Real-Time Diagnosis of Life-Threatening Necrotizing Soft Tissue Infections (NSTI) Using Indocyanine Green (ICG) Kinetic Modeling

NCT06877793 | Recruiting

• 2 other identifiers: 020027191R01AI184513-01
• Study Type: observational
• Target: 420
• Locations: 1 country
• Sites: 8

Brief Summary

Necrotizing soft-tissue infections (NSTIs, a.k.a. "necrotizing fasciitis" or "flesh-eating bacteria") are aggressive infections that can progress rapidly from mild symptoms to sepsis, multi-organ failure, and death. NSTI cases present with non-specific clinical, imaging, and laboratory findings, and standard-of-care techniques for NSTI diagnosis lack sensitivity and specificity, resulting in frequent misdiagnosis and delayed care, which is the single most important predictor of survival. Consequently, the cumulative mortality rate for patients with NSTIs is 20- 30%; a dire need exists for more accurate and rapid detection of NSTIs. Fluorescence-guided surgery is a nascent technology seeking to improve the recognition of anatomical structures and disease processes using fluorescent probes (fluorophores). Indocyanine green (ICG) is an FDA-approved, near-infrared fluorophore with a \>60-year safety record for vascular perfusion assessment. A distinguishing histological feature of NSTIs is prominent blood vessel thrombosis in affected tissues. Leveraging these pro-thrombotic effects, our study group has demonstrated in a first-in-human study (NCT04839302) that intravenous administration of ICG and immediate fluorescence imaging reveals prominent signal deficits in NSTI-positive tissues that differentiate significantly with increased signal seen with more common-and less virulent-infections such as cellulitis. We seek now to evaluate this imaging technique on a broader scale and determine if our findings are consistent for patients affected by NSTI-causing pathogens that are not endemic to our region. This prospective, observational, multicenter clinical study will involve video-rate ICG fluorescence imaging of patients suspected of having NSTIs who present to eight tertiary, Level 1 medical centers across the United States (Aim 1). Using dynamic contrast-enhanced fluorescence imaging (DCE-FI), time profiles of ICG fluorescence intensity from different tissue pixels/regions will be extracted and parameterized to extract first-pass kinetic features. These DCE-FI features, which characterize tissue perfusion, will be evaluated alone and in combination with anonymized electronic medical record data to create a DCE-FI-based clinical decision tool and a machine- learning-based fusion (DCE FI+lab/imaging data) tool; these will be compared to identify the most accurate means of diagnosing NSTIs (Aim 2). The best-performing tool will then be evaluated-compared to current diagnostic tests-in a prospective observational clinical study of patients presenting to tertiary emergency departments with findings concerning for NSTIs (Aim 3). Based on our human study, fluorescence imaging will not delay current standard of care. To ensure data fidelity, all sites will use similar: 1) commercial fluorescence imaging systems and accessories; and 2) validated commercial fluorescence reference phantoms. Based on our early results, we have strong confidence that following rigorous testing, ICG DCE-FI will lead to an entirely new methodology for rapid identification of patients with NSTIs, which will ultimately reduce patient morbidity and improve survival.

Conditions

Necrotizing Fascitis

Outcome Measures

Primary Outcomes (1)

• Determine if tissue perfusion, determined by first-pass ICG fluorescence kinetics, is reliably reduced in the setting of a necrotizing infection compared to a non-necrotizing infection.

  We will evaluate first-pass fluorescence signal intensity changes from indocyanine green (ICG), a vascular perfusion fluorophore, in the setting of severe soft-tissue infections to determine if ICG fluorescence may be an accurate and reliable diagnostic test for differentiating life-threatening necrotizing infections from non-life-threatening non-necrotizing infections.

  From enrollment to the end of fluorescence imaging (about 1 day)

Secondary Outcomes (1)

• Determine if first-pass ICG fluorescence kinetics in patients with necrotizing infections vary based on the causative bacterial species.

  From enrollment to the end of imaging and lab results (about 30 days)

Interventions

Administration of indocyanine green (ICG) and fluorescence imaging DIAGNOSTIC_TEST

Patients with clinical and lab findings consistent with a diagnosis of NSTI who consent to this study will receive a one-time, weight-appropriate dose of ICG (0.2 mg/kg, in accordance with FDA-approved recommendations). Each patient will undergo fluorescence imaging immediately before and after administration of ICG.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to the ED or clinic who are considered at intermediate- or high-risk for NSTI.

You may qualify if:

• Age ≥18 years.
• Clinical suspicion of NSTI based on the local standard of care warranting:
• Hospital admission for observation due to suspected NSTI; and/or
• Soft tissue biopsy to rule in/out suspected NSTI; and/or
• Surgical debridement for suspected NSTI; and/or
• Specific institutional threshold criteria for triggering NSTI work-up; and
• Ability to give written informed consent.

You may not qualify if:

• History of allergy to ICG and/or iodine.
• Pregnant women or nursing mothers.

Sponsors & Collaborators

• Eric R. Henderson: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (8)

University of California, Los Angeles

Los Angeles, California, 90095, United States

NOT YET RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Emory University/Grady Memorial Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48104, United States

RECRUITING

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

Vanderbilt University

Nashville, Tennessee, 37235, United States

RECRUITING

MeSH Terms

Conditions

Fasciitis, Necrotizing

Interventions

Optical Imaging

Condition Hierarchy (Ancestors)

Fasciitis; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Central Study Contacts

Eric R Henderson, MD

CONTACT

603-650-5133; Eric.R.Henderson@hitchcock.org

Morgan T Mazanec, MPH

CONTACT

603-308-9233; Morgan.T.Mazanec@Hitchcock.ORG

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Orthopaedics

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 14, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)