<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/NCT04440631</url>
  </required_header>
  <id_info>
    <org_study_id>Microbiome</org_study_id>
    <nct_id>NCT04440631</nct_id>
  </id_info>
  <brief_title>Gut Microbiome of Patients Undergoing Antibiotic Therapy for Orthopedic Device-related Infection</brief_title>
  <acronym>IMPAT-ODRI</acronym>
  <official_title>Investigation of the Microbiome of Patients Receiving Antibiotic Therapy for Orthopedic Device-related Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AO Research Institute Davos</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AO Research Institute Davos</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>
      The microbiome of 80 orthopedic-device related infection (ODRI) patients treated with&#xD;
      antibiotics and 10 healthy controls will be investigated. Samples (blood, stool, saliva,&#xD;
      skin-swab) are collected 4x within 6 months. Composition and diversity of the microbiome will&#xD;
      be assessed by 16sRNA sequencing, skins swabs are screened for rifampicin-resistant&#xD;
      staphylococci onto Mannitol-salt-agar plates supplemented with rifampicin, inflammation&#xD;
      markers and antibodies in blood and saliva are monitored to track changes in the immune&#xD;
      response. For further analysis patients are assigned to one of two groups: 1) antibiotic&#xD;
      therapy including rifampicin and 2) non-rifampicin antibiotic therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">June 1, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Composition of the the gut microbiota following two weeks of intravenous antibiotic therapy</measure>
    <time_frame>Two weeks</time_frame>
    <description>The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following two weeks of intravenous (iv) antibiotic treatment will be compared to baseline samples of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composition of the gut microbiota following four weeks of oral antibiotic therapy</measure>
    <time_frame>Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)</time_frame>
    <description>The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following four weeks of oral antibiotic treatment will be compared to baseline samples of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composition of the gut microbiota 24 weeks after antibiotic therapy start</measure>
    <time_frame>24 weeks</time_frame>
    <description>The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition 24 weeks after antibiotic therapy start, including an at least 6-week antibiotic free period, will be compared to baseline samples of the patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Monitoring Rifampicin resistant S. aureus on the skin following two weeks of iv antibiotic therapy</measure>
    <time_frame>Two weeks</time_frame>
    <description>Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monitoring Rifampicin resistant S. aureus on the skin following four weeks of oral antibiotic therapy</measure>
    <time_frame>Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)</time_frame>
    <description>Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monitoring Rifampicin resistant S. aureus on the skin 24 weeks after antibiotic therapy start</measure>
    <time_frame>24 weeks</time_frame>
    <description>Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Level of systemic Inflammation following two weeks of iv antibiotic therapy</measure>
    <time_frame>Two weeks</time_frame>
    <description>Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of systemic Inflammation following four weeks of oral antibiotic therapy</measure>
    <time_frame>Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)</time_frame>
    <description>Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of systemic Inflammation 24 weeks after antibiotic therapy start</measure>
    <time_frame>24 weeks</time_frame>
    <description>Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Monitoring mucosal immune response following two weeks of iv antibiotic therapy</measure>
    <time_frame>Two weeks</time_frame>
    <description>IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Monitoring mucosal immune response following four weeks of oral antibiotic therapy</measure>
    <time_frame>Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)</time_frame>
    <description>IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Monitoring mucosal immune response 24 weeks after antibiotic therapy start</measure>
    <time_frame>24 weeks</time_frame>
    <description>IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">12</enrollment>
  <condition>Fractures, Bone</condition>
  <condition>Infection, Bacterial</condition>
  <condition>Joint Infection</condition>
  <condition>Bone Infection</condition>
  <arm_group>
    <arm_group_label>Antibiotic therapy including rifampicin</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-rifampicin antibiotic therapy</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group (healthy volunteers)</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>no intervention, observational only</intervention_name>
    <description>no intervention, observational only</description>
    <arm_group_label>Antibiotic therapy including rifampicin</arm_group_label>
    <arm_group_label>Control group (healthy volunteers)</arm_group_label>
    <arm_group_label>Non-rifampicin antibiotic therapy</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The project population will include patients suffering from an ODRI (orthopedic&#xD;
        device-related infection). This includes any patient with a bone infection with a current&#xD;
        or previous involvement of an implant. The majority of patients are expected to be&#xD;
        prosthetic joint infection (PJI) and fracture-related infection (FRI) patients, although&#xD;
        also patients with spinal implantation with an infection, or patients who have had an&#xD;
        implant removed yet develop an osteomyelitis will also be included.&#xD;
&#xD;
        These patients all have a deep bone implant infection and will receive antibiotic therapy,&#xD;
        including at least two weeks IV therapy and at least 4 weeks of oral rifampicin. The&#xD;
        investigators expect the distribution of patients getting rifampicin or non-rifampicin to&#xD;
        be approximately 50/50 overall and anticipate PJI patients will be older, receive more&#xD;
        concomitant medications and have underlying co-morbidities than patients with an FRI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient is planned to undergo revision surgery due to suspected bone or joint&#xD;
             infection.&#xD;
&#xD;
          -  The patient is at least 18 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient took antibiotics in the previous six weeks of recruitment (a single&#xD;
             dose/&quot;shot&quot; of antibiotics during this period is not considered).&#xD;
&#xD;
          -  The patient suffers from gut-associated morbidities such as Morbus Crohn or colitis&#xD;
             ulcerosa.&#xD;
&#xD;
          -  The patient suffers from psychiatric disorders/cognitive impairment affecting&#xD;
             understanding.&#xD;
&#xD;
          -  The patient is unable to give consent and follow procedures and/or has insufficient&#xD;
             knowledge of the project language.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Universitätsspital Basel</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Schulthess Klinik Zürich</name>
      <address>
        <city>Zürich</city>
        <zip>8008</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>February 2, 2023</last_update_submitted>
  <last_update_submitted_qc>February 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gut Microbiome</keyword>
  <keyword>Joint Infection</keyword>
  <keyword>Bone Infection</keyword>
  <keyword>Antibiotic Therapy</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>Bacterial Infections</mesh_term>
    <mesh_term>Prosthesis-Related Infections</mesh_term>
    <mesh_term>Fractures, Bone</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/NCT04440631
org study id: Microbiome
nct id: NCT04440631
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The microbiome of 80 orthopedic-device related infection (ODRI) patients treated with
      antibiotics and 10 healthy controls will be investigated. Samples (blood, stool, saliva,
      skin-swab) are collected 4x within 6 months. Composition and diversity of the microbiome will
      be assessed by 16sRNA sequencing, skins swabs are screened for rifampicin-resistant
      staphylococci onto Mannitol-salt-agar plates supplemented with rifampicin, inflammation
      markers and antibodies in blood and saliva are monitored to track changes in the immune
      response. For further analysis patients are assigned to one of two groups: 1) antibiotic
      therapy including rifampicin and 2) non-rifampicin antibiotic therapy.
observational model: Cohort
time perspective: Prospective
measure: Composition of the the gut microbiota following two weeks of intravenous antibiotic therapy
time frame: Two weeks
description: The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following two weeks of intravenous (iv) antibiotic treatment will be compared to baseline samples of the patients.
measure: Composition of the gut microbiota following four weeks of oral antibiotic therapy
time frame: Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
description: The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition following four weeks of oral antibiotic treatment will be compared to baseline samples of the patients.
measure: Composition of the gut microbiota 24 weeks after antibiotic therapy start
time frame: 24 weeks
description: The gut microbiota will be characterized by means of 16s rRNA sequencing. The gut microbiota composition 24 weeks after antibiotic therapy start, including an at least 6-week antibiotic free period, will be compared to baseline samples of the patients.
measure: Monitoring Rifampicin resistant S. aureus on the skin following two weeks of iv antibiotic therapy
time frame: Two weeks
description: Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.
measure: Monitoring Rifampicin resistant S. aureus on the skin following four weeks of oral antibiotic therapy
time frame: Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
description: Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.
measure: Monitoring Rifampicin resistant S. aureus on the skin 24 weeks after antibiotic therapy start
time frame: 24 weeks
description: Skin and nose swabs will be plated on (rifampicin supplemented ) Mannitol-Salt-Agar plates and colonies will be compared to baseline samples of the patients.
measure: Level of systemic Inflammation following two weeks of iv antibiotic therapy
time frame: Two weeks
description: Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.
measure: Level of systemic Inflammation following four weeks of oral antibiotic therapy
time frame: Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
description: Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.
measure: Level of systemic Inflammation 24 weeks after antibiotic therapy start
time frame: 24 weeks
description: Inflammatory cytokines in the blood will be measured and compared to baseline samples of the patients.
measure: Monitoring mucosal immune response following two weeks of iv antibiotic therapy
time frame: Two weeks
description: IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.
measure: Monitoring mucosal immune response following four weeks of oral antibiotic therapy
time frame: Six weeks (including two weeks iv and four weeks of oral antibiotic therapy)
description: IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.
measure: Monitoring mucosal immune response 24 weeks after antibiotic therapy start
time frame: 24 weeks
description: IgA levels will measured in saliva of the patients and compared to baseline samples of the patients.
arm group label: Antibiotic therapy including rifampicin
arm group label: Non-rifampicin antibiotic therapy
arm group label: Control group (healthy volunteers)
intervention type: Other
intervention name: no intervention, observational only
description: no intervention, observational only
arm group label: Antibiotic therapy including rifampicin
arm group label: Control group (healthy volunteers)
arm group label: Non-rifampicin antibiotic therapy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
facility: 
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Bacterial Infections
mesh term: Prosthesis-Related Infections
mesh term: Fractures, Bone
sharing ipd: Undecided