Outcomes of Patients Who Fail to Respond to Fluconazole Treatment of Severe Candida Albicans Infections

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Jerome Schentag, CPL Associates
ClinicalTrials.gov Identifier:
NCT00721487
First received: July 22, 2008
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The primary aims of this study are to identify and characterize the immediate consequences of patients who fail fluconazole treatment during the treatment of severe infection, and to determine if fluconazole failures are more frequently associated with fluconazole-resistant or fluconazole-susceptible strains of C. albicans.


Condition Intervention
Fungal Infection by Site
Drug: Fluconazole

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: A Case Series of Investigator-Identified Fluconazole Failures: Outcome Characterization of Patients Who Fail to Respond to Fluconazole Treatment of Severe Infections Caused by Candida Albicans

Resource links provided by NLM:


Further study details as provided by CPL Associates:

Enrollment: 28
Study Start Date: July 2008
Study Completion Date: December 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Fluconazole
30 evaluable patients hospitalized with severe infection caused by C. albicans, documented by standard clinical signs, symptoms, and radiology, and having failed at least four days of fluconazole therapy.
Drug: Fluconazole
Patients hospitalized with severe infection caused by C. albicans, documented by standard clinical signs, symptoms, and radiology, and having failed at least four days of fluconazole therapy

Detailed Description:

The primary aims of this study are to identify and characterize the immediate consequences of patients who fail fluconazole treatment during the treatment of severe infection, and to determine if fluconazole failures are more frequently associated with fluconazole-resistant or fluconazole-susceptible strains of C. albicans (i.e. does in vitro resistance matter?). Perhaps the breakpoints are not correct and need to be changed, as has recently happened with vancomycin.

A third objective is to calculate fluconazole PK/PD parameters such as AUIC, and compare the calculated AUIC values of patients who fail with fluconazole-susceptible vs fluconazole-resistant isolates. Specifically for fluconazole, the question here is whether dose matters, and can aggressive dosing offset higher MICs. Thus in all cases, we will also determine the AUIC of fluconazole in order to fully characterize the impact of dose chosen on the outcomes of treated patients who fail to respond to fluconazole. The clinical, microbiological, and pharmacoeconomic outcomes of patients who fail fluconazole therapy and are subsequently hospitalized with severe infections caused by C. albicans will be documented and described.

  Eligibility

Ages Eligible for Study:   4 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

This is a multi-center study of adult and pediatric patients hospitalized with severe infection caused by C. albicans. An announcement of this case series collection study will be sent to our ongoing list of primary care practitioners, hospitalists, specialists in infectious diseases, pulmonologists, clinical pharmacists, and other investigators throughout the USA.

Criteria

Inclusion Criteria:

  1. Medical history, clinical signs and symptoms, and radiological findings consistent with severe C. albicans infection. For example, the criteria for pneumonia are as follows:

    1. A core body temperature >38C [100.4F] or <36.1 C [97oF] or leukocytosis (blood leukocyte count >10,000 cells/mm3) or bandemia (>10% bands).
    2. Chest radiographic examination that shows a new or progressive infiltrate, consolidation, cavitation, or pleural effusion.
    3. Rales, dullness to percussion, or decreased breath sounds on physical examination of the chest, new onset of purulent sputum, or change in character of sputum.
  2. A positive culture must demonstrate the presence of C. albicans, isolated from a properly obtained respiratory or blood sample, collected within 72 hours of admission to a hospital. All patients with respiratory cultures must produce sputum with Gram stain analysis indicating the relative absence of contaminating oropharyngeal squamous cells and the presence of a significant number of WBCs and morphologically distinct bacteria. Fluconazole sensitivity testing results must be available for the initial C. albicans isolate.
  3. Must have received, and failed to respond to, at least 4 days of treatment with fluconazole.

4. Admitted to a hospital or ICU for treatment of a severe infection.

Exclusion Criteria:

  1. Pregnant or lactating women
  2. Cystic fibrosis
  3. Life expectancy <3 months from underlying disease
  4. Underlying lung carcinoma
  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: NCT00721487

Locations
United States, New York
CPL Associates,LLC
Buffalo, New York, United States, 14226
Sponsors and Collaborators
CPL Associates
Astellas Pharma US, Inc.
Investigators
Principal Investigator: Jerome Schentag, Pharm.D. CPL Associates, LLC
Principal Investigator: Joseph Paladino, Pharm.D. CPL Associates, LLC
  More Information

No publications provided

Responsible Party: Jerome Schentag, CEO, CPL Associates
ClinicalTrials.gov Identifier: NCT00721487     History of Changes
Other Study ID Numbers: MYCA-8F16
Study First Received: July 22, 2008
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by CPL Associates:
C. albicans
fluconazole

Additional relevant MeSH terms:
Communicable Diseases
Infection
Mycoses
Fluconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014