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

Burn Wound Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05593523
• Other study ID #: 2022-1070
• Secondary ID: Protocol Version
• Status: Recruiting
• Start date: March 9, 2023
• Est. completion date: March 2028

Study information

• Verified date: January 2024
• Source: University of Wisconsin, Madison
• Contact: Adam Krajewski
• Phone: (608) 265-6460
• Email: krajewski[@]wisc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2028
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Burn Wound
• Inflammation
• Necrosis

Intervention

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.

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Depth of Necrotic Tissue as a Percentage of the Tissue Biopsy Thickness		sample collected up to 4 days on study
Secondary	Spatial Correlation of ICG fluorescence and Cell Necrosis and Inflammation		sample collected up to 4 days on study