<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/NCT03228108</url>
  </required_header>
  <id_info>
    <org_study_id>pro-SWAP104622</org_study_id>
    <nct_id>NCT03228108</nct_id>
  </id_info>
  <brief_title>Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.</brief_title>
  <acronym>pro-SWAP</acronym>
  <official_title>The Effect of Rectal Swab Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy on Infectious Complications and Cost of Care: A Randomized Controlled Trial in the Netherlands.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ZonMw: The Netherlands Organisation for Health Research and Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to assess the effectiveness and cost-effectiveness of rectal swab&#xD;
      culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal&#xD;
      prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral&#xD;
      ciprofloxacin (control group), while the other half will receive rectal culture-guided oral&#xD;
      antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal&#xD;
      swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis,&#xD;
      comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative&#xD;
      oral antibiotic based on the culture results will be prescribed&#xD;
      (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin).&#xD;
&#xD;
      The investigators hypothesise that the targeted prophylaxis group (intervention group) will&#xD;
      have a lower rate of post-biopsy infectious complications compared to the control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Several classes of antibiotics are proven effective for prophylaxis during transrectal&#xD;
      prostate biopsy, reducing infectious complications to less than 1% in case of susceptible&#xD;
      rectal flora. Ciprofloxacin has been best studied and is recommended as first choice&#xD;
      prophylaxis in urology guidelines. However, due to increasing fluoroquinolone resistance in&#xD;
      gram negative bacilli (currently more than 20% in E.coli), a significant increase up to 6% in&#xD;
      infectious complications after transrectal prostate biopsy was recently noticed. Antibiotic&#xD;
      treatment of these infections and hospitalization may account for increased health care&#xD;
      associated costs and will contribute to the further development of antibiotic resistance.&#xD;
&#xD;
      Besides, in urology guidelines no clear recommendations are made on the duration of&#xD;
      prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin schedules are&#xD;
      used, of which 2 to 3 day regimens are most common. Prolonged duration of prophylaxis during&#xD;
      prostate biopsy is not proven to be more effective than a 1-day regimen, but it is more&#xD;
      likely to select more fluoroquinolone (FQ) resistance.&#xD;
&#xD;
      This study aims to assess the effectiveness and cost-effectiveness of rectal culture-guided&#xD;
      antimicrobial prophylaxis to reduce infectious complications after transrectal prostate&#xD;
      biopsy. Also, duration of antibiotic prophylaxis will be minimized to 24 hours, thereby&#xD;
      controlling further development of resistant bacteria.&#xD;
&#xD;
      The culture method used in this study with four phenotypic screening agars to support the&#xD;
      choice of one of the oral prophylactic antibiotics is innovative. Culture results become&#xD;
      available rapidly, within 48 hours, the method is simple, relatively inexpensive, as it does&#xD;
      not need full susceptibility testing of separate colonies, and useful in daily practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 3, 2018</start_date>
  <completion_date type="Actual">September 26, 2021</completion_date>
  <primary_completion_date type="Actual">September 26, 2021</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Any registered clinical infectious complication after prostate biopsy</measure>
    <time_frame>within 7 days post-biopsy</time_frame>
    <description>Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cost of care</measure>
    <time_frame>within 30 days after prostate biopsy</time_frame>
    <description>Difference of costs between the intervention and the control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive microbiological results</measure>
    <time_frame>within 7 and 30 days after prostate biopsy</time_frame>
    <description>Urine or blood culture results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any registered clinical infectious complication after prostate biopsy</measure>
    <time_frame>within 7 and 30 days after prostate biopsy</time_frame>
    <description>Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization after prostate biopsy</measure>
    <time_frame>within 30 days after prostate biopsy</time_frame>
    <description>Any hospital admission, including ICU admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall mortality</measure>
    <time_frame>within 30 days after prostate biopsy</time_frame>
    <description>Mortality of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects of used antibiotics</measure>
    <time_frame>within 30 days after prostate biopsy</time_frame>
    <description>All side effects mentioned in the Summary of Product Characteristics (SPC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora</measure>
    <time_frame>rectal swabs are taken 14 days before biopsy</time_frame>
    <description>Assessed through microbiological rectal swab cultures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall antibiotic use after prostate biopsy</measure>
    <time_frame>within 30 days after prostate biopsy</time_frame>
    <description>Number of antibiotic prescriptions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1538</enrollment>
  <condition>Complication</condition>
  <condition>Infection</condition>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Targeted antimicrobial prophylaxis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy (equal to the active comparator arm), and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative oral antibiotics, based on culture results, in the following order:&#xD;
trimethoprim/sulfamethoxazole (SXT) 960 mg orally 2 hours before and 12 hours after prostate biopsy, or&#xD;
fosfomycin 3 g orally 2 hours before prostate biopsy, or&#xD;
pivmecillinam/augmentin respectively 400 mg and 500/125 mg 2 hours before prostate biopsy followed by 2 days with three divided doses each day after prostate biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Routine empirical prophylaxis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciprofloxacin</intervention_name>
    <description>see study arms.</description>
    <arm_group_label>Routine empirical prophylaxis</arm_group_label>
    <arm_group_label>Targeted antimicrobial prophylaxis</arm_group_label>
    <other_name>Ciproxin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimethoprim/Sulfamethoxazole</intervention_name>
    <description>see study arms.</description>
    <arm_group_label>Targeted antimicrobial prophylaxis</arm_group_label>
    <other_name>Co-trimoxazole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fosfomycin</intervention_name>
    <description>see study arms.</description>
    <arm_group_label>Targeted antimicrobial prophylaxis</arm_group_label>
    <other_name>Monuril</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pivmecillinam/augmentin</intervention_name>
    <description>see study arms.</description>
    <arm_group_label>Targeted antimicrobial prophylaxis</arm_group_label>
    <other_name>Selexid</other_name>
    <other_name>Amoxicillin/clavulanic acid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is able and willing to sign the Informed Consent Form.&#xD;
&#xD;
          -  Subject undergoes a transrectal prostate biopsy as part of the standard care in the&#xD;
             Radboudumc (Nijmegen), Canisius Wilhelmina hospital (Nijmegen) or Catharina hospital&#xD;
             (Nijmegen) (because of suspicion of prostate cancer).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to receive ciprofloxacin (e.g. documented history of sensitivity to&#xD;
             medicinal products or excipients similar to those found in the antibiotic prophylaxis,&#xD;
             relevant history or presence of cardiovascular disorders)&#xD;
&#xD;
          -  Inability to receive either co-trimoxazole, fosfomycin and pivmecillinam/augmentin&#xD;
             prophylaxis for any reason (e.g. documented history of sensitivity to medicinal&#xD;
             products or excipients similar to those found in the antibiotic prophylaxis)&#xD;
&#xD;
          -  Inability to understand the nature of the trial and the procedures required.&#xD;
&#xD;
          -  Individuals with an urinary tract infection or acute prostatitis within 14 days prior&#xD;
             to intervention.&#xD;
&#xD;
          -  Individuals who receive antibiotics within 14 days before prostate biopsy.&#xD;
&#xD;
          -  Individuals who fail to send a rectum swab to the microbiology laboratory.&#xD;
&#xD;
          -  Individuals whose rectal swab shows no growth on a (growth) control MacConkey agar&#xD;
             without antibiotics.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heiman Wertheim, Prof. dr.</last_name>
    <role>Study Director</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jeroen Bosch Hospital</name>
      <address>
        <city>'s-Hertogenbosch</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bravis</name>
      <address>
        <city>Bergen Op Zoom</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Hospital</name>
      <address>
        <city>Breda</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catharina Hospital</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuyderland Hospital</name>
      <address>
        <city>Heerlen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canisius Wilhelmina Hospital</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud University Medical Center</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bravis</name>
      <address>
        <city>Roosendaal</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuyderland Hospital</name>
      <address>
        <city>Sittard</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elisabeth Tweesteden Hospital</name>
      <address>
        <city>Tilburg</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bernhoven Hospital</name>
      <address>
        <city>Uden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>July 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>May 9, 2022</last_update_submitted>
  <last_update_submitted_qc>May 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Culture-guided</keyword>
  <keyword>Targeted prophylaxis</keyword>
  <keyword>Prostate biopsy</keyword>
  <keyword>Antibiotic prophylaxis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Amoxicillin-Potassium Clavulanate Combination</mesh_term>
    <mesh_term>Clavulanic Acids</mesh_term>
    <mesh_term>Clavulanic Acid</mesh_term>
    <mesh_term>Fosfomycin</mesh_term>
    <mesh_term>Trimethoprim, Sulfamethoxazole Drug Combination</mesh_term>
    <mesh_term>Amdinocillin Pivoxil</mesh_term>
    <mesh_term>Trimethoprim</mesh_term>
    <mesh_term>Sulfamethoxazole</mesh_term>
  </intervention_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/NCT03228108
org study id: pro-SWAP104622
nct id: NCT03228108
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study aims to assess the effectiveness and cost-effectiveness of rectal swab
      culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal
      prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral
      ciprofloxacin (control group), while the other half will receive rectal culture-guided oral
      antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal
      swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis,
      comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative
      oral antibiotic based on the culture results will be prescribed
      (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin).

      The investigators hypothesise that the targeted prophylaxis group (intervention group) will
      have a lower rate of post-biopsy infectious complications compared to the control group.
Several classes of antibiotics are proven effective for prophylaxis during transrectal
      prostate biopsy, reducing infectious complications to less than 1% in case of susceptible
      rectal flora. Ciprofloxacin has been best studied and is recommended as first choice
      prophylaxis in urology guidelines. However, due to increasing fluoroquinolone resistance in
      gram negative bacilli (currently more than 20% in E.coli), a significant increase up to 6% in
      infectious complications after transrectal prostate biopsy was recently noticed. Antibiotic
      treatment of these infections and hospitalization may account for increased health care
      associated costs and will contribute to the further development of antibiotic resistance.

      Besides, in urology guidelines no clear recommendations are made on the duration of
      prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin schedules are
      used, of which 2 to 3 day regimens are most common. Prolonged duration of prophylaxis during
      prostate biopsy is not proven to be more effective than a 1-day regimen, but it is more
      likely to select more fluoroquinolone (FQ) resistance.

      This study aims to assess the effectiveness and cost-effectiveness of rectal culture-guided
      antimicrobial prophylaxis to reduce infectious complications after transrectal prostate
      biopsy. Also, duration of antibiotic prophylaxis will be minimized to 24 hours, thereby
      controlling further development of resistant bacteria.

      The culture method used in this study with four phenotypic screening agars to support the
      choice of one of the oral prophylactic antibiotics is innovative. Culture results become
      available rapidly, within 48 hours, the method is simple, relatively inexpensive, as it does
      not need full susceptibility testing of separate colonies, and useful in daily practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Any registered clinical infectious complication after prostate biopsy
time frame: within 7 days post-biopsy
description: Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis
measure: Cost of care
time frame: within 30 days after prostate biopsy
description: Difference of costs between the intervention and the control group
measure: Positive microbiological results
time frame: within 7 and 30 days after prostate biopsy
description: Urine or blood culture results
measure: Any registered clinical infectious complication after prostate biopsy
time frame: within 7 and 30 days after prostate biopsy
description: Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis
measure: Hospitalization after prostate biopsy
time frame: within 30 days after prostate biopsy
description: Any hospital admission, including ICU admission
measure: Overall mortality
time frame: within 30 days after prostate biopsy
description: Mortality of any cause
measure: Side effects of used antibiotics
time frame: within 30 days after prostate biopsy
description: All side effects mentioned in the Summary of Product Characteristics (SPC)
measure: Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora
time frame: rectal swabs are taken 14 days before biopsy
description: Assessed through microbiological rectal swab cultures
measure: Overall antibiotic use after prostate biopsy
time frame: within 30 days after prostate biopsy
description: Number of antibiotic prescriptions
arm group label: Targeted antimicrobial prophylaxis
arm group type: Experimental
description: Men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy (equal to the active comparator arm), and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative oral antibiotics, based on culture results, in the following order:
trimethoprim/sulfamethoxazole (SXT) 960 mg orally 2 hours before and 12 hours after prostate biopsy, or
fosfomycin 3 g orally 2 hours before prostate biopsy, or
pivmecillinam/augmentin respectively 400 mg and 500/125 mg 2 hours before prostate biopsy followed by 2 days with three divided doses each day after prostate biopsy.
arm group label: Routine empirical prophylaxis
arm group type: Active Comparator
description: Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.
intervention type: Drug
intervention name: Ciprofloxacin
description: see study arms.
arm group label: Routine empirical prophylaxis
arm group label: Targeted antimicrobial prophylaxis
other name: Ciproxin
intervention type: Drug
intervention name: Trimethoprim/Sulfamethoxazole
description: see study arms.
arm group label: Targeted antimicrobial prophylaxis
other name: Co-trimoxazole
intervention type: Drug
intervention name: Fosfomycin
description: see study arms.
arm group label: Targeted antimicrobial prophylaxis
other name: Monuril
intervention type: Drug
intervention name: Pivmecillinam/augmentin
description: see study arms.
arm group label: Targeted antimicrobial prophylaxis
other name: Selexid
other name: Amoxicillin/clavulanic acid
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Heiman Wertheim, Prof. dr.
role: Study Director
affiliation: Radboud University Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Amoxicillin
mesh term: Ciprofloxacin
mesh term: Amoxicillin-Potassium Clavulanate Combination
mesh term: Clavulanic Acids
mesh term: Clavulanic Acid
mesh term: Fosfomycin
mesh term: Trimethoprim, Sulfamethoxazole Drug Combination
mesh term: Amdinocillin Pivoxil
mesh term: Trimethoprim
mesh term: Sulfamethoxazole
sharing ipd: No