Biomarkers in Patients With Flesh-eating Bacterial Infections (BIONEC)
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|ClinicalTrials.gov Identifier: NCT02180906|
Recruitment Status : Completed
First Posted : July 3, 2014
Last Update Posted : February 17, 2016
|Condition or disease|
|Necrotizing Soft Tissue Infection Necrotizing Fasciitis Gas Gangrene Fournier Gangrene|
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:
- 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 groups are unequal the investigators will need to include 82 patients (N'=52(1+4)^2/4*4).
- Cytokines: In a pilot study with seven NSTI patients, the investigators found a minimal clinically relevant difference in IL-6 concentration in NSTI patients with LRINEC < 6 and ≥ 6 to be 1050 pg/ml. With an estimated standard deviation at 2000 pg/ml, the inclusion of 114 patients will be able to detect a significant difference with a statistical power of 80% at a 5% significance level.
- Vasoactive proteins: The investigators expect a mean NOx-concentration at admission at 90 μmol/L in patients without septic shock and a mean NOx-concentration at 145 μmol/Lin patients with septic shock. With an estimated standard deviation at 70 μmol/L, the inclusion of 70 patients will be able to detect a significant difference with a statistical power of 90% at a 5% significance level. Since the groups are unequal the investigators will need to include 110 patients (N'=70(1+4)^2/4*4).
Data: Data will be handled according to the National Data Protection Agency. All original records (incl. consent forms and questionnaires) will be archived at trial site for 15 years. The National Data Protection Agency has approved the biobank (2007-58-0015, J. nr. 30-1282).
Ethics: The trial will adhere to the Helsinki Declaration and Danish law. The National Ethics Committee and the Regional Ethics Committee have approved the inclusion of the NSTI patients (CVK-1211709) and the control patients, including biomarker analyses (H-2-2014-071).
Biomarker analyses, data extraction and interpretation will be performed once the recruiting of participants has ended.
|Study Type :||Observational|
|Actual Enrollment :||169 participants|
|Official Title:||Biomarkers in Necrotizing Soft Tissue Infections - Aspects of the Innate Immune Response|
|Study Start Date :||February 2013|
|Actual Primary Completion Date :||February 2016|
|Actual Study Completion Date :||February 2016|
Patients with NSTI
Definition: 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 are spreading along tissue structures.
- 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
- 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.
Biospecimen Retention: Samples Without DNA
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): NCT02180906
|Copenhagen University Hospital, Rigshospitalet|
|Copenhagen, Denmark, 2100|
|Principal Investigator:||Marco Bo Hansen, MD||Rigshospitalet, Denmark|
|Study Director:||Ole Hyldegaard, MD, PhD||Rigshospitalet, Denmark|