ICG Fluorescence Imaging in Post-traumatic Infection

Real-time Fluorescence-based Measurement of Bone Perfusion in Post-traumatic Infection

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.

Study Overview

• Status: Recruiting
• Conditions: Trauma Injury
• Intervention / Treatment: Other: Immunofluorescence Imaging; Other: DCE-MRI

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 170

Contacts and Locations

• Study Contact: Name: Jon Mikael Anderson; Phone Number: 603-653-3306; Email: jon.mikael.anderson@hitchcock.org

Study Locations

• United States
  • California
    • Irvine, California, United States, 92614
      • Recruiting
      • University of California, Irvine
      • Contact: Susan Demas; Phone Number: 714-456-7710; Email: sdemas@hs.uci.edu
      • Principal Investigator: John Scolaro, MD
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland, Baltimore R. Adams Cowley Shock Trauma
      • Contact: Heather Phipps; Phone Number: 410-706-7180; Email: hphipps@som.umaryland.edu
      • Principal Investigator: Gerard Slobogean, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Completed
      • Brigham and Women's Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Hitchcock Medical Center
      • Contact: Ida L Gitajn, MD; Phone Number: 603-650-5000; Email: ida.l.gitajn@hitchcock.org
      • Contact: Jon Mikael Anderson; Phone Number: 603-653-3306; Email: jon.mikael.anderson@hitchcock.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients 18 years of age or older who present with SSI following fracture or joint fusion Established SSI fracture cohort (Cohort 1). A subset of Cohort 1 will be considered for the Subset DCE-MRI cohort (Cohort 1-1).

Description

Inclusion Criteria:

Established SSI Fracture (Cohort Cohort 1, Group 1)

1. Patients 18 years of age or older.
2. Extremity fracture.
3. Prior definitive fracture management with external fixation, internal fixation, or joint fusion.
4. Superficial, deep, or organ space SSI (as per CDC criteria) at the fracture site that requires operative management.
5. Will have all fracture care surgeries performed by a participating surgeon or delegate.
6. Provision of informed consent.

Subset: DCE-MRI (Cohort 1-1, Group 2)

1. Patients 18 years of age or older.
2. Closed extremity fracture.
3. Planned definitive fracture management with external fixation, internal fixation, or joint fusion.
4. Will have all planned fracture care surgeries performed by a participating surgeon or delegate.
5. Provision of informed consent.

Exclusion Criteria:

Established SSI Fracture Cohort (Cohort 1, Group 1)

1. Fracture of the hand.
2. Iodine allergy.
3. Received previous surgical debridement to manage the SSI.
4. Incarceration.

5. Problems, in the judgment of study personnel, with maintaining follow-up with the patient.

   Subset: DCE-MRI (Cohort 1-1, Group2)

6. the presence of an electronic implant, such as a pacemaker
7. the presence of a metal implant, such as an aneurysm clip
8. the presence of other contraindication(s), as determined by the MRI technologists and radiologists.
9. A history of allergy to iodides
10. A GFR < 30 ml/min as determined by blood test on the day of NIR/MR imaging, or from lab results within 3 months of DCE-MRI for this study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Established SSI Fracture Cohort; 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	Other: Immunofluorescence Imaging; 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.
Established SSI Fracture Cohort Subset (DCE-MRI); 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	Other: Immunofluorescence Imaging; 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.; Other: DCE-MRI; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients experiencing post procedure surgical site infections	Post-procedure surgical site infection using CDC criteria will be documented at each follow-up appointment up to one year	1 year
Number of patients requiring unplanned fracture-related reoperations	All unplanned reoperations will be documented	1 year

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: University of Maryland, Baltimore; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Brigham and Women's Hospital; University of California, Irvine; Dartmouth College
• Investigators: Principal Investigator: Ida L Gitajn, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Infection; Trauma; Immunofluorescence; Orthopaedic
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: D20057; 1R01AR077157-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No