Clinical Research Directory

The Management of Necrotizing Soft Tissue Infection Wounds With Cytal® Wound Matrix and MicroMatrix®

This is a prospective, pilot, parallel group, randomized controlled trial with 1:1 allocation. This will be a single center study coordinated at the Cleveland Clinic Foundation (CCF) Main Campus in Cleveland, Ohio. Data will be collected in a secure manner using REDCap housed at CCF. The study will consist of 2 arms: treatment with Cytal® Wound Matrix 2-Layer and MicroMatrix® (Integra LifeSciences, Plainsboro Township, NJ, U.S.A.) versus standard of care dressings. Wound debridement procedures will be performed by surgical staff at CCF. A co-investigator trained in the application of Cytal® Wound Matrix and MicroMatrix® will apply these treatments as outlined in section 6.1.2 Administration. This study will be conducted with IRB approval and written informed consent of each participant enrolled. The trial will be registered at ClinicalTrials.gov before the first participant is enrolled.

Validation of the Use of the Arteriovenous Tension Difference in CO2 Under Hyperbaric Conditions

The central venous-arterial carbon dioxide tension difference is used daily in intensive care to establish peripheral tissue hypoperfusion, mainly mediated by a low cardiac index. The partial pressures of gases (oxygen, carbon dioxide) increase in the blood of patients breathing 100% oxygen in hyperbaric conditions. Thus, the validity of this biomarker in situations of acute circulatory failure during a hyperbaric oxygen therapy session has not been established. The objective of the study is therefore to establish the diagnostic performance of the central venous-arterial carbon dioxide tension difference in the diagnosis of a low cardiac index in patients with septic shock undergoing hyperbaric oxygen therapy for necrotizing fasciitis.

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

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.

FATAL-NSTI Study (Factors Associated With In-hospital mortALity in NSTI).

Necrotizing soft tissue infections (NSTIs) are rare but potentially life-threatening infections involving the skin and underlying tissues such as fat, fascia, and sometimes muscle. They can progress rapidly and, despite modern antibiotics, surgery, and intensive care, are still associated with high in-hospital mortality. A major challenge in the management of NSTIs is early diagnosis. Initial signs and symptoms are often nonspecific and may resemble less severe soft tissue infections, leading to diagnostic and therapeutic delays. Once identified, treatment requires urgent surgery, broad-spectrum antibiotics, and close monitoring, frequently in an intensive care setting. Even with appropriate treatment, the clinical course of NSTIs is highly variable. Some patients recover, while others develop severe complications such as septic shock or multiple organ failure and may die during hospitalization. Predicting outcomes early in the hospital stay remains difficult for clinicians. The aim of this observational study is to identify factors associated with in-hospital mortality in adult patients with NSTIs. In-hospital mortality, defined as death from any cause during the hospital stay for NSTI treatment, represents the most severe outcome and is of major relevance to patients and caregivers. The study focuses on clinical and laboratory data routinely available at hospital admission or during initial emergency department evaluation. These include patient demographics, vital signs, and standard blood test results commonly obtained in early clinical assessment. No additional diagnostic tests or procedures are required for study purposes. Identifying early predictors of mortality is particularly important in NSTIs, given the rapid progression of the disease. Early recognition of high-risk patients may allow closer monitoring and more timely interventions. The study will be conducted in high-volume referral centers with extensive experience in NSTIs management, where care is delivered according to established international guidelines. All patients will receive standard treatment based on clinical judgment. No experimental therapies or changes in routine care will be involved.

Hyperbaric Oxygen Treatment for Necrotizing Fasciitis and Necrotizing Soft Tissue Infections

The goal of this clinical trial is to learn if hyperbaric oxygen is beneficial in treating necrotizing infections and decreasing rates of morbidity and mortality. This study therefore has two aims: 1. Determine if hyperbaric oxygen improve morbidity and mortality compared to standard of care using a prospective model. 2. Determine if faster diagnosis to debridement times negate the need for hyperbaric oxygen treatments in necrotizing infections.