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

BMC Infect Dis. 2014 Feb 21:14:97. doi: 10.1186/1471-2334-14-97.

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 (i.v.) to oral step-down strategy. Patients with C/IC were treated with i.v. anidulafungin and after 5 days of i.v. 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 i.v. 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.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous*
  • Administration, Oral*
  • Adult
  • Aged
  • Aged, 80 and over
  • Anidulafungin
  • Antifungal Agents / administration & dosage
  • Candida
  • Candidemia / drug therapy*
  • Candidiasis
  • Candidiasis, Invasive / drug therapy*
  • Echinocandins / administration & dosage*
  • Female
  • Fluconazole / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Republic of Korea
  • Research Design
  • Risk
  • Treatment Outcome
  • United States
  • Voriconazole / administration & dosage
  • Young Adult

Substances

  • Antifungal Agents
  • Echinocandins
  • Fluconazole
  • Anidulafungin
  • Voriconazole

Supplementary concepts

  • Systemic candidiasis

Associated data

  • ClinicalTrials.gov/NCT00496197