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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)

5. november 2026 oppdatert av: Assistance Publique - Hôpitaux de Paris

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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

312

Fase

  • Fase 3

Kontakter og plasseringer

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Studiekontakt

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Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

75 år og eldre (Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Hunn

Beskrivelse

Inclusion Criteria:

  1. Female.
  2. Age ≥ 75 years.
  3. Body temperature ≥ 38°C on at least once during the 72 hours preceding diagnosis.
  4. 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.
  5. 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.
  6. Ability to reveive oral medication
  7. 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:

  1. Presence of an infectious focus other than the urinary tract.
  2. Severe infection and/or initial infectious complications, including septic shock, requirement for an emergency upper urinary tract intervention, or renal abscess.
  3. Indwelling urinary catheter, including bladder, ureteral, or nephrostomy catheters.
  4. Inability to take oral medication.
  5. Immunosuppression, including sold-organ transplant, ongoing immunosuppressive therapy, ongoing chemotherapy.
  6. Hypersensitivity to fosfomycin trometamol or to any of the excipients of the study medication
  7. End-stage chronic kidney disease with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2.
  8. Lack of health insurance coverage.
  9. Patient under legal protection or guardianship.
  10. 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.
  11. Participation in another interventional clinical research protocole

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Fosfomycin-trometamol (FT)
Legemiddel: 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.
Aktiv komparator: Alternative antibiotic treatment
Legemiddel: 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.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Clinical resolution
Tidsramme: Day 17

Clinical cure defined as :

  • Body temperature < 38 °C and resolution of all urinary symptoms present at the time of the APN diagnosis, with no occurrence of new clinical signs (urinary urgency, dysuria, increased urinary frequency, gross hematuria, painful/burningurination, flank pain [spontaneous or provoked], suprapubic pain, or urinary incontinence) between treatment discontinuation and assessment of the primary endpoint at Day 17, except for a temperature ≥ 38°C unrelated to a urinary tract condition
  • No resumption of antibiotic therapy active against the causative pathogen responsible for the APN following completion of the antibiotic treatment course
Day 17

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Occurence of antibiotic-related adverse events
Tidsramme: 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
Tidsramme: Up to 37 days
  • Occurrence of delirium, defined according the Confusion Assessment Method (CAM)
  • Fall(s) (one or more episodes)
  • Weight loss, assessed as the percentage change between admission body weight and discharge body weight or Day 17 weight if the patient remains hospitalized
  • Occurrence of pressure ulcers, staged according to the National Pressure Ulcer Advisory Panel (NPUAP) pressure ulcer staging classification (HAS Guidelines, Prevention and Treatment of Pressure Ulcers in Adults and Older Persons, 2001)
Up to 37 days
Functional autonomy
Tidsramme: 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
Tidsramme: Up to day 7
  • Renal abscess (yes/no)
  • Need for urinary drainage
  • Transfer to an continuous care unit or intensive care unit due to the infection At the end of antibiotic treatment (Day 7)
Up to day 7
Cumulative incidence of recurrent febrile or non-febrile urinary tract infectious (UTIs) (relapse or reinfection)
Tidsramme: From Day 17 to Day 37
  • Cystitis : recurrence of urinary symptoms in the absence of fever, associated with a positive urine culture.
  • Acute pyelonephritis :; recurrence of urinary symptoms with fever and a positive urine culture.
  • Reinfection : new infection caused by a microorganism different from that isolated during the initial episode.
  • Relapse : recurrence of infection due to the same microorganism as that isolated during the initial episode.
From Day 17 to Day 37
Rate of hospitalization or rehospitalization following treatment for APN
Tidsramme: Up to day 37
Up to day 37
Length of hospital stay following randomization
Tidsramme: Up to day 37
Up to day 37
All-cause mortality
Tidsramme: Up to day 37
Up to day 37
Rate of rectal colonization with antibiotic-resistant Enterobacterales
Tidsramme: Up to day 37

fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and third-generation cephalosporins
Up to day 37

Samarbeidspartnere og etterforskere

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Sponsor

Assistance Publique - Hôpitaux de Paris

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. desember 2026

Primær fullføring (Antatt)

17. januar 2030

Studiet fullført (Antatt)

15. februar 2030

Datoer for studieregistrering

Først innsendt

29. oktober 2026

Først innsendt som oppfylte QC-kriteriene

5. november 2026

Først lagt ut (Faktiske)

10. november 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

10. november 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

5. november 2026

Sist bekreftet

1. oktober 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • APHP240802

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