Clinical trial NCT03305627: Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy
Official title: Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Radical Cystectomy
Surgical Site Infection
Urologic Cancer
Perioperative/Postoperative Complications
Antibiotic Resistant Infection
Antibiotic Side Effect
Antibiotic-associated Diarrhea
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2017-10-10
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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,

Primary outcomes:
measure: Rate of Surgical Site infections (SSI)
timeFrame: 90 days
measure: Time to event of SSI
timeFrame: 90 days
measure: Rate of Urinary tract infections (UTI)
timeFrame: 90 days
measure: Time to event of UTI
timeFrame: 90 days
Secondary outcomes:
measure: Rate and type of Antibiotic associated adverse events (AEs)
timeFrame: 30 days
measure: Frequency of multi-drug-resistant bacteria in urinary samples
timeFrame: 30 days
measure: Changes in fecal flora
timeFrame: 30 days
measure: Antibiotic associated costs
timeFrame: 30 days
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Infectious Diseases, University Hospital Bern
city: Bern
country: Switzerland
facility: Department of Urology, University Hopspital Bern
Study officials:
affiliation: Department of Infectious Diseases, University Hospital Bern
name: Maria C Thurnheer, MD
role: PRINCIPAL_INVESTIGATOR
References: