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

A double-blind randomized comparative phase II study of flutrimazole site-r elease(R) vaginal cream (1, 2 and 4 %) with placebo site-release(R) vaginal cream was undertaken in patients with acute vulvovaginal candidosis. Vagin itis was demonstrated by both positive findings on microscopic examination of vaginal smears and positive culture as well as by the presence of clinic al signs and symptoms. The vaginal monodose treatment was inserted in the e vening at bedtime using a vaginal applicator and, in addition, all four gro ups of patients received additional topical external cream for application to the vulva twice-daily for 7days; the placebo group received a placebo cr eam and the active therapy groups all received a 2% flutrimazole cream. A t otal 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 exclud ed from the study, leaving 124 patients who were randomly allocated to rece ive a monodose vaginal 1% cream (regimen A, 28 patients), a monodose vagina l 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 patie nts who were cured was 82% in group A, 87.4% in group B, 83.8% in group C a nd 63.5% in group D. Three patients (10.7%) in group A, four (12.5%) in gro up B, one (3.2%) in group C and 12 (36.36%) in group D did not respond to t he treatment. One patient (3.5%) in group A, and two patients (6.4%) in gro up C terminated the treatment prematurely due to intolerance. There was a s ignificant 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 gro up A, 78% in group B, 80.6% in group C and 48.4% in group D. Group D (place bo) 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 diffe rences in clinical and mycological activity between the three active groups , group B (flutrimazole 2% site-release(R) vaginal cream) was chosen for cl inical use due to its tolerance profile. Seven patients (25%) in group A, t hree (9.3%) in group B, two (6.4%) in group C and five (15.1%) in group D r elapsed 4 weeks after the end of therapy; the relapse rate was not signific antly associated with positive culture results 9 days after treatment. Ther e 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 c ompared with placebo (P=0.01 and P=0.003, respectively).