<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/NCT02225821</url>
  </required_header>
  <id_info>
    <org_study_id>SB155014</org_study_id>
    <secondary_id>NTR 4393</secondary_id>
    <nct_id>NCT02225821</nct_id>
  </id_info>
  <brief_title>Wound Infections Following Implant Removal</brief_title>
  <acronym>WIFI</acronym>
  <official_title>Antibiotic Prophylaxis to Prevent Wound Infections Following Implant Removal</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</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>
    <collaborator>
      <agency>AO Research Fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In the Netherlands about 18,000 surgical procedures with implant removal are annually&#xD;
      performed after fracture healing, of which 30-80% concern the foot, ankle and lower leg&#xD;
      region. For clean surgical procedures, the rate of postoperative wound infections (POWIs)&#xD;
      should be less than 5%. However, rates of 10-12% following implant removal, specifically&#xD;
      after foot, ankle and lower leg fractures are reported. Currently, surgeons decide&#xD;
      individually if antibiotics prophylaxis is given, since no guideline exists. This leads to&#xD;
      undesirable practice variation.&#xD;
&#xD;
      Therefore, the investigators propose a double-blind randomized controlled trial (RCT) in&#xD;
      patients scheduled for implant removal following a foot, ankle or lower leg fracture, to&#xD;
      assess the (cost-)effectiveness of a single gift of antibiotic prophylaxis. Primary outcome&#xD;
      is a POWI within 30 days after implant removal. Secondary outcomes are quality of life,&#xD;
      functional outcome at 30 days and 6 months after implant removal and costs.&#xD;
&#xD;
      With 2 x 250 patients a decrease in POWI from 10% to 3.3% (expected rate in&#xD;
      clean-contaminated elective orthopedic trauma procedures) can be detected (Power=80%, 2-sided&#xD;
      alpha=5%, including 15% lost to follow up).&#xD;
&#xD;
      If the assumption of the investigators, that prophylactic antibiotics prior to implant&#xD;
      removal reduces the infectious complication rate, is confirmed by this RCT, this will offer a&#xD;
      strong argument to adopt a single gift of antibiotic prophylaxis as standard practice of&#xD;
      care. This will reduce the incidence of POWIs and consequently will lead to less physical and&#xD;
      social disabilities and health care use. In addition, it will decrease the rate of use of&#xD;
      empiric broad-spectrum antibiotics (and antibiotic resistance) prescribed upon suspicion or&#xD;
      diagnosis of a POWI. A preliminary, conservative estimation suggests yearly cost savings in&#xD;
      the Netherlands of €3.5 million per year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      See study protocol&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Postoperative wound infection (POWI)</measure>
    <time_frame>30 days</time_frame>
    <description>The primary outcome variable is a POWI within 30 days after implant removal as defined by the criteria applied by the Centers for Disease and Control.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>baseline, one month, 6 months</time_frame>
    <description>Health-related quality of life (as measured by the EQ-5D questionnaire)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome</measure>
    <time_frame>baseline, 1 month, 6 months</time_frame>
    <description>Functional outcome following implant removal as assessed with the Lower Extremity Functional Scale (LEFS). The LEFS can be used by clinicians as a measure of patients' initial function, ongoing progress and outcome, as well as to set functional goals. The LEFS can be used to evaluate the functional impairment of a patient with a disorder of one or both lower extremities. It can be used to monitor the patient over time and to evaluate the effectiveness of an intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>1 month, 6 months</time_frame>
    <description>Patient satisfaction following implant removal as measured by a ten-point Visual Analog Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health care resources utilization</measure>
    <time_frame>baseline, 1 month, 6 months</time_frame>
    <description>Health care resources utilization at baseline, 1 month and 6 months after implant removal (including amongst others, number of visits to the general practitioner and use of home care organizations) as measured by way of a combination of the Dutch iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) (adapted to the study setting).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Costs</measure>
    <time_frame>Costs per quality adjusted life year</time_frame>
    <description>Costs (economic evaluation including budget impact analysis): the economic evaluation of antibiotic prophylaxis in patients scheduled for implant removal (following a foot, ankle or lower leg fracture) against no prophylaxis as its best alternative will be performed as a cost-effectiveness (CEA) as well as a cost-utility (CUA) analysis.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">500</enrollment>
  <condition>Surgical Wound Infection</condition>
  <arm_group>
    <arm_group_label>antibiotic prophylaxis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a single gift of 1000 mg cefazolin in 10 cc of NaCl 0.9% (intervention group)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No antibiotic prophylaxis</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>a single gift of 10 cc NaCl 0.9%, given in the same manner (control group).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cephalozin</intervention_name>
    <description>1000 mg Cephalozin</description>
    <arm_group_label>antibiotic prophylaxis</arm_group_label>
    <other_name>Kefzol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sodium chloride</intervention_name>
    <description>10 cc of NaCl 0.9%</description>
    <arm_group_label>No antibiotic prophylaxis</arm_group_label>
    <other_name>NaCl 0.9%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥18 years and ≤75 years of all ethnic backgrounds&#xD;
&#xD;
          -  Implant removal following foot, ankle and/or lower leg surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Removing and re-implanting osteosynthesis material in the same session&#xD;
&#xD;
          -  Active wound infection or (plate) fistula&#xD;
&#xD;
          -  Antibiotic treatment at time of elective implant removal for a concomitant disease or&#xD;
             infection&#xD;
&#xD;
          -  A medical history of an allergic reaction to a cephalosporin, penicillin, or any other&#xD;
             β-lactam antibiotic.&#xD;
&#xD;
          -  Insufficient comprehension of the Dutch language to understand the patient information&#xD;
             to make an informed decision to participate.&#xD;
&#xD;
          -  Kidney disease (eGFR &lt;60 ml/min/1.73m^2).&#xD;
&#xD;
          -  Treatment with probenecide, anticoagulants (see SPC)&#xD;
&#xD;
          -  Pregnancy and lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manouk Backes, MD, MSc</last_name>
    <role>Study Chair</role>
    <affiliation>Academic Medical Center/Sint Lucas Andreas Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tim Schepers, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medisch Centrum Alkmaar</name>
      <address>
        <city>Alkmaar</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Flevoziekenhuis</name>
      <address>
        <city>Almere</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amstelland Ziekenhuis</name>
      <address>
        <city>Amstelveen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BovenIJ Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onze Lieve Vrouwe Gasthuis</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Lucas Andreas Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VU Medisch Centrum</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gelre Ziekenhuizen</name>
      <address>
        <city>Apeldoorn</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rode Kruis Ziekenhuis</name>
      <address>
        <city>Beverwijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis</name>
      <address>
        <city>Breda</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reinier de Graaf</name>
      <address>
        <city>Delft</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MC Haaglanden</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer Ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catharina Ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elkerliek Ziekenhuis</name>
      <address>
        <city>Helmond</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tergooiziekenhuizen</name>
      <address>
        <city>Hilversum</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaarne Ziekenhuis</name>
      <address>
        <city>Hoofddorp</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westfries Gasthuis</name>
      <address>
        <city>Hoorn</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnland Ziekenhuis</name>
      <address>
        <city>Leiderdorp</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vlietland Ziekenhuis</name>
      <address>
        <city>Schiedam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Backes M, Schep NW, Luitse JS, Goslings JC, Schepers T. Indications for implant removal following intra-articular calcaneal fractures and subsequent complications. Foot Ankle Int. 2013 Nov;34(11):1521-5. doi: 10.1177/1071100713502466. Epub 2013 Sep 13.</citation>
    <PMID>24038057</PMID>
  </reference>
  <reference>
    <citation>Backes M, Dingemans SA, Schep NW, Bloemers FW, Van Dijkman B, Garssen FP, Haverlag R, Hoogendoorn JM, Joosse P, Mirck B, Postma V, Ritchie E, Roerdink WH, Sintenie JB, Soesman NM, Sosef NL, Twigt BA, Van Veen RN, Van der Veen AH, Van Velde R, Vos DI, De Vries MR, Winkelhagen J, Goslings JC, Schepers T. Wound Infections Following Implant removal below the knee: the effect of antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled trial. BMC Surg. 2015 Feb 6;15:12. doi: 10.1186/1471-2482-15-12.</citation>
    <PMID>25972101</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>December 21, 2016</last_update_submitted>
  <last_update_submitted_qc>December 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</investigator_affiliation>
    <investigator_full_name>J.C. Goslings</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>Implant Removal</keyword>
  <keyword>Antibiotic Prophylaxis</keyword>
  <keyword>Postoperative wound infection</keyword>
  <keyword>Orthopedics</keyword>
  <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>Wound Infection</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
    <mesh_term>Surgical Wound</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02225821
org study id: SB155014
secondary id: NTR 4393
nct id: NCT02225821
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
In the Netherlands about 18,000 surgical procedures with implant removal are annually
      performed after fracture healing, of which 30-80% concern the foot, ankle and lower leg
      region. For clean surgical procedures, the rate of postoperative wound infections (POWIs)
      should be less than 5%. However, rates of 10-12% following implant removal, specifically
      after foot, ankle and lower leg fractures are reported. Currently, surgeons decide
      individually if antibiotics prophylaxis is given, since no guideline exists. This leads to
      undesirable practice variation.

      Therefore, the investigators propose a double-blind randomized controlled trial (RCT) in
      patients scheduled for implant removal following a foot, ankle or lower leg fracture, to
      assess the (cost-)effectiveness of a single gift of antibiotic prophylaxis. Primary outcome
      is a POWI within 30 days after implant removal. Secondary outcomes are quality of life,
      functional outcome at 30 days and 6 months after implant removal and costs.

      With 2 x 250 patients a decrease in POWI from 10% to 3.3% (expected rate in
      clean-contaminated elective orthopedic trauma procedures) can be detected (Power=80%, 2-sided
      alpha=5%, including 15% lost to follow up).

      If the assumption of the investigators, that prophylactic antibiotics prior to implant
      removal reduces the infectious complication rate, is confirmed by this RCT, this will offer a
      strong argument to adopt a single gift of antibiotic prophylaxis as standard practice of
      care. This will reduce the incidence of POWIs and consequently will lead to less physical and
      social disabilities and health care use. In addition, it will decrease the rate of use of
      empiric broad-spectrum antibiotics (and antibiotic resistance) prescribed upon suspicion or
      diagnosis of a POWI. A preliminary, conservative estimation suggests yearly cost savings in
      the Netherlands of €3.5 million per year.
See study protocol
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Postoperative wound infection (POWI)
time frame: 30 days
description: The primary outcome variable is a POWI within 30 days after implant removal as defined by the criteria applied by the Centers for Disease and Control.
measure: Health-related quality of life
time frame: baseline, one month, 6 months
description: Health-related quality of life (as measured by the EQ-5D questionnaire)
measure: Functional outcome
time frame: baseline, 1 month, 6 months
description: Functional outcome following implant removal as assessed with the Lower Extremity Functional Scale (LEFS). The LEFS can be used by clinicians as a measure of patients' initial function, ongoing progress and outcome, as well as to set functional goals. The LEFS can be used to evaluate the functional impairment of a patient with a disorder of one or both lower extremities. It can be used to monitor the patient over time and to evaluate the effectiveness of an intervention
measure: Patient satisfaction
time frame: 1 month, 6 months
description: Patient satisfaction following implant removal as measured by a ten-point Visual Analog Scale
measure: Health care resources utilization
time frame: baseline, 1 month, 6 months
description: Health care resources utilization at baseline, 1 month and 6 months after implant removal (including amongst others, number of visits to the general practitioner and use of home care organizations) as measured by way of a combination of the Dutch iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) (adapted to the study setting).
measure: Costs
time frame: Costs per quality adjusted life year
description: Costs (economic evaluation including budget impact analysis): the economic evaluation of antibiotic prophylaxis in patients scheduled for implant removal (following a foot, ankle or lower leg fracture) against no prophylaxis as its best alternative will be performed as a cost-effectiveness (CEA) as well as a cost-utility (CUA) analysis.
arm group label: antibiotic prophylaxis
arm group type: Active Comparator
description: a single gift of 1000 mg cefazolin in 10 cc of NaCl 0.9% (intervention group)
arm group label: No antibiotic prophylaxis
arm group type: Placebo Comparator
description: a single gift of 10 cc NaCl 0.9%, given in the same manner (control group).
intervention type: Drug
intervention name: Cephalozin
description: 1000 mg Cephalozin
arm group label: antibiotic prophylaxis
other name: Kefzol
intervention type: Other
intervention name: Sodium chloride
description: 10 cc of NaCl 0.9%
arm group label: No antibiotic prophylaxis
other name: NaCl 0.9%
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Manouk Backes, MD, MSc
role: Study Chair
affiliation: Academic Medical Center/Sint Lucas Andreas Hospital
last name: Tim Schepers, MD, PhD
role: Study Director
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
facility: 
facility: 
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facility: 
facility: 
facility: 
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facility: 
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country: Netherlands
citation: Backes M, Schep NW, Luitse JS, Goslings JC, Schepers T. Indications for implant removal following intra-articular calcaneal fractures and subsequent complications. Foot Ankle Int. 2013 Nov;34(11):1521-5. doi: 10.1177/1071100713502466. Epub 2013 Sep 13.
PMID: 24038057
citation: Backes M, Dingemans SA, Schep NW, Bloemers FW, Van Dijkman B, Garssen FP, Haverlag R, Hoogendoorn JM, Joosse P, Mirck B, Postma V, Ritchie E, Roerdink WH, Sintenie JB, Soesman NM, Sosef NL, Twigt BA, Van Veen RN, Van der Veen AH, Van Velde R, Vos DI, De Vries MR, Winkelhagen J, Goslings JC, Schepers T. Wound Infections Following Implant removal below the knee: the effect of antibiotic prophylaxis; the WIFI-trial, a multi-centre randomized controlled trial. BMC Surg. 2015 Feb 6;15:12. doi: 10.1186/1471-2482-15-12.
PMID: 25972101
responsible party type: Principal Investigator
investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
investigator full name: J.C. Goslings
investigator title: Prof. Dr.
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Wound Infection
mesh term: Surgical Wound Infection
mesh term: Wounds and Injuries
mesh term: Surgical Wound
sharing ipd: Undecided