Efficacy, Safety and Tolerability of an Optimized Avulsion Technique with Onyster® (40% Urea Ointment with Plastic Dressing) Ointment Compared to Bifonazole-Urea Ointment for Removal of the Clinically Infected Nail in Toenail Onychomycosis: a Randomized Evaluator-Blinded Controlled Study

Abstract

Background: Toenail onychomycosis is highly prevalent, with 14-28% of people aged 60 or over suffering from the disease. Use of a topical antifungal alone in toenail onychomycosis is associated with low cure rates. This may be due to limited penetration of the topical antifungal through the diseased nail. The objective of the present study was to compare two treatment modalities to obtain diseased nail chemical avulsion in toenail onychomycosis. Methods: In this European, multicenter, randomized, parallel-group, open-label, active-controlled study, male or female adult patients with distal-lateral or lateral subungual dermatophyte onychomycosis on at least 12.5% of the great toenail were randomized either to a 40% urea ointment with plastic dressing group (n = 53) or to a bifonazole-urea ointment group (n = 52). The ointments were applied daily for a maximum of 3 weeks according to the summary of product characteristics. After assessment of infected nail debridement, topical antifungal treatment with bifonazole cream was applied daily in both groups for 8 weeks. 102 patients were evaluated, i.e. 51 in the 40% urea ointment with plastic dressing group and 51 in the bifonazole-urea group. The primary end point was complete removal of the nail plate at day 21 (D21). Secondary end points were: complete cure and mycological cure evaluated at D105. Ease of use and local tolerability were also assessed. Results: Complete removal of the clinically infected target nail plate area, assessed by blinded evaluators, was significantly higher in the 40% urea ointment with plastic dressing group (61.2%) than in the control group (39.2%), showing the superiority of 40% urea ointment with plastic dressing (p = 0.028). The same results were observed in the per-protocol population (63.0 vs. 36.6%; p = 0.014). Complete removal of the infected area assessed by the investigator at D21 showed a significantly higher success rate in patients treated with 40% urea ointment with plastic dressing (86.3%) as compared to patients treated with bifonazole-urea (60.8%), confirming the superiority of 40% urea ointment with plastic dressing (p = 0.004). At D105, the complete cure of onychomycosis, a criterion combining clinical and mycological assessments, showed a success rate of 27.7% for 40% urea ointment with plastic dressing versus 20.8% for the control group. No statistical difference was observed between the two treatment groups. The number of patients with at least one adverse event was twice as high in the bifonazole-urea group in comparison to the 40% urea ointment with plastic dressing group. Overall assessment of local tolerability by the investigator was considered good/very good in 98.0% of the 40% urea ointment with plastic dressing patients versus 90.4% of the bifonazole-urea patients, at D21, with no significant difference between both groups. Conclusion: This study shows the superiority of 40% urea ointment with plastic dressing to bifonazole-urea ointment for complete removal of the infected target nail assessed by blinded evalua...

A Multicenter, Randomized, Open-Label, Controlled Study Comparing the Efficacy, Safety and Cost-Effectiveness of a Sequential Therapy with RV4104A Ointment, Ciclopiroxolamine Cream and Ciclopirox Film-Forming Solution with Amorolfine Nail Lacquer Alone in Dermatophytic Onychomycosis

“…Debridement alone was shown to be ineffective in achieving mycological cure [27] . As shown recently by our group in a randomized clinical trial, an optimized avulsion technique associated with topical antifungal treatment is associated with a high cure rate of dermatophytic onychomycosis [22] . Debridement, when used as an adjunct therapy, improved treatment satisfaction and reduced symptom frequency [28] .…”

“…In a recent controlled study [22] , it was shown that chemical nail avulsion using RV4104A ointment (class I medical device containing 40% urea) followed by mechanical debridement was an effective procedure to remove clinically infected nail. As a result of its composition, RV4104A ointment (with specific plastic dressing) will exert a keratinolytic effect on nail keratin.…”

Patient‐reported outcomes from two randomised studies comparing once‐weekly application of amorolfine 5% nail lacquer to other methods of topical treatment in distal and lateral subungual onychomycosis

“…Although urea ointments are available OTC, the success rate of home debridement, without the support of a health professional, remains largely unexplored. Based on the available evidence, home debridement with urea ointment may be challenging, with reported failure to completely debride the affected nail area after 3 weeks ranging between 40%‐60% . A previous study on onychomycosis, comparing the efficacy of urea and bifonazole alone to that of the same local therapy combined with short‐term oral griseofulvin, showed that the mean time to detachment of the diseased nail was longer than the recommended 2‐3 weeks of treatment (24.9 days) .…”

“…The combination regimen of urea 40% ointment and bifonazole 1% cream (Canesten ® Fungal Nail Treatment Set; Bayer, Pymble, Australia) provides chemical nail ablation followed by topical antifungal treatment. Urea 40% ointment under occlusion possesses keratolytic properties and is indicated for the softening and removal of the diseased/dystrophic nails in onychomycosis . Bifonazole 1% cream is a broad‐spectrum imidazole with antifungal activity, rubbed into the nail bed after nail debridement .…”

“…Urea 40% ointment under occlusion possesses keratolytic properties and is indicated for the softening and removal of the diseased/dystrophic nails in onychomycosis. 26,27 Bifonazole 1% cream is a broad-spectrum imidazole with antifungal activity, rubbed into the nail bed after nail debridement. 28 According to the label recommendation, the urea/bifonazole regimen must be applied on a daily basis.…”