Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: Results from an open-label trial

Jose Vazquez, Annette C. Reboli, Peter G. Pappas, Thomas F. Patterson, John Reinhardt, Peter Chin-Hong, Ellis Tobin, Daniel H. Kett, Pinaki Biswas, Robert Swanson

Research output: Contribution to journalArticle

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Abstract

Background: Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed.Methods: An open-label, non-comparative study evaluated an intravenous (IV) to oral step-down strategy. Patients with C/IC were treated with IV anidulafungin and after 5 days of IV therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days' anidulafungin) were identified as the "early switch" subpopulation.Results: In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7-88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each).Conclusions: A short course of IV anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC.Trial registration: ClinicalTrials.gov: NCT00496197.

Original languageEnglish (US)
Article number97
JournalBMC Infectious Diseases
Volume14
Issue number1
DOIs
StatePublished - Feb 21 2014

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anidulafungin
Invasive Candidiasis
Candidemia
Azoles
Therapeutics
Candida
Population
Pharmaceutical Economics
Fluconazole
Antifungal Agents
Nausea
Vomiting

Keywords

  • Anidulafungin
  • Azole
  • Candidemia
  • Step-down strategy

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis : Results from an open-label trial. / Vazquez, Jose; Reboli, Annette C.; Pappas, Peter G.; Patterson, Thomas F.; Reinhardt, John; Chin-Hong, Peter; Tobin, Ellis; Kett, Daniel H.; Biswas, Pinaki; Swanson, Robert.

In: BMC Infectious Diseases, Vol. 14, No. 1, 97, 21.02.2014.

Research output: Contribution to journalArticle

Vazquez, Jose ; Reboli, Annette C. ; Pappas, Peter G. ; Patterson, Thomas F. ; Reinhardt, John ; Chin-Hong, Peter ; Tobin, Ellis ; Kett, Daniel H. ; Biswas, Pinaki ; Swanson, Robert. / Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis : Results from an open-label trial. In: BMC Infectious Diseases. 2014 ; Vol. 14, No. 1.
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AU - Reboli, Annette C.

AU - Pappas, Peter G.

AU - Patterson, Thomas F.

AU - Reinhardt, John

AU - Chin-Hong, Peter

AU - Tobin, Ellis

AU - Kett, Daniel H.

AU - Biswas, Pinaki

AU - Swanson, Robert

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AB - Background: Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed.Methods: An open-label, non-comparative study evaluated an intravenous (IV) to oral step-down strategy. Patients with C/IC were treated with IV anidulafungin and after 5 days of IV therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days' anidulafungin) were identified as the "early switch" subpopulation.Results: In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7-88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each).Conclusions: A short course of IV anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC.Trial registration: ClinicalTrials.gov: NCT00496197.

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