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

Not Applicable

Completed

Interventions: Drug: Preemptive Therapy with Anidulafungin
Drug: Empiric antifungal therapy based on physician discretion.

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
1	Preemptive Therapy with Anidulafungin	Active surveillance/ preemptive therapy group
2	Empiric antifungal therapy based on physician discretion.	Standard care/empiric therapy group

Primary Outcome Measures

Name	Time	Method
Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients.	Participants were followed until ICU discharge, an average of 17 days	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.
Safety and Tolerability of Preemptive Anidulafungin	weekly until ICU discharge	reported as the Number of Adverse Events Possibly Related to Study Drug

Secondary Outcome Measures

Name	Time	Method
Validate Gene Expression Signatures Predictive of IC	Study Completion, an average of 17 days
Incidence of Proven or Probable Invasive Fungal Infection (IFI)	Participants were followed until ICU discharge, an average of 17 days	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.