Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis: A randomized, double-blind trial

J. N. Galgiani, A. Catanzaro, G. A. Cloud, R. H. Johnson, P. L. Williams, L. F. Mirels, F. Nassar, J. E. Lutz, D. A. Stevens, P. K. Sharkey, V. R. Singh, R. A. Larsen, K. L. Delgado, C. Flanigan, M. G. Rinaldi

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242 Scopus citations

Abstract

Background: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. Objective: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. Design: Randomized, double-blind, placebo-controlled trial. Setting: 7 treatment centers in California, Arizona, and Texas. Patients: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. Measurements: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. Results: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, -2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. Conclusions: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.

Original languageEnglish
Pages (from-to)676-686
Number of pages11
JournalAnnals of Internal Medicine
Volume133
Issue number9
DOIs
StatePublished - 7 Nov 2000
Externally publishedYes

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