Clinical trial NCT01851590: Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis
Official title: Efficacy of Topical Resin Lacquer, Amorolfine, and Oral Terbinafine for Treating Toenail Onychomycosis: a Prospective, Randomized, Controlled, Investigator-blinded, Parallel-group Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Onychomycosis
Keywords: Dermatophyte onychomycosis
Fungal nail infection
Resin Lacquer
Amorolfine
Terbinafine
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Repolar Pharmaceuticals Oy
First posted: 2013-05-10
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Positive dermatophyte culture in the beginning of the study obtained from the toenail sample.
* Positive KOH stain in the beginning of the study obtained from the toenail sample.

Exclusion Criteria:

* Any other nail disease than dermatophyte culture or KOH stain verified onychomycosis
* Onychomycosis caused by yeasts or nondermatophyte molds
* Kidney failure determined by plasma creatinine level (P-Krea \> 100 μmol/l)
* Liver failure determined by plasma γ-glutamyltransferase level (P-GT \> 120 U/I)
* Sensitivity or allergy to Resin, Amorolfine or Terbinafine
* Potential adverse cross-reaction of Terbinafine, Amorolfine or Resin with the patient's permanent medication
* Presence of total dystrophic onychomycosis (TDO)
* Any topical or oral antifungal treatment within the 6 months before the beginning of the study (washout period \> 6 months).

Primary outcomes:
measure: Mycological Cure
timeFrame: At 4- and 10 months time-points from the beginning of the study.
Secondary outcomes:
measure: Clinical Responses to the Treatments
timeFrame: At 4- and 10 months time-points from the beginning of the study.
measure: Cost-effectiveness 1
timeFrame: At 10-month time-point
measure: Cost-effectiveness 2
timeFrame: At 10-month time-point
measure: Compliance to the Treatment
timeFrame: At 4-month time-point
Other outcomes:
Locations:
city: Vääksy
country: Finland
facility: Vääksyn Lääkärikeskus
Study officials:
affiliation: Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, FI-00029, Helsinki, Finland
name: Janne J. Jokinen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sigurgeirsson B et al. Efficacy of amorfine nail lacquer for the prophylaxis of onychomycosis over 3 years. J Eur Acad Dermatol Venereol 2010;24: 910-5. Rautio M et al. Antibacterial effects of home-made resin salve from Norway spruce (Picea abies). APMIS 2007;115: 335-340. Rautio M et al. In vitro fungistatic effects of natural coniferous rosin from Norway spruce (Picea abies). Eur J Clin Microbiol Infect Dis 2012;31:1783-9. Sipponen A et al. Effects of Norway spruce (Picea abies) resin on cell wall and cell membrane of Staphylococcus aureus. Ultrastruct Pathol 2009;33: 128-135. Sipponen P et al. Natural coniferous resin lacquer in treatment of toenail onychomycosis: an observational study. Mycoses 2012, Accepted. Roberts DT et al. British Association of Dermatologists. Guidelines for treatment of onychomycosis. Br J Dermatol 2003;148:402-10. Baran R et al. A new classification of onychomycosis. Br J Dermatol 1998;139: 567-71.