IJMDAT 2018; 1(1):e116 Nail acidification vs. amorolfine in the local management of onychomycosis: a comparative, prospective, randomized, blinded trial F. Eertmans1, N. Doss2, B. Rossel1, P. A. Regidor3 1Oystershell Laboratories, Drongen, Belgium 2Department of Dermatology, Université Tunis El Manar, Military Hospital of Tunis, Tunis, Tunisia 3Outdoor Department Frauenklinik München West, Frauenklinik, München West, Germany ABSTRACT — INTRODUCTION: Onychomy- All patients underwent microbiological testing cosis is a fungal infection, frequently caused at baseline and at the end of the treatment. by dermatophytes, that affects hand and foot Primary objective of this trial was the change nails. Infection rates in Western adult popu- in the percentage of healthy nail surface at lations range from 2% to 14%, although up study end. to 50% of people over 70 years of age may RESULTS: The percentage of healthy sur- be affected. Prevalence of onychomycosis is face between baseline and D168 increased also higher in immuno-compromised and pa- with 11.4% (± 17.0%) in the acid-based treat- tients with diseases that affect peripheral ed patient group and 5.2% (± 12.6%) in the circulation, such as diabetes mellitus. The amorolfine group respectively. The observed aim of the present study was to evaluate difference in increase of percentage of healthy clinical efficacy of a nail acidifying solution surface after application of the acidifying solu- vs. nail lacquer containing 5% amorolfine for tion was statistically significant (95% CI: 0.4; the local treatment of mild to moderate nail 12.1, p = 0.037) in comparison to the amorolf- onychomycosis. ine group. Both treatments resulted in signif- PATIENTS AND METHODS: 112 adults with icant (p < 0.05) improvement after 168 days confirmed onychomycosis (at least one great (vs. baseline) for nail dystrophy, discoloration, toenail) were randomized in this open, pro- nail thickening, and healthy aspect but ef- spective, blinded trial. The acetic acid/eth- fects were more pronounced in the acetic acid yl lactate-based solution was brushed on group. Microbiological results and improved twice-daily and the amorolfine lacquer ap- quality of life further confirmed clinical effi- plied and removed weekly for 168 days. Out cacy. Both treatments were well tolerated and of these 112 patients, a fully data analysis appreciated for their properties and efficacy. could be performed in 102 patients (53 acetic CONCLUSIONS: The present trial con- acid group and 49 amorolfine group, respec- firmed clinical performance of daily acidi- tively). Clinical efficacy was evaluated at the fication of the nail, as reflected by 1) the following time points: day (D) D0 = baseline, superior increase of percentage of healthy D14, D28, D56, D112, and D168, respectively. nail surface when compared to amorolf- Corresponding Author Pedro-Antonio Regidor, MD; e-mail: [email protected] 1 F. Eertmans, N. Doss, B. Rossel, P. A. Regidor ine; 2) the overall improvement of other brush-on solution (Excilor®, 0.96% acetic acid in onychomycosis-related parameters; 3) the ethyl lactate) vs. a medicated nail lacquer containing convenience and absence of significant side 5% amorolfine (Loceryl®). After penetration, the effects. These data indicate that acid/acid acid/ester solution acidify the nail and consequently ester solutions can be a convenient, safe and block fungal spreading, hereby allowing the infected equally effective alternative for the topical part of the nail to grow out9-10. The amorolfine nail management of onychomycosis. lacquer elicits its action by destroying the fungal cell membrane11. The primary objective of the present study was KEYWORDS to assess variation in the percentage of healthy sur- Onychomycosis, Nail acidification, 5% amo- face of the great toenail after a treatment period of rolfine nail lacquer. 168 days with both products, in combination with changes in microbiological findings at baseline and at the end of the treatment (KOH staining and fungal culture). Clinical diagnosis was performed INTRODUCTION by blinded investigators by using digital image analysis (contour tracing). Secondary objectives Onychomycosis is a common nail infection with included evaluation of clinical efficacy against a worldwide prevalence of 5%, but this value may onychomycosis of the great toenail at distinct time vary in function of the studied area. Most common points (day 14, 28, 56, and 112), microbiological pathogens are dermatophytes, but also yeasts (e.g. efficacy of both products, product safety, impact on Candida albicans), and non-dermatophyte molds1. quality of life (QoL), and finally product efficacy, Depending on the location and the route of pathogen tolerance and acceptability by subject’s self-assess- penetration, four different types of onychomycosis ment and medical exam. have been characterized: 1) disto-lateral onychomy- cosis; 2) white superficial onychomycosis; 3) proxi- mal subungual onychomycosis; 4) candidal onycho- PATIENTS AND METHODS mycosis. Disto-lateral subungual onychomycosis is the most common form and is usually caused by Trial set-up Trichophyton rubrum, which invades the nail bed and the underside of the nail plate2-4. This randomized, controlled, multicentre, compara- Onychomycosis gradually destructs the nail by tive, investigator-blinded, open label study, was ap- affecting the nail plate, the nail bed and the periun- proved by the Ethics committee of the principal clin- gual tissue. Depending on the degree of infection, ical trial centre (Military Hospital of Tunis, Tunisia) nail discoloration, thickening (onychogryphosis), on December 16th 2014. The study was conducted in degeneration (dystrophy), brittleness, and loosening accordance with the principles of the Declaration of (onycholysis) are observed5. Although the disease Helsinki 2013, Good Clinical Practice, and of the is not life-threatening, its morbidity may negatively European Union Directive 2001/20/EC. impact patient’s quality of life6. The entire study took place in two clinical trial Efficient treatment is challenging because of the facilities in Tunis (Tunisia), specialized in treatment inherent slow growth of the nail and its composition of skin and nail disorders. Recruitment was per- as well as patient compliance. Also, comorbidity formed by the principal investigator (dermatologist) in risk groups (e.g. elderly, diabetic, immunosup- of each trial centre and continued from January 16th pressed, or psoriasis patients) will further hamper (first patient, first visit) to November th16 2015 (last treatment7. patient, last visit). Early oral medication has been shown to be rather ineffective against specific forms of onycho- mycosis, in particular superficial onychomycosis Inclusion and exclusion criteria and endonyx forms. Manufacturers have focused on the development of topical products, that affect Patients (>18 years) were included after confirmed dermatophytes through a physical, non-specific or a diagnosis of superficial onychomycosis on at least pharmacological mode of action, respectively8. Most one great toe nail or light to moderate disto-lateral of the topical products are lacquers that need to be onychomycosis (without matrix involvement, infect- removed with solvents on weekly basis, a fact that ed area being smaller than 2/3 of the nail surface). stands in the way of patient compliance. Potassium hydroxide (KOH) staining was used to A randomized, controlled, multicentre, open la- confirm diagnosis [11]. Briefly, collected nail frag- bel trial was performed to assess the clinical efficacy ments were treated with 30% KOH solution and against onychomycosis of an acetic acid/ethyl lactate incubated for 5-10 min. Next, microscopic analysis 2 Nail acidification vs. amorolfine in the local management of onychomycosis was performed to assess the presence of dermato- Study medication, dosage phytes, which were identified by their hyphae. Only and administration patients with positive staining were included. Fungal culture was performed on samples of KOH-positive The acetic acid solution (Excilor®) was supplied in subjects to further characterize dermatophyte infec- glass bottles (with brush applicator) by Oystershell tion via macroscopic and microscopic analysis. Yet, Laboratories (Ghent, Belgium). This product consists outcome of these fungal cultures did not restrict sub- of acetic acid (active ingredient), solvent (ethyl lactate), ject inclusion since false negative results regularly a penetration enhancer, a film former, water, preserva- occur in clinically confirmed cases12. tives, acetylated lanolin alcohols, glycerol, and biotin. Beside positive diagnosis, patients must have The amorolfine nail lacquer reference (Loceryl®; stopped any systemic and/or topical antifungal treat- available in glass bottle) was provided be the prin- ment for at least 6 and 3 months, respectively, before cipal investigator. This medicated nail lacquer con- inclusion. Finally, female subjects of childbearing tains 5% amorolfine (as amorolfine hydrochloride potential should use an accepted contraceptive reg- in ethanol, triacetin, butyl acetate, ethyl acetate and imen at least 12 weeks prior to study start, during ammonium methacrylate polymer). the study, and at least 1 month after the study end. The acetic acid solution was applied twice daily Exclusion criteria were: non-compliance with the with the brush, covering the complete (cleaned) nail protocol, enrolment in another clinical trial during and the underside of the