β-D-Glucan (BDG) Surveillance With Preemptive Anidulafungin vs. Standard Care for Invasive Candidiasis in Surgical Intensive Care Unit (SICU) Patients

Study Overview
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Brief Summary
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This is a single center, prospective, open label assessment of β-D-glucan surveillance with preemptive anidulafungin therapy versus standard care for the prevention of invasive candidiasis in at-risk surgical intensive care unit (SICU) patients. Subjects will be stratified by APACHE II score and randomized in 3:1 fashion to either biweekly surveillance using the β-D-glucan assay or standard care. Subjects in the active monitoring arm will receive intravenous anidulafungin should the β-D-glucan exceed 60 pg/mL on a single determination. Subjects in the standard care arm will have biweekly blood draws for β-D-glucan, but the specimens will be batched and tested retrospectively. Antifungal use in the standard care arm is at the discretion of the treating physicians. The primary study end-points are the feasibility of a preemptive antifungal strategy in a SICU setting, β-D-glucan test characteristics, and the safety and tolerability of preemptive anidulafungin. Risks associated with study participation include the risks associated with blood draws, study drug related side effects, and the potential for loss of confidentiality.

Official Title
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Randomized Comparison of β-D-Glucan Surveillance With Preemptive Anidulafungin Versus Standard Care for the Management of Invasive Candidiasis in Surgical Intensive Care Unit Patients

Conditions
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Invasive Candidiasis

Intervention / Treatment
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* Drug: Preemptive Therapy with Anidulafungin
* Drug: Empiric antifungal therapy based on physician discretion.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Admission to the intensive care unit for ≥ 72 hours and expected to stay an additional 48 hours IV access for administration of study drug Subject (or subject's legal representative) able to give written informed consent Exclusion Criteria: History of hypersensitivity or intolerance to echinocandin antifungals Liver function test (ALT, AST (aspartate aminotransferase), and/or total bilirubin) greater than 10 times the upper limits of normal (ULN) Pregnant or lactating women Treatment with systemic antifungal therapy within the preceding 7 days Documented invasive fungal infection at baseline/screening Life expectancy less than 2 days or moribund

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>Standard care/empiric therapy group | Drug: Empiric antifungal therapy based on physician discretion.<br>* Patients in the standard care group may receive antifungal prophylaxis and/or treatment at any time based on the discretion of the treating physician.<br>|
| Experimental: 1<br>Active surveillance/ preemptive therapy group | Drug: Preemptive Therapy with Anidulafungin<br>* Subjects in the active surveillance arm who develop a single positive β-D-glucan test will receive preemptive anidulafungin intravenously. Preemptive therapy will include a loading dose of 200mg followed by 100mg maintenance therapy once a day. The loading and maintenance doses are derived from the FDA cleared schedule for Invasive Candidiasis and candidemia. Preemptive therapy will continue for 14 days.<br>* Other names: Eraxis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. | Clinical utility was defined as β-D-glucan test performance. Biweekly βDG testing used a threshold of ≥ 60 pg/ml to indicate a positive test for invasive candidiasis. True and false positives, and true and false negatives were confirmed using a composite clinical definition of invasive candidiasis that combines physical symptom/signs and microbiology. Cases of proven/probable invasive fungal infection (IFI) were adjudicated by a single reviewer blinded to group assignment and BDG results. | Participants were followed until ICU discharge, an average of 17 days | 
| Safety and Tolerability of Preemptive Anidulafungin | reported as the Number of Adverse Events Possibly Related to Study Drug | weekly until ICU discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate Gene Expression Signatures Predictive of IC |  | Study Completion, an average of 17 days | 
| Incidence of Proven or Probable Invasive Fungal Infection (IFI) | Institution specific criteria were used to establish a diagnosis of proven or probable invasive candidiasis. Other IFIs were classified according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria. However, BDG results were not factored into the EORTC/MSG criteria. | Participants were followed until ICU discharge, an average of 17 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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candidemia, invasive candidiasis, preemptive antifungal therapy, surveillance, β-D-Glucan (BDG)