IMPACT-Introduction of Mycotic Prophylaxis At Cystectomy Trial: perioperative mycotic prophylaxis with fluconazole to reduce postoperative complications following cystectomy-study protocol for a national multi-center, double-blinded, placebo-controlled, randomized clinical trial.

INTRODUCTION AND

objectivesCystectomy with urinary diversion is one of the most complex surgeries in the urological specialty involving surgery on multiple organ systems. The postoperative risk of mortality and complications is considerable, and the first months after surgery are often the most critical. When creating the urinary diversion, the abdominal cavity is exposed to bacteria and fungus from the small intestine, and after the surgery, micro-leakage from the intestinal anastomosis may also contribute to a local infectious response. This contamination is suspected to increase the risk of bowel paralysis that, even with modern ERAS protocols, significantly impacts the postoperative recovery. Emerging data show that approximately 50% of the patients undergoing cystectomy have Candida albicans in samples from the terminal ileum. Current guidelines support the use of perioperative antibiotics, but there are currently no guidelines on antimycotic prophylaxis. We present a randomized clinical trial that tests whether incorporating antimycotics into the perioperative antimicrobial prophylactic regimen can reduce major complications after cystectomy. MATERIALS AND

methodsThis is a multi-center, double-blinded, randomized clinical trial including participants from all five centers in Denmark performing cystectomy. The study includes adult patients planned for cystectomy with an ileal conduit with no contraindications to fluconazole and no active treatment for mycotic infections. The 420 participants are randomized 1:1 to receive a single dose of perioperative fluconazole or placebo. Primary outcome is major postoperative complications, defined as Clavien-Dindo classification III-V, within 90 days following cystectomy. Secondary outcomes are days alive and out of hospital, gastrointestinal function, nasogastric tube placement, length of stay, readmissions, quality of life, and microbiological test results. We aim to reduce the absolute rate of Clavien-Dindo III-V complications from 30 to 18%. The study is a superiority study and analysis will be performed as intention-to-treat. DISCUSSION: Patients undergoing cystectomy face a high risk of surgical complications, many of which can be attributed to infections. There is a growing concern about the consequences of fungal infections after abdominal surgery. This trial aims to explore whether prophylactic antifungal treatment at the time of cystectomy can prevent major postoperative complications.

trial registrationCTIS EU trial number: 2023-506226-36-00. Registered on February 16, 2024. CLINICALTRIALS: gov: NCT06770530. Registered on March 31, 2024.