ICG Fluorescence Imaging in Post-traumatic Infection

• ClinicalTrials.gov Identifier: NCT04403204
• Recruitment Status: Recruiting
• First Posted: May 27, 2020
• Last Update Posted: February 21, 2023
• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Dartmouth College; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Brigham and Women's Hospital; University of California, Irvine; University of Maryland, Baltimore
• Information provided by (Responsible Party): Ida Leah Gitajn, Dartmouth-Hitchcock Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Trauma Injury	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 Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 358 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 1 Year
• Official Title: Real-time Fluorescence-based Measurement of Bone Perfusion in Post-traumatic Infection
• Actual Study Start Date: September 14, 2020
• Estimated Primary Completion Date: May 31, 2024
• Estimated Study Completion Date: May 31, 2025

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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).

Criteria

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

Contacts and Locations

Contacts

Contact: Melanie L Christian; 603-650-3556; melanie.l.christian@hitchcock.org

Locations

United States, California

University of California, Irvine; Recruiting

Irvine, California, United States, 92614

Contact: Susan Demas 714-456-7710 sdemas@hs.uci.edu

Principal Investigator: John Scolaro, MD

United States, Maryland

University of Maryland, Baltimore R. Adams Cowley Shock Trauma; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Heather Phipps 410-706-7180 hphipps@som.umaryland.edu

Principal Investigator: Gerard Slobogean, MD

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Abigail Sagona 617-732-5322 asagona@bwh.harvard.edu

Principal Investigator: Michael J Weaver, MD

United States, New Hampshire

Dartmouth Hitchcock Medical Center; Recruiting

Lebanon, New Hampshire, United States, 03756

Contact: Ida L Gitajn, MD 603-650-5000 ida.l.gitajn@hitchcock.org

Contact: Melanie L Christian 603-650-3556 melanie.l.christian@hitchcock.org

Sponsors and Collaborators

Dartmouth-Hitchcock Medical Center

Dartmouth College

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brigham and Women's Hospital

University of California, Irvine

University of Maryland, Baltimore

Investigators

• Principal Investigator: Ida L Gitajn, MD; Dartmouth-Hitchcock Medical Center

More Information

• Responsible Party: Ida Leah Gitajn, Physician, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT04403204
• Other Study ID Numbers: D20057; 1R01AR077157-01 ( U.S. NIH Grant/Contract )
• First Posted: May 27, 2020
• Last Update Posted: February 21, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ida Leah Gitajn, Dartmouth-Hitchcock Medical Center:

Immunofluorescence; Orthopaedic; Trauma; Infection

Additional relevant MeSH terms:

Infections