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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00672841
First received: May 4, 2008
Last updated: March 13, 2013
Last verified: November 2012
  Purpose

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.


Condition Intervention
Invasive Candidiasis
Drug: Preemptive Therapy with Anidulafungin
Drug: Empiric antifungal therapy based on physician discretion.

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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. [ Time Frame: Participants were followed until ICU discharge, an average of 17 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: weekly until ICU discharge ] [ Designated as safety issue: Yes ]
    reported as the Number of Adverse Events Possibly Related to Study Drug


Secondary Outcome Measures:
  • Validate Gene Expression Signatures Predictive of IC [ Time Frame: Study Completion, an average of 17 days ] [ Designated as safety issue: No ]
  • Incidence of Proven or Probable Invasive Fungal Infection (IFI) [ Time Frame: Participants were followed until ICU discharge, an average of 17 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 64
Study Start Date: June 2008
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2
Standard care/empiric therapy group
Drug: 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.
Experimental: 1
Active surveillance/ preemptive therapy group
Drug: Preemptive Therapy with Anidulafungin
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.
Other Name: Eraxis

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672841

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Pfizer
Investigators
Principal Investigator: Kimberly E Hanson, MD Utah
Principal Investigator: Barbara D Alexander, MD Duke
Principal Investigator: John Perfect, MD Duke
  More Information

No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00672841     History of Changes
Other Study ID Numbers: Pro00003161, GA88517X
Study First Received: May 4, 2008
Results First Received: February 21, 2012
Last Updated: March 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
candidemia
invasive candidiasis
preemptive antifungal therapy
surveillance
β-D-Glucan (BDG)

Additional relevant MeSH terms:
Candidiasis
Candidiasis, Invasive
Mycoses
Anidulafungin
Antifungal Agents
Echinocandins
Miconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014