<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/NCT02227446</url>
  </required_header>
  <id_info>
    <org_study_id>W81XWH-10-2-0134</org_study_id>
    <nct_id>NCT02227446</nct_id>
  </id_info>
  <brief_title>Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO)</brief_title>
  <acronym>VANCO</acronym>
  <official_title>Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (Vancomycin Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Major Extremity Trauma Research Consortium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Major Extremity Trauma Research Consortium</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Vancomycin Study is a multi-center, prospective randomized controlled trial that will&#xD;
      compare the proportion of deep surgical site infections within 6 months in patients treated&#xD;
      with local Vancomycin powder compared to those treated without local Vancomycin powder at the&#xD;
      time of fracture fixation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Aim: Compare the proportion of deep surgical site infections within 6 months in&#xD;
      patients treated with local Vancomycin powder compared to those treated without local&#xD;
      Vancomycin powder.&#xD;
&#xD;
      Primary Hypothesis: The proportion of deep surgical site infections will be lower for&#xD;
      patients treated with local Vancomycin powder.&#xD;
&#xD;
      Secondary Aim #1: Compare antibiotic sensitivities of the bacteria in the patients who&#xD;
      develop deep surgical site infections in study patients treated with local Vancomycin powder&#xD;
      compared to those treated without local Vancomycin powder.&#xD;
&#xD;
      Hypothesis 1: In the patients who develop infections, the antibiotic sensitivity profiles&#xD;
      between patients treated with local Vancomycin powder will be non-inferior to those treated&#xD;
      without local Vancomycin powder.&#xD;
&#xD;
      Secondary Aim #2: Build and validate a risk prediction model for the development of deep&#xD;
      surgical site infections in patients treated without local Vancomycin powder. (b) Explore&#xD;
      whether the effect of local Vancomycin powder is modified by the predicted risk of infection.&#xD;
&#xD;
      Hypothesis 2: Patient (e.g. medical co-morbidities) and injury (e.g open fractures) factors&#xD;
      will be highly predictive of infection risk.&#xD;
&#xD;
      Hypothesis 3: Patients with higher predictive risk will experience greater benefit from local&#xD;
      antibiotics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">November 2019</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>Phase 3</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>Number of Clinically Significant Deep Surgical Site Infection (SSI)</measure>
    <time_frame>26 weeks</time_frame>
    <description>The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months.&#xD;
Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS).&#xD;
The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bacterial Antibiotic Resistance Rate of Infected Participants</measure>
    <time_frame>26 weeks</time_frame>
    <description>Secondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis.&#xD;
The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify Risk Factors for Infection</measure>
    <time_frame>26 weeks</time_frame>
    <description>A secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique.&#xD;
Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days.&#xD;
Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries.&#xD;
Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1036</enrollment>
  <condition>Post Operative Surgical Site Infection</condition>
  <arm_group>
    <arm_group_label>Vancomycin Antibotic Powder</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution.&#xD;
In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vancomycin antibiotic powder</intervention_name>
    <description>At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.</description>
    <arm_group_label>Vancomycin Antibotic Powder</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All &quot;high energy&quot; tibial plateau fractures treated operatively with plate and screw&#xD;
             fixation.&#xD;
&#xD;
          -  We define &quot;high energy&quot; tibial plateau fractures as patients who are either:&#xD;
&#xD;
               -  Initially treated with an external fixation (with or without limited internal&#xD;
                  fixation) and treated definitively more than 3 days later after swelling has&#xD;
                  resolved.&#xD;
&#xD;
               -  Any open type I, II, or IIIA fracture, regardless of timing of definitive&#xD;
                  treatment.&#xD;
&#xD;
               -  Any tibial plateau fracture associated with ipsilateral leg compartment syndrome&#xD;
                  fasciotomy wounds.&#xD;
&#xD;
          -  All &quot;high energy&quot; pilon (distal tibial plafond) fractures treated operatively with&#xD;
             plate and screw fixation. We define &quot;high energy&quot; pilon fractures as patients who are&#xD;
             either:&#xD;
&#xD;
               -  Initially treated with an external fixation (with or without fibula fixation or&#xD;
                  limited internal fixation) and treated definitively more than 3 days later after&#xD;
                  swelling has resolved.&#xD;
&#xD;
               -  Any open type I, II, or IIIA fracture, regardless of timing of definitive&#xD;
                  treatment.&#xD;
&#xD;
               -  Any tibial pilon fracture associated with ipsilateral leg compartment syndrome&#xD;
                  fasciotomy wounds.&#xD;
&#xD;
          -  Ages 18 to 80 years&#xD;
&#xD;
          -  Patients may have co-existing non-tibial infection, with or without antibiotic&#xD;
             treatment.&#xD;
&#xD;
          -  Patients may have risk factors for infection including diabetes, immunosuppression&#xD;
             from steroids or other medications, HIV, or other infections.&#xD;
&#xD;
          -  Patients may have a head injury&#xD;
&#xD;
          -  Patients may have a portion of the fixation (e.g. fibula fixation in pilon or&#xD;
             percutaneous screws across a tibial plateau fracture) prior to definitive plate&#xD;
             fixation, at the initial surgery before randomization.&#xD;
&#xD;
          -  Patients may have other orthopedic and non-orthopaedic injuries.&#xD;
&#xD;
          -  Patients may have pre-existing musculoskeletal injuries, be non ambulators, or have&#xD;
             spinal cord injuries.&#xD;
&#xD;
          -  Women and minorities are included&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The study injury: tibial plateau, pilon, is already infected at time of study&#xD;
             enrollment.&#xD;
&#xD;
          -  Patient speaks neither English nor Spanish.&#xD;
&#xD;
          -  Patients who have already had definitive fixation prior to enrollment in the study.&#xD;
&#xD;
          -  Severe problems with maintaining follow-up (e.g. patients who are homeless at the time&#xD;
             of injury or those how are intellectually challenged without adequate family support).&#xD;
&#xD;
          -  Patients with allergies, drug administration reactions, or other sensitivities to&#xD;
             Vancomycin (such as a history of Redman's Syndrome).&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  The study injury is a type IIIB or IIIC open fracture.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Renan Castillo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert O'Toole, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland R Adams Cowley Shock Trauma Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anthony Carlini, MS</last_name>
    <role>Study Director</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Maryland R Adams Cowley Shock Trauma Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://metrc.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <results_first_submitted>July 23, 2020</results_first_submitted>
  <results_first_submitted_qc>May 6, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 1, 2021</results_first_posted>
  <last_update_submitted>May 6, 2021</last_update_submitted>
  <last_update_submitted_qc>May 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Surgical site infection risk prevention</keyword>
  <keyword>Bacterial species type and antibacterial sensitives</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>Surgical Wound Infection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Vancomycin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 6, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT02227446/Prot_ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT02227446/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Approximately 1000 participants (500 per treatment arm) were enrolled across 36 METRC trauma centers over a 30-month period. Participants were recruited during the initial hospitalization for the their injury.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder.</description>
        </group>
        <group group_id="P2">
          <title>Vancomycin Powder</title>
          <description>Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="521"/>
                <participants group_id="P2" count="515"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="499"/>
                <participants group_id="P2" count="481"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>not eligible post randomization</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vancomycin Antibiotic Powder</title>
          <description>Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution.&#xD;
In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.&#xD;
Vancomycin antibiotic powder: At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care</title>
          <description>Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="481"/>
            <count group_id="B2" value="499"/>
            <count group_id="B3" value="980"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Mean age (SD) in each study arm.</description>
          <population>Numbers differ because each arm had a different number of participants.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.4" spread="14"/>
                    <measurement group_id="B2" value="46.1" spread="13.5"/>
                    <measurement group_id="B3" value="45.75" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="182"/>
                    <measurement group_id="B2" value="181"/>
                    <measurement group_id="B3" value="363"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="299"/>
                    <measurement group_id="B2" value="318"/>
                    <measurement group_id="B3" value="617"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="339"/>
                    <measurement group_id="B2" value="346"/>
                    <measurement group_id="B3" value="685"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Refused/Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Clinically Significant Deep Surgical Site Infection (SSI)</title>
        <description>The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months.&#xD;
Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS).&#xD;
The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.</description>
        <time_frame>26 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vancomycin Antibotic Powder</title>
            <description>Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution.&#xD;
In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.&#xD;
Vancomycin antibiotic powder: At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Deep Surgical Site Infection (SSI)</title>
          <description>The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months.&#xD;
Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS).&#xD;
The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.</description>
          <units>surgical site infections</units>
          <param>Count of Units</param>
          <units_analyzed>surgical site infections</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="481"/>
                <count group_id="O2" value="499"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>surgical site infections</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="481"/>
                <count group_id="O2" value="499"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total deep Surgical Site Infections</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Culture negative deep SSI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gram positive deep SSI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gram negative deep SSI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anerobe/fungal deep SSI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Contaminated sample</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bacterial Antibiotic Resistance Rate of Infected Participants</title>
        <description>Secondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis.&#xD;
The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.</description>
        <time_frame>26 weeks</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Identify Risk Factors for Infection</title>
        <description>A secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique.&#xD;
Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days.&#xD;
Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries.&#xD;
Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.</description>
        <time_frame>26 weeks</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>36 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder.</description>
        </group>
        <group group_id="E2">
          <title>Vancomycin Powder</title>
          <description>Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="499"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="499"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Venous thromboembolism (VTE)</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="499"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal laboratory values</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Reaction to antibiotic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="499"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Nonunion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="499"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Manipulation under anesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Amputation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="499"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
              <event>
                <sub_title>Thoracic injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="499"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="499"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="481"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Susan Collins</name_or_title>
      <organization>METRC</organization>
      <phone>4105028966</phone>
      <email>scolli21@jhu.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02227446
org study id: W81XWH-10-2-0134
nct id: NCT02227446
lead sponsor: 
has dmc: Yes
The Vancomycin Study is a multi-center, prospective randomized controlled trial that will
      compare the proportion of deep surgical site infections within 6 months in patients treated
      with local Vancomycin powder compared to those treated without local Vancomycin powder at the
      time of fracture fixation.
Primary Aim: Compare the proportion of deep surgical site infections within 6 months in
      patients treated with local Vancomycin powder compared to those treated without local
      Vancomycin powder.

      Primary Hypothesis: The proportion of deep surgical site infections will be lower for
      patients treated with local Vancomycin powder.

      Secondary Aim #1: Compare antibiotic sensitivities of the bacteria in the patients who
      develop deep surgical site infections in study patients treated with local Vancomycin powder
      compared to those treated without local Vancomycin powder.

      Hypothesis 1: In the patients who develop infections, the antibiotic sensitivity profiles
      between patients treated with local Vancomycin powder will be non-inferior to those treated
      without local Vancomycin powder.

      Secondary Aim #2: Build and validate a risk prediction model for the development of deep
      surgical site infections in patients treated without local Vancomycin powder. (b) Explore
      whether the effect of local Vancomycin powder is modified by the predicted risk of infection.

      Hypothesis 2: Patient (e.g. medical co-morbidities) and injury (e.g open fractures) factors
      will be highly predictive of infection risk.

      Hypothesis 3: Patients with higher predictive risk will experience greater benefit from local
      antibiotics.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Clinically Significant Deep Surgical Site Infection (SSI)
time frame: 26 weeks
description: The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months.
Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS).
The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.
measure: Bacterial Antibiotic Resistance Rate of Infected Participants
time frame: 26 weeks
description: Secondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis.
The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.
measure: Identify Risk Factors for Infection
time frame: 26 weeks
description: A secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique.
Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days.
Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries.
Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.
arm group label: Vancomycin Antibotic Powder
arm group type: Experimental
description: Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution.
In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.
arm group label: Standard of Care
arm group type: No Intervention
description: Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder.
intervention type: Drug
intervention name: Vancomycin antibiotic powder
description: At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.
arm group label: Vancomycin Antibotic Powder
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Renan Castillo, PhD
role: Principal Investigator
affiliation: Johns Hopkins Bloomberg School of Public Health
last name: Robert O'Toole, MD
role: Principal Investigator
affiliation: University of Maryland R Adams Cowley Shock Trauma Center
last name: Anthony Carlini, MS
role: Study Director
affiliation: Johns Hopkins Bloomberg School of Public Health
facility: 
country: United States
url: http://metrc.org
description: Related Info
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection
mesh term: Anti-Bacterial Agents
mesh term: Vancomycin
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 