Fluorescence-based Detection of Inflammation and Necrosis to Inform Surgical Decision-making and Enhance Outcomes

This study investigates fluorescence image-guided surgery to allow precise identification of necrotic tissue both preoperatively and intraoperatively in burn patients. Furthermore, it uses a multi-model approach to elucidate the localization of ICG in inflammation and necrosis to determine how this novel use of a well-known fluorescence marker can be optimized to aid in surgical decision making. This proposal will provide the necessary data to support the design of a larger clinical trial to study the feasibility and efficacy of this technology to improve the precision of necrosis detection and removal and improve wound healing outcomes. Up to 100 participants will be on study for up to approximately 24 days.

Study Overview

• Status: Recruiting
• Conditions: Burn Wound
• Intervention / Treatment: Drug: Indocyanine green (ICG); Device: OnLume

Detailed Description

Tissue necrosis is a form of cell death caused by a wide variety of diseases and injuries. Current methods of detecting tissue necrosis to guide surgical decision making are limited. In burn injury, clinical visualization of tissue necrosis is the standard of care; however, it is an imprecise method that can result in delays in care, unnecessary surgery, and removal of viable tissue. There is a critical need to identify novel methods to improve the detection of necrosis in burn injury to aid perioperative clinical decision making. While Indocyanine Green Angiography (ICGA) has been shown to identify burn depth using perfusion as a surrogate marker for necrosis, it has not been widely adopted for clinical decision making. Recently, clinical trials using delayed imaging of high dose ICG (Second Window Indocyanine Green - SWIG) have shown promise in image-guided surgical resection of tumors. The investigators propose that SWIG imaging can be employed to enhance surgical decision-making in burn injury, as well as in many disease processes involving necrosis. The knowledge gained from this project will fill the critical need to prevent unnecessary surgery, improve surgical precision, and provide insight into ICG localization in inflamed and necrotic tissue.

The goal of this project is to characterize the SWIG fluorescence in burn inflammation and necrosis on a macroscopic and microscopic level.

Cohort 1 - The investigators will characterize fluorescent signals from SWIG in the healing potential of indeterminate depth burns in humans.

Cohort 2 - The investigators will examine the association between SWIG fluorescence and depth of necrosis in surgically excised burns, and in cases where surgery is canceled due to unexpected healing, in human subjects.

This project will result in clinical data testing of ICG for direct detection of necrotic tissue using a fluorescence imaging device optimized for burn surgery, while developing a platform for quantification of tissue necrosis and characterization of ICG-avid necrosis. These studies will provide necessary data to inform the design of a larger clinical trial to determine the efficacy and validity of ICG fluorescence-guided clinical decision making to improve outcomes for burn patients.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Adam Krajewski; Phone Number: (608) 265-6460; Email: krajewski@wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University Of Wisconsin

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

Aim 1: Human subjects with partial thickness burn wounds admitted to the UW Burn Center within 24 hours of burn injury and expected to be admitted for 3 days Aim 2: Human subjects with 1-30% total body surface area (TBSA) deep partial or full thickness burn wounds that require surgery.

Description

Inclusion Criteria:

• English speaker
• Patients with partial thickness indeterminate depth burn wounds that occurred within 24 hours of admission and are expected to require admission for at least 3 days (Aim 1) or with deep partial thickness or full thickness burn wounds that are 1-30% TBSA and will likely require surgery (Aim 2)
• Subject understands the study procedures and can provide informed consent to participate in the study and authorization for release of relevant protected health information to the study investigator

Exclusion Criteria:

• Contraindication to Indocyanine Green (ICG) injection, i.e. previous reaction to ICG (adverse event rate: 1 in 42,000) or Iodine allergy.
• Inability to obtain consent
• Subject with pre-existing inflammatory diseases or chronically treated before admission to the hospital with steroids or nonsteroidal anti-inflammatory drugs or biologics
• Subject with immune deficiency (HIV infection or use of corticosteroids, cytostatic drugs, tetracycline and certain bisphosphonates)
• Subject with known or suspected infections or on antibiotic therapy
• Subject known or suspected to be pregnant

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
Aim 1: Partial Thickness Burn Wounds; Participants with 1-30% total body surface area (TBSA) partial thickness burn wounds admitted to the University of Wisconsin (UW) Burn Center within 24 hours of burn injury and expected to be admitted for 3 days. Indocyanine green angiography (ICGA) fluorescence imaging immediately after administration of 7mg of ICG, and second window indocyanine green (SWIG) fluorescence imaging ~24 hours after administration of up to 5 mg/kg ICG of human burn wounds. ICGA within 72 hours of admission with the OnLume Clinical Imaging System (CIS). SWIG fluorescence imaging will also be performed perioperatively if applicable.	Drug: Indocyanine green (ICG); ICG is a well, known, FDA-approved dye; Device: OnLume; The OnLume Clinical Imaging System (CIS), also known as the Asimov-MSK Imaging System, used in this study is a clinical fluorescence-guided imaging system.; Other Names: Asimov-MSK Imaging System
Aim 2: Deep Partial or Full Thickness Burn Wounds; Participants with 1-30% total body surface area (TBSA) deep partial or full thickness burn wounds that will likely require surgery. ICGA fluorescence imaging immediately after administration of 7mg of ICG, and second window indocyanine green (SWIG) fluorescence imaging ~24 hours after administration of up to 5 mg/kg ICG of human burn wounds. Imaging will occur with the OnLume Clinical Imaging System (CIS).	Drug: Indocyanine green (ICG); ICG is a well, known, FDA-approved dye; Device: OnLume; The OnLume Clinical Imaging System (CIS), also known as the Asimov-MSK Imaging System, used in this study is a clinical fluorescence-guided imaging system.; Other Names: Asimov-MSK Imaging System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signal to Background Ratio (SBR) of ICGA and SWIG Fluorescence Images	Quantitative assessment of all ICGA and SWIG fluorescence images will be achieved in part by measuring the fluorescence signal-to-background ratio (SBR).	up to 96 hours after injury (up to 4 days on study)
Standard Deviation of ICGA and SWIG Fluorescence Images	Quantitative assessment of all ICGA and SWIG fluorescence images will be achieved in part by measuring the fluorescence standard deviation.	up to 96 hours after injury (up to 4 days on study)
Spatial Pattern of ICGA and SWIG Fluorescence Images	Qualitative characterization of all ICGA and SWIG fluorescence images will be achieved by evaluating the fluorescence spatial patterns and features.	up to 96 hours after injury (up to 4 days on study)
Burn Surgeon Assessment of Wound Healing (Yes/No)	For Aim 1, a burn surgeon blinded to the fluorescence data will perform an assessment of complete wound healing without surgery (Yes/No) at 21 ± 3 days from burn injury.	up to 24 days from burn injury (up to 21 days on study)
Burn Surgeon Assessment of Graft Loss (Yes/No)	For Aim 2, a burn surgeon blinded to the fluorescence data will perform an assessment of presence or absence of graft loss (Yes/No) 14 ± 7 days after discharge following skin grafting.	up to 21 days after discharge following skin grafting (up to 31 days on study)
Depth of Necrotic Tissue as a Percentage of the Tissue Biopsy Thickness		sample collected up to 4 days on study

Secondary Outcome Measures

Outcome Measure	Time Frame
Spatial Correlation of ICG fluorescence and Cell Necrosis and Inflammation	sample collected up to 4 days on study

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Angela Gibson, MD, PHD, University of Wisconsin - Madison School of Medicine and Public Health

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 20, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: imaging; detection; necrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Necrosis
• Other Study ID Numbers: 2022-1070; A539714 (Other Identifier: UW Madison); 1R01GM145723-01 (U.S. NIH Grant/Contract); Protocol Version 1/3/2024 (Other Identifier: UW Madison)

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: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No