Review of Clinical Trials of Topical Antifungal Therapy

Author: Anne D. Walling
Date: Nov 15, 1999

The principal topical therapies for fungal infections of the feet are allylamines (e.g., terbinafine [Lamasil]), azoles (e.g., ketoconazole [Nizoral]), undecylenic acid (e.g., Desenex) and tolnaftate (e.g., Tinactin). Hart and colleagues systematically reviewed data from 72 randomized controlled trials to determine the relative efficacy and cost-effectiveness of these four topical therapies for fungal infections of the feet.

Clinical trials were identified by searching 10 electronic databases, three podiatry journals, one dermatology journal and the bibliographies of all review articles identified. In addition, data from unpublished trails were obtained from pharmaceutical companies and investigators at schools of podiatry. Only trials in which the diagnosis of fungal infection was confirmed by culture were included in the analysis. Each trial was assessed for quality using 12 criteria, and cure rates for each trial were calculated based on no growth of dermatophytes on culture and negative results on microscopic examination. The cost of treatment was also estimated. Data were analyzed from 70 trials of fungal infections of the skin and two trials of toenail infections. The mean number of quality criteria met by the 72 trials was 6.3 out of 12. Common problems related to the lack of a blinded outcome assessment and the method of randomization. Azoles were evaluated in 46 trials, allylamines in 27, tolnaftate in five and undecylenic acid in four. The most common fungal organism was Trichophytum rubrum, and most trials followed patients for fewer than 12 weeks.

Meta-analysis of the data from 17 placebo-controlled studies of azoles demonstrated a relative risk of failure to cure of 0.54. For 12 placebo-controlled trails of allylamines, the relative risk of failure to cure was 0.30. The authors found that the efficacy of azoles seemed to depend on the duration of treatment. Three placebo-controlled trials of 1 percent tolnaftate demonstrated a pooled relative risk of failure to cure of 0.46.

The authors conclude that allylamines, azoles and undecylenic acid have demonstrated efficacy in placebo-controlled trials. Although comparative data are limited, allylamines are associated with slightly higher cure rates than azoles but are much more expensive than azoles. The authors state that the most cost-effective strategy is to initiate treatment with azoles or undecylenic acid and use allylamines if the initial therapy is unsuccessful.


Hart R, et al. Systematic review of topical treatments for fungal infections of the skin and nails of the feet. BMJ July 10, 1999;319:79-82.

COPYRIGHT 1999 American Academy of Family PhysiciansCOPYRIGHT 2000 Gale Group

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