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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: ProTreat - Prognosis and Treatment of Necrotizing Soft Tissue Infections: A Prospective Cohort Study

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.

Detailed Summary:

Introduction:

Necrotizing soft-tissue infections (NSTI) are among the most serious and deadly infections known. They are characterized by rapidly progressing soft-tissue inflammation with necrosis and can quickly cause multiple organ failure and death. Mortality has been shown to be 25-35 %, with survivors coping with amputations and prolonged rehabilitation.

Currently, there is a lack of proper tools to evaluate the severity and prognosis of NSTI in individual patients. This results in necessary, yet sometimes overzealous surgical debridement, culminating in prolonged patient rehabilitation and invalidity. Hyperbaric oxygen therapy (HBOT) may be added as adjunctive therapy of NSTI. However, there is no clear understanding of the effectiveness of HBOT on NSTI. The investigators seek to remedy these two issues by examining multiple biomarkers over the course of several studies.

Methodology:

Location: Copenhagen University Hospital, Rigshospitalet, Denmark.

Design: Observational cohort study.

Cohort: All NSTI patients in Denmark since 2013.

Controls: 50-100 Patients undergoing elective, orthopedic surgery at Rigshospitalet.

Biomarkers: soluble thrombomodulin, syndecan-1, sE-selectin, VE-cadherin, protein C, suPAR.

Sample size calculations:

1: The test kits the investigators will be using to measure the primary outcome sTM (Human sCD141 ELISA kit, Nordic Biosite) have an interassay standard variation of 0.58 ng/ml. In order to be cer
Sponsor: Ole Hyldegaard

Current Primary Outcome:

  • sTM and sE-selectin as biomarkers of HBOT effect in NSTI patients [ Time Frame: At admission, and during the next 3 days in the ICU ]
    Changes in plasma sTM and sE-selectin concentrations in NSTI patients, compared with the control group
  • suPAR as a biomarker of disease severity and prognosis in NSTI patients with and without septic shock [ Time Frame: At admission ]
    Association between plasma suPAR levels and NSTI mortality, and SAPS II and SOFA scores


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mortality [ Time Frame: While in the ICU, and at 28, 90, 180 days ]
    Mortality
  • Amputation rate [ Time Frame: During ICU admission (expected average of 8 days) ]
    At any anatomical site
  • ICU scoring systems [ Time Frame: During ICU admission (expected average of 8 days) ]
    SAPS II (day 1) APACHE II (day 1) SOFA, GCS excluded (day 1-7)
  • Multiple organ failure [ Time Frame: During ICU admission (expected average of 8 days) ]
    Multiple organ failure
  • Debridements [ Time Frame: During ICU admission (expected average of 8 days) ]
    Number of debridements
  • Microbial etiology [ Time Frame: During ICU admission (expected average of 8 days) ]
    Tissue and blood samples
  • Time from admission to primary hospital until first surgery/debridement [ Time Frame: 2 days ]
  • Ventilator treatment [ Time Frame: During ICU admission (expected average of 8 days) ]
    Ventilator treatment during stay at ICU
  • Renal replacement therapy [ Time Frame: During ICU admission (expected average of 8 days) ]
    Renal replacement therapy during stay at ICU
  • Vasopressor treatment [ Time Frame: During ICU admission (expected average of 8 days) ]
    Vasopressor treatment during stay at ICU
  • Steroid treatment [ Time Frame: Up to 7 days before surgical diagnose at primary hospital ]
    Steroid treatment (injection/oral intake) up to development of NSTI
  • HBOT and endothelial biomarkers [ Time Frame: At admission, and the next 3 days in the ICU ]
    Any differences in sTM, syndecan-1, sE-selectin, VE-cadherin and protein C levels between NSTI patients who do not receive HBOT within the first 24 hours of ICU admission (because they are deemed too unstable for HBOT) vs. those who receive HBOT within the first 12 and 24 hours of ICU admission
  • Biomarkers and disease severity [ Time Frame: At admission, and the next 3 days in the ICU ]
    Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock will be diagnosed according to standardized criteria (American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee) and suPAR, sTM and sE-selectin will be investigated to see if there is a correlation between disease severity in these groups


Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: April 26, 2017
Date Started: February 2013
Date Completion: January 2018
Last Updated: May 6, 2017
Last Verified: May 2017