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

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ClinicalTrials.gov Identifier: NCT01790698
Recruitment Status : Completed
First Posted : February 13, 2013
Last Update Posted : April 23, 2018
Rigshospitalet, Denmark
Karolinska University Hospital
Blekinge County Council Hospital
Sahlgrenska University Hospital, Sweden
University of Bergen
Helmholtz Centre for Infection Research
Wageningen University
University of Lyon
LifeGlimmer GmbH
Anagnostics Bioanalysis GmbH
Lee Spark NF Foundation
Tel Aviv University
Information provided by (Responsible Party):
Anna Norrby-Teglund, Karolinska Institutet

Brief Summary:
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.

Condition or disease
Soft Tissue Infections Necrotizing Fasciitis Necrotizing Soft Tissue Infections

Detailed Description:

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.

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Study Type : Observational [Patient Registry]
Actual Enrollment : 409 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 3 Months
Official Title: Improving Outcome of Necrotizing Fasciitis: Elucidation of Complex Host and Pathogen Signatures That Dictate Severity of Tissue Infection
Study Start Date : January 2013
Actual Primary Completion Date : June 2017
Actual Study Completion Date : January 2018

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Prognostic/diagnostic value (ROC curves: specificity, sensitivity, predictive values) of classification and severity scores in NSTIs [ Time Frame: 3 months - further oservation up to 24 month may apply ]

Secondary Outcome Measures :
  1. Effect of IVIG and HBO-therapy on mortality rates in matched (defined by severity scores and aetiology) NSTI patients [ Time Frame: 3 months - further observation up to 24 month may apply ]
  2. Presence of hypotension, multiorgan failure, or fatal outcome of NSTI in relation to microbiologic aetiology [ Time Frame: 3 months - further observation up to 60 month may apply ]

Biospecimen Retention:   Samples With DNA
Bacterial isolates, whole blood, plasma, tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Hospitalized patients with NSTI

Inclusion Criteria:

Necrotizing soft tissue infections

Exclusion Criteria:

Patients under the age of 18 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01790698

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Copenhagen, Denmark, 2100
University of Bergen
Bergen, Norway, 5021
Sahlgrenska University Hospital
Gothenburg, Sweden, SE-416 50
Blekinge Hospital
Karlskrona, Sweden, SE-371 85
Karolinska University Hospital
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
Karolinska Institutet
Rigshospitalet, Denmark
Karolinska University Hospital
Blekinge County Council Hospital
Sahlgrenska University Hospital, Sweden
University of Bergen
Helmholtz Centre for Infection Research
Wageningen University
University of Lyon
LifeGlimmer GmbH
Anagnostics Bioanalysis GmbH
Lee Spark NF Foundation
Tel Aviv University
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Anna Norrby-Teglund, Professor, Coordinator of INFECT, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT01790698    
Other Study ID Numbers: INFECT-FP7305340
First Posted: February 13, 2013    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018
Keywords provided by Anna Norrby-Teglund, Karolinska Institutet:
Necrotizing fasciitis
Streptococcus pyogenes
Staphylococcus aureus
Additional relevant MeSH terms:
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Communicable Diseases
Soft Tissue Infections
Fasciitis, Necrotizing
Disease Attributes
Pathologic Processes
Musculoskeletal Diseases