A randomized controlled trial assessing the efficacy of fluconazole in the treatment of pediatric tinea capitis

Abstract

Griseofulvin is considered first-line therapy for tinea capitis, and the Physician's Desk Reference currently recommends 11 mg/kg per day microsize formulation for use in children. Diverse selective pressures have resulted in waning clinical efficacy of griseofulvin, such that higher doses and longer courses of treatment are required. These events have prompted the search for therapeutic alternatives. Fluconazole is one such treatment option, and a variety of studies using this drug have shown promise in the treatment of pediatric tinea capitis. We sought to assess the efficacy, safety, and optimal dose and duration of fluconazole therapy compared with standard-dose griseofulvin (11 mg/kg per day microsize formulation) in the treatment of pediatric tinea capitis. This randomized, multicenter, third-party-blind, 3-arm trial was designed as a superiority study to identify a therapeutically superior agent/regimen from the 3 treatment arms: (1) fluconazole 6 mg/kg per day for 3 weeks followed by 3 weeks of placebo, (2) fluconazole 6 mg/kg per day for 6 weeks, and (3) griseofulvin 11 mg/kg per day for 6 weeks. Efficacy variables included mycological, clinical, and combined outcomes. The primary efficacy variable was the combined outcome of the modified intent-to-treat population at week 6. Patient safety was assessed throughout the study. Statistical analysis of the efficacy variables was conducted by means of the Cochran-Mantel-Haenszel test. At the end of treatment, mycological cures were present in 44.5%, 49.6%, and 52.2% of the fluconazole 3-week, fluconazole 6-week, and griseofulvin groups, respectively. Analysis of the primary efficacy variable failed to identify any superior agent, and differences between the combined outcomes of the fluconazole 6-week and griseofulvin groups at week 6 were not significant (P = .32). Regarding mycological, clinical, and combined outcomes, no significant differences between the fluconazole 6-week and griseofulvin groups were detected at any time point in the study. No new safety concerns were raised by this trial, and the incidence of treatment-related adverse events noted in this study is concordant with previous reports. Patients in the fluconazole arms of the study fared similarly. At the end of the trial, the difference in mycological cures between the fluconazole arms was only 7.5%, and increases in the incidence of certain treatment-related adverse events were observed in the fluconazole 6-week group. Adjunctive topical therapies and the impact of infected contacts were not assessed in this trial. Systemic therapy with fluconazole 6 mg/kg per day and standard-dose griseofulvin produces comparable but low mycological and clinical cure rates. The limited efficacy of standard-dose griseofulvin and the lack of consensus regarding dose and duration of griseofulvin therapy in tinea capitis emphasize the need for controlled trials to identify optimal treatment parameters. Although the efficacy of fluconazole is no better than that of standard-dose griseofulvin, it may still be useful in select patients with a contraindication or intolerance to high-dose griseofulvin. The outcomes observed in this trial highlight the need to more clearly define the relative importance of adjunctive topical therapies and the evaluation and treatment of infected contacts as factors affecting cure rates.