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.
RCT Entities:
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.
Authors: David Moher; Sally Hopewell; Kenneth F Schulz; Victor Montori; Peter C Gøtzsche; P J Devereaux; Diana Elbourne; Matthias Egger; Douglas G Altman Journal: BMJ Date: 2010-03-23
Authors: Brahm H Segal; Raoul Herbrecht; David A Stevens; Luis Ostrosky-Zeichner; Jack Sobel; Claudio Viscoli; Thomas J Walsh; Johan Maertens; Thomas F Patterson; John R Perfect; Bertrand Dupont; John R Wingard; Thierry Calandra; Carol A Kauffman; John R Graybill; Lindsey R Baden; Peter G Pappas; John E Bennett; Dimitrios P Kontoyiannis; Catherine Cordonnier; Maria Anna Viviani; Jacques Bille; Nikolaos G Almyroudis; L Joseph Wheat; Wolfgang Graninger; Eric J Bow; Steven M Holland; Bart-Jan Kullberg; William E Dismukes; Ben E De Pauw Journal: Clin Infect Dis Date: 2008-09-01 Impact factor: 9.079
Authors: George K Siberry; Mark J Abzug; Sharon Nachman; Michael T Brady; Kenneth L Dominguez; Edward Handelsman; Lynne M Mofenson; Steve Nesheim Journal: Pediatr Infect Dis J Date: 2013-11 Impact factor: 2.129
Authors: Neil M Ampel; Larissa A Kramer; Lijin Li; Deborah S Carroll; Kathleen M Kerekes; Suzanne M Johnson; Demosthenes Pappagianis Journal: Clin Diagn Lab Immunol Date: 2002-09