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

Soft Tissue Infections Clinical Trial

— INFECT  

Official title:

Improving Outcome of Necrotizing Fasciitis: Elucidation of Complex Host and Pathogen Signatures That Dictate Severity of Tissue Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01790698
• Other study ID #: INFECT-FP7305340
• Status: Completed
• First received: February 4, 2013
• Last updated: April 20, 2018
• Start date: January 2013
• Est. completion date: January 2018

Study information

• Verified date: April 2018
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 409
• Est. completion date: January 2018
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Necrotizing soft tissue infections

Exclusion Criteria:

Patients under the age of 18 years

Related Conditions & MeSH terms

• Communicable Diseases
• Fasciitis
• Fasciitis, Necrotizing
• Infection
• Necrotizing Fasciitis
• Necrotizing Soft Tissue Infections
• Soft Tissue Infections

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
Norway	University of Bergen	Bergen
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Blekinge Hospital	Karlskrona
Sweden	Karolinska University Hospital	Stockholm

Sponsors (13)

Lead Sponsor	Collaborator
Karolinska Institutet	Anagnostics Bioanalysis GmbH, Blekinge County Council Hospital, Helmholtz Centre for Infection Research, Karolinska University Hospital, Lee Spark NF Foundation, LifeGlimmer GmbH, Rigshospitalet, Denmark, Sahlgrenska University Hospital, Sweden, Tel Aviv University, University of Bergen, University of Lyon, Wageningen University

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prognostic/diagnostic value (ROC curves: specificity, sensitivity, predictive values) of classification and severity scores in NSTIs		3 months - further oservation up to 24 month may apply
Secondary	Effect of IVIG and HBO-therapy on mortality rates in matched (defined by severity scores and aetiology) NSTI patients		3 months - further observation up to 24 month may apply
Secondary	Presence of hypotension, multiorgan failure, or fatal outcome of NSTI in relation to microbiologic aetiology		3 months - further observation up to 60 month may apply

External Links

•   website of INFECT