Radical CystectomyPAPRACNCT03305627
Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy
A study testing Short PAP and Extended PAP in people with Radical Cystectomy and Surgical Site Infection, run by Insel Gruppe AG, University Hospital Bern at 2 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Radical Cystectomy, Surgical Site Infection, Urologic Cancer
- What is being tested?
- Short PAP and Extended PAP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 9 Apr 2018to 28 Feb 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Age >18 years
- Planned radical cystectomy at the Department of Urology, Bern University Hospital
Who cannot join
- 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,
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
Department of Infectious Diseases, University Hospital Bern
Bern, 3010
Department of Urology, University Hopspital Bern
Bern, 3010
About this study
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..
Read more
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
- Being tested
- Short PAP, Extended PAP
- Medical subject headings
- Surgical Wound Infection, Urologic Neoplasms, Postoperative Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short PAPOther
Perioperative antibiotic prophylaxis for 24h
Extended PAPOther
Perioperative antibiotic prophylaxis for >48h
| Study group | Role | What they receive |
|---|---|---|
| Short PAP | Experimental | Perioperative antibiotic prophylaxis will be stopped after 24h Receives: Other: Short PAP |
| Extended PAP | Active comparator | Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed) Receives: Other: Extended PAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Surgical Site infections (SSI)
Rate of surgical site infections occurring within 90 days post surgery will be calculated for each patient.
Measured: 90 days
Time to event of SSI
Time to event of SSI (event free survival analysis)
Measured: 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.
Measured: 90 days
Time to event of UTI
Time to event of UTI (event free survival analysis)
Measured: 90 days
Secondary outcomes (4)
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.
Measured: 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
Measured: 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
Measured: 30 days
Antibiotic associated costs
Directly antibiotic associated costs incurred during 30days post surgery will be assessed
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2017
- Study start9 Apr 2018
- Primary completion28 Feb 2024
- Study completion28 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Radical CystectomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria C Thurnheer, MD, Principal investigator, Department of Infectious Diseases, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03305627
- Sponsor's protocol ID
- 2017-01480
- Other IDs
- 2017
- Acronym
- PAPRAC
- Status last verified
- May 2024
- First submitted
- 27 Sep 2017
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39422911