xml: <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/NCT06023238</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY22070087</org_study_id>
      <nct_id>NCT06023238</nct_id>
    </id_info>
    <brief_title>Knee Prosthetic Joint Infection Antibiotic Elution</brief_title>
    <official_title>Antibiotic Elution Profile and Outcomes in the Treatment of Prosthetic Joint Infections of the Knee</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Pittsburgh</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Pittsburgh</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Patients presenting with prosthetic joint infections of a total knee replacement who are&#xD;
        treated with an antibiotic spacer will be observed prospectively for their response to&#xD;
        treatment and antibiotic elution profiles will be measured post-operatively utilizing mass&#xD;
        spectrometry from synovial fluid acquired as part of standard of care in the management of&#xD;
        prosthetic joint infection. Secondary outcomes including post-operative complications,&#xD;
        re-operation rates, and re-admission rates will also be compared.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The current study aims to assess the surgical and patient-reported outcomes and in vivo&#xD;
        antibiotic elution profile of the management of total knee arthroplasty (TKA) prosthetic&#xD;
        joint infection (PJI). Within the standard of care, TKA PJI is treated via a resection&#xD;
        arthroplasty and antibiotic cement spacer placement. Patients will be enrolled if they are&#xD;
        undergoing surgical management for a chronic TKA PJI and will receive surgical treatment&#xD;
        according to the standard of care. In the post-operative period, patients will be monitored&#xD;
        for surgical and patient-reported outcomes including re-operation rate, pain scores,&#xD;
        complication rates, and re-infection rates. Synovial fluid obtained from intra-articular&#xD;
        postoperative drains and at postoperative knee aspirations during reimplantation evaluations&#xD;
        will also be utilized for antibiotic concentration quantification via mass spectrometry, if&#xD;
        sufficient specimen is available. Patient who undergo surgical management for their chronic&#xD;
        TKA PJI will then have their measured antibiotic elution concentrations compared. The study&#xD;
        hypothesizes that patients undergoing treatment of a PJI with antibiotic spacer + antibiotic&#xD;
        cement spacer will have better surgical and patient-related outcomes with higher antibiotic&#xD;
        elution concentrations. These improved outcomes would include lower re-operation rates, lower&#xD;
        pain scores, lower wound healing complications, and higher rates of second stage&#xD;
        re-implantation observed in patients with higher antibiotic elution concentrations.&#xD;
  &#xD;
        Specific aims:&#xD;
  &#xD;
          1. To evaluate the antibiotic elution profile and post-operative intra-synovial&#xD;
             concentrations in the treatment of chronic PJI after TKA.&#xD;
  &#xD;
          2. To evaluate surgical and patient-related outcomes in chronic TKA PJI patients following&#xD;
             implant resection and knee spacer placement, including amount of post-operative drain&#xD;
             output, wound healing complications, 30- and 90-day risk of re-operation, pain scores,&#xD;
             and rate of second stage re-implantation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 5, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Intra-articular Antibiotic Elution Profile</measure>
      <time_frame>Post-operative day 2 and during 2nd stage re-implantation evaluation (around 10 weeks according to standard of care)</time_frame>
      <description>Antibiotic concentration will be quantified utilizing mass spectrometry from intra-articular synovial fluid obtained from post-operative drain and knee aspirations performed for re-implantation evaluation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Drain Output</measure>
      <time_frame>Each 12 hours period until removal of the drain up to 5 days postoperatively based on drain output less than 30cc in 12 hours.</time_frame>
      <description>Measured volume of output from post-operative drain will be quantified every 12 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Wound Healing Complications</measure>
      <time_frame>up to 6 months following surgery</time_frame>
      <description>Any issues with wound healing including closure, occurrence of infection, high drainage, or hematoma formation will be among wound healing complications which are measured.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Re-operation Rates</measure>
      <time_frame>30 days and 90 days post-operatively.</time_frame>
      <description>Rates of return to operating room will be quantified over course of 30 days and 90 days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Re-admission Rates</measure>
      <time_frame>30 days and 90 days post-operatively.</time_frame>
      <description>Rates of re-admission will be quantified over course of 30 days and 90 days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pain Scores</measure>
      <time_frame>Daily on postop day 0 until postop day 5, 3 weeks, 6 weeks and 10 weeks, 6 months postoperatively.</time_frame>
      <description>Pain scores utilizing visual analog scale from 0 to 10 will be quantified during post-operative course.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Second Stage Re-implantation Rates</measure>
      <time_frame>Through study completion up to 1 year</time_frame>
      <description>Rates of successful second stage re-implantation will be quantified during the post-operative course.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Knee aspiration cell count</measure>
      <time_frame>3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.</time_frame>
      <description>Knee aspiration with number of white cells less than 1300</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Knee aspiration culture</measure>
      <time_frame>3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.</time_frame>
      <description>Knee aspiration without evidence of bacteria on bacterial culture</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-reactive protein assessment</measure>
      <time_frame>baseline, 10 weeks to 6 months posteroperatively</time_frame>
      <description>C-reactive protein normalization (less than 1mg/dl)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ESR assessment</measure>
      <time_frame>baseline, 10 weeks to 6 months posteroperatively</time_frame>
      <description>Erythrocyte sedimentation rate normalization (less than 20 mm/hr)</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Prosthetic-joint Infection</condition>
    <condition>Arthroplasty Complications</condition>
    <arm_group>
      <arm_group_label>Chronic TKA PJI Group</arm_group_label>
      <description>Patients presenting for surgical management of a chronic total knee arthroplasty (TKA) prosthetic joint infection (PJI). Patients will be excluded if they are less than 18 years of age, have a prior history of ipsilateral or contralateral PJI warranting operative management, or are unable to provide informed consent.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Treatment of Chronic TKA PJI</intervention_name>
      <description>Patients will all undergo standard of care treatment for a chronic total knee arthroplasty prosthetic joint infection.</description>
      <arm_group_label>Chronic TKA PJI Group</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Synovial fluid obtained in the post-operative setting as part of standard of care&#xD;
        intra-articular post-operative drains or as part of standard of care intra-articular knee&#xD;
        aspiration performed during re-implantation revaluation.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          The study population will comprise of patients who have had a previous total knee&#xD;
          arthroplasty (TKA), presenting with clinical and laboratory findings concerning for a&#xD;
          chronic TKA prosthetic joint infection (PJI) undergoing staged surgical management&#xD;
          consisting of resection arthroplasty followed by mobile antibiotic spacer placement.&#xD;
          Patients who have had prior surgical treatment of a PJI and are less than 18 years of age&#xD;
          will not be included in the study population.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients planned for treatment of a total knee arthroplasty prosthetic joint infection&#xD;
  &#xD;
            -  Patients greater than 18 years of age&#xD;
  &#xD;
            -  Patients able to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior history of ipsilateral or contralateral prosthetic joint infection warranting&#xD;
               operative management&#xD;
  &#xD;
            -  Patients less than 18 years of age&#xD;
  &#xD;
            -  Patients unable to provide informed consent.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Johannes F Plate, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Pittsburgh Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Johannes F Plate, MD, PhD</last_name>
      <phone>412-802-4100</phone>
      <email>platefj2@upmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Matthew F Gong, MD</last_name>
      <phone>412-605-3262</phone>
      <email>gongm2@upmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>UPMC Shadyside</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15232</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Johannes F Plate, MD, PhD</last_name>
        <phone>412-802-4100</phone>
        <email>platefj2@upmc.edu</email>
      </contact>
      <contact_backup>
        <last_name>Matthew F Gong, MD</last_name>
        <phone>412-605-3262</phone>
        <email>gongm2@upmc.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Johannes F Plate, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Chen AF, Parvizi J. Antibiotic-loaded bone cement and periprosthetic joint infection. J Long Term Eff Med Implants. 2014;24(2-3):89-97. doi: 10.1615/jlongtermeffmedimplants.2013010238.</citation>
      <PMID>25272207</PMID>
    </reference>
    <reference>
      <citation>Slane J, Gietman B, Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res. 2018 Apr;36(4):1078-1085. doi: 10.1002/jor.23722. Epub 2017 Sep 20.</citation>
      <PMID>28876459</PMID>
    </reference>
    <reference>
      <citation>Anagnostakos K, Wilmes P, Schmitt E, Kelm J. Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo. Acta Orthop. 2009 Apr;80(2):193-7. doi: 10.3109/17453670902884700.</citation>
      <PMID>19404802</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>F. Johannes Plate</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Prosthetic Joint Infection</keyword>
    <keyword>Revision Total Knee Arthroplasty</keyword>
    <keyword>Antibiotic Elution Profile</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>Arthritis, Infectious</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>There are no plans at present to make individual participant data (IPD) available to other researchers, however we may share de-identified data with other researchers in the future.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023238
  org study id: STUDY22070087
  nct id: NCT06023238
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Patients presenting with prosthetic joint infections of a total knee replacement who are
        treated with an antibiotic spacer will be observed prospectively for their response to
        treatment and antibiotic elution profiles will be measured post-operatively utilizing mass
        spectrometry from synovial fluid acquired as part of standard of care in the management of
        prosthetic joint infection. Secondary outcomes including post-operative complications,
        re-operation rates, and re-admission rates will also be compared.
  The current study aims to assess the surgical and patient-reported outcomes and in vivo
        antibiotic elution profile of the management of total knee arthroplasty (TKA) prosthetic
        joint infection (PJI). Within the standard of care, TKA PJI is treated via a resection
        arthroplasty and antibiotic cement spacer placement. Patients will be enrolled if they are
        undergoing surgical management for a chronic TKA PJI and will receive surgical treatment
        according to the standard of care. In the post-operative period, patients will be monitored
        for surgical and patient-reported outcomes including re-operation rate, pain scores,
        complication rates, and re-infection rates. Synovial fluid obtained from intra-articular
        postoperative drains and at postoperative knee aspirations during reimplantation evaluations
        will also be utilized for antibiotic concentration quantification via mass spectrometry, if
        sufficient specimen is available. Patient who undergo surgical management for their chronic
        TKA PJI will then have their measured antibiotic elution concentrations compared. The study
        hypothesizes that patients undergoing treatment of a PJI with antibiotic spacer + antibiotic
        cement spacer will have better surgical and patient-related outcomes with higher antibiotic
        elution concentrations. These improved outcomes would include lower re-operation rates, lower
        pain scores, lower wound healing complications, and higher rates of second stage
        re-implantation observed in patients with higher antibiotic elution concentrations.
  
        Specific aims:
  
          1. To evaluate the antibiotic elution profile and post-operative intra-synovial
             concentrations in the treatment of chronic PJI after TKA.
  
          2. To evaluate surgical and patient-related outcomes in chronic TKA PJI patients following
             implant resection and knee spacer placement, including amount of post-operative drain
             output, wound healing complications, 30- and 90-day risk of re-operation, pain scores,
             and rate of second stage re-implantation.
  observational model: Case-Only
  time perspective: Prospective
  measure: Intra-articular Antibiotic Elution Profile
  time frame: Post-operative day 2 and during 2nd stage re-implantation evaluation (around 10 weeks according to standard of care)
  description: Antibiotic concentration will be quantified utilizing mass spectrometry from intra-articular synovial fluid obtained from post-operative drain and knee aspirations performed for re-implantation evaluation.
  measure: Drain Output
  time frame: Each 12 hours period until removal of the drain up to 5 days postoperatively based on drain output less than 30cc in 12 hours.
  description: Measured volume of output from post-operative drain will be quantified every 12 hours
  measure: Wound Healing Complications
  time frame: up to 6 months following surgery
  description: Any issues with wound healing including closure, occurrence of infection, high drainage, or hematoma formation will be among wound healing complications which are measured.
  measure: Re-operation Rates
  time frame: 30 days and 90 days post-operatively.
  description: Rates of return to operating room will be quantified over course of 30 days and 90 days.
  measure: Re-admission Rates
  time frame: 30 days and 90 days post-operatively.
  description: Rates of re-admission will be quantified over course of 30 days and 90 days.
  measure: Pain Scores
  time frame: Daily on postop day 0 until postop day 5, 3 weeks, 6 weeks and 10 weeks, 6 months postoperatively.
  description: Pain scores utilizing visual analog scale from 0 to 10 will be quantified during post-operative course.
  measure: Second Stage Re-implantation Rates
  time frame: Through study completion up to 1 year
  description: Rates of successful second stage re-implantation will be quantified during the post-operative course.
  measure: Knee aspiration cell count
  time frame: 3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.
  description: Knee aspiration with number of white cells less than 1300
  measure: Knee aspiration culture
  time frame: 3 weeks, 6 weeks and 10 weeks - 6 months postoperatively.
  description: Knee aspiration without evidence of bacteria on bacterial culture
  measure: C-reactive protein assessment
  time frame: baseline, 10 weeks to 6 months posteroperatively
  description: C-reactive protein normalization (less than 1mg/dl)
  measure: ESR assessment
  time frame: baseline, 10 weeks to 6 months posteroperatively
  description: Erythrocyte sedimentation rate normalization (less than 20 mm/hr)
  arm group label: Chronic TKA PJI Group
  description: Patients presenting for surgical management of a chronic total knee arthroplasty (TKA) prosthetic joint infection (PJI). Patients will be excluded if they are less than 18 years of age, have a prior history of ipsilateral or contralateral PJI warranting operative management, or are unable to provide informed consent.
  intervention type: Procedure
  intervention name: Treatment of Chronic TKA PJI
  description: Patients will all undergo standard of care treatment for a chronic total knee arthroplasty prosthetic joint infection.
  arm group label: Chronic TKA PJI Group
  Synovial fluid obtained in the post-operative setting as part of standard of care
        intra-articular post-operative drains or as part of standard of care intra-articular knee
        aspiration performed during re-implantation revaluation.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Johannes F Plate, MD, PhD
  role: Principal Investigator
  affiliation: University of Pittsburgh Medical Center
  last name: Johannes F Plate, MD, PhD
  phone: 412-802-4100
  email: platefj2@upmc.edu
  last name: Matthew F Gong, MD
  phone: 412-605-3262
  email: gongm2@upmc.edu
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: United States
  citation: Chen AF, Parvizi J. Antibiotic-loaded bone cement and periprosthetic joint infection. J Long Term Eff Med Implants. 2014;24(2-3):89-97. doi: 10.1615/jlongtermeffmedimplants.2013010238.
  PMID: 25272207
  citation: Slane J, Gietman B, Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res. 2018 Apr;36(4):1078-1085. doi: 10.1002/jor.23722. Epub 2017 Sep 20.
  PMID: 28876459
  citation: Anagnostakos K, Wilmes P, Schmitt E, Kelm J. Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo. Acta Orthop. 2009 Apr;80(2):193-7. doi: 10.3109/17453670902884700.
  PMID: 19404802
  responsible party type: Principal Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: F. Johannes Plate
  investigator title: Associate Professor
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Arthritis, Infectious
  sharing ipd: Undecided
  ipd description: There are no plans at present to make individual participant data (IPD) available to other researchers, however we may share de-identified data with other researchers in the future.