Clinical Trial: Biomarkers in Patients With Flesh-eating Bacterial Infections

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Biomarkers in Necrotizing Soft Tissue Infections - Aspects of the Innate Immune Response

Brief Summary: The purpose of this study is to investigate the immune response in patients with necrotizing soft tissue infections (NSTI). The investigation will focus on inflammatory and vasoactive biomarkers as prognostic markers of severity and mortality at admission to Rigshospitalet and the following 3 days

Detailed Summary:

Necrotizing soft tissue infection (NSTI) is a complex, multi-factorial disease with diverse microbiological etiology and varying co-morbidities. The rapidly spreading infection may cause extensive soft tissue damage, limb loss, and multiple organ failure. The incidence of NSTIs has increased over the past years and the fatality rates are still high despite increased focus on these patients (20-30%). The extensive inflammatory response is thought to be a main course of death. However, it is unknown which biomarkers that are responsible for the deleterious effects and how these molecular mediators are modulated during the infection and treatment regimes. Thus, there is a need for novel insight into the immune system disturbances in order to improve outcome of NSTIs.

Location: Copenhagen University Hospital, Rigshospitalet, Denmark.

Design: Observational cohort study.

Cohort: NSTI patients in Denmark.

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

Biomarkers: The investigators will focus on three major groups of biomarkers: Acute-phase proteins, cytokines and vasoactive biomarkers.

Sample size calculations:

  1. Acute-phase proteins: The investigators expect a mean PTX3-concentration at admission at 120 nmol/L in patients without septic shock and a mean PTX3-concentration at 210 nmol/L in patients with septic shock. With an estimated standard deviation at 100 nmol/L, the inclusion of 52 patients will be able to detect a significant difference with a statistical power of 90% at a 5% significance level. Since the group
    Sponsor: Ole Hyldegaard

    Current Primary Outcome: PTX3, NOx and IL-6 as early markers of disease severity in NSTI patients with and without septic shock [ Time Frame: Admission, first 24 hours ]

    Primary analysis: Association between PTX3-, NOx-, and IL6-concentration and septic shock (PTX3, NOx) or LRINEC ≥ 6 (IL-6) in NSTI patients at time of admission to Rigshospitalet


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Mortality [ Time Frame: 28, 90, 180 days ]
    • 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), Anaya-score
    • Multiple organ failure [ Time Frame: During ICU admission (expected average of 8 days) ]
    • Number of debridements [ Time Frame: During ICU admission (expected average of 8 days) ]
    • 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, renal replacement therapy, vasopressor treatment during stay at ICU [ Time Frame: During ICU admission (expected average of 8 days) ]
    • Steroid treatment (injection/oral intake) up to development of NSTI [ Time Frame: Up to 7 days before surgical diagnose at primary hospital ]
    • Inflammatory biomarkers [ Time Frame: Admission and the following 3 days ]
      Secondary analysis: The association between inflammatory biomarkers such as CRP, procalcitonin, mannose-binding-lectin and ficolin-1,2,3, cytokines and septic shock, LRINEC ≥ 6 and SAPS II at admission and the following 3 days
    • Vasoactive biomarkers [ Time Frame: Admission and the following 3 days ]
      Secondary analysis: The association between vasoactive biomarkers such as NOx (nitrite, NO2-, and nitrate, NO3-,), L-arginine, asymmetric dimethylarginine, hydrogen sulfide, reactive oxygen species, ICAM-1, E-selectin and septic shock, LRINEC ≥ 6 and SAPS II at admission and the following 3 days
    • The effects of immunoglobulin on inflammatory biomarkers [ Time Frame: Admission and the following 3 days ]
      A subgroup analysis will be performed on patients randomized to immunoglobulin or saline as immunoglobulin might affect the biomarker response (PTX3, NO, IL-6). The randomized double-blinded study was initiated April 2014 and registered at ClinicalTrials.gov (NCT02111161).
    • Biomarkers and Severity of disease [ Time Frame: Admission and the following 3 days ]
      Subgroup analysis: 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 the biomarkers will be investigated to see if there is a correlation between disease severity and mortality in these groups.


    Original Secondary Outcome: Same as current

    Information By: Rigshospitalet, Denmark

    Dates:
    Date Received: June 29, 2014
    Date Started: February 2013
    Date Completion:
    Last Updated: February 14, 2016
    Last Verified: February 2016