Evaluation of Targeted Antibiotic Prophylaxis Versus Empiric Prophylaxis in Reducing Infection-Related Readmissions Post-Cystectomy: A Multicenter Randomized Trial

The primary objective of the study is to evaluate the efficacy of **targeted antibiotic prophylaxis** in reducing infection-related readmissions following cystectomy, compared to the current empiric prophylaxis regimen administered at ureteral stent removal. This is clinically relevant as it aims to address the high incidence of bacterial infections post-cystectomy, which can lead to significant morbidity and healthcare resource utilization. The study seeks to determine if a more individualized approach to antibiotic prophylaxis can improve patient outcomes by minimizing the risk of infection-related complications and subsequent hospital readmissions.

The clinical trial focuses on individuals undergoing cystectomy, with a primary aim to assess the efficacy of targeted antibiotic prophylaxis in reducing infection-related readmissions. The study population includes **adults aged 18 years and older**, encompassing both male and female participants. Participants are selected based on their ability to understand and sign informed consent, and they must have a malignant or benign indication for undergoing cystectomy with a planned ileal conduit as urinary diversion. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial is designed to address **bacterial infections** associated with the surgical procedure.

The clinical trial is designed to evaluate the efficacy of targeted **antibiotic prophylaxis** in reducing infection-related readmissions following cystectomy, compared to the current empiric prophylaxis regimen administered at ureteral stent removal. This is a multicenter, randomized, double-blind, controlled trial. The trial is categorized as a phase IV study and is considered low intervention. The estimated duration of the trial is from December 2024 to March 2027, with the primary endpoint being the 90-day infection-related hospital readmission rate. Secondary endpoints include the timing of ureteral stent removal, type of antimicrobial prophylaxis, all-cause readmissions within 30 and 90 days, postoperative complications, days alive and out of hospital, quality of life assessments, and microbiological findings.

Participants will be involved in the study for a maximum of 90 days post-surgery. The sequence of study visits includes an initial inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), ability to provide informed consent, and planned ileal conduit as urinary diversion. Follow-up visits will be scheduled to monitor the timing and type of antimicrobial prophylaxis, assess postoperative complications, and collect quality of life data. The end-of-study visit will occur at 90 days post-surgery to evaluate the primary and secondary endpoints. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety.

The trial will utilize a variety of oral pharmaceutical forms, including film-coated tablets and capsules, with active substances such as **pivmecillinam hydrochloride**, **trimethoprim**, **fluconazole**, **amoxicillin**, **ciprofloxacin**, **sulfamethoxazole**, **clavulanic acid**, **cefuroxime axetil**, **nitrofurantoin**, and **linezolid**. The maximum treatment period for each participant is one day, with specific dosing regimens tailored to the individual needs of the study protocol. The trial aims to provide robust data on the effectiveness of targeted antibiotic prophylaxis in reducing infection-related complications following cystectomy.

The clinical trial involves the administration of several **experimental medications** to evaluate their efficacy in reducing infection-related readmissions following cystectomy. The first medication is **Pivmecillinam hydrochloride**, provided as 400 mg film-coated tablets. This medication is administered orally with a maximum daily dose of 1200 mg, and the treatment period is limited to one day. The pharmaceutical form is a film-coated tablet, and the medication is manufactured by Karo Pharma AB.

Another medication used in the trial is **Trimethoprim**, available as film-coated tablets under the brand name Trimopan. The dosage is set at a maximum of 400 mg per day, administered orally, with a treatment period of one day. The manufacturer of this medication is Orion Corporation.

**Fluconazole** is also included in the trial, provided in the form of 200 mg hard capsules. The maximum daily dose is 800 mg, administered orally, with a treatment period of one day. This medication is produced by Crescent Pharma Limited.

**Amoxicillin** is administered as 500 mg film-coated tablets, with a maximum daily dose of 3000 mg. The route of administration is oral, and the treatment period is one day. Brown & Burk UK Limited is the manufacturer of this medication.

The trial also includes **Ciprofloxacin**, available as 500 mg film-coated tablets. The maximum daily dose is 1500 mg, administered orally, with a treatment period of one day. This medication is manufactured by Wise Pharmaceuticals Limited.

**Sulfamethoxazole and Trimethoprim** are provided as tablets under the brand name Sulfametoxazol med trimetoprim SAD. The maximum daily dose is 6400 mg, administered orally, with a treatment period of one day. AMGROS I/S is the manufacturer of this medication.

**Amoxicillin and Clavulanic Acid** are administered as 500 mg/125 mg film-coated tablets under the brand name Bioclavid. The maximum daily dose is 3500 mg, administered orally, with a treatment period of one day. Sandoz GmbH is the manufacturer of this medication.

**Cefuroxime Axetil** is provided as 500 mg film-coated tablets under the brand name Zinnat. The maximum daily dose is 1500 mg, administered orally, with a treatment period of one day. This medication is manufactured by Sandoz Pharmaceuticals D.D.

**Nitrofurantoin** is included in the trial as 50 mg tablets, with a maximum daily dose of 400 mg. The route of administration is oral, and the treatment period is one day. Generics [UK] Limited is the manufacturer of this medication.

Lastly, **Linezolid** is administered as 600 mg film-coated tablets under the brand name Linezolid Teva. The maximum daily dose is 1200 mg, administered orally, with a treatment period of one day. This medication is produced by Teva Sweden AB.

All medications are administered orally, and participant compliance is monitored throughout the trial. The trial aims to determine the superiority of individualised targeted antibiotic prophylaxis over empiric prophylaxis at ureteral stent removal in reducing infection-related readmissions following cystectomy.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the 90-day infection-related hospital readmission rate following cystectomy. This will provide a direct measure of the effectiveness of targeted antibiotic prophylaxis compared to the current empiric regimen.

Secondary endpoints include several parameters to further evaluate efficacy. These include the timing of ureteral stent removal and the type of antimicrobial prophylaxis administered at that time, as well as all-cause readmissions within 30 and 90 days post-surgery. These readmissions will be analyzed for main cause, timing, duration, microbiological tests, and antimicrobial treatment. Postoperative complications will be assessed using the Clavien-Dindo classification score within 30 and 90 days of surgery. Additionally, the days-alive-and-out-of-hospital (DAOH) at postoperative day (POD) 30 and 90 will be recorded.

Quality of life will be evaluated using the EORTC QLQ-C30 and QLQ-BLM30 questionnaires, which will be completed preoperatively and on POD 90. Microbiological findings and antimicrobial susceptibility analyses will be conducted on pre- and postoperative microbiological samples to provide further insights into the efficacy of the prophylactic strategies being tested.