We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Combination Antifungal Therapy for Invasive Aspergillosis.
- Authors
Marr, Kieren A.; Schlamm, Haran T.; Herbrecht, Raoul; Rottinghaus, Scott T.; Bow, Eric J.; Cornely, Oliver A.; Heinz, Werner J.; Jagannatha, Shyla; Liang Piu Koh; Kontoyiannis, Dimitrios P.; Dong-Gun Lee; Nucci, Marcio; Pappas, Peter G.; Slavin, Monica A.; Queiroz-Telles, Flavio; Selleslag, Dominik; Walsh, Thomas J.; Wingard, John R.; Maertens, Johan A.
- 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.
- Subjects
ANTIFUNGAL agents; ASPERGILLOSIS treatment; HEMATOLOGIC malignancies; VORICONAZOLE; PLACEBOS; GALACTOMANNANS; RADIOGRAPHY; THERAPEUTICS
- Publication
Annals of Internal Medicine, 2015, Vol 162, Issue 2, p81
- ISSN
0003-4819
- Publication type
Article
- DOI
10.7326/M13-2508