Patients and Methods
Males (n = 60) who met the inclusion/exclusion criteria with ages ranging from 18 to 60 years (mean 35.4 years) with clinical evidence of tinea pedis, both interdigital and moccasin types, were recruited to the study and were treated as out-patients.
Prior to initiation, the study protocol was approved by an independent institutional review committee. Following the Declaration of Helsinki (Venice Revision), all the participants were well informed regarding the possible adverse effects of the trial medication, and accordingly informed consent was obtained from all the patients.
At entry, a medical history was taken and a complete physical examination was conducted, and skin scrapings from the lesions were collected and treated with 10% potassium hydroxide (KOH) for direct microscopy. For isolation and identification of causative dermatophytes, cultures were grown on Sabouraud glucose agar with 0.05% chloramphenicol and 0.05% cycloheximide (to inhibit the growth of bacteria and nonpathogenic fungi) and incubated at 25°C for a maximum of 4 weeks. At baseline and the subsequent clinic visits, signs and symptoms of erythema, pustules, desquamation, vesiculation, incrustation and pruritus were graded on the following scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. Blood and urine specimens were obtained for routine laboratory tests.
The inclusion criteria into the study were: at least grade 2 erythema, pustules or pruritus and a positive KOH test for fungal hyphae. Participants were excluded if they had used systemic anti-mycotic drugs in the 4 weeks preceding study entry or any topical antifungal medication during the 2 weeks preceding entry.
The selected participants were sequentially randomised into three parallel groups (butenafine cream, terbinafine cream and placebo cream). Butenafine 1% and terbinafine 1% by weight incorporated into a cream base and matching placebo were prepared at a university-affiliated laboratory. Study samples were packed in identical precoded 25g tubes and were kept at ambient temperature. Trial medications were similar in physical appearance, so neither the patient nor the investigator could identify the investigational sample. Coded trial preparations were randomly assigned to each patient in a double-blind manner. Patients were instructed to apply the medication to all of their tinea pedis lesions once daily at bedtime for 5 consecutive days per week (maximum 2 weeks of active treatment).
To evaluate the clinical efficacy of the trial drugs, patients were examined on a weekly basis. Cure was defined as negative KOH test results and negative fungal culture (mycological cure). At the cessation of the treatment (after week 2) and at the follow-up monitoring (at week 4), a combined evaluation of the mycological and the clinical response was examined to determine the overall effectiveness of the trial preparations. Participants cured during the treatment were allowed to discontinue the treatment. The global response in clinical signs and symptoms of the treated lesions was assessed by the investigator as follows:
complete response = 100%remission of clinical signs and symptoms
excellent = 80 to 99% improvement from base-line observations (0 on 0 - 3 scale)
good = 50 to 79% improvement (1 on 0 - 3 scale)
fair=25 to 49%improvement(2 on 0 -3 scale)
poor = less than 25% improvement.
Patients were assessed by the same investigator.
Treatment failure or resistance to the study medication was defined as no significant clinical response to the trial preparation, repeated abnormal microscopy observations, and/or positive culture for causative dermatophytes.
The tolerability of the study medication was assessed at the scheduled visit by direct questioning of the patient by the investigator about drug-related subjective and objective adverse events. The study was followed up on a monthly basis for 10 months starting from week 8 after baseline. Compliance was determined at these times as all patients returned to the clinic during follow up.
Variables such as race,height,bodyweight, age, severity of tinea pedis history, experience of previous therapy and duration of disease were determined to rule out differences among the three treatment groups. Mycological efficacy, clinical effectiveness and overall success of the treatment were compared among treatment groups following the Cochran-Mantel-Haenszel test. The Breslow-Day test was used to ascertain whether the observed relation between treatment and cure was uniform. Fisher's exact tests with 2-tailed evaluation were used to compare the relation between outcome and treatment. Clinical effectiveness of the treatments were compared among treatment groups by the Cochran-Mantel-Haenszel test. All calculations of signs and indications and the change from baseline in total signs and indications were analysed using the Wilcoxon rank sum test. The power of the study was 80% at the 5% significance level.
Clin Drug Invest. 2000;19(6) © 2000 Adis Data Information BV
Cite this: Butenafine 1% Versus Terbinafine 1% in Cream for the Treatment of Tinea Pedis: A Placebo Controlled, Double-Blind, Comparative Study - Medscape - Jun 01, 2000.