Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy

NCT ID: NCT03305627

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-09
• Study Completion Date: 2024-02-28

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.

Conditions

Radical Cystectomy; Surgical Site Infection; Urologic Cancer; Perioperative/Postoperative Complications; Antibiotic Resistant Infection; Antibiotic Side Effect; Antibiotic-associated Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Short PAP

Perioperative antibiotic prophylaxis will be stopped after 24h

Group Type: EXPERIMENTAL

Short PAP

Intervention Type: OTHER

Perioperative antibiotic prophylaxis for 24h

Extended PAP

Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed)

Group Type: ACTIVE_COMPARATOR

Extended PAP

Intervention Type: OTHER

Perioperative antibiotic prophylaxis for \>48h

Interventions

Short PAP

Perioperative antibiotic prophylaxis for 24h

Intervention Type: OTHER

Extended PAP

Perioperative antibiotic prophylaxis for \>48h

Intervention Type: OTHER

Eligibility Criteria

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,

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria C Thurnheer, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Infectious Diseases, University Hospital Bern

Locations

Department of Infectious Diseases, University Hospital Bern

Bern, , Switzerland

Department of Urology, University Hopspital Bern

Bern, , Switzerland

Countries

Switzerland

References

Thurnheer MC, Schurmann A, Huber M, Marschall J, Wuethrich PY, Burkhard FC. Perioperative Antibiotic Prophylaxis Duration in Patients Undergoing Cystectomy With Urinary Diversion: A Randomized Clinical Trial. JAMA Netw Open. 2024 Oct 1;7(10):e2439382. doi: 10.1001/jamanetworkopen.2024.39382.

Reference Type: DERIVED

PMID: 39422911 (View on PubMed)

Other Identifiers

2017-01480

Identifier Type: -

Identifier Source: org_study_id