Format

Send to

Choose Destination
See comment in PubMed Commons below
Ann Intern Med. 2015 Jan 20;162(2):81-9. doi: 10.7326/M13-2508.

Combination antifungal therapy for invasive aspergillosis: a randomized trial.

Abstract

BACKGROUND:

Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy.

OBJECTIVE:

To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA.

DESIGN:

Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479).

SETTING:

93 international sites.

PATIENTS:

454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed.

MEASUREMENTS:

The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures.

RESULTS:

Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P  = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different.

LIMITATIONS:

Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability.

CONCLUSION:

Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority.

PRIMARY FUNDING SOURCE:

Pfizer.

PMID:
25599346
DOI:
10.7326/M13-2508
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center