urinary tract intervention, or renal abscess.
- Indwelling urinary catheter, including bladder, ureteral, or nephrostomy catheters.
- Inability to take oral medication.
- Immunosuppression, including sold-organ transplant, ongoing immunosuppressive therapy, ongoing chemotherapy.
- Hypersensitivity to fosfomycin trometamol or to any of the excipients of the study medication
- End-stage chronic kidney disease with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2.
- Lack of health insurance coverage.
- Patient under legal protection or guardianship.
- Absence of written informed consent from the patient or, if the patient is unable to provide consent, absence of agreement from the designated trusted person or a close relative.
- Participation in another interventional clinical research protocole
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Fosfomycin-trometamol (FT)
|
One sachet (3g), once daily, orally for 6 or 7 days, following 4 or 3 days, respectivelly of effective antibiotic therapy, for a total of 10 days of effective antibiotic treatment. |
|
Comparador activo: Alternative antibiotic treatment
|
Treatment will be selected at the investigator's discretion, in accordance with the 2017 recommandations of the French Society for Infectious Diseases (SPILF) and the 2025 French National Authority for Health (HAS) guidelines. Therapy will be administrated for 6 or 7 days (Day 1 - Day 6/7), following 4 or 3 days, respectively of effective antibiotic therapy. The total duration of effective antibiotic therapy will be 10 days. Injection antibiotic therapy will be offered in the absence of an active oral antibiotic option. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Clinical resolution
Periodo de tiempo: Day 17
|
Clinical cure defined as :
|
Day 17
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Occurence of antibiotic-related adverse events
Periodo de tiempo: Up to 37 days
|
Occurrence, nature, and severity of antibiotic-related adverse events, assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scale. |
Up to 37 days
|
|
Occurence of geriatric complications
Periodo de tiempo: Up to 37 days
|
|
Up to 37 days
|
|
Functional autonomy
Periodo de tiempo: Up to 37 days
|
According to the Activities of Daily Living (ADL) scale: score ranges from 0 (complete dependence) to 6 (complete independence), with higher scores indicating greater independence in basic daily activities such as bathing, dressing, toileting, transferring and eating. |
Up to 37 days
|
|
Incidence of Infectious and urological complications
Periodo de tiempo: Up to day 7
|
|
Up to day 7
|
|
Cumulative incidence of recurrent febrile or non-febrile urinary tract infectious (UTIs) (relapse or reinfection)
Periodo de tiempo: From Day 17 to Day 37
|
|
From Day 17 to Day 37
|
|
Rate of hospitalization or rehospitalization following treatment for APN
Periodo de tiempo: Up to day 37
|
Up to day 37
|
|
|
Length of hospital stay following randomization
Periodo de tiempo: Up to day 37
|
Up to day 37
|
|
|
All-cause mortality
Periodo de tiempo: Up to day 37
|
Up to day 37
|
|
|
Rate of rectal colonization with antibiotic-resistant Enterobacterales
Periodo de tiempo: Up to day 37
|
fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and third-generation cephalosporins |
Up to day 37
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Infecciones
- Infecciones bacterianas y micosis
- Infecciones por bacterias gramnegativas
- Nefritis
- Infecciones por enterobacterias
- Nefritis Intersticial
- Pielitis
- Infecciones por Escherichia coli
- Infecciones bacterianas
- Pielonefritis
- Químicos orgánicos
- Compuestos organofosforados
- Organofosfosados
- Fosfomicina
Otros números de identificación del estudio
- APHP240802
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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