Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy

Not Applicable

Completed

• Conditions: Urologic Cancer; Radical Cystectomy; Antibiotic Side Effect; Surgical Site Infection; Antibiotic-associated Diarrhea; Antibiotic Resistant Infection; Perioperative/Postoperative Complications
• Interventions: Other: Extended PAP; Other: Short PAP

• Registration Number: NCT03305627
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

Cystectomy with urinary diversion (ileal conduit, orthotopic ileal bladder substitute, continent catheterizable pouch) is the best treatment option for patients with muscle-invasive bladder cancer. This intervention is one of the most challenging in urology and has a high rate of postoperative complications including around 30% of postoperative infections.

Perioperative antibiotic prophylaxis (PAP) is widely accepted as a crucial preventive measure to reduce the incidence of surgical site infections (SSI). The rationale for PAP is the reduction of the local bacterial load at the site and time of intervention, and therefore a short duration of PAP of 24 to maximal 48 hours is recommended for all clean to clean-contaminated procedures..

Evidence supporting the optimal duration of PAP for radical cystectomy with urinary diversion is lacking. Based on data extrapolated from abdominal surgery, current guidelines recommend short-term PAP (≤24h) for all clean-contaminated procedures including radical cystectomy.

However, a recent evaluation revealed a significant inter-hospital variability of PAP and showed that extended use (\>48h) was common in patients undergoing radical cystectomy. Importantly, this study also demonstrated that longer duration of PAP incurred higher costs and was associated with an increased rate of C. difficile colitis. A small, prospective, non-randomized study showed equal efficacy of short-term PAP in preventing postoperative infections in patients undergoing radical cystectomy with ileum conduit compared to extended PAP. Nonetheless, larger randomized clinical trials supporting these findings are lacking.

The unwarranted extended use of antibiotics is a major concern as exposure to antibiotics is a driving force for the development of (multi-) resistant bacteria and will lead to an increasing number of difficult-to-treat infections. This has been recognized on both national and international levels and is addressed within antimicrobial stewardship frameworks.

This study will compare current practice (\>48h PAP, "extended PAP") with the guideline recommended approach (24h PAP, "short term PAP") in a single-centre, prospective, randomised clinical non-inferiority trial. The primary outcome is the rate of SSI within 90 days post surgery. The aim of the study is to generate currently lacking evidence allowing for an optimised PAP strategy in a challenging surgical setting.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-27
• Study First Submitted QC: 2017-10-04
• Study First Posted: 2017-10-10
• Study Start: 2018-04-09
• Primary Completion: 2024-02-28
• Study Completion: 2024-02-28
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 196

Inclusion Criteria

• Written informed consent
• Age >18 years
• Planned radical cystectomy at the Department of Urology, Bern University Hospital

Exclusion Criteria

• Contraindications to the classes of drugs under study, e.g. known hypersensitivity or allergy to class of drugs including alternatives described in the protocol or the investigational product,
• Women who are pregnant or breast feeding (exclusion for surgery),
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Extended PAP	Extended PAP	Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed)
Short PAP	Short PAP	Perioperative antibiotic prophylaxis will be stopped after 24h

Primary Outcome Measures

Name	Time	Method
Time to event of SSI	90 days	Time to event of SSI (event free survival analysis)
Rate of Surgical Site infections (SSI)	90 days	Rate of surgical site infections occurring within 90 days post surgery will be calculated for each patient.
Rate of Urinary tract infections (UTI)	90 days	Rate of urinary tract infections occurring within 90 days post surgery will be calculated for each patient.
Time to event of UTI	90 days	Time to event of UTI (event free survival analysis)

Secondary Outcome Measures

Name	Time	Method
Rate and type of Antibiotic associated adverse events (AEs)	30 days	Rates and types of antibiotic associated AEs occurring within 30 days post surgery (direct AEs such as hypersensitivity reaction, hepatotoxicity, renal toxicity etc and indirect AEs such as line associated infections, C.difficile diarrhoea) will be assessed for each patient.
Antibiotic associated costs	30 days	Directly antibiotic associated costs incurred during 30days post surgery will be assessed
Changes in fecal flora	30 days	Changes in the composition of the fecal flora will be assessed in fecal samples collected at pre-specified time points
Frequency of multi-drug-resistant bacteria in urinary samples	30 days	The frequency of multi-drug-resistant bacteria in urine samples obtained at predefined time points during the first 30 days post surgery will be calculated for each patient

Trial Locations

Locations (2)

Department of Infectious Diseases, University Hospital Bern; 🇨🇭 Bern, Switzerland

Department of Urology, University Hopspital Bern; 🇨🇭 Bern, Switzerland