Evaluation of Perioperative Fluconazole Prophylaxis Versus Placebo in Reducing Postoperative Complications Following Radical Cystectomy in Patients with Fungal Infection

The primary objective of the IMPACT trial is to evaluate whether **prophylactic antimycotic** treatment can effectively reduce postoperative complications following radical cystectomy when compared to a placebo. This is clinically relevant as it addresses the potential for reducing the incidence of **fungal infections**, which can complicate recovery and increase morbidity in patients undergoing this surgical procedure. The trial is designed as a double-blinded, placebo-controlled, randomized study to ensure the reliability and validity of the results.

The clinical trial focuses on individuals diagnosed with **fungal infection** and aims to assess the efficacy of prophylactic antimycotic treatment in reducing complications post-radical cystectomy. The study population includes both male and female participants over the age of 18, with no specific vulnerable populations targeted. Participants must have an indication for cystectomy, with urinary diversion limited to the ileal conduit. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants are required to demonstrate a willingness to participate and the ability to understand and sign an informed consent in Danish. The selection criteria ensure that the study population is appropriate for evaluating the trial's main objective.

The clinical trial is designed to evaluate the efficacy of **fluconazole** as a prophylactic treatment to reduce postoperative complications following radical cystectomy. This study is a **randomized**, **double-blind**, **placebo-controlled** trial, categorized as a phase IV study. The trial aims to compare the effects of fluconazole with a placebo in patients undergoing cystectomy, with the primary objective of assessing postoperative complications using the Clavien Dindo III-V classification score. Secondary endpoints include the number of days alive and out of the hospital within 90 days postoperatively, time to gastrointestinal function recovery, and quality of life assessments.

Participants will be involved in the study for a maximum treatment period of 30 days, with the trial expected to conclude by December 31, 2026. The study will commence recruitment on January 1, 2024. Eligible participants must be over 18 years of age, able to provide informed consent in Danish, and have an indication for cystectomy with urinary diversion limited to the ileal conduit. The study excludes any specific exclusion criteria.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor the administration of the study drug and assess any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints. Participants may be withdrawn from the study if they experience significant adverse effects or if they withdraw consent. The study drug, fluconazole, will be administered via **intravenous infusion**, with a maximum daily dose of 400 mg and a total dose not exceeding 12,000 mg. The placebo will be administered in a similar manner to maintain the double-blind nature of the trial.

The clinical trial involves the administration of **Fluconazole Kabi 2mg/ml solution for infusion**, which is an experimental medication used in the study. This pharmaceutical product is formulated as a **solution for infusion** and contains the active substance **fluconazole**. The medication is administered via **intravenous infusion**. The maximum daily dose is 400 mg, with a total maximum dose of 12,000 mg over a treatment period of up to 30 days. The product is manufactured by Fresenius Kabi Italia S.R.L. and is authorized for use in Malta under the marketing authorization number MA1123/00802. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental medication, the trial utilizes **Natriumklorid "B. Braun"** as a non-experimental treatment. This product serves as a placebo and is also formulated as a **solution for injection/infusion**. The active substance in this product is **sodium chloride**, and it is administered via **intravenous infusion**. The maximum daily dose is 6 mmol/kg, with a total maximum dose of 10,000 ml over a treatment period of 1 day. This product is manufactured by B. Braun Melsungen AG and is authorized for use in Denmark. The use of this placebo is integral to maintaining the double-blinded nature of the trial, ensuring unbiased assessment of the experimental treatment's efficacy.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the evaluation of postoperative complications, which will be measured using the Clavien-Dindo classification score, specifically focusing on grades III to V. This classification is a validated tool for assessing surgical complications, providing a standardized method to quantify and compare outcomes.

Secondary endpoints include several parameters: the number of days patients are alive and out of the hospital within the first 90 postoperative days, the time to the first bowel movement postoperatively, and the reduction in the percentage of patients requiring nasogastric tube placement after surgery. Additionally, the trial will assess the quality of life using the EORTC QLQ-C30 and QLQ-BLM30 questionnaires, administered at day 0 and day 90. Other secondary measures include the length of stay for the index admission, rates of re-admission within 30 and 90 days, development of microbiome resistance in the urinary tract, and the incidence of urinary tract infections requiring treatment.

The data collection for these endpoints will occur at specified time points, ensuring a comprehensive evaluation of the treatment's efficacy. The use of validated scales and questionnaires will facilitate the accurate measurement of outcomes, contributing to the robustness of the trial's findings. The trial aims to determine whether prophylactic treatment with **fluconazole** can effectively reduce complications following radical cystectomy compared to a placebo.