Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy (PAPRAC)

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Infectious Diseases, University Hospital Bern
  • Bern, Switzerland, 3010
    • Department of Urology, University Hopspital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short PAP; Perioperative antibiotic prophylaxis will be stopped after 24h	Other: Short PAP; Perioperative antibiotic prophylaxis for 24h
Active Comparator: Extended PAP; Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed)	Other: Extended PAP; Perioperative antibiotic prophylaxis for >48h

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate and type of Antibiotic associated adverse events (AEs)	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.	30 days
Frequency of multi-drug-resistant bacteria in urinary samples	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	30 days
Changes in fecal flora	Changes in the composition of the fecal flora will be assessed in fecal samples collected at pre-specified time points	30 days
Antibiotic associated costs	Directly antibiotic associated costs incurred during 30days post surgery will be assessed	30 days

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Maria C Thurnheer, MD, Department of Infectious Diseases, University Hospital Bern

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: October 4, 2017
• First Posted (Actual): October 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Disease Attributes; Signs and Symptoms, Digestive; Wound Infection; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Diarrhea; Postoperative Complications; Surgical Wound Infection; Urologic Neoplasms
• Other Study ID Numbers: 2017-01480

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No