Systems Medicine to Study Necrotizing Soft Tissue Infections (NSTIs).

NCT ID: NCT01790698

Last Updated: 2018-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

409 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-01-31

Study Completion Date

2018-01-31

Brief Summary

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This proposal focuses on highly lethal destructive tissue infections, i.e. necrotizing fasciitis and other necrotizing soft tissue infections (NSTIs), which are associated with high morbidity and mortality. The fulminant course of NSTIs demands immediate diagnosis and adequate interventions in order to salvage lives and limbs. However, diagnosis and management are difficult due to heterogeneity in clinical presentation, in co-morbidities and in microbiological aetiology. Thus, there is an urgent need for novel diagnostics and therapeutics in order to improve outcome of NSTIs. A comprehensive knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) is required for an improved diagnosis and management of NSTIs. The current proposal is designed to obtain such insights through an integrated systems biology approach in patients and experimental models. The project is based on a prospective NSTI patients cohort including a clinical registry to document clinical data and treatment strategies, combined with an isolate and biobank collection. The samples will be analyzed through advanced bioinformatics and computational modelling work flow to identify and quantify pathogen signatures and underlying networks that contribute to disease outcome. One aim is to translate clinical and systems biology data into development of novel diagnostics.

Detailed Description

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Patients will be prospectively recruited at 5 clinical centers (Rigshospitalet, Karolinska University Hospital, Blekinge University, Sahlgrenska University and University of Bergen). Clinical definition criteria for NSTI: NSTI is a clinical diagnosis. Initial signs are the occurrence of erythema, pain or tenderness beyond margins of erythema and swelling. Imaging and laboratory tests have little predictive value in the early stage. The gold standard modality for diagnosis of NSTI remains operative exploration. Operative findings that are consistent with NSTI include "dishwater or foul smelling discharge, necrosis or lack of bleeding and loss of the normal resistance of the fascia to finger dissection. A patient admitted for critical care and / or surgery due to severe soft tissue infection of the fascia, muscle or subcutaneous tissues will be enrolled in this NSTI study. The patients will be stratified based on several clinical parameters including among others SAPS score, presence of multiorgan failure, and hypotensive shock. This stratification serves to classify the patients in defined severity classes to be used in analyses and modeling. Detailed demographic and clinical information will be documented in the interactive database including: age, gender, medical history, clinical presentation (shock, multiorgan failure etc), treatment and outcome. Disease progress: The clinical database is to contain information on the spread of the infection at the different times of inspection/surgical intervention. Severity of the infections will be documented by use of the updated CREST classification scheme, SAPS III score, and the LRINEC score. Detailed information regarding antimicrobial therapy, surgical intervention, innovative therapy (IVIG and HBO) will be documented.

Samples will be collected from all enrolled patients. Standard operating procedures will be generated and implemented at all sites to ensure a quality assured collection and handling of samples. Samples to be collected include (a) isolates, (b) blood samples to be processed for DNA, RNA and plasma/cells and (c) tissue biopsies in all patients whenever surgical interventions are indicated. The samples will be analyzed using genomics, transcriptomics, metabolomics and proteomics.

Conditions

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Soft Tissue Infections Necrotizing Fasciitis Necrotizing Soft Tissue Infections

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

Necrotizing soft tissue infections

Exclusion Criteria

Patients under the age of 18 years
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role collaborator

Blekinge County Council Hospital

OTHER

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

University of Bergen

OTHER

Sponsor Role collaborator

Helmholtz Centre for Infection Research

OTHER

Sponsor Role collaborator

Wageningen University

OTHER

Sponsor Role collaborator

University of Lyon

OTHER

Sponsor Role collaborator

LifeGlimmer GmbH

UNKNOWN

Sponsor Role collaborator

Anagnostics Bioanalysis GmbH

UNKNOWN

Sponsor Role collaborator

Lee Spark NF Foundation

UNKNOWN

Sponsor Role collaborator

Tel Aviv University

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Anna Norrby-Teglund

Professor, Coordinator of INFECT

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Rigshospitalet

Copenhagen, , Denmark

Site Status

University of Bergen

Bergen, , Norway

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Blekinge Hospital

Karlskrona, , Sweden

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Countries

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Denmark Norway Sweden

References

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Hyldegaard O, Nekludov M, Arnell P, Nedrebo T, Karlsson Y, Madsen MB, Skrede S, Dos Santos VM, Svensson M, Perner A, Vinkel J, Kjellberg A, Rosen A, Douglas J, Bruun T, Hardt C, Norrby-Teglund A, Hedetoft M. Use of Hyperbaric Oxygen in Patients with Necrotizing Soft Tissue Infections: A Scandinavian Multicenter, Prospective, Observational Cohort. Infect Dis Ther. 2025 Aug;14(8):1715-1738. doi: 10.1007/s40121-025-01184-5. Epub 2025 Jul 4.

Reference Type DERIVED
PMID: 40613866 (View on PubMed)

Vinkel J, Buil A, Hyldegaard O. Blood from septic patients with necrotising soft tissue infection treated with hyperbaric oxygen reveal different gene expression patterns compared to standard treatment. BMC Med Genomics. 2025 Jan 14;18(1):12. doi: 10.1186/s12920-024-02075-3.

Reference Type DERIVED
PMID: 39810178 (View on PubMed)

Vinkel J, Rib L, Buil A, Hedetoft M, Hyldegaard O. Key pathways and genes that are altered during treatment with hyperbaric oxygen in patients with sepsis due to necrotizing soft tissue infection (HBOmic study). Eur J Med Res. 2023 Nov 10;28(1):507. doi: 10.1186/s40001-023-01466-z.

Reference Type DERIVED
PMID: 37946314 (View on PubMed)

Vinkel J, Rib L, Buil A, Hedetoft M, Hyldegaard O. Investigating the Effects of Hyperbaric Oxygen Treatment in Necrotizing Soft Tissue Infection With Transcriptomics and Machine Learning (the HBOmic Study): Protocol for a Prospective Cohort Study With Data Validation. JMIR Res Protoc. 2022 Nov 25;11(11):e39252. doi: 10.2196/39252.

Reference Type DERIVED
PMID: 36427229 (View on PubMed)

Palma Medina LM, Rath E, Jahagirdar S, Bruun T, Madsen MB, Stralin K, Unge C, Hansen MB, Arnell P, Nekludov M, Hyldegaard O, Lourda M, Santos VAMD, Saccenti E, Skrede S, Svensson M, Norrby-Teglund A. Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections. J Clin Invest. 2021 Jul 15;131(14):e149523. doi: 10.1172/JCI149523.

Reference Type DERIVED
PMID: 34263738 (View on PubMed)

Bergsten H, Madsen MB, Bergey F, Hyldegaard O, Skrede S, Arnell P, Oppegaard O, Itzek A, Perner A, Svensson M, Norrby-Teglund A; INFECT Study Group. Correlation Between Immunoglobulin Dose Administered and Plasma Neutralization of Streptococcal Superantigens in Patients With Necrotizing Soft Tissue Infections. Clin Infect Dis. 2020 Oct 23;71(7):1772-1775. doi: 10.1093/cid/ciaa022.

Reference Type DERIVED
PMID: 31916575 (View on PubMed)

Related Links

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http://www.fp7infect.eu

website of INFECT

Other Identifiers

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INFECT-FP7305340

Identifier Type: -

Identifier Source: org_study_id

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