Clinical trial NCT01851590
Conditions: Onychomycosis
Keywords: Dermatophyte onychomycosis Fungal nail infection Resin Lacquer Amorolfine Terbinafine
Sponsor: Helsinki University Central Hospital
Start date: 2013-10-01; Completion date: 2014-10-01
Enrollment: 129 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The current study is conducted to corroborate the previous observational clinical trial with more valid methods and a more clinically relevant experimental design. This study aims to compare efficacy, safety, and cost between topically administered 30% resin lacquer for the treatment of dermatophyte toenail onychomycosis and the current "best practices": topical 5% amorolfine and systemic terbinafine.

Detailed description:
The aim of this prospective, investigator-blinded, randomized and controlled clinical trial is to explore potential differences between 5 % amorolfine and 30 % resin lacquer in topical treatment of onychomycosis. In addition, topical treatment methods are compared with the most effective 'drug of choice' for onychomycosis according the current guidelines i.e. oral medication with terbinafine.

Altogether 90 patients (the aim is to collect the 30 patients per group) who have culture or potassium hydroxide (KOH) stain verified dermatophyte onychomycosis are randomly allocated into 3 treatment groups to receive either topical treatment or oral medication for toenail onychomycosis classified as follows:

1. White superficial onychomycosis (WSO)
2. Distal and lateral subungual onychomycosis (DLSO)
3. Proximal subungual onychomycosis (PSO)
4. \[Total dystrophic onychomycosis) (TDO)\] \[Excluded\]
5. \[Candidal onychomycosis\] \[Excluded\]

Participants are randomized into 3 groups to receive:

1. Topical treatment: 30 % resin lacquer (Abicin®) applied once daily for 9 months.
2. Topical treatment: 5 % amorolfine lacquer (Loceryl®) applied once weekly for 9 months.
3. Oral medication: 250 mg terbinafine taken orally once daily for 3 months.

All patients visit at outpatient department before the launch of the study, and 3 and 9 months thereafter. Clinical examination is done by 4 physicians. During the 42-week study period, laboratory tests are conducted on samples collected before treatment, at 20 weeks, and at 42 weeks. The tests include a fungal culture, KOH staining of the toenail sample, and blood tests. Cultures and KOH microscopy are performed in an independent, specialised mycology laboratory with standard techniques (Medix Laboratories Ltd., Helsinki, Finland). The blood tests measure plasma γ-glutamyl transferase levels (also at 2 weeks); plasma creatinine levels; the total number of white blood cells, including neutrophils, monocytes, basophils, lymphocytes, and eosinophils; the total number of red blood cells, including erythrocytes and haematocrit; erythrocyte indices, including the mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, and haemoglobin level; and the total number thrombocytes (initially and at 42 weeks). During the control visits, sequential digital photographs of the most disfigured and brittle toenails are acquired.

In the three phone calls, patients are asked about potential treatment-related side effects, compliance with treatment, patients' perception of treatment outcome, and their willingness to continue in the study. In each treatment arm, the treatment regimen is discontinued 5 weeks before the last toenail sampling to provide an appropriate washout period before the final culture and KOH analysis.

To ensure safety and to assess potential contraindications for the treatment regimens, all patients included in the study undergo a comprehensive medical interview and physical examination. To identify patients who may develop intolerable adverse events due to drug combinations, all concurrent medications are cross-checked to verify compatibility with resin, amorolfine, and terbinafine regimens at the beginning of the study. All patients are informed of the possibility of developing a hypersensitivity to resin, amorolfine, or terbinafine. If patients experienced symptoms that corresponded to any level of hypersensitivity, they are dropped from the study.

Arms: arm 1: Topical 30% Resin Lacquer applied once daily for 9 months (Abicin® 30% Nail Lacquer). arm 2: Topical 5% Amorolfine Lacquer applied once weekly for 9 months (Loceryl® 5% Nail Lacquer). arm 3: 250 mg of Terbinafine taken orally once daily for 3 months (Generics).
Interventions: intervention 1: Resin Lacquer intervention 2: Amorolfine intervention 3: Terbinafine
Intervention descriptions: intervention 1: 30% Resin Lacquer is applied once daily for 9 months (Abicin®) in toenail onychomycosis. intervention 2: 5% Amorolfine Lacquer is applied once weekly for 9 months (Loceryl®) in toenail onychomycosis. intervention 3: 250 mg of Terbinafine is taken orally once daily for 3 months (Generics) in toenail onychomycosis.

Protocol documents: