TREATMENT OF ONYCHOMYCOSIS - A RANDOMIZED, DOUBLE-BLIND COMPARISON STUDY WITH TOPICAL BIFONAZOLE-UREA OINTMENT ALONE AND IN COMBINATION WITH SHORT-DURATION ORAL GRISEOFULVIN

A parallel-group double-blind study was carried out which compared the efficacy of chemical avulsion of affected nail by urea 40% and bifona zole 1% cream alone with that of the same local therapy combined with short-term oral griseofulvin in onychomycosis. A total of 120 patients were included in the study. Patients' characteristics were comparable in both treatment groups. Of the 98 patients fully evaluated, 91 had toenail involvement and only seven had fingernail involvement. Forty-s ix of the patients were men and 51 were women. The mean age of the pat ients was 47.14 +/- 13.84 years (range 17-80 years). The duration of o nychomycosis was for more than 1 year in 96 patients and for 3 months duration in only one patient, who was in the placebo group. Forty pati ents had received different previous therapies. All topical treatments were discontinued for at least 2 weeks and oral therapy for at least 2 months prior to the beginning of the study. The diagnosis was confir med by positive mycologic cultures. Trychophyton rubrum was identified as the pathogen in 90 patients, 45 in each group, T. tonsurans in fou r patients, two in each group, and T. mentagrophytes in three patients , two in the griseofulvin treated group, and one in the placebo group. The first phase of treatment given to all patients consisted of occlu sive dressing every 24 h with urea 40% and bifonazole 1% ointment unti l the infected nail became completely detached. Subsequently, in the s econd phase bifonazole 1% cream was applied to the nail bed every 24 h for 4 weeks. In addition, concomitantly with the bifonazole cream the patients were randomly allocated to a daily oral double-blind treatme nt with griseofulvin 500 mg or placebo, for 4 weeks. Clinical and myco logic evaluations were carried out at baseline, immediately after remo val of the nail, and. at 3 days, 4 weeks, and 4 months after the end o f treatment with bifonazole cream and griseofulvin/placebo tablets. My cologic examination included identification of fungi by KOH preparatio n and culture on potato dextrose agar. Positive cultures were transfer red for identification on Sabouraud's. Criteria for evaluation of effi cacy comprised: ''cure'' defined as clinical and mycologic cure (fresh specimen and culture negative) at both investigation times after the end of treatment; ''late cure'' defined as mycologic cure at both inve stigation times after the end of treatment, clinical clearing of the n ail only 4 months after the end of treatment; ''improvement'' defined as mycologic cure and only partial clinical improvement at both times after the end of treatment; ''failure'' indicating no mycologic cure ( fresh specimen and/or culture positive); and ''relapse'' signifying a change from negative findings 1 month after the end of treatment to po sitive findings 4 months after the end of treatment. Adverse reactions were evaluated on each visit. Only those patients who had completed c linical and mycologic evaluation during the entire study were included in the final statistical analysis. Those patients with partial evalua tion were included only in the evaluation of adverse events. Based on the assumptions of a failure rate (failure and relapse) of 30% with bi fonazole cream alone and of 10% with bifonazole cream and griseofulvin tablets, a = 0.05 and b = 0.2, the required sample size was at least 58 patients for each treatment group (Casagrande formula, one-sided te st). The primary efficacy variable ''assessment of treatment'' (cure a nd improvement versus failure and relapse) was tested for treatment di fferences by Fisher's exact test (a = 0.05, one-sided test; H-0, no ad vantage with additional systemic therapy of griseofulvin). Additionall y, the relapse rates of both treatments were tested exploratively in t he same way as the primary efficacy variable. All other data were anal yzed descriptively.