Evaluation of Fosfomycin Trometamol, Cefixime, and Ciprofloxacin Hydrochloride in Acute Bacterial Prostatitis: A Randomized, Open-Label, Multicenter Trial

The primary objective of this study is to evaluate the **clinical cure** of acute bacterial prostatitis, defined as the resolution of urinary symptoms, 6-10 days post end-of-treatment. Clinical cure is characterized by a patient being alive with a reduction of all initial local and systemic febrile urinary tract infection-related symptoms. Obstructive urinary symptoms may persist if deemed unrelated to the infection by the investigator. This objective is clinically relevant as it directly assesses the effectiveness of the treatment in alleviating the primary symptoms associated with acute bacterial prostatitis, thereby providing critical insights into the therapeutic efficacy of the tested antimicrobials.

Secondary objectives include:

• Evaluating the clinical cure (resolution of urinary symptoms) 24-36 days post end-of-treatment.
• Assessing the microbiological cure at 6-10 days and 24-36 days post end-of-treatment.
• Evaluating combined clinical and microbiological cure at 6-10 days and 24-36 days post end-of-treatment.
• Assessing relapse within 24-36 days and 80-100 days post end-of-treatment.
• Evaluating reinfection within 24-36 days and 80-100 days post end-of-treatment.
• Assessing adverse events possibly or probably related to the study protocol until 30 days post end-of-treatment.
• Evaluating acquired resistance at 24-36 days post end-of-treatment.
• Comparing the impact of different antimicrobials on rectal colonization by multidrug-resistant microorganisms at baseline, 6-10 days, and 24-36 days post end-of-treatment.

The clinical trial focuses on evaluating the clinical cure of **acute bacterial prostatitis** in a specific study population. The trial exclusively involves male participants, aged 18 years and older, who have been diagnosed with acute bacterial prostatitis. The study population is characterized by the acute presentation of voiding symptoms, a temperature of at least 37.8°C, and the presence of bacteriuria or leukocyturia in a clean-catch midstream urine specimen without prostate massage. Participants must have received appropriate empirical intravenous antibiotics for a specified duration and have an isolation of enterobacterales microorganism in urine or blood culture sensitive to certain antibiotics. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. Participants are expected to be able to understand and comply with protocol requirements and are considered appropriate candidates for participation in a clinical trial with oral medication. The selection process ensures that participants are likely to complete the study as planned and are free from exclusion criteria.

The clinical trial is designed to evaluate the **clinical efficacy** of oral **Fosfomycin Trometamol** and **Cefixime** in the treatment of **acute bacterial prostatitis**. This is a comparative, randomized, open, multicenter trial. The primary objective is to assess the clinical cure, defined as the resolution of urinary symptoms, 6-10 days post end-of-treatment. The trial is categorized as a Phase IV, low-intervention study, meeting the criteria outlined in RD 1090/2015.

The trial will involve male participants aged 18 years or older who have been diagnosed with acute bacterial prostatitis. Participants must have an acute presentation of voiding symptoms, a temperature of at least 37.8°C, and bacteriuria or leukocyturia in a clean-catch midstream urine specimen. They must have received appropriate empirical intravenous antibiotics for 24 to 96 hours and have an isolation of enterobacterales microorganism in urine or blood culture sensitive to at least two of the following drugs: **ciprofloxacin**, **fosfomycin**, or **cefixime**. Participants must be able to comply with protocol requirements and be likely to complete the study as planned.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria. Participants will then be randomized to receive either Fosfomycin or Cefixime for a maximum treatment period of 20 days. The study will include follow-up visits to monitor the resolution of symptoms and any adverse effects. The end-of-study visit will occur 6-10 days after the completion of treatment to assess the primary endpoint of clinical cure. The expected duration of participant involvement is approximately 30 days, including the treatment and follow-up periods.

Participants may be terminated early from the study if they experience significant adverse effects, require additional systemic antibiotic therapy for urinary tract infection, or fail to comply with the study protocol. The trial is expected to start recruitment on June 28, 2024, and conclude by June 28, 2027. The study will adhere to ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Fosfomycin**, an antimicrobial agent provided in the form of granules for oral solution. The active substance, fosfomycin, is of chemical origin. Participants will receive a maximum daily dose of 1.5 grams, with a total maximum dose of 30 grams over a treatment period not exceeding 20 days. The route of administration is oral, and the medication is not formulated for pediatric use. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

**Cefixime** is another experimental medication used in this study, presented as a hard capsule. The active substance, cefixime, is also chemically derived. The maximum daily dose for participants is set at 800 milligrams, with a cumulative maximum dose of 16,000 milligrams over a 20-day treatment period. The administration route is oral, and the formulation is not intended for pediatric patients. Participant compliance will be closely monitored to maintain the integrity of the dosing schedule.

The trial also includes **Ciprofloxacin Hydrochloride**, provided in tablet form. This antimicrobial agent contains the active substance ciprofloxacin hydrochloride, which is of chemical origin. Participants will receive a maximum daily dose of 1,500 milligrams, with a total maximum dose of 30,000 milligrams over a 20-day treatment period. The medication is administered orally and is not designed for pediatric use. Adherence to the dosing regimen will be tracked to ensure participant compliance.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this trial. The focus remains on evaluating the clinical efficacy of the experimental medications in treating acute bacterial prostatitis. The trial's objective is to assess the clinical cure, defined as the resolution of urinary symptoms, within 6-10 days post end-of-treatment.

The efficacy of the clinical trial titled "Clinical Efficacy of oral Fosfomycin Trometamol and Cefixime in the Treatment of Acute Bacterial Prostatitis (CEFOSPROST)" will be assessed primarily through the evaluation of **clinical cure**. This is defined as the resolution of urinary symptoms 6-10 days post end-of-treatment. Clinical cure is characterized by the patient being alive with a reduction of all initial local and systemic febrile urinary tract infection (UTI) related symptoms, without the need for additional systemic antibiotic therapy for UTI, except for antibiotic prophylaxis. Obstructive urinary symptoms may persist if deemed unrelated to the infection by the investigator.