This prospective randomized multicenter study evaluates whether the decision to prescribe antifungals guided by (1,3)-β-D-glucan in comparison to standard of care shortens time to antifungal therapy and reduces mortality in patients with severe sepsis or septic shock and a high risk of invasive candida infection.
(1,3)-β-D-glucan is a component of the cell wall of many fungi including candida spp. and is present in the blood of patients with invasive candida infection (ICI). Several studies showed a good diagnostic accuracy (1,3)-β-D-glucan in predicting ICI. However, others have challenged (1,3)-β-D-glucan as a diagnostic tool in critically ill patients as many substances used in the intensive care unit might affect the results of the assay. The goal of this study is to investigate whether (1,3)-β-D-glucan can early identify sepsis patients in need of antifungal therapy. Patients randomized to the standard of care group receive antifungals depending on microbiological results according to current guidelines. Patients randomized to the BDG group receive antifungals depending on the (1,3)-β-D-glucan plasma concentration on day 1 and day after diagnosing sepsis. Therapy may be modified according to microbiological results.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
342
Patients are treated according to the ESCMID guidelines. Antifungal therapy is started if fungi are detected in the blood culture or other primary sterile body fluids.
Serum for (1,3)-β-D-glucan measurement is obtained after enrollment and 24 hours later. Antifungal therapy is started if at least one sample is 80 pg/ml or higher. If concomitantly taken microbiological cultures remain negative, antifungal therapy is continued only, if both (1,3)-β-D-glucan were at least 80 pg/ml. Blood cultures or other samples from primary sterile body fluids positive for fungi are treated with antifungals irrespective the (1,3)-β-D-glucan results.
Hospital Augsburg
Augsburg, Germany
HELIOS Klinikum Bad Saarow
Bad Saarow, Germany
University Hospital Bonn
28 day mortality
Time frame: 28 days
28 day antifungal-free survival
Time frame: 28 days
Candida Colonization
Candida colonization assessed by Candida Colonization Index
Time frame: 14 days
Time to antifungal therapy
Time frame: 14 days
Duration of organ support
Time frame: 14 days
Mean total SOFA score
Measure of organ dysfunction
Time frame: 14 days
ICU and hospital length of stay
Time frame: Hospital length of stay
ICU and hospital mortality
Time frame: Hospital length of stay
Adverse events
Time frame: 14 days
Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics
Time frame: 2 days
Pharmacoeconomics
Time frame: 14 days
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Bonn, Germany
Hospital Emden
Emden, Germany
University Hospital Erlangen
Erlangen, Germany
University Hospital Frankfurt
Frankfurt, Germany
University Hospital Göttingen
Göttingen, Germany
University Hospital Greifswald
Greifswald, Germany
University Hospital Halle
Halle, Germany
University Hospital Hamburg-Eppendorf
Hamburg, Germany
...and 8 more locations