OnychomycosisPhase 4NCT01851590
Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis
A Phase 4 study testing Resin Lacquer, Amorolfine and Terbinafine in people with Onychomycosis, run by Helsinki University Central Hospital at 2 sites in Finland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Onychomycosis
- What is being tested?
- Resin Lacquer, Amorolfine and Terbinafine
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 2 sitesFinland
- Study dates
- Oct 2013to Oct 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country.
Finland2 sites
Vääksyn Lääkärikeskus
Vääksy, Vääksy, FI-17200
Vääksyn Lääkärikeskus
Vääksy, FI-17200
About this study
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
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.
Read the 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:
- White superficial onychomycosis (WSO)
- Distal and lateral subungual onychomycosis (DLSO)
- Proximal subungual onychomycosis (PSO)
- [Total dystrophic onychomycosis) (TDO)] [Excluded]
- [Candidal onychomycosis] [Excluded]
Participants are randomized into 3 groups to receive:
- Topical treatment: 30 % resin lacquer (Abicin®) applied once daily for 9 months.
- Topical treatment: 5 % amorolfine lacquer (Loceryl®) applied once weekly for 9 months.
- 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.
- Conditions
- Onychomycosis
- Being tested
- Resin Lacquer, Amorolfine, Terbinafine
- Keywords
- Dermatophyte onychomycosis, Fungal nail infection, Resin Lacquer, Amorolfine, Terbinafine
- Medical subject headings
- Onychomycosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Resin LacquerDevice
Also called Resin Lacquer arm
30% Resin Lacquer is applied once daily for 9 months (Abicin®) in toenail onychomycosis.
AmorolfineDrug
Also called Amorolfine Lacquer arm
5% Amorolfine Lacquer is applied once weekly for 9 months (Loceryl®) in toenail onychomycosis.
TerbinafineDrug
Also called Terbinafine arm
250 mg of Terbinafine is taken orally once daily for 3 months (Generics) in toenail onychomycosis.
| Study group | Role | What they receive |
|---|---|---|
| Resin Lacquer | Experimental | Topical 30% Resin Lacquer applied once daily for 9 months (Abicin® 30% Nail Lacquer). Receives: Device: Resin Lacquer |
| Amorolfine | Active comparator | Topical 5% Amorolfine Lacquer applied once weekly for 9 months (Loceryl® 5% Nail Lacquer). Receives: Drug: Amorolfine |
| Terbinafine | Active comparator | 250 mg of Terbinafine taken orally once daily for 3 months (Generics). Receives: Drug: Terbinafine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mycological Cure
To analyze the rate of complete mycological cure i.e. fungal eradication in terms of negative mycological culture AND negative potassium hydroxide (KOH) stain at 4- and 10 months time-points from the beginning of the study.
Measured: At 4- and 10 months time-points from the beginning of the study.
Secondary outcomes (4)
Clinical Responses to the Treatments
Clinical responses to treatment were based on the proximal linear growth of healthy nail; thus, the clinical responses were classified as partial (evident proximal linear growth of healthy nail) or complete. Partial responses were defined as significant reductions in onycholysis, subungual hyperkeratosis, and streaks. A complete response was a fully normal appearance of the toenail.
Measured: At 4- and 10 months time-points from the beginning of the study.
Cost-effectiveness 1
Cost analysis was based on the retail price (€) and consumption of a 10 ml bottle of Abicin® 30% resin lacquer, a 5 ml bottle of Loceryl® 5% amorolfine lacquer, and 98 tablets of generic 250 mg terbinafine, sold by the University Pharmacy in Helsinki, Finland, January 2014. The cost was expressed as the average treatment cost per patient; for the total cost, this average was extrapolated to the entire study treatment arm. The results show the treatment costs (€) per day per patient in each group.
Measured: At 10-month time-point
Cost-effectiveness 2
Cost analysis was based on the retail price (€) and consumption of a 10 ml bottle of Abicin® 30% resin lacquer, a 5 ml bottle of Loceryl® 5% amorolfine lacquer, and 98 tablets of generic 250 mg terbinafine, sold by the University Pharmacy in Helsinki, Finland, January 2014. The cost was expressed as the average treatment cost per patient; for the total cost, this average was extrapolated to the entire study treatment arm. The results show the treatment costs (€) during the treatment period per patient in each group.
Measured: At 10-month time-point
Compliance to the Treatment
Evaluation of compliance was based on patient self-reports of whether the treatment protocol was followed 100% (complete), 80% (good), 60% (moderate), or 40% (poor) of the time.
Measured: At 4-month time-point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OnychomycosisStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Repolar Pharmaceuticals Oy
- Responsible party
- Principal investigator, Janne J. Jokinen, Helsinki University Central Hospital
- Investigators
- Janne J. Jokinen, MD, PhD, Principal investigator, Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, FI-00029, Helsinki, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851590
- Sponsor's protocol ID
- 334/13/03/01/2012
- Other IDs
- 2012-004822-48
- Status last verified
- Oct 2015
- First submitted
- 8 May 2013
- Last updated
- 30 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01851590
- Acronym / sponsor ID
- 334/13/03/01/2012
- Conditions
- Onychomycosis
- Keywords
- Dermatophyte onychomycosis, Fungal nail infection, Resin Lacquer, Amorolfine, Terbinafine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Repolar Pharmaceuticals Oy
- Study start
- Oct 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 10 May 2013 (estimated)
- Results
- Posted 30 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- White superficial onychomycosis (WSO)
- Distal and lateral subungual onychomycosis (DLSO)
- Proximal subungual onychomycosis (PSO)
- [Total dystrophic onychomycosis) (TDO)] [Excluded]
- [Candidal onychomycosis] [Excluded]
Participants are randomized into 3 groups to receive:
- Topical treatment: 30 % resin lacquer (Abicin®) applied once daily for 9 months.
- Topical treatment: 5 % amorolfine lacquer (Loceryl®) applied once weekly for 9 months.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Resin Lacquer | Experimental | Device: Resin LacquerTopical 30% Resin Lacquer applied once daily for 9 months (Abicin® 30% Nail Lacquer). |
| Amorolfine | Active comparator | Drug: AmorolfineTopical 5% Amorolfine Lacquer applied once weekly for 9 months (Loceryl® 5% Nail Lacquer). |
| Terbinafine | Active comparator | Drug: Terbinafine250 mg of Terbinafine taken orally once daily for 3 months (Generics). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Resin LacquerAlso: Resin Lacquer arm30% Resin Lacquer is applied once daily for 9 months (Abicin®) in toenail onychomycosis. | Device | Resin Lacquer |
| AmorolfineAlso: Amorolfine Lacquer arm5% Amorolfine Lacquer is applied once weekly for 9 months (Loceryl®) in toenail onychomycosis. | Drug | Amorolfine |
| TerbinafineAlso: Terbinafine arm250 mg of Terbinafine is taken orally once daily for 3 months (Generics) in toenail onychomycosis. | Drug | Terbinafine |
Primary outcome
Mycological Cure
Time frame: At 4- and 10 months time-points from the beginning of the study.
To analyze the rate of complete mycological cure i.e. fungal eradication in terms of negative mycological culture AND negative potassium hydroxide (KOH) stain at 4- and 10 months time-points from the beginning of the study.
4 secondary outcomes
Clinical Responses to the Treatments
Time frame: At 4- and 10 months time-points from the beginning of the study.
Cost-effectiveness 1
Time frame: At 10-month time-point
Cost-effectiveness 2
Time frame: At 10-month time-point
Compliance to the Treatment
Time frame: At 4-month time-point
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundSigurgeirsson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janne J. Jokinen, MD, PhD principal investigator
Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, FI-00029, Helsinki, Finland
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Resin Lacquer, Amorolfine and Terbinafine in people with Onychomycosis, run by Helsinki University Central Hospital at 2 sites in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mycological Cure (time frame: At 4- and 10 months time-points from the beginning of the study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01851590, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2015.