Septic Shock, Severe Sepsis
Conditions
Keywords
Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill
Brief summary
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.
Detailed description
(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.
Interventions
OTHERStandard of care
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.
OTHER(1,3)-β-D-glucan guided therapy
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.
Sponsors
Center for Clinical Studies, University Hospital Jena, Germany
Dept. of Microbiology, University Hospital Erlangen, Germany
Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany
Federal Ministry of Education and Research, Berlin, Germany
Associates of Cape Cod, Inc., East Falmouth, MA, USA
Center for Sepsis Control and Care, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
investigator-initiated prospective, multicenter, randomized, open, and parallel group study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Severe sepsis or septic shock * Onset of sepsis no longer than 24 hours * Increased risk of invasive candida infection with at least one of the following criteria: * total parenteral nutrition ≥48 hours * abdominal surgery within the last 7 days * antimicrobial therapy for at least 48 hours within the last 7 days * Acute or chronic renal failure with renal replacement therapy * Age ≥18 years * Informed consent of the patient or legal representative or delayed consent process is started if patient is incapable of giving informed consent and no legal representative is available.
Exclusion criteria
* Pregnant or lactating women * Ongoing invasive candida infection * systemic antifungal therapy * liver cirrhosis Child C * cardiopulmonary bypass within the last 4 weeks * treatment with immunoglobulins within the last 14 days * immunosuppression (solid organ transplantation, AISA, leukopenia) * participation in another intervention study * no commitment to full therapy (i.e. DNR order) * Infauste Prognose aufgrund von Nebenerkrankungen * kin to or colleague of study personnel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 28 day mortality | 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Candida Colonization | 14 days | Candida colonization assessed by Candida Colonization Index |
| Time to antifungal therapy | 14 days | — |
| Duration of organ support | 14 days | — |
| Mean total SOFA score | 14 days | Measure of organ dysfunction |
| 28 day antifungal-free survival | 28 days | — |
| ICU and hospital mortality | Hospital length of stay | — |
| Adverse events | 14 days | — |
| Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics | 2 days | — |
| Pharmacoeconomics | 14 days | — |
| ICU and hospital length of stay | Hospital length of stay | — |
Countries
Germany
Outcome results
None listed