<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/NCT02971657</url>
  </required_header>
  <id_info>
    <org_study_id>2011-02</org_study_id>
    <nct_id>NCT02971657</nct_id>
  </id_info>
  <brief_title>Bacterial Phenotype of Staphylococcus Aureus Has no Effect on Patients' Clinical Outcome in Orthopedic Device Related Bone Infections</brief_title>
  <acronym>StaphType</acronym>
  <official_title>Bacterial Phenotype of Staphylococcus Aureus Has no Effect on Patients' Clinical Outcome in Orthopedic Device Related Bone Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BG Unfallklinik</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AO Research Institute Davos</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>BG Unfallklinik</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a prospective study performed between November 2011 and September 2013. Patients&#xD;
      with a confirmed S. aureus infection after fracture fixation or prosthetic joint infection&#xD;
      were included. Exclusion criteria included infections involving external fixation pins,&#xD;
      infections without any implanted hardware and culture positive patients not displaying any&#xD;
      clinical sign of infection. The following surgical parameters were documented: affected bone&#xD;
      or joint; type of implant; time between implantation of the device and onset of symptoms.&#xD;
      Personal characteristics and patients'health status were also documented. Any revision&#xD;
      surgeries involving the site of interest and all isolated pathogens were recorded throughout&#xD;
      the course of treatment and follow-up.&#xD;
&#xD;
      A follow up examination was performed an average of 23 months after discharge. Primary&#xD;
      outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of&#xD;
      interest) or systemic signs of infection, terminated surgical and systemic therapy and&#xD;
      restoration of joint or limb function.&#xD;
&#xD;
      At the first surgical procedure after enrolment, at least four deep bone biopsies were taken&#xD;
      from the interface between implant and affected bone. Identification and antibiotic&#xD;
      susceptibility testing of all growth was performed. Multi-drug-resistance (MDR) was defined&#xD;
      according to the definitions of the European Committee of Antimicrobial Susceptibility&#xD;
      Testing (EUCAST). Biofilm formation was analysed and quantified in microtitre plate assays&#xD;
      according to protocol of Stepanovic et al.(see references).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a prospective study performed between November 2011 and September 2013. All patients&#xD;
      provided informed written consent prior to inclusion in the study. Inclusion criteria were&#xD;
      deep S. aureus infections after fracture fixation or prosthetic joint surgery. Fracture&#xD;
      fixation infections includes fractures involving the long bones as well as the pelvis and the&#xD;
      spine. Bacterial growth at the site of interest in combination with either pseudarthrosis,&#xD;
      implant-loosening/failure or local and systemic signs of surgical site infection were&#xD;
      required for inclusion. Exclusion criteria included infections involving external fixation&#xD;
      pins, infections without any implanted hardware and culture positive patients not displaying&#xD;
      any clinical sign of infection.&#xD;
&#xD;
      Upon entry into the study, the following surgical parameters were documented: affected bone&#xD;
      or joint; type of implant; time between implantation of the device and onset of symptoms.&#xD;
      Personal characteristics were also documented and included: gender; age; body mass index&#xD;
      (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic&#xD;
      immunosuppressive conditions (Diabetes mellitus, chronic alcoholism, Child's class C&#xD;
      cirrhosis, neoplasia, transplantation, AIDS and steroid medication). Any revision surgeries&#xD;
      involving the site of interest and all isolated pathogens were recorded throughout the course&#xD;
      of treatment and follow-up.&#xD;
&#xD;
      A follow up examination was performed an average of 23 months after discharge. Primary&#xD;
      outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of&#xD;
      interest) or systemic signs of infection and terminated surgical and systemic therapy.&#xD;
&#xD;
      At the first surgical procedure after enrolment, at least four deep bone biopsies were taken&#xD;
      from the interface between implant and affected bone. The tissue samples were placed in a&#xD;
      sterile container with thioglycollate liquid medium (bioMérieux, Hazelwood, MO, USA). The&#xD;
      samples were cultured for ten days at 37°C and examined each day macroscopically. Any growth&#xD;
      was inoculated onto a blood agar plate (bioMérieux, Hazelwood, MO, USA) for further growth&#xD;
      and subsequent identification. In all cases, additional swabs and soft tissue samples may&#xD;
      have been taken as per clinical routine, however, only samples adjacent to the implant were&#xD;
      used for diagnosis in this study.&#xD;
&#xD;
      Identification and antibiotic susceptibility testing of all growth was performed using a&#xD;
      Vitek2 (bioMerieux Vitek Inc, Hazelwood, MO, USA). Multi-drug-resistance (MDR) was defined&#xD;
      according to the definitions of the European Committee of Antimicrobial Susceptibility&#xD;
      Testing (EUCAST). Oxacillin resistance was used as an indicator for methicillin resistant S.&#xD;
      aureus (MRSA).&#xD;
&#xD;
      Biofilm formation was analysed and quantified in microtitre plate assays according to the&#xD;
      well-established protocol of Stepanovic et al.(see references).&#xD;
&#xD;
      The key variables with regards to bacterial phenotype were: biofilm formation; methicillin&#xD;
      resistance;multidrug resistance;staphyloxanthin production and hemolysis. The primary outcome&#xD;
      measure was whether the infection was &quot;cured&quot; or not. Primary outcome parameters were&#xD;
      calculated as a function of all patients for whom data was complete. Statistical comparison&#xD;
      was restricted to the lower extremity cohort since the other patients are not scored for many&#xD;
      of the functional outcome measures and as such incomplete.&#xD;
&#xD;
      Univariate logistic regression models were used to determine the influence of each prognostic&#xD;
      factor (obesity, smoking, diabetes mellitus, chronic immune suppression, open fracture&#xD;
      (initially), early onset infection, biofilm formation, methicillin resistance, MDR and&#xD;
      Charlson comorbidity index) on cure. P-values &lt;0.05 were considered significant. Statistical&#xD;
      analyses were performed using SAS software (Version 9.2; Cary, NC, USA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2011</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Cure</measure>
    <time_frame>23 months</time_frame>
    <description>Cure was defined by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic antibiotic therapy. All Parameters had to be positive to fulfill the outcome parameter &quot;cure&quot;.If one of the mentioned parameters was negative, outcome was defined as &quot;not cured&quot;. Local signs of infection were defined as the appearance of: redness, tenderness, swelling or persisting wound drainage.</description>
  </primary_outcome>
  <enrollment type="Actual">126</enrollment>
  <condition>Staphylococcal Infections</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bacterial samples from orthopaedic device related infections&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Orthopaedic device related infection involving longbones of the upper and lower extremities&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infections after fracture fixation or prosthetic joint surgery&#xD;
&#xD;
          -  Affected bone or joint: Long bones of the lower and upper extremity&#xD;
&#xD;
          -  Bacterial growth of S. aureus at the site of interest&#xD;
&#xD;
          -  Written consent&#xD;
&#xD;
          -  Age: 18 and older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no prove of bacterial growth at site of interest&#xD;
&#xD;
          -  missing consent&#xD;
&#xD;
          -  infections involving external fixation pins, infections without any implanted&#xD;
             hardware.&#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>
  <reference>
    <citation>Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I, Ruzicka F. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007 Aug;115(8):891-9. doi: 10.1111/j.1600-0463.2007.apm_630.x.</citation>
    <PMID>17696944</PMID>
  </reference>
  <reference>
    <citation>Post V, Wahl P, Uckay I, Ochsner P, Zimmerli W, Corvec S, Loiez C, Richards RG, Moriarty TF. Phenotypic and genotypic characterisation of Staphylococcus aureus causing musculoskeletal infections. Int J Med Microbiol. 2014 Jul;304(5-6):565-76. doi: 10.1016/j.ijmm.2014.03.003. Epub 2014 Apr 3.</citation>
    <PMID>24768432</PMID>
  </reference>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>November 23, 2016</last_update_submitted>
  <last_update_submitted_qc>November 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 25, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>BG Unfallklinik</investigator_affiliation>
    <investigator_full_name>Dr. Mario Morgenstern</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Staphylococcus aureus phenotypic characterization</keyword>
  <keyword>Antibiotic resistance</keyword>
  <keyword>Orthopedic device related infections</keyword>
  <keyword>Phenotypic characterization</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>Staphylococcal Infections</mesh_term>
  </condition_browse>
  <!-- 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/NCT02971657
org study id: 2011-02
nct id: NCT02971657
lead sponsor: 
collaborator: 
has dmc: No
This was a prospective study performed between November 2011 and September 2013. Patients
      with a confirmed S. aureus infection after fracture fixation or prosthetic joint infection
      were included. Exclusion criteria included infections involving external fixation pins,
      infections without any implanted hardware and culture positive patients not displaying any
      clinical sign of infection. The following surgical parameters were documented: affected bone
      or joint; type of implant; time between implantation of the device and onset of symptoms.
      Personal characteristics and patients'health status were also documented. Any revision
      surgeries involving the site of interest and all isolated pathogens were recorded throughout
      the course of treatment and follow-up.

      A follow up examination was performed an average of 23 months after discharge. Primary
      outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of
      interest) or systemic signs of infection, terminated surgical and systemic therapy and
      restoration of joint or limb function.

      At the first surgical procedure after enrolment, at least four deep bone biopsies were taken
      from the interface between implant and affected bone. Identification and antibiotic
      susceptibility testing of all growth was performed. Multi-drug-resistance (MDR) was defined
      according to the definitions of the European Committee of Antimicrobial Susceptibility
      Testing (EUCAST). Biofilm formation was analysed and quantified in microtitre plate assays
      according to protocol of Stepanovic et al.(see references).
This was a prospective study performed between November 2011 and September 2013. All patients
      provided informed written consent prior to inclusion in the study. Inclusion criteria were
      deep S. aureus infections after fracture fixation or prosthetic joint surgery. Fracture
      fixation infections includes fractures involving the long bones as well as the pelvis and the
      spine. Bacterial growth at the site of interest in combination with either pseudarthrosis,
      implant-loosening/failure or local and systemic signs of surgical site infection were
      required for inclusion. Exclusion criteria included infections involving external fixation
      pins, infections without any implanted hardware and culture positive patients not displaying
      any clinical sign of infection.

      Upon entry into the study, the following surgical parameters were documented: affected bone
      or joint; type of implant; time between implantation of the device and onset of symptoms.
      Personal characteristics were also documented and included: gender; age; body mass index
      (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic
      immunosuppressive conditions (Diabetes mellitus, chronic alcoholism, Child's class C
      cirrhosis, neoplasia, transplantation, AIDS and steroid medication). Any revision surgeries
      involving the site of interest and all isolated pathogens were recorded throughout the course
      of treatment and follow-up.

      A follow up examination was performed an average of 23 months after discharge. Primary
      outcome at follow up was cure. Cure was defined by the authors as: missing local (at site of
      interest) or systemic signs of infection and terminated surgical and systemic therapy.

      At the first surgical procedure after enrolment, at least four deep bone biopsies were taken
      from the interface between implant and affected bone. The tissue samples were placed in a
      sterile container with thioglycollate liquid medium (bioMérieux, Hazelwood, MO, USA). The
      samples were cultured for ten days at 37°C and examined each day macroscopically. Any growth
      was inoculated onto a blood agar plate (bioMérieux, Hazelwood, MO, USA) for further growth
      and subsequent identification. In all cases, additional swabs and soft tissue samples may
      have been taken as per clinical routine, however, only samples adjacent to the implant were
      used for diagnosis in this study.

      Identification and antibiotic susceptibility testing of all growth was performed using a
      Vitek2 (bioMerieux Vitek Inc, Hazelwood, MO, USA). Multi-drug-resistance (MDR) was defined
      according to the definitions of the European Committee of Antimicrobial Susceptibility
      Testing (EUCAST). Oxacillin resistance was used as an indicator for methicillin resistant S.
      aureus (MRSA).

      Biofilm formation was analysed and quantified in microtitre plate assays according to the
      well-established protocol of Stepanovic et al.(see references).

      The key variables with regards to bacterial phenotype were: biofilm formation; methicillin
      resistance;multidrug resistance;staphyloxanthin production and hemolysis. The primary outcome
      measure was whether the infection was "cured" or not. Primary outcome parameters were
      calculated as a function of all patients for whom data was complete. Statistical comparison
      was restricted to the lower extremity cohort since the other patients are not scored for many
      of the functional outcome measures and as such incomplete.

      Univariate logistic regression models were used to determine the influence of each prognostic
      factor (obesity, smoking, diabetes mellitus, chronic immune suppression, open fracture
      (initially), early onset infection, biofilm formation, methicillin resistance, MDR and
      Charlson comorbidity index) on cure. P-values <0.05 were considered significant. Statistical
      analyses were performed using SAS software (Version 9.2; Cary, NC, USA).
observational model: Case-Only
time perspective: Prospective
measure: Cure
time frame: 23 months
description: Cure was defined by the authors as: missing local (at site of interest) or systemic signs of infection and terminated surgical and systemic antibiotic therapy. All Parameters had to be positive to fulfill the outcome parameter "cure".If one of the mentioned parameters was negative, outcome was defined as "not cured". Local signs of infection were defined as the appearance of: redness, tenderness, swelling or persisting wound drainage.
Bacterial samples from orthopaedic device related infections
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
citation: Stepanovic S, Vukovic D, Hola V, Di Bonaventura G, Djukic S, Cirkovic I, Ruzicka F. Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. APMIS. 2007 Aug;115(8):891-9. doi: 10.1111/j.1600-0463.2007.apm_630.x.
PMID: 17696944
citation: Post V, Wahl P, Uckay I, Ochsner P, Zimmerli W, Corvec S, Loiez C, Richards RG, Moriarty TF. Phenotypic and genotypic characterisation of Staphylococcus aureus causing musculoskeletal infections. Int J Med Microbiol. 2014 Jul;304(5-6):565-76. doi: 10.1016/j.ijmm.2014.03.003. Epub 2014 Apr 3.
PMID: 24768432
responsible party type: Principal Investigator
investigator affiliation: BG Unfallklinik
investigator full name: Dr. Mario Morgenstern
investigator title: MD
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Staphylococcal Infections