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

NCT00672841 | Completed Results DMC

• 2 other identifiers: Pro00003161GA88517X
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Candidiasis

Keywords

candidemia; invasive candidiasis; preemptive antifungal therapy; surveillance; β-D-Glucan (BDG)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (2)

2

ACTIVE COMPARATOR

Standard care/empiric therapy group

Drug: Empiric antifungal therapy based on physician discretion.

1

EXPERIMENTAL

Active surveillance/ preemptive therapy group

Drug: Preemptive Therapy with Anidulafungin

Interventions

Preemptive Therapy with Anidulafungin DRUG

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.

Also known as: Eraxis

1

Empiric antifungal therapy based on physician discretion. DRUG

Patients in the standard care group may receive antifungal prophylaxis and/or treatment at any time based on the discretion of the treating physician.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Pfizer: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD. beta-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PLoS One. 2012;7(8):e42282. doi: 10.1371/journal.pone.0042282. Epub 2012 Aug 6.

  PMID: 22879929 DERIVED

MeSH Terms

Conditions

Candidiasis, Invasive; Candidemia

Interventions

Anidulafungin

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Fungemia; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Echinocandins; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This study represents a 1st attempt at preemptive antifungal therapy based on the fungal biomarker 1,3-Beta-D-Glucan in the intensive care unit. Main limitation: the small number of subjects with proven/probable invasive candidiasis.

Results Point of Contact

• Title: Kimberly E. Hanson, MD, MHS
• Organization: University of Utah

kim.hanson@hsc.utah.edu

801.585.2867

Study Officials

• Kimberly E Hanson, MD

  Utah

  PRINCIPAL INVESTIGATOR

• Barbara D Alexander, MD

  Duke

  PRINCIPAL INVESTIGATOR

• John Perfect, MD

  Duke

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2008
• First Posted: May 6, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: February 6, 2015
• Results First Posted: April 22, 2013

Record last verified: 2012-11

Locations

US (1)