Jn. Galgiani et al., Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis - A randomized, double-blind trial, ANN INT MED, 133(9), 2000, pp. 676-686
Citations number
42
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background: In previous open-label noncomparative clinical trials, bath flu
conazole and itraconazole were effective therapy for progressive forms of c
occidioidomycosis.
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 coc
cidioidal infections.
Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice dai
ly.
Measurements: After 4, 8, and 12 months, a predefined scoring system was us
ed to assess severity of infection. Findings were compared with those at ba
seline.
Results: Overall, 50% of patients (47 of 94) and 63% of patients (67 of 97)
responded to 8 months of treatment with fluconazole and itraconazole, resp
ectively (difference, 13 percentage points [95% CI, -2 to 28 percentage poi
nts]; P = 0.08). Patients with skeletal infections responded twice as frequ
ently 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 outc
ome. Relapse rates after discontinuation of therapy did not differ signific
antly between groups (28% after fluconazole treatment and 18% after itracon
azole treatment). Both drugs were well tolerated.
Conclusions: Neither fluconazole nor itraconazole showed statistically supe
rior efficacy in nonmeningeal coccidioidomycosis, although there is a trend
toward slightly greater efficacy with itraconazole at the doses studied.