Modulation of Biomarkers in Patients With Flesh-eating Bacterial Infections After With Hyperbaric Oxygen Treatment

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of hyperic oxygen treatment on the immune response in patients with necrotizing soft tissue infections

Detailed Description
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Necrotizing soft tissue infections (NSTI) is a complex, multi-factorial disease and the bacteria show a diverse microbial etiology. The exentisive inflammatory response caused by these bacteria is thought to be a main course of death. In Denmark, most NSTI patients are treated with hyperic oxygen therapy (HBOT). However, the effects of HBOT have never been investigated in NSTI patients. Location: Copenhagen University Hospital, Rigshospitalet, Denmark. Design: Observational cohort study. Cohort: NSTI patients in Denmark treated with HBOT. Biomarkers: Cytokines, acute-phase proteins, vasoactive biomarkers and other inflammatory biomarkers. Sample size calculation: The investigators expect a mean IL-6 concentration before HBOT of 3500 pg/ml (standard deviation 1500 pg/ml) and consider a reduction of 800 pg/ml to be clinically relevant. With an alpha = 0.05 and a power of 80%, 112 patients will be required. Data: The Danish Data Protection Agency has approved the processing of personal data for the NSTI patients (J. no. 30-0900). Ethics: The trial will adhere to the Helsinki Declaration and the Danish law. The National Ethics Committee and the Regional Scientific Ethics Committee of Copenhagen have approved the study (CVK-1211709 and H-2-2014-071). Analysis: Biomarker analyses will be performed once the recruitment of patients has ended.

Official Title
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Biomarkers in Necrotizing Soft Tissue Infections - Effects of Hyperbaric Oxygen Treatment on the Immune Response

Conditions
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Necrotizing Soft Tissue Infection, Necrotizing Fasciitis, Gas Gangrene, Fournier Gangrene

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Necrotizing soft tissue infection based on surgical findings Admitted to/planned to be admitted to the ICU at Rigshospitalet and/or operated for NSTI at Rigshospitalet Receving a minimum of 1 HBOT Exclusion criteria: Patients who at the operating theatre were categorized as a non-NSTI patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with NSTI treated with HBOT<br>NSTI definition: An infection that requires acute hospitalization with intensive care treatment and/or surgery as a consequence of severe soft tissue infection causing necrosis in subcutis, muscle and/or fascia. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL-6 as a marker of treatment effects after HBOT |  | Change from baseline in IL-6 concentration after first HBOT administered during the first 24 hours of admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory biomarkers as indicators of treatment effects after HBOT |  | The first 5 days of admission | 
| Vasoactive biomarkers as indicators of treatment effects after HBOT |  | The first 5 days of admission | 
| Mortality |  | 30, 90, 180 days | 
| Amputation rate |  | During the first 7 days of ICU admission | 
| SAPS II assessment |  | During the first 24 hours of ICU admission | 
| APACHE II assessment |  | During the first 7 days of ICU admission | 
| SOFA score assessment |  | During the first 7 days of ICU admission | 
| Anaya score assessment |  | During the first 7 days of ICU admission | 
| LRINEC score assessment |  | During the first 7 days of ICU admission | 
| Multiple organ failure assessed by the MODS score |  | During the first 7 days of ICU admission | 
| Number of debridements |  | During the first 7 days of ICU admission | 
| Microbial etiology results from blood and tissue samples |  | During the first 7 days of ICU admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fasciitis, Fasciitis, Necrotizing, Soft tissue infections, Fournier's gangrene, Immunopathogenesis