<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03305627</url>
  </required_header>
  <id_info>
    <org_study_id>2017-01480</org_study_id>
    <nct_id>NCT03305627</nct_id>
  </id_info>
  <brief_title>Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy</brief_title>
  <acronym>PAPRAC</acronym>
  <official_title>Optimized Perioperative Antibiotic Prophylaxis in Radical Cystectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cystectomy with urinary diversion (ileal conduit, orthotopic ileal bladder substitute,&#xD;
      continent catheterizable pouch) is the best treatment option for patients with&#xD;
      muscle-invasive bladder cancer. This intervention is one of the most challenging in urology&#xD;
      and has a high rate of postoperative complications including around 30% of postoperative&#xD;
      infections.&#xD;
&#xD;
      Perioperative antibiotic prophylaxis (PAP) is widely accepted as a crucial preventive measure&#xD;
      to reduce the incidence of surgical site infections (SSI). The rationale for PAP is the&#xD;
      reduction of the local bacterial load at the site and time of intervention, and therefore a&#xD;
      short duration of PAP of 24 to maximal 48 hours is recommended for all clean to&#xD;
      clean-contaminated procedures..&#xD;
&#xD;
      Evidence supporting the optimal duration of PAP for radical cystectomy with urinary diversion&#xD;
      is lacking. Based on data extrapolated from abdominal surgery, current guidelines recommend&#xD;
      short-term PAP (≤24h) for all clean-contaminated procedures including radical cystectomy.&#xD;
&#xD;
      However, a recent evaluation revealed a significant inter-hospital variability of PAP and&#xD;
      showed that extended use (&gt;48h) was common in patients undergoing radical cystectomy.&#xD;
      Importantly, this study also demonstrated that longer duration of PAP incurred higher costs&#xD;
      and was associated with an increased rate of C. difficile colitis. A small, prospective,&#xD;
      non-randomized study showed equal efficacy of short-term PAP in preventing postoperative&#xD;
      infections in patients undergoing radical cystectomy with ileum conduit compared to extended&#xD;
      PAP. Nonetheless, larger randomized clinical trials supporting these findings are lacking.&#xD;
&#xD;
      The unwarranted extended use of antibiotics is a major concern as exposure to antibiotics is&#xD;
      a driving force for the development of (multi-) resistant bacteria and will lead to an&#xD;
      increasing number of difficult-to-treat infections. This has been recognized on both national&#xD;
      and international levels and is addressed within antimicrobial stewardship frameworks.&#xD;
&#xD;
      This study will compare current practice (&gt;48h PAP, &quot;extended PAP&quot;) with the guideline&#xD;
      recommended approach (24h PAP, &quot;short term PAP&quot;) in a single-centre, prospective, randomised&#xD;
      clinical non-inferiority trial. The primary outcome is the rate of SSI within 90 days post&#xD;
      surgery. The aim of the study is to generate currently lacking evidence allowing for an&#xD;
      optimised PAP strategy in a challenging surgical setting.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 9, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">October 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Surgical Site infections (SSI)</measure>
    <time_frame>90 days</time_frame>
    <description>Rate of surgical site infections occurring within 90 days post surgery will be calculated for each patient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to event of SSI</measure>
    <time_frame>90 days</time_frame>
    <description>Time to event of SSI (event free survival analysis)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of Urinary tract infections (UTI)</measure>
    <time_frame>90 days</time_frame>
    <description>Rate of urinary tract infections occurring within 90 days post surgery will be calculated for each patient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to event of UTI</measure>
    <time_frame>90 days</time_frame>
    <description>Time to event of UTI (event free survival analysis)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate and type of Antibiotic associated adverse events (AEs)</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of multi-drug-resistant bacteria in urinary samples</measure>
    <time_frame>30 days</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fecal flora</measure>
    <time_frame>30 days</time_frame>
    <description>Changes in the composition of the fecal flora will be assessed in fecal samples collected at pre-specified time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic associated costs</measure>
    <time_frame>30 days</time_frame>
    <description>Directly antibiotic associated costs incurred during 30days post surgery will be assessed</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">196</enrollment>
  <condition>Radical Cystectomy</condition>
  <condition>Surgical Site Infection</condition>
  <condition>Urologic Cancer</condition>
  <condition>Perioperative/Postoperative Complications</condition>
  <condition>Antibiotic Resistant Infection</condition>
  <condition>Antibiotic Side Effect</condition>
  <condition>Antibiotic-associated Diarrhea</condition>
  <arm_group>
    <arm_group_label>Short PAP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Perioperative antibiotic prophylaxis will be stopped after 24h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Extended PAP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Short PAP</intervention_name>
    <description>Perioperative antibiotic prophylaxis for 24h</description>
    <arm_group_label>Short PAP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Extended PAP</intervention_name>
    <description>Perioperative antibiotic prophylaxis for &gt;48h</description>
    <arm_group_label>Extended PAP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Planned radical cystectomy at the Department of Urology, Bern University Hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to the classes of drugs under study, e.g. known hypersensitivity or&#xD;
             allergy to class of drugs including alternatives described in the protocol or the&#xD;
             investigational product,&#xD;
&#xD;
          -  Women who are pregnant or breast feeding (exclusion for surgery),&#xD;
&#xD;
          -  Inability to follow the procedures of the study, e.g. due to language problems,&#xD;
             psychological disorders, dementia, etc. of the participant,&#xD;
&#xD;
          -  Previous enrolment into the current study,&#xD;
&#xD;
          -  Enrolment of the investigator, his/her family members, employees and other dependent&#xD;
             persons,&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria C Thurnheer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Infectious Diseases, University Hospital Bern</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Infectious Diseases, University Hospital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Urology, University Hopspital Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
    <mesh_term>Urologic Neoplasms</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
    <mesh_term>Postoperative Complications</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03305627
org study id: 2017-01480
nct id: NCT03305627
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of Surgical Site infections (SSI)
time frame: 90 days
description: Rate of surgical site infections occurring within 90 days post surgery will be calculated for each patient.
measure: Time to event of SSI
time frame: 90 days
description: Time to event of SSI (event free survival analysis)
measure: Rate of Urinary tract infections (UTI)
time frame: 90 days
description: Rate of urinary tract infections occurring within 90 days post surgery will be calculated for each patient.
measure: Time to event of UTI
time frame: 90 days
description: Time to event of UTI (event free survival analysis)
measure: Rate and type of Antibiotic associated adverse events (AEs)
time frame: 30 days
description: 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.
measure: Frequency of multi-drug-resistant bacteria in urinary samples
time frame: 30 days
description: 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
measure: Changes in fecal flora
time frame: 30 days
description: Changes in the composition of the fecal flora will be assessed in fecal samples collected at pre-specified time points
measure: Antibiotic associated costs
time frame: 30 days
description: Directly antibiotic associated costs incurred during 30days post surgery will be assessed
arm group label: Short PAP
arm group type: Experimental
description: Perioperative antibiotic prophylaxis will be stopped after 24h
arm group label: Extended PAP
arm group type: Active Comparator
description: Perioperative antibiotic prophylaxes will be continued for 48h or more (until all indwelling urinary catheters have been removed)
intervention type: Other
intervention name: Short PAP
description: Perioperative antibiotic prophylaxis for 24h
arm group label: Short PAP
intervention type: Other
intervention name: Extended PAP
description: Perioperative antibiotic prophylaxis for >48h
arm group label: Extended PAP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria C Thurnheer, MD
role: Principal Investigator
affiliation: Department of Infectious Diseases, University Hospital Bern
facility: 
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection
mesh term: Urologic Neoplasms
mesh term: Diarrhea
mesh term: Postoperative Complications
sharing ipd: No