Prognosis and Treatment of Necrotizing Soft Tissue Infections: A Prospective Cohort Study

NCT03147352 | Completed DMC

• 1 other identifier: PROTREAT1-PP-2017
• Study Type: observational
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will analyze biomarkers related to the prognosis and treatment of necrotizing soft tissue infections (NSTI). The focus will be on whether certain endothelial and immune system biomarkers can function as markers of disease severity, mortality as well as the effects of hyperbaric oxygen therapy (HBOT). Biomarkers will be measured upon admission to an intensive care unit at Copenhagen University Hospital and during the following 3 days.

Conditions

Necrotizing Soft Tissue Infection; Necrotizing Fascitis; Gas Gangrene; Fournier Gangrene

Keywords

Fasciitis; Gangrene; Fasciitis, Necrotizing; Soft Tissue Infections; Fournier's Gangrene; Streptococcal septic shock syndrome; Flesh eating bacteria; Meleneys ulcer; Wounds and Injuries; Streptococcus pyogenes; Staphylococcus aureus; Soft Tissue Infections/blood; Necrosis/blood; Necrosis/diagnosis; Necrosis/mortality; Necrosis/surgery; Prognosis; Risk Factors; Bacterial Infections; Infection; Skin Diseases, Bacterial; Observational study; Biological markers; Endothelium; suPAR; sTM; syndecan-1; sE-selectin; VE-cadherin; protein C; Hyperbaric oxygen therapy; HBOT

Outcome Measures

Primary Outcomes (2)

• sTM and sE-selectin as biomarkers of HBOT effect in NSTI patients

  Changes in plasma sTM and sE-selectin concentrations in NSTI patients, compared with the control group

  At admission, and during the next 3 days in the ICU

• suPAR as a biomarker of disease severity and prognosis in NSTI patients with and without septic shock

  Association between plasma suPAR levels and NSTI mortality, and SAPS II and SOFA scores

  At admission

Secondary Outcomes (13)

• Mortality

  While in the ICU, and at 28, 90, 180 days

• Amputation rate

  During ICU admission (expected average of 8 days)

• ICU scoring systems

  During ICU admission (expected average of 8 days)

• Multiple organ failure

  During ICU admission (expected average of 8 days)

• Debridements

  During ICU admission (expected average of 8 days)

Study Arms (2)

NSTI patients

NSTI is an infection that requires acute hospitalization with intensive care treatment and/or surgery as a consequence of severe soft tissue infection in subcutis, muscle and/or fascia and that spreads along tissue structures.

Device: Hyperbaric oxygen therapy

Orthopaedic control patients

Elective orthopaedic control patients.

Interventions

Hyperbaric oxygen therapy DEVICE

Hyperbaric oxygen therapy with 100 % oxygen at 1.8 ATA for 2 hours.

NSTI patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

NSTI cohort: All NSTI patients treated at the University Hospital of Copenhagen, Rigshospitalet. Orthopaedic control cohort: Undergoing elective orthopedic surgery (non-pathological fractures, joint replacement surgery or spine surgery) at Copenhagen University Hospital

You may qualify if:

• Diagnosed with NSTI based on surgical findings (necrosis of any soft tissue compartment; dermis, hypodermis, fascia or muscle)
• Admitted to the Intensive Care Unit (ICU) and/or operated for NSTI at Copenhagen University Hospital

You may not qualify if:

• They are categorized as non NSTI in the operating theatre
• Undergoing elective orthopedic surgery (non-pathological fractures, joint replacement surgery or spine surgery) at Copenhagen University Hospital
• Ongoing infection or inflammatory condition

Sponsors & Collaborators

• Ole Hyldegaard: lead
• Seventh Framework Programme: collaborator

Study Sites (1)

Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (8)

• Kayal S, Jais JP, Aguini N, Chaudiere J, Labrousse J. Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):776-84. doi: 10.1164/ajrccm.157.3.9705034.

  PMID: 9517590 BACKGROUND

• Huttunen R, Syrjanen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J. Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med. 2011 Jul;270(1):32-40. doi: 10.1111/j.1365-2796.2011.02363.x. Epub 2011 Mar 21.

  PMID: 21332843 BACKGROUND

• Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med. 2012 Sep;38(9):1418-28. doi: 10.1007/s00134-012-2613-1. Epub 2012 Jun 16.

  PMID: 22706919 BACKGROUND

• Blann A, Seigneur M. Soluble markers of endothelial cell function. Clin Hemorheol Microcirc. 1997 Jan-Feb;17(1):3-11.

  PMID: 9181753 BACKGROUND

• Buras JA, Stahl GL, Svoboda KK, Reenstra WR. Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am J Physiol Cell Physiol. 2000 Feb;278(2):C292-302. doi: 10.1152/ajpcell.2000.278.2.C292.

  PMID: 10666024 BACKGROUND

• Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007 Jun;454(3):345-59. doi: 10.1007/s00424-007-0212-8. Epub 2007 Jan 26.

  PMID: 17256154 BACKGROUND

• Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007 Oct 23;116(17):1896-906. doi: 10.1161/CIRCULATIONAHA.106.684852. Epub 2007 Oct 8.

  PMID: 17923576 BACKGROUND

• Polzik P, Johansson PI, Hyldegaard O. How biomarkers reflect the prognosis and treatment of necrotising soft tissue infections and the effects of hyperbaric oxygen therapy: the protocol of the prospective cohort PROTREAT study conducted at a tertiary hospital in Copenhagen, Denmark. BMJ Open. 2017 Oct 5;7(10):e017805. doi: 10.1136/bmjopen-2017-017805.

  PMID: 28982834 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and plasma/serum

MeSH Terms

Conditions

Fasciitis, Necrotizing; Gas Gangrene; Fournier Gangrene; Fasciitis; Gangrene; Soft Tissue Infections; Wounds and Injuries; Staphylococcal Infections; Necrosis; Disease; Bacterial Infections; Infections; Skin Diseases, Bacterial

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections and Mycoses; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Peter V Polzik, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Ole Hyldegaard, MD, PhD

  Rigshospitalet, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 10, 2017
• Study Start: February 1, 2013
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: June 24, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)