<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/NCT04403204</url>
  </required_header>
  <id_info>
    <org_study_id>D20057</org_study_id>
    <secondary_id>1R01AR077157-01</secondary_id>
    <nct_id>NCT04403204</nct_id>
  </id_info>
  <brief_title>ICG Fluorescence Imaging in Post-traumatic Infection</brief_title>
  <official_title>Real-time Fluorescence-based Measurement of Bone Perfusion in Post-traumatic Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dartmouth College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, Irvine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The focus of this prospective observational study is to (1) establish the range and variation&#xD;
      associated with bone/soft tissue perfusion in fracture patients, using ICG fluorescence&#xD;
      imaging; (2) examine the relationship between perfusion and complications such as surgical&#xD;
      site infection (SSI), persistent SSI, and fracture nonunion; (3) to determine whether the&#xD;
      quantitative ICG fluorescence can be used to guide bony debridement in the setting of&#xD;
      infected fracture to minimize complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a prospective observational trial to better understand the range and variation&#xD;
      associated with bone/soft tissue perfusion in fracture patients and examine the relationship&#xD;
      between perfusion, measured using quantitative Indocyanine green (ICG) fluorescence and&#xD;
      complications such as surgical site infection (SSI), persistent SSI, and fracture nonunion.&#xD;
      Primary outcome measure is complication (either infection, recurrent infection or nonunion).&#xD;
&#xD;
      Eligible consenting patients will receive standard of care treatment for their fracture or&#xD;
      infection including irrigation and debridement of their operative site and/or fracture&#xD;
      fixation. After exposure, 0.1 mg/Kg ICG will be injected intravenously and video rate ICG&#xD;
      fluorescence images will be acquired 20 seconds before and 4 minutes after the injection,&#xD;
      each before and after debridement.&#xD;
&#xD;
      A subset of 30 post-fracture complication patients will undergo surgical treatment for their&#xD;
      infection in Center of Innovation Surgery (CIS) and have either an intraoperative Dynamic&#xD;
      contrast-enhanced magnetic resonance imaging (DCE-MRI) after exposure but before the ICG&#xD;
      injection or a preoperative DCE-MRI. Patients receiving surgery in the CIS will be required&#xD;
      to sign an additional CIS-specific consent document.&#xD;
&#xD;
      The need for repeat surgical procedure will be left up to the treating surgeon. If repeat&#xD;
      procedure is needed, pre- and post-debridement quantitative ICG fluorescence images will be&#xD;
      obtained at each procedure.&#xD;
&#xD;
      Study participants will be followed at 2 weeks, 6 weeks, 3 months, 6 months, and one year&#xD;
      from their index study surgery. Complication including index infection, recurrent infection&#xD;
      or delaying union/nonunion will be identified at the time of diagnosis and/or during each&#xD;
      participants assessment that occurs during routine outpatient clinic visit. Detailed&#xD;
      information on the infection including date of diagnosis, participant signs and symptoms,&#xD;
      culture test results, method of treatment(s), and date of resolution will be documented.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>Number of patients experiencing post procedure surgical site infections</measure>
    <time_frame>1 year</time_frame>
    <description>Post-procedure surgical site infection using CDC criteria will be documented at each follow-up appointment up to one year</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients requiring unplanned fracture-related reoperations</measure>
    <time_frame>1 year</time_frame>
    <description>All unplanned reoperations will be documented</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">358</enrollment>
  <condition>Trauma Injury</condition>
  <arm_group>
    <arm_group_label>Established SSI Fracture Cohort</arm_group_label>
    <description>Patients 18 years of age or older. Extremity fracture. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. Will have all fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Established SSI Fracture Cohort Subset (DCE-MRI)</arm_group_label>
    <description>Patients 18 years of age or older. Extremity fracture. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. Will have all fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Immunofluorescence Imaging</intervention_name>
    <description>Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system.</description>
    <arm_group_label>Established SSI Fracture Cohort</arm_group_label>
    <arm_group_label>Established SSI Fracture Cohort Subset (DCE-MRI)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DCE-MRI</intervention_name>
    <description>Characterize the relationship between bone perfusion as quantified by ICG based DCE-FI and DCE-MRI in human patients to develop an accurate depth-sensitive fluorescence imaging model that will correct for the surface-weighted feature of fluorescence imaging</description>
    <arm_group_label>Established SSI Fracture Cohort Subset (DCE-MRI)</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients 18 years of age or older who present with SSI following fracture or joint fusion&#xD;
        Established SSI fracture cohort (Cohort 1). A subset of Cohort 1 will be considered for the&#xD;
        Subset DCE-MRI cohort (Cohort 1-1).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Established SSI Fracture (Cohort Cohort 1, Group 1)&#xD;
&#xD;
          1. Patients 18 years of age or older.&#xD;
&#xD;
          2. Extremity fracture.&#xD;
&#xD;
          3. Prior definitive fracture management with external fixation, internal fixation, or&#xD;
             joint fusion.&#xD;
&#xD;
          4. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that&#xD;
             requires operative management.&#xD;
&#xD;
          5. Will have all fracture care surgeries performed by a participating surgeon or&#xD;
             delegate.&#xD;
&#xD;
          6. Provision of informed consent.&#xD;
&#xD;
        Subset: DCE-MRI (Cohort 1-1, Group 2)&#xD;
&#xD;
          1. Patients 18 years of age or older.&#xD;
&#xD;
          2. Closed extremity fracture.&#xD;
&#xD;
          3. Planned definitive fracture management with external fixation, internal fixation, or&#xD;
             joint fusion.&#xD;
&#xD;
          4. Will have all planned fracture care surgeries performed by a participating surgeon or&#xD;
             delegate.&#xD;
&#xD;
          5. Provision of informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Established SSI Fracture Cohort (Cohort 1, Group 1)&#xD;
&#xD;
          1. Fracture of the hand.&#xD;
&#xD;
          2. Iodine allergy.&#xD;
&#xD;
          3. Received previous surgical debridement to manage the SSI.&#xD;
&#xD;
          4. Incarceration.&#xD;
&#xD;
          5. Problems, in the judgment of study personnel, with maintaining follow-up with the&#xD;
             patient.&#xD;
&#xD;
             Subset: DCE-MRI (Cohort 1-1, Group2)&#xD;
&#xD;
          6. the presence of an electronic implant, such as a pacemaker&#xD;
&#xD;
          7. the presence of a metal implant, such as an aneurysm clip&#xD;
&#xD;
          8. the presence of other contraindication(s), as determined by the MRI technologists and&#xD;
             radiologists.&#xD;
&#xD;
          9. A history of allergy to iodides&#xD;
&#xD;
         10. A GFR &lt; 30 ml/min as determined by blood test on the day of NIR/MR imaging, or from&#xD;
             lab results within 3 months of DCE-MRI for this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ida L Gitajn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melanie L Christian</last_name>
    <phone>603-650-3556</phone>
    <email>melanie.l.christian@hitchcock.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92614</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Demas</last_name>
      <phone>714-456-7710</phone>
      <email>sdemas@hs.uci.edu</email>
    </contact>
    <investigator>
      <last_name>John Scolaro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Maryland, Baltimore R. Adams Cowley Shock Trauma</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heather Phipps</last_name>
      <phone>410-706-7180</phone>
      <email>hphipps@som.umaryland.edu</email>
    </contact>
    <investigator>
      <last_name>Gerard Slobogean, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abigail Sagona</last_name>
      <phone>617-732-5322</phone>
      <email>asagona@bwh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Michael J Weaver, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ida L Gitajn, MD</last_name>
      <phone>603-650-5000</phone>
      <email>ida.l.gitajn@hitchcock.org</email>
    </contact>
    <contact_backup>
      <last_name>Melanie L Christian</last_name>
      <phone>603-650-3556</phone>
      <email>melanie.l.christian@hitchcock.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>February 16, 2023</last_update_submitted>
  <last_update_submitted_qc>February 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Ida Leah Gitajn</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </responsible_party>
  <keyword>Immunofluorescence</keyword>
  <keyword>Orthopaedic</keyword>
  <keyword>Trauma</keyword>
  <keyword>Infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04403204
org study id: D20057
secondary id: 1R01AR077157-01
nct id: NCT04403204
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The focus of this prospective observational study is to (1) establish the range and variation
      associated with bone/soft tissue perfusion in fracture patients, using ICG fluorescence
      imaging; (2) examine the relationship between perfusion and complications such as surgical
      site infection (SSI), persistent SSI, and fracture nonunion; (3) to determine whether the
      quantitative ICG fluorescence can be used to guide bony debridement in the setting of
      infected fracture to minimize complications.
This will be a prospective observational trial to better understand the range and variation
      associated with bone/soft tissue perfusion in fracture patients and examine the relationship
      between perfusion, measured using quantitative Indocyanine green (ICG) fluorescence and
      complications such as surgical site infection (SSI), persistent SSI, and fracture nonunion.
      Primary outcome measure is complication (either infection, recurrent infection or nonunion).

      Eligible consenting patients will receive standard of care treatment for their fracture or
      infection including irrigation and debridement of their operative site and/or fracture
      fixation. After exposure, 0.1 mg/Kg ICG will be injected intravenously and video rate ICG
      fluorescence images will be acquired 20 seconds before and 4 minutes after the injection,
      each before and after debridement.

      A subset of 30 post-fracture complication patients will undergo surgical treatment for their
      infection in Center of Innovation Surgery (CIS) and have either an intraoperative Dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) after exposure but before the ICG
      injection or a preoperative DCE-MRI. Patients receiving surgery in the CIS will be required
      to sign an additional CIS-specific consent document.

      The need for repeat surgical procedure will be left up to the treating surgeon. If repeat
      procedure is needed, pre- and post-debridement quantitative ICG fluorescence images will be
      obtained at each procedure.

      Study participants will be followed at 2 weeks, 6 weeks, 3 months, 6 months, and one year
      from their index study surgery. Complication including index infection, recurrent infection
      or delaying union/nonunion will be identified at the time of diagnosis and/or during each
      participants assessment that occurs during routine outpatient clinic visit. Detailed
      information on the infection including date of diagnosis, participant signs and symptoms,
      culture test results, method of treatment(s), and date of resolution will be documented.
observational model: Cohort
time perspective: Prospective
measure: Number of patients experiencing post procedure surgical site infections
time frame: 1 year
description: Post-procedure surgical site infection using CDC criteria will be documented at each follow-up appointment up to one year
measure: Number of patients requiring unplanned fracture-related reoperations
time frame: 1 year
description: All unplanned reoperations will be documented
arm group label: Established SSI Fracture Cohort
description: Patients 18 years of age or older. Extremity fracture. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. Will have all fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent
arm group label: Established SSI Fracture Cohort Subset (DCE-MRI)
description: Patients 18 years of age or older. Extremity fracture. Prior definitive fracture management with external fixation, internal fixation, or joint fusion. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management. Will have all fracture care surgeries performed by a participating surgeon or delegate. Provision of informed consent
intervention type: Other
intervention name: Immunofluorescence Imaging
description: Patients will be administered FDA approved ICG through intravenous injection and imaged by a FDA approved surgical microscope (Spy Elite) which is 0.5 meter away from the subject. Both ICG fluorescence and the two imaging systems have been used for routine clinical practice for many years. Figure (a) shows the Schematic sketch of the imaging systems. ICG fluorescence imaging utilizes intravenously injected ICG, which is a fluorescent dye that is FDA-approved for clinical use, illuminated with near-infrared light. The ICG dye is indirectly activated and the dynamic fluorescence due to bone perfusion can be captured by a video rate imaging system.
arm group label: Established SSI Fracture Cohort
arm group label: Established SSI Fracture Cohort Subset (DCE-MRI)
intervention type: Other
intervention name: DCE-MRI
description: Characterize the relationship between bone perfusion as quantified by ICG based DCE-FI and DCE-MRI in human patients to develop an accurate depth-sensitive fluorescence imaging model that will correct for the surface-weighted feature of fluorescence imaging
arm group label: Established SSI Fracture Cohort Subset (DCE-MRI)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ida L Gitajn, MD
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
last name: Melanie L Christian
phone: 603-650-3556
email: melanie.l.christian@hitchcock.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Ida Leah Gitajn
investigator title: Physician
mesh term: Infections
sharing ipd: No