(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection in Sepsis

Study Overview
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Brief Summary
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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
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(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.

Official Title
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(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection Versus Culture Based Diagnosis in Patients With Severe Sepsis or Septic Shock

Conditions
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Severe Sepsis, Septic Shock

Intervention / Treatment
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* Other: Standard of care
* Other: (1,3)-β-D-glucan guided therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: investigator-initiated prospective, multicenter, randomized, open, and parallel group study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Diagnosis of invasive candida infection according to standard of care. | Other: Standard of care<br>* 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.<br>|
| Experimental: (1,3)-β-D-glucan guidance<br>Treatment according to BDG-result | Other: Standard of care<br>* 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.<br>Other: (1,3)-β-D-glucan guided therapy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day mortality |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day antifungal-free survival |  | 28 days | 
| Candida Colonization | Candida colonization assessed by Candida Colonization Index | 14 days | 
| Time to antifungal therapy |  | 14 days | 
| Duration of organ support |  | 14 days | 
| Mean total SOFA score | Measure of organ dysfunction | 14 days | 
| ICU and hospital length of stay |  | Hospital length of stay | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill