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

Invasive Candidiasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00672841
• Other study ID #: Pro00003161
• Secondary ID: GA88517X
• Status: Completed
• Phase: N/A
• First received: May 4, 2008
• Last updated: January 20, 2015
• Start date: June 2008
• Est. completion date: January 2011

Study information

• Verified date: November 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Candidiasis
• Candidiasis, Invasive
• Invasive Candidiasis

Intervention

Drug:
• Preemptive Therapy with Anidulafungin
Subjects in the active surveillance arm who develop a single positive ß-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.
• Empiric antifungal therapy based on physician discretion.
Patients in the standard care group may receive antifungal prophylaxis and/or treatment at any time based on the discretion of the treating physician.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Utility of Biweekly ß-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients.	Clinical utility was defined as ß-D-glucan test performance. Biweekly ßDG 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	No
Primary	Safety and Tolerability of Preemptive Anidulafungin	reported as the Number of Adverse Events Possibly Related to Study Drug	weekly until ICU discharge	Yes
Secondary	Validate Gene Expression Signatures Predictive of IC		Study Completion, an average of 17 days	No
Secondary	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	No