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Trial record 6 of 39 for:    Terbinafine

Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis

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ClinicalTrials.gov Identifier: NCT01851590
Recruitment Status : Completed
First Posted : May 10, 2013
Results First Posted : November 30, 2015
Last Update Posted : November 30, 2015
Sponsor:
Collaborator:
Repolar Ltd.
Information provided by (Responsible Party):
Janne J. Jokinen, Helsinki University Central Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Onychomycosis
Interventions Device: Resin Lacquer
Drug: Amorolfine
Drug: Terbinafine
Enrollment 129
Recruitment Details In November 2013, on the basis of a newspaper advertisement, a total of 129 adult volunteers were assessed for eligibility at Vääksy Medical Center, Finland. Eligible subjects were required to provide toenail samples for screening. Inclusion criteria were a positive dermatophyte culture and a positive potassium hydroxide (KOH) stain.
Pre-assignment Details Of those 129 patients screened, 48 (37%) were excluded due to negative KOH staining or cultures and 8 (6%) were excluded because onychomycosis was caused by nondermatophyte mold or yeast. At baseline, 73 (57%) patients who met the entry criteria were randomly allocated to receive 1 of 3 therapies for dermatophyte onychomycosis (3 treatment arms).
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Hide Arm/Group Description

Topical treatment: 30 % Resin Lacquer (Abicin®)

Resin Lacquer was administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % Amorolfine Lacquer (Loceryl®)

Amorolfine: Amorolfine was administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine: Terbinafine 250 mg was administered orally once a day for 3 months in toenail onychomycosis.

Period Title: Overall Study
Started 23 [1] 25 [1] 25 [1]
At 3 Month: End of Terbinafine Treatment 23 [2] 24 [3] 22 [4]
At 4 Month: Follow-up Visit and Control 23 [5] 24 [5] 22 [5]
At 9 Month: End of Topical Treatments 23 [6] 24 [7] 22 [8]
At 10 Month: Follow-up Visit and Control 23 [9] 24 [9] 22 [9]
Completed 23 [10] 24 [11] 22 [11]
Not Completed 0 1 3
Reason Not Completed
Withdrawal by Subject             0             0             1
Adverse Event             0             0             2
Lack of Efficacy             0             1             0
[1]
In addition to clinical control visits, patients were contacted by phone during weeks 6, 13, and 29.
[2]
Topical Resin Lacquer treatment continues ->
[3]
Topical Amorolfine Lacquer Treatment continues ->
[4]
End of oral Terbinafine treatment. Washout period of the Terbinafine treatment arm begins.
[5]
Clinical response to treatment, toenails samples and laboratory exams were controlled.
[6]
End of topical Resin Lacquer treatment. Washout period of the Resin Lacquer treatment arm begins.
[7]
End of topical Amorolfine Lacquer treatment. Washout period of the Amorolfine treatment arm begins.
[8]
Washout period of the Terbinafine treatment arm continues.
[9]
Study completed. Clinical response to treatment, toenails samples and lab. exams were controlled.
[10]
All patients (23) were included in the ITT population and final outcome analyses.
[11]
All patients (25) were included in the ITT population and final outcome analyses.
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm Total
Hide Arm/Group Description

Topical treatment: 30 % Resin Lacquer (Abicin®)

Resin Lacquer is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % Amorolfine Lacquer (Loceryl®)

Amorolfine Lacquer is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg Terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Total of all reporting groups
Overall Number of Baseline Participants 23 25 25 73
Hide Baseline Analysis Population Description
Primary and secondary outcome analyses were based on the intent-to-treat (ITT) population and missing values were imputed using the last observation carried forward (LOCF) method. At baseline, 73 patients who met the entry criteria were randomized to one of the three arms: topical Resin Lacquer, topical Amorolfine Lacquer or oral Terbinafine.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 25 participants 25 participants 73 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
  78.3%
20
  80.0%
20
  80.0%
58
  79.5%
>=65 years
5
  21.7%
5
  20.0%
5
  20.0%
15
  20.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 25 participants 25 participants 73 participants
Female
2
   8.7%
5
  20.0%
8
  32.0%
15
  20.5%
Male
21
  91.3%
20
  80.0%
17
  68.0%
58
  79.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Finland Number Analyzed 23 participants 25 participants 25 participants 73 participants
23 25 25 73
Positive mycological culture in toenail samples  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 25 participants 25 participants 73 participants
23 25 25 73
BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 23 participants 25 participants 25 participants 73 participants
25  (3) 27  (4) 27  (4) 26  (4)
[1]
Measure Description: kg/m2
Specific dermatophyte species in mycological culture  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 25 participants 25 participants 73 participants
Trichophyton rubrum 20 24 21 65
Trichophyton mentagrophytes 3 1 4 8
Plasma creatinine  
Mean (Standard Deviation)
Unit of measure:  μmol/l
Number Analyzed 23 participants 25 participants 25 participants 73 participants
76  (15) 78  (13) 79  (11) 78  (14)
Plasma γ-glutamyl transferase  
Median (Inter-Quartile Range)
Unit of measure:  U/I
Number Analyzed 23 participants 25 participants 25 participants 73 participants
29
(17 to 41)
21
(14 to 41)
27
(18 to 47)
25
(20 to 50)
1.Primary Outcome
Title Mycological Cure
Hide Description 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.
Time Frame At 4- and 10 months time-points from the beginning of the study.
Hide Outcome Measure Data
Hide Analysis Population Description
Primary and secondary outcome analyses were based on the intent-to-treat (ITT) population and missing values were imputed using the last observation carried forward (LOCF) method.
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Hide Arm/Group Description:

Topical treatment with 30 % Resin Lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % Amorolfine Lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg Terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Overall Number of Participants Analyzed 23 25 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Mycological cure at 4-month
17
(1 to 34)
28
(9 to 47)
16
(0 to 31)
Mycological cure at 10-month
13
(0 to 28)
8
(0 to 19)
56
(35 to 77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resin Lacquer Arm, Amorolfine Lacquer Arm, Terbinafine Arm
Comments The sample size was estimated according to complete mycological cure at 10 months. Estimation was based on the design of a binary-outcome head-to-head superiority trial. Orally administered terbinafine treatment was considered the active control. Approximately 25 patients / arm were required to have 80% power (β=0.2) at a two-sided α=0.05 significance level to detect a decrease in primary outcome from 50% in the terbinafine arm to 15% in the amorolfine or resin lacquer treatment arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Proportions and 95% confidence intervals (CIs) were calculated for negative KOH staining, negative cultures, and a combination of these at 4- and 10-month time points. Cochran–Mantel–Haenszel and χ2-tests were used to analyse efficacy criteria.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Clinical Responses to the Treatments
Hide Description 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.
Time Frame At 4- and 10 months time-points from the beginning of the study.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat population, last observation carried forward.
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Hide Arm/Group Description:

Topical treatment with 30 % resin lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % amorolfine lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Overall Number of Participants Analyzed 23 25 25
Measure Type: Number
Unit of Measure: percentage of participants
Partial clinical response at 4-month 0 0 44
Complete clinical response at 4-month 0 0 0
Partial clinical response at 10-month 30 28 36
Complete clinical response at 10-month 0 0 16
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resin Lacquer Arm, Amorolfine Lacquer Arm, Terbinafine Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Differences between quantitative data were assessed with one-way analysis of variances, and pairwise comparisons were performed with Bonferroni’s post hoc test.
Method ANOVA
Comments [Not Specified]
3.Secondary Outcome
Title Cost-effectiveness 1
Hide Description 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.
Time Frame At 10-month time-point
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Resin Lacquer Arm Amorolfine Treatment Arm Terbinafine Arm
Hide Arm/Group Description:

Topical treatment with 30 % resin lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % amorolfine lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Overall Number of Participants Analyzed 23 25 25
Mean (95% Confidence Interval)
Unit of Measure: Euros (€)
0.15
(0.14 to 0.15)
0.21
(0.20 to 0.21)
0.56
(0.52 to 0.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resin Lacquer Arm, Amorolfine Treatment Arm, Terbinafine Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Differences between quantitative data were assessed with one-way analysis of variances, and pairwise comparisons were performed with Bonferroni’s post hoc test.
Method ANOVA
Comments [Not Specified]
4.Secondary Outcome
Title Cost-effectiveness 2
Hide Description 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.
Time Frame At 10-month time-point
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Resin Lacquer Arm Amorolfine Treatment Arm Terbinafine Arm
Hide Arm/Group Description:

Topical treatment with 30 % resin lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % amorolfine lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Overall Number of Participants Analyzed 23 25 25
Mean (95% Confidence Interval)
Unit of Measure: Euros (€)
40.7
(38.8 to 42.6)
55.2
(52.9 to 57.5)
52.1
(46.8 to 53.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resin Lacquer Arm, Amorolfine Treatment Arm, Terbinafine Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Differences between quantitative data were assessed with one-way analysis of variances, and pairwise comparisons were performed with Bonferroni’s post hoc test.
Method ANOVA
Comments [Not Specified]
5.Secondary Outcome
Title Compliance to the Treatment
Hide Description 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.
Time Frame At 4-month time-point
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage describes the proportion of patients who declared that they have been followed the instructions completely (100%).
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Hide Arm/Group Description:

Topical treatment with 30 % resin lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % amorolfine lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

Overall Number of Participants Analyzed 23 25 25
Measure Type: Number
Unit of Measure: percentage of participants
100 96 100
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resin Lacquer Arm, Amorolfine Lacquer Arm, Terbinafine Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Qualitative data are expressed as frequencies and percentages, and differences between parallel groups were compared with the χ2-test or Fisher’s exact test, as appropriate.
Method Chi-squared
Comments [Not Specified]
Time Frame Adverse effects or side-effects during the 10-month follow-up
Adverse Event Reporting Description All side-effects or adverse events were recorded systematically. Information on the side-effects were specifically asked by the research coordinator during the two follow-up visits (at 4- and 10-month) and three telephone contacts. Patients were asked to contact research coordinator if any obvious or suspected side-effect would emerge.
 
Arm/Group Title Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Hide Arm/Group Description

Topical treatment with 30 % resin lacquer (Abicin®)

Resin is administered locally in the form of lacquer (Abicin®) onto infected nail once a day for 9 months in toenail onychomycosis.

Topical treatment with 5 % amorolfine lacquer (Loceryl®)

Amorolfine is administered locally in the form of lacquer (Loceryl®) onto infected nail once a week for 9 months in toenail onychomycosis.

Oral medication with 250 mg terbinafine / day

Terbinafine 250 mg is administered orally once a day for 3 months in toenail onychomycosis.

All-Cause Mortality
Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/23 (0.00%)      0/25 (0.00%)      0/25 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Resin Lacquer Arm Amorolfine Lacquer Arm Terbinafine Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/23 (0.00%)      0/25 (0.00%)      2/25 (8.00%)    
Gastrointestinal disorders       
Diarrhoea   0/23 (0.00%)  0 0/25 (0.00%)  0 1/25 (4.00%)  1
Skin and subcutaneous tissue disorders       
Rash   0/23 (0.00%)  0 0/25 (0.00%)  0 1/25 (4.00%)  1
Indicates events were collected by systematic assessment
  • Relatively short treatment period for the toenail onychomycosis (9 months).
  • Patients with total dystrophic onychomycosis (46%) - the most difficult subtype to treat - may not have been amenable to monotherapy with a topical antifungal treatment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Janne Jokinen, MD, PhD, Consultant Cardiothoracic Surgeon
Organization: Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, Finland
Phone: 50 554 8103 ext +358
EMail: janne.jokinen@helsinki.fi
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.
Layout table for additonal information
Responsible Party: Janne J. Jokinen, Helsinki University Central Hospital
ClinicalTrials.gov Identifier: NCT01851590     History of Changes
Other Study ID Numbers: 334/13/03/01/2012
2012-004822-48 ( EudraCT Number )
First Submitted: May 8, 2013
First Posted: May 10, 2013
Results First Submitted: March 20, 2015
Results First Posted: November 30, 2015
Last Update Posted: November 30, 2015