Evaluation of Fosfomycin Trometamol Efficacy in Treating Male Urinary Tract Infections in Primary Care: A Pragmatic Clinical Trial

The primary objective of this study is the evaluation of the **efficacy** of sequential treatment with **Fosfomycin Trometamol** for 14 days in the management of **male urinary tract infections**. This is clinically relevant as it aims to determine the effectiveness of this treatment regimen in a primary care setting, potentially offering a targeted therapeutic option for this patient population.

Secondary objectives include:

• Nosological description (clinical and biological) of non-febrile male urinary infections (MUIs) managed in primary care.
• Assessment of the clinical cure rate 10 to 12 weeks after inclusion, which corresponds to 8 to 10 weeks post-treatment.
• Evaluation of the microbiological cure rate, determined by urine cytobacteriological examination, at 14 to 21 days and 10 to 12 weeks after inclusion.
• Creation of a strain collection of uropathogens responsible for urinary tract infections (UTIs).

The clinical trial focuses on evaluating the efficacy of sequential treatment with **Fosfomycin Trometamol** for 14 days in male patients with **Male Urinary Tract Infection**. The study population consists exclusively of men aged 18 and over, who are consultant patients in a general practice setting. Participants are suspected of having a urinary tract infection by their investigating physician and must present at least one recent acute sign, such as urinary burning, urgency, pollakiuria, dysuria, haematuria, or pelvic pain independent of micturition. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. Participants are required to have read and understood the information letter and signed the consent form, and they must be members of a social security scheme or beneficiaries of such a scheme. The selection criteria ensure that participants are capable of understanding the conditions required for participation in the protocol and are able to give informed consent.

The clinical trial is designed to evaluate the efficacy of **fosfomycin trometamol** in treating male urinary tract infections. This study is a randomized, double-blind, controlled trial with a low-intervention classification. The trial will span approximately three years, with an estimated end date of June 1, 2027. Participants will be involved for a maximum of 14 days, corresponding to the treatment period with the investigational product, FOSFOMYCINE ARROW 3 g, administered as an oral solution. The trial will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as being male, aged 18 or over, and presenting with acute urinary symptoms.

Following the screening, eligible participants will be randomized to receive the study medication. The primary endpoint is the absence of clinical treatment failure up to 14 days post-treatment, defined by criteria such as the need for alternative antibiotic therapy or hospitalization. Secondary endpoints include the improvement of urinary symptoms and negative urine cultures at specified intervals post-treatment. Study visits will include follow-up assessments at 2-5 days, 28-35 days, and 3 months after treatment initiation, with additional evaluations 10 to 12 weeks post-treatment to monitor symptom regression and adverse events.

Participants may be withdrawn from the study if they experience significant adverse events, require alternative treatments, or fail to adhere to the study protocol. The trial's design ensures rigorous monitoring and data collection to assess the therapeutic potential of fosfomycin trometamol in this patient population. The study's findings will contribute to understanding the feasibility of sequential antibiotic therapy in primary care settings for male urinary tract infections.

The clinical trial involves the administration of **Fosfomycin Trometamol**, marketed under the name **FOSFOMYCINE ARROW 3 g**, which is formulated as granules for oral solution in sachets. This experimental medication is classified as an antibiotic and is intended for the treatment of male urinary tract infections. The pharmaceutical form is an oral solution, and the active substance is of chemical origin. The maximum daily dose is 1.5 grams, with a total maximum dose of 21 grams over the course of the treatment. The treatment period is set for a maximum of 14 days, with the medication administered orally. The dosing schedule requires careful adherence to ensure efficacy, and participant compliance will be monitored throughout the trial.

The efficacy of the treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is defined as the absence of clinical treatment failure up to 14 days after the end of antibiotic treatment with **Fosfomycin Trometamol**. Clinical treatment failure is determined based on specific criteria, including a change of antibiotic treatment to a reference treatment for urinary tract infection, hospitalization for urinary tract infection, acute retention of urine, a new consultation for worsening or persistence of symptoms, or the onset of fever greater than 38°C.

Secondary endpoints include the improvement in functional urinary symptomatology at various timepoints: 2-5 days, 28-35 days, and 3 months after the start of treatment. Additionally, the trial will assess the presence of a negative ECBU (urine culture) 10 to 12 weeks after the end of treatment, and another negative ECBU taken 14 to 21 days after the end of antibiotic treatment, defined by specific leukocyturia and bacteriuria levels. The regression of urinary signs 10 to 12 weeks after the end of treatment will also be evaluated. Adverse events reported by the patient and recorded by the investigating physician during antibiotic treatment and in the 14 days following the end of treatment will be monitored as part of the efficacy assessment.