Double-blind randomized dose-finding study in acute vulvovaginal candidosis. Comparison of flutrimazole site-release cream (1, 2 and 4%) with placebo site-release vaginal cream.

A double-blind randomized comparative phase II study of flutrimazole site-release vaginal cream (1, 2 and 4%) with placebo site-release vaginal cream was undertaken in patients with acute vulvovaginal candidosis. Vaginitis was demonstrated by both positive findings on microscopic examination of vaginal smears and positive culture as well as by the presence of clinical signs and symptoms. The vaginal monodose treatment was inserted in the evening at bedtime using a vaginal applicator and, in addition, all four groups of patients received additional topical external cream for application to the vulva twice-daily for 7 days; the placebo group received a placebo cream and the active therapy groups all received a 2% flutrimazole cream. A total of 133 patients who were seen over a 10-month period were screened and randomized: five patients did not take the allocated medication, and four patients whose menstrual period began shortly after study entry were excluded from the study, leaving 124 patients who were randomly allocated to receive a monodose vaginal 1% cream (regimen A, 28 patients), a monodose vaginal 2% cream (regimen B, 32 patients), a monodose vaginal 4% cream (regimen C, 31 patients) or a monodose vaginal placebo cream (regimen D, 33 patients). At the assessment 9 days after the end of therapy the proportion of patients who were cured was 82% in group A, 87.4% in group B, 83.8% in group C and 63.5% in group D. Three patients (10.7%) in group A, four (12.5%) in group B, one (3.2%) in group C and 12 (36.36%) in group D did not respond to the treatment. One patient (3.5%) in group A, and two patients (6.4%) in group C terminated the treatment prematurely due to intolerance. There was a significant association between Candida glabrata and treatment failure (P < 0.04) and C. glabrata and carrier state (P = 0.01) in vagina (chi 2 test, P = 0.01) and vulvovagina (chi 2 test, P = 0.00001). At the assessment 4 weeks after the end of therapy the proportion of cured patients was 60.6% in group A, 78% in group B, 80.6% in group C and 48.4% in group D. Group D (placebo) versus group B (2%) and group C (4%) showed a significant difference (P = 0.01 and P = 0.007, respectively). Although there were no significant differences in clinical and mycological activity between the three active groups, group B (flutrimazole 2% site-release vaginal cream) was chosen for clinical use due to its tolerance profile. Seven patients (25%) in group A, three (9.3%) in group B, two (6.4%) in group C and five (15.1%) in group D relapsed 4 weeks after the end of therapy; the relapse rate was not significantly associated with positive culture results 9 days after treatment. There was a significant association between C. glabrata and the carrier state (P < 0.01). The overall ineffective treatment (includes failures at control 1, relapses at control 2 and premature terminations) was 39% in group A, 21.7% in group B, 16% in group C and 51.3% in group D. There was a significant difference in the overall ineffective treatment when C and D groups were compared with placebo (P = 0.01 and P = 0.003, respectively).

Topical treatment of dermatophytosis and cutaneous candidosis with flutrimazole 1% cream: double-blind, randomized comparative trial with ketoconazole 2% cream.

In a double-blind, randomized study the efficacy and tolerance of flutrimazole 1% cream were compared with ketoconazole 2% cream, applied once daily for 4 weeks, in 60 patients with culturally proven dermatophytosis (47 patients) or cutaneous candidosis (13 patients). Both groups of patients and distribution of target lesions were similar. The sum of clinical scores had an even distribution in both groups at the end of treatment. The proportion of patients with negative microscopy and culture after 4 weeks of treatment was 70% in the flutrimazole group and 53% in the ketoconazole group; seven ketoconazole-treated patients (23%) compared with two flutrimazole-treated patients (6.6%) were asymptomatic carriers (clinically cured with positive cultures) at the end of treatment. At the assessment 6 weeks after the end of therapy the percentages of flutrimazole- and ketoconazole-treated patients with negative mycology were 57 and 70%, respectively. There were one relapse (3.3%) in the ketoconazole group and four (13.3%) in the flutrimazole group. One patient treated with ketoconazole (3%) had a premature termination due to adverse events attributable to the medication. The results of this study show that flutrimazole 1% cream is as effective and safe as ketoconazole 2% cream for Candida and dermatophyte skin infections.