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Topical treatments for fungal infections of the skin and nails of the foot.

  1. Fay Crawford1,*,
  2. Sally Hollis2

Editorial Group: Cochrane Skin Group

Published Online: 18 JUL 2007

Assessed as up-to-date: 22 MAY 2007

DOI: 10.1002/14651858.CD001434.pub2

How to Cite

Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot.. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD001434. DOI: 10.1002/14651858.CD001434.pub2.

Author Information

  1. 1

    The University of Edinburgh, Division of Community Health Sciences, Edinburgh, UK

  2. 2

    University of Nottingham, c/o Cochrane Skin Group, Nottingham, UK

*Fay Crawford, Division of Community Health Sciences, The University of Edinburgh, 20 West Richmond Street, Edinburgh, EH8 9DX, UK. fay.crawford@ed.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 JUL 2007

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Characteristics of included studies [ordered by study ID]
Ablon 1996

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: not stated
Participants comparable at baseline for age: not stated
Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: 11


ParticipantsTotal evaluable sample size: 90
Inclusion criteria: male
Exclusion criteria: onychomychosis
Treatment setting: Ambulatory care dermatology clinic


Interventionsa. Naftifine cream
Duration: two weeks
Frequency: applied once daily
b. Terbinafine cream
Duration: two weeks
Frequency: applied once daily
c. Oxiconazole lotion
Duration: two weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, exudation, pruritus, maceration, vesiculation, burning
Adverse events: none


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Akers 1989

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age:yes
Sex: yes
Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: yes
Number of drop outs stated: 30


ParticipantsTotal evaluable sample size: 229


Interventionsa. Sulconazole nitrate 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: Cure
Secondary Outcomes: Signs and symptoms
- itching, erythems, scaling, fissuring, exudation, pustules, maceration, vesiculation


NotesChronic moccasin type tinea pedis.

Data extracted for T. rubrum only (92% of those with + ve cultures)


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Aly 2003

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes
Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: yes
Number of drop outs stated: 57


ParticipantsTotal evaluable sample size: 317

Setting: Multicentre study in USA.

Exclusion criteria
treatment with any medication that could affect the course of the disease. Fungal infection else where on the body. Topical antifungals had a 14 day wash-out period and systemic a 28 day washout period.


Interventionsa. Ciclopirox Gel 0.77%
Duration X 2 daily for 28 days
b. Vehicle
Duration X 2 daily for 28 days


OutcomesPrimary outcome:
treatment success defined as mycological cure and > % 75% clinical improvement


NotesInterdigital tinea pedis

Adverse effects; 14 ciclopirox and 13 vehicle subjects reported burning sensations of the skin. Four ciclopirox and one vehicle subjects reported pruritus.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Bagatell 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes
Sex: yes Duration of complaint:yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 47
Inclusion criteria: tinea pedis interdigitalis
Exclusion criteria: use of topical/systemic antifungal therapy within one week prior to study, use of Griseofulvin four weeks prior to study
Treatment setting: out-patient department


Interventionsa. Bifonazole 1% solution
Duration: four weeks
Frequency: applied once daily
b. Placebo solution
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Adverse events: a. two burning sensations b. one(three) burning sensations


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Bagatell 1991a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: 13


ParticipantsTotal evaluable sample size: 88
Treatment setting: Four different sites


Interventionsa. Naftifine 1% gel
Duration: four weeks
Frequency: applied twice daily
b. Placebo gel
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: Cure
Secondary Outcomes: Signs and symptoms
- fissuring, pruritus,vesiculation
Global improvement
Adverse events: a. 8 b. 18 burning, stinging, itching


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Bagatell 1991b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: 13


ParticipantsTotal evaluable sample size: 88
Treatment setting: Four different sites


Interventionsa. Naftifine 1% gel
Duration: four weeks
Frequency: applied twice daily
b. Placebo gel
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: Cure
Secondary Outcomes: Signs and symptoms
- fissuring, pruritus,vesiculation
Global improvement
Adverse events: a. 8 b. 18 burning, stinging, itching


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Bergstresser 1993

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: not stated
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 193
Inclusion criteria: baseline total score for the target lesion of six or more, including a score of at least two for erythema or a score of two or more for each of the two other signs
Treatment setting: eight multicentres


Interventionsa. Terbinafine
Duration: one week
Frequency: applied twice daily
b. Terbinafine
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, exudation, pruritus, maceration, vesiculation, burning and stinging


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Berman 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: yes
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: no
Number of drop outs stated: 18


ParticipantsTotal evaluable sample size: 159
Inclusion criteria: total score for target lesion of six or more including a score of two or more for erythema or two for at least two other signs
Exclusion criteria: Non-interdigital lesions (i.e. Moccasin type), onychomychosis, systemic fungal disease
Treatment setting: multicentre


Interventionsa. Terbinafine
Duration: one week
Frequency: applied twice daily
b. Placebo
Duration: one week
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, desquamation, fissuring, maceration, vesiculation, exudation, pruritus, burning/stinging


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Bojanovsky 1985

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: no
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 99
Exclusion criteria: onychomycosis


Interventionsa. Bifonazol cream
Duration: five weeks
Frequency: applied once a day
b. Naftifine cream
Duration: five weeks
Frequency: applied once a day


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. dermatitis,dry skin, burning sensation (5)


NotesTranslated from German


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Buck 1994

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: yes
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size:117

Exclusion criteria:immune suppressant therapy within the previous 6 months. Had used a topical agent on the toenails in the previous two weeks, a history of HIV or psoriasis


Interventionsa. 1% clotrimazole soln
b. Tea tree oil


OutcomesPrimary outcome; cure
Secondary outcomes;
a. measuring the distance between the cuticle and the most proximal onychomycotic border

b. recording the percentage of involvement in 25% increments


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Carter 1972

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 81
Exclusion criteria: any therapeutic or prophylactic medication taken within three weeks prior to study
Treatment setting: prison


Interventionsa. Haloprogin 1% foam, solution or cream
Duration: four weeks
Frequency: applied twice daily
b. Tolnaftate 1% solution
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: lesion scores
Adverse events: none in either group


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Chretien 1980

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: not stated Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: not stated
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 85


InterventionsA. 2% undecylenic acid and 20% zinc acid powder

Duration: four weeks
Frequency: applied twice daily

b. Placebo powder
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary outcomes:signs and symptoms - erthythema, scaling, fissuring, hyperkeratosis


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used

Coffey 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: not stated Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: not stated
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 43
Exclusion criteria: Topical and systemic antifungal treatments used within one week prior to study
Treatment setting: Dermatology medical clinic


Interventionsa. Bifonazole 1% cream
Duration: four weeks
Frequency: applied once daily
b. Placebo cream
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythems, scaling, fissuring, exudation, pustules, maceration, vesiculation


NotesTinea pedis interdigital


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Del Palacio 1989

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: nine
Exclusion criteria: use of antifungal therapy within two weeks prior to study


Interventionsa. Bifonazole 1% cream
Duration: max six weeks
Frequency: once daily
b. Amorolfine 0.5% cream
Duration: max six weeks
Frequency: once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, burning, redness, weeping, scaling, pustulation, incrustation
Adverse events: none


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Dobson 1989

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: 41


ParticipantsTotal evaluable sample size: 183
Inclusion criteria: 12 yrs and older
Exclusion criteria: Hyperkeratotic plantar type tinea pedis
Treatment setting: eight different sites


Interventionsa. Naftifine 1% cream
Duration: four weeks
Frequency: applied once daily
b. Placebo cream
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: Cure
Secondary Outcomes: Signs and symptoms
- erythems, maceration, pruritus
Global improvement
Adverse events: a. 2 b. 5 soreness, burning, eczema, exacerbation of folliculitis, itching


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Elewski 1996

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: three


ParticipantsTotal evaluable sample size: 321
Inclusion criteria: minimum severity score of six at least 1.5 for erythema and 2 for pruritus
Treatment setting: 17 centres U.S.A


Interventionsa. Oxiconazole nitrate 1% and fluticazole 0.05% combination cream
Duration: one week of above, 3 weeks of oxiconazole nitrate 1%
Frequency: applied twice daily
b. Oxiconazole nitrate 1% cream
Duration: four weeks
Frequency: applied twice daily
c. Placebo cream
Duration: four weeks
Frequency: Twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. 5.3% b. 7.5% c. 6% burning and pruritus


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Ellis 1989

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified:yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: 108


ParticipantsTotal evaluable sample size: 163
Exclusion criteria: use of topical antifungal therapy within 7 days prior to study
use of systemic antifungal therapy within 30 days prior to study
Treatment setting: twelve centres


Interventionsa. Oxiconazole nitrate cream
Duration: four weeks
Frequency: once daily plus once daily Placebo
b. oxiconazole nitrate cream
Duration: four weeks
Frequency: twice daily
c. Placebo
Duration: four weeks
Frequency: twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, pustules, maceration, burning, crusting
Global response
Adverse events: burning, irritation, pruritus


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Evans 1991

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes
Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: 38


ParticipantsTotal evaluable sample size: 48
Exclusion criteria: use of systemic antifungal therapy within two weeks prior to study


Interventionsa. Terbinafine 1% cream
Duration: two weeks
Frequency: applied once daily
b. Placebo cream
Duration: two weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. 2 b. 1 erythematous rash


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Evans 1993a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes


ParticipantsTotal evaluable sample size: 63
Inclusion criteria: symptom/sign score greater than three
Treatment setting: multicentre


Interventionsa. Naftifine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. 1% Clotrimazole and 1% hydrocortisone cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, exudation, pustules, vesiculation, pruritus and crusting
Adverse events


NotesData extracted only for patients who were microscopy and culture positive at baseline only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Evans 1993b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: yes
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: 44


ParticipantsTotal evaluable sample size: 211
Exclusion criteria: use of topical antifungal within seven days prior to study
use of systemic antifungal within six weeks prior to study
Treatment setting: General practice and hospital


Interventionsa. Terbinafine 1% cream
Duration: one week plus three weeks Placebo
Frequency: applied twice daily
b. Clotrimazole 1% cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. 4 stinging, cracks, itching, eye irritation, erythema, swelling
b. 4 erythema, soreness, rash, cellulitis


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Evans 1994

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: 13


ParticipantsTotal evaluable sample size: 65
Exclusion criteria: use of topical antifungal within seven days of study
use of systemic antifungal within six weeks prior to study
use of oral Terbinafine within three months prior to study
Treatment setting: general practice


Interventionsa. Terbinafine 1% cream
Duration: one day plus six days Placebo
Frequency: applied once daily
b. Terbinafine 1% cream
Duration: three days plus four days Placebo
Frequency: once daily
c. Terbinafine 1% cream
Duration: five days plus two days Placebo
Frequency: once daily
d. Terbinafine 1% cream
Duration: seven days
Frequency: once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: c. 1 mild pruritus


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Friederich 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: not stated
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: no
Adverse events reported: no
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 73
Inclusion criteria: patients consent to remain in hospital for 21 days
Exclusion criteria: use of antimycotic treatment four weeks prior to study


Interventionsa. Bifonazol cream
Duration: three weeks
Frequency: applied once daily
b. Bifonazol cream
Duration: three weeks
Frequency: applied once daily, washed off after one hour


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation


NotesTranslated from German
Culture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Fuerst 1980

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: yes Duration of complaint:
not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 103
Exclusion criteria: use of antifungal therapy within two weeks prior to study, use of Griseofulvin within six weeks prior to study
Treatment setting: Prison rehabilitation centre


Interventionsa. Undecylenic acid ointment
Duration: four weeks
Frequency: applied twice daily
b. Tolnaftate cream
Duration: four weeks
Frequency: applied twice daily
c. Placebo
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: b. 1 worsening of symptoms


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Gentles 1974

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: no
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 45


Interventionsa. Miconazole cream and powder
Duration: four weeks
Frequency: cream - pm powder - am
b. Placebo cream and powder
Duration: four weeks
Frequency: cream - pm powder - am


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms


NotesData extracted for positive culture at baseline only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Gomez 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: no
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 40
Exclusion criteria: use of any topical/systemic antifungal treatment within two weeks prior to study
Treatment setting: University of California


Interventionsa. Tolciclate 1% solution
Duration: six weeks
Frequency: applied twice daily
b. Placebo solution
Duration: six weeks
Frequency: applied twice daily:


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, maceration, suppuration
Adverse events: none in either group


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Gupta 2000a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 211
Exclusion criteria: white superficial or proximal subungual onychomycosis. Nail dystrophy. Infection which led to epinychium, antifungal therapy 24 weeks prior to study. Treatment setting; Multicentre studies USA


Interventionsa. Ciclopirox nail lacquer 8% solution
Duration: 48 weeks
Frequency: applied once daily
b. Placebo solution
Duration: 48 weeks
Frequency: applied once daily:


OutcomesPrimary outcome: cure
Secondary Outcomes: Planimetric measurements % affected nail, Global evaluation score 0=cured, 1=excellent improvement, 2=moderate improvement; 3=slight improvement; 4= no change.
Adverse events: 10 (9%) group a,
7 (6%) group b.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Gupta 2000b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 237
Exclusion criteria: white superficial or proximal subungual onychomycosis. Nail dystrophy. Infection which led to epinychium, antifungal therapy 24 weeks prior to study. Treatment setting; Multicentre studies USA


Interventionsa. Ciclopirox nail lacquer 8% solution
Duration: 48 weeks
Frequency: applied once daily
b. Placebo solution
Duration: 48 weeks
Frequency: applied once daily:


OutcomesPrimary outcome: cure
Secondary Outcomes: Planimetric measurements % affected nail, Global evaluation score 0=cured, 1=excellent improvement, 2=moderate improvement; 3=slight improvement; 4= no change.
Adverse events: 10 (9%) group a,
7 (6%) group b.

Data not presented


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Haas 1985

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes
Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 204
Exclusion criteria: onychomychosis, use of systemic/topical antifungal treatment within four weeks prior to study


Interventionsa. Naftifine cream
Duration: four weeks
Frequency: applied twice daily
b. Clotrimazole cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: ten patients in each group complained of either irritation, burning or dryness


Notesmulticenter trial
Translated from German


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Hollmen 2002

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: yes Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: yes
Fungi identified: not stated
Distribution of species between groups: not stated
Adverse events reported: not stated
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 70
Exclusion criteria: less than 12 years of age.
Inclusion criteria; tinea pedis.
Treatment setting Six centres (three Belgium, three Finland)


Interventionsa. Terbinafine 1% gel
Duration: Seven days
Frequency: applied once daily
b. Placebo
Duration: seven days
Frequency: applied once daily


OutcomesPrimary outcome; Mycological cure
Minimal signs of clinical disease erythema, desquamation, pruritis < 2 with no individual score > 1 and a severity score for pustulation, encrustation, and vesiculation of 0

Clinical cure; 6 symptoms assessed; 0= absent, 3= severe


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Holti 1970

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 12
Treatment setting: multicentre


Interventionsa. Whitfields ointment
Duration: eight weeks
Frequency: once daily
b. Varotin ointment
Duration: eight weeks
Frequency: once daily


OutcomesPrimary outcome: cure
Adverse events: none


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Ison 1990

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: 13


ParticipantsTotal evaluable sample size: 111
Exclusion criteria: onychomycosis
use of systemic antifungal therapy within two weeks prior to study
topical treatment stopped at entry


Interventionsa. Econazole nitrate 1% cream
Duration: four weeks
Frequency: applied once daily
b. Placebo cream
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Adverse events: six patients in each group complained of either upper respiratory tract infections, back pain, tooth ache, headache, pleurisy or swollen ankles


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Izuno 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size:38
Exclusion criteria: use of topical/systemic antifungal therapy one week prior to study, use of Griseofulvin four weeks prior to study


Interventionsa. Bifonazole 1% cream
Duration: four weeks
Frequency: applied once daily
b. Placebo
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Adverse events: none


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Kagawa 1985

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Single blind study
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: 55


ParticipantsTotal evaluable sample size: 379
Exclusion criteria: Hyperkeratotic tinea pedis
use of systemic antifungals one month prior to study
use of topical antifungals one week prior to study


Interventionsa. Naftifine
Duration: five weeks
Frequency: applied twice daily
b. Clotrimazole
Duration: five weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, exudation, papules, vesiculation, erosion
Global efficacy
Adverse events: slight


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Klaschka 1984

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported:yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 60
Exclusion criteria: use of other systemic/topical antifungal therapies


Interventionsa. Naftifine gel
Duration: four weeks
Frequency: applied twice daily
b. Placebo gel
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. 11 b. 15 slight burning sensation, dryness of skin


NotesTranslated from German


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Kligman 1985a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: 12


ParticipantsTotal evaluable sample size: 168
Exclusion criteria: use of antifungal therapy one week prior to study
Treatment setting: Multicentre


Interventionsa. Ciclopiroxolamine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: one person in each group had worsening of symptoms


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Kligman 1985b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 87
Exclusion criteria: use of antifungal therapy within one week prior to study
Treatment setting: multicenter


Interventionsa. Ciclopiroxolamine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Clotrimazole 1% cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Clinical cure
Adverse events: none


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Korting 1997

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: yes
Fungi identified: no
Distribution of species between groups: no
Adverse events reported: no
Number of drop outs stated: 111


ParticipantsTotal evaluable sample size: 424


Interventionsa. Econazole liposome 1% gel
Duration: two weeks
Frequency: once daily
b. Branded econazole 1% cream
Duration: two weeks
Frequency: applied once daily
c. Generic Clotrimazole 1% cream
Duration: two weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- pruritus, erythema, scaling, fissuring, maceration
Tolerability


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Korting 2001

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated.
Fungi identified: no
Distribution of species between groups: no
Adverse events reported: reported none occurred
Number of drop outs stated: 30


ParticipantsTotal evaluable sample size: 70
Exclusion criteria;concomitant toenail/finger nail onychomycosis,
use of cytotoxic immunosuppressants.


Interventionsa. Terbinafine cream 1% 7 days once daily.

b. Placebo (vehicle cream) seven days once daily.


OutcomesPrimary outcome: cure

Secondary outcomes: Total clinical signs and symptoms and clinical response.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used

Kuhlwein 1990

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: not stated
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 36
Exclusion criteria: use of other systemic/topical antimycotic therapy


Interventionsa. Croconazole 1% cream
Duration: three weeks
Frequency: applied once daily
b. Bifonazole cream
Duration: three weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Adverse events: none in either group


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Ledezma 2000

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Adverse events reported: no
Number of drop outs stated: yes


ParticipantsTotal evaluable sample; 47/70
Participants; Venezuelan army soldiers
Exclusion criteria; use of topical antifungals within 30 days of commencement of study.


Interventionsa. 0.6% ajone (alcoholic extract of garlic)

b. 1% ajone

1% Terbinafine

all applied twice daily for one week


OutcomesCure = negative culture

Effective treatment = cured and signs and symptoms less than 2 on the following scale;
0=absent
1=light
2=moderate
3=intense


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used

Leenutaphong 1999

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: not stated
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 48
Exclusion criteria: not stated


Interventionsa. Terbinafine cream 1% 1x daily for 1 week (3 weeks Placebo)

Miconazole cream 2% 2 x daily for 4 weeks.


OutcomesPrimary outcomes: Mycological cure

Secondary cure: Clinical efficacy, erythema, scaling, pustules and pruritis.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Mandy 1974

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 12
Treatment setting: USAF medical centre- Keesler air force base


Interventionsa. Miconazole nitrate 2% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, exudation, maceration, erosions, cellulitis
Adverse events: none


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Mensing 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: no
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: no
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 34

Treatment setting: not clear

Exclusion criteria:pregnancy, patients with concomitant disease predisposing to onychomycosis, abnormal baseline laboratory values,treatment with topical or systemic antifungal during the 4 weeks preceding treatment with amorolfine, treatment with another topical or systemic antifungal during the course of the study.


Interventionsa. 5% amorolfine in a methylene chloride vehicle

b. 5% amorolfine in an ethanol vehicle


OutcomesPrimary outcome: cure

Secondary outcome: Inhibition zones


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Montana 1994

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: no
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: no
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 20

Treatment setting: not clear,
Exclusion criteria: psoriasis, lichen planus, any other disease which affects the nails. Hypersensitivity, use of topical antifungal medication within one month, use of a systematic antifungal medication with in three months.


Interventionsa. Fungoid tincture
b. Placebo


OutcomesPrimary outcome: cure

Secondary outcome: Global assessment. Measuring the distance between the cuticle and the most proximal onychomycotic border.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Pereda 2003

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: no
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: ten


ParticipantsTotal evaluable sample size:264

Treatment setting: 11 Dermatology outpatient clinics in Spain

Inclusion criteria: + ve KOH and culture systemic antimycotic within four weeks of trial entry, topical antifungals within seven days. Concurrent therapy with steroids or other antifungal agent.


Interventionsa. Bifonazole 1% powder

b. Flutrimazole 1% powder

Both applied 2 X daily for 4 weeks.


OutcomesPrimary outcome:Clinical cure = total signs and symptoms score of < 2.

Global cure clinical cure plus negative microscopy


NotesAdverse events;non serious. Dishydrotic eczema by one in bifonazole group.

Itching by one in bifonazole group and one in fluconazole group.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Plotkin 1990

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: not stated
Distribution of species between groups: not stated
Adverse events reported: yes
Number of drop outs stated: 23


ParticipantsTotal evaluable sample size: 57
Exclusion criteria: Systemic fungal infection
use of topical antifungals within four weeks prior to study
Treatment setting: Colleges of Podiatric Medicine


Interventionsa. Naftifine 1% cream
Duration: four to six weeks
Frequency: applied twice daily
b. Clotrimazole 1% cream
Duration: four to six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, fissuring, maceration, pruritus
Adverse events: a. erythema and itching b. tingling


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Qadripur 1979

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: yes Sex : yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 60


Interventionsa. Clotrimazole cream
Duration: four weeks
Frequency:
b. Econazole cream
Duration: four weeks
Frequency:


OutcomesPrimary outcome: cure
Adverse events: a. 0 b. 4


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Roberts 1985

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: not stated
Participants comparable at baseline for age: not stated Sex: not staed Duration of complaint: not stated
Inclusion and exclusion criteria specified: no
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: no
Adverse events reported: no
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 31
Treatment setting: Dermatology out-patient department


Interventionsa. Bifonazole 15 cream
Duration: three weeks
Frequency: applied twice daily
b. Miconazole 2% cream
Duration: three weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- weeping, itching, fissuring,maceration, burning, peeling


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Sanchez 1994

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: not stated
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified:yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 43
Exclusion criteria: Bacterial/ yeast infection, use of topical antifungal therapy within two weeks prior to study, use of systemic griseofulvin or ketoconazole within four weeks prior to study
Treatment setting: Dermatological departments


Interventionsa. Terbinafine 1% cream
Duration: four weeks
Frequency: applied once daily
b. Bifonazole 1% cream
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling
Adverse events: none in either group


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Satchell 2002

MethodsRCT. Study aim clearly described: yes

Assessor blind to treatment allocation; not stated
Blinding of subjects: not stated
Study groups comparable at baseline for age; yes, Sex: yes, duration; not stated
Were the inclusion/exclusion criteria specified; yes
Were the interventions welldescribed; no
Was there an assessment of compliance; not stated
Was data included from subjects who withdrew after randomisation;no
Was an A priori sample size calculation performed;yes


ParticipantsTotal evaluable sample size: 137
Inclusion criteria: aged 14 +, intertriginious tinea pedis
Exclusion criteria: use of antifungal treatment within seven days (topical) or 6 months (systemic) prior to study


Interventionsa. Placebo (20% ethanol)
b. 25% Tea tree oil
c. 50% Tea tree oil


OutcomesPrimary outcome; cure
Secondary outcomes clinical cure (burnng, itching) graded as absent, mild, moderate, severe, or very severe.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Savin 1990

MethodsRCT
Study aim clearly defined: yes
Blinded assesor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Reoccurrence status: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: five


ParticipantsTotal evaluable sample size: 22
Inclusion criteria: Men
Exclusion criteria: Use of sysytemic antifungals within four weeks prior to study
Use of topical antifungals within two weeks prior to study


Interventionsa. Terbinafine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: none reported


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Savin 1994

MethodsRCT
Study aim clearly defined: yes
Blinded assesor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Reoccurrence status: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 193
Inclusion criteria: baseline score of four or more (signs and symptoms)
Exclusion criteria: more than 30% nail involvement
Treatment setting: five different sites


Interventionsa. Terbinafine 1% cream
Duration: two weeks
Frequency: applied twice daily
b. Placebo cream
Duration: two weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Patients own assessment
Overall assessment by physicians
Adverse events: a. four b. three


NotesMoccasin type tinea pedis


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Savin 1997

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 271
Inclusion criteria: Erythema and at least scaling or pruritus
Exclusion criteria: concomittant fungal infections
diffuse moccasin type tinea pedis
use of topical antifungals within two weeks prior to study
use of systemic antifungals within two months of study
Treatment setting: ten study sites


Interventionsa. Butenafine 1% cream
Duration: one week
Frequency: applied twice daily
b. Placebo cream
Duration: one week
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. burning and stinging b. burning, tingling, elevated AST and ALT levels


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Schachner 1990

MethodsRCT
Study aim clearly defined: yes
Blinded assesor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: nine


ParticipantsTotal evaluable sample size: 91


Interventionsa. Naftifine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. pruritus, burning, erythema b. pruritus, burning, drying


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Schopf 1999

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: 9


ParticipantsTotal evaluable sample size: 429
Inclusion criteria: radiation, systematic immunosuppresants, topical antifungal drugs within two weeks, oral antifungals in six weeks.

35 centres in Germany.


Interventionsa. Terbinafine 1% solution 2 x daily for 1 week.

b. Clotrimazole 1% solution 2 x daily for 2 weeks


OutcomesPrimary outcomes;


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1977

MethodsRCT
Study aim clearly defined: yes
Blinded assesor of primary outcome: yes
Double blind study: yes
Participants comparable at baseline for age: yes Sex: not stated Duration of complaint: yes
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not stated
Adverse events reported: yes
Number of drop outs stated: nine


ParticipantsTotal evaluable sample size: 104
Treatment setting: Health Center


Interventionsa. 20% zinc undecylenate and 2% undecylenic acid - new commercial powder
Duration: six weeks
Frequency: applied once daily
b. 20% Undecylenate and 2% undecylenic acid - over the counter powder
Duration: six weeks
Frequency: applied once daily
c. Placebo powder
Duration: six weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Adverse events: a. two patients with pruritus


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Smith 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 54
Inclusion criteria: interdigital type tinea pedis
Exclusion criteria: use of anti-infective medications within one week prior to study, use of Griseofulvin within four weeks prior to study


Interventionsa. Bifonazole 15 solution
Duration: four weeks
Frequency: applied once daily
b. Placebo solution
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation
Adverse events: a. 3 mild burning b. 2 mild burning, tingling


NotesCulture results only


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1988a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yess
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described:yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: yes
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: not stated


ParticipantsTotal evaluable sample size: 60
Exclusion criteria: recent use of antifungal agents


Interventionsa. Ticonazole 1% cream
Duration: six weeks
Frequency: applied twice daily
b. Placebo cream
Duration: six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Adverse events: both groups encountered transient stinging or burning after application two in a. and seven in b.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1988b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 64


Interventionsa. Ticonazole 1% cream
Duration: six weeks
Frequency: applied twice daily
b. Miconazole 2% cream
Duration: six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Adverse events: Three patients in each group complained of stinging


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1988c

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: no
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: yes
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 59


Interventionsa. Tioconazole 1% cream
Duration: six weeks
Frequency: applied twice daily
b. Miconazole 2% cream
Duration: six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Adverse events: Five patients in group 1 and eight in group 2 complained of stinging


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1990a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: no Sex: yes Duration of complaint:
no
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: yes
A Priori sample size calculation: no
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 20
Exclusion criteria: use of systemic antifungals within four weeks prior to study, use of topical antifungals within two weeks prior to study


Interventionsa. Terbinafine 1% cream
Duration: four weeks
Frequency: applied twice daily
b. Placebo cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Overall efficacy- complete mycologic cure with total or substatial remission of signs and symptoms
Adverse events: a: elevated AST b: mild itching, neutropenia, elevated ALT


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1990b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Doublr blind study: not stated
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 207


Interventionsa. Naftifine
Duration: four weeks
Frequency: applied once daily plus Placebo once daily
b. Naftifine
Duration: four weeks
Frequency: applied twice daily
c. Clotrimazole
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, fissuring, pruritus
Adverse events: a: four b: four c: three


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Smith 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: not stated
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: not given
Adverse events reported: yes
Number of drop outs stated: four


ParticipantsTotal evaluable sample size: 172


Interventionsa. Naftifine cream
Duration: four weeks
Frequency: applied twice daily
b. Clotrimazole betamethasone dipropionate cream
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- erythema, scaling, papules, pruritus
Adverse reactions: two patients in group 1 complained of erythema, eczema, burning and five patients in group 2 complained of fissuring, erythema, burning, edema, pruritus,vesicular infection


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Spiekermann 1976a

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 267
Exclusion criteria: use of topical/systemic anti infective or anti-inflammatory agents within two weeks prior to study


Interventionsa. Clotrimazole 1% solution
Duration: six weeks
Frequency: applied twice daily
b. Placebo solution
Duration: six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation, inflammation, edema
Adverse events: a: irritation, stinging, urticaria


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Spiekermann 1976b

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: not stated Sex: not stated Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 41
Exclusion criteria: use of topical/systemic anti infective or anti-inflammatory agents within two weeks prior to study


Interventionsa. Clotrimazole 1% cream
Duration: six weeks
Frequency: applied twice daily
b. Placebo cream
Duration: six weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation, inflammation, edema
Adverse events: a. irritation, stinging, burning


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Sushka 2001

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: no
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: no
Intention to treat analysis: no
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: eight


ParticipantsTotal evaluable sample size; 100

Setting:not stated

Exclusion criteria: less that 18 years of age, - ve KOH, tinea pedis of the maccasin type or concomitant onychomycosissystemic corticosteroids or antibiotics


Interventionsa. Clotrimazole 1% once daily

b. Ketoconazole 2% twice daily


OutcomesPrimary outcome: cure

Secondary outcomes;Signs and symptoms; fissuring, erythema, masceration, vesiculation, desquamation, exsudation, pruritis, and burning stinging.


NotesInterdigital tinea pedis

Adverse events; burning, scaling, redness and scaling of the skin


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Syed 1999

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants;yes comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: no drop outs
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 60
Exclusion criteria: use of topical/systemic anti fungals within two weeks or 3 months prior to study


Interventionsa. Butenafine 2% + 5% melaleuca alternafolia

b. Placebo
Duration: eight weeks
Frequency: applied three times weekly


OutcomesPrimary outcome: cure
Secondary Outcomes: clinical success resolution of all clincal symptoms Signs and symptoms
- itching, erythema, scaling, fissuring, exudation, pustules, maceration, vesiculation, inflammation, edema
Adverse events: a. irritation, stinging, burning


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Syed 2000

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 40
Exclusion criteria: women.
Inclusion criteria: men.
Moccasin and ID type tinea pedis and


Interventionsa. Butenafine 1% 1x daily for 2 weeks

b. Terbinafine 1% 1 x daily for 2 weeks.

c. Placebo 1 x daily for 2 weeks.


OutcomesPrimary outcome; cure

Secondary outcomes; erythema, pustules, encrustation, pruritis.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Tong 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: yes Sex: no Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: yes
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 104
Exclusion criteria: use of systemic antifungals within six months prior to study, use of topical antifungals within one week prior to study


Interventionsa. Tolnaftate 1% cream
Duration: four weeks
Frequency: applied twice dialy
b. Tea Tree Oil 10% in cream
Duration: four weeks
Frequency: applied twice daily
c. Placebo
Duration: four weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, scaling, inflammation and burning
Adverse events: a: mild erythema


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Tschen 1997

MethodsRCT
Study aim clearly defined: yes
Blinded assesor of primary outcome: not stated
Double blind study
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated:


ParticipantsTotal evaluable sample size: 80
Inclusion criteria: minimum erythema score of two, minimum score of two for pruritus or scaling
Exclusion criteria: recently used antifungals


Interventionsa. Butenafine 1% cream
Duration: four weeks
Frequency: applied once daily
b. Placebo cream
Duration: four weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Investigator's and patient's assessment of treatment
Adverse events: a: mild burning sensation (1) b: burning, itching, stinging (4)


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?NoC - Inadequate

Vermeer 1996

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study:yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: no
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 191
Treatment setting: Department of Dermatology (hospital)


Interventionsa. Terbinafine cream
Duration: one week plus one week Placebo
Frequency:
b. Miconazole cream
Duration: four weeks
Frequency:


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, vesiculation


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Weller 1998

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study; yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: yes
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: no
Number of drop outs stated: no


ParticipantsTotal evaluable sample size; 35

Exclusion criteria;
psoriasis, treatment with antifungals, and steroids in previous weeks. Topical antifungals within 1 week or oral drugs within weeks.


Interventionsa. Salicylic acid 3% + Nitrite acid 3% 2 x daily for 4 weeks

Salicylic acid 3%
2 x daily for 4 weeks.


OutcomesPrimary outcomes; cure

Secondary outcomes; clinical signs; scaling, pruritis, masceration, erythema, blistering, crusting, fissures and burning


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Woscoff 1986

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: no Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described:
Assessment of compliance: not stated
Intention to treat analysis: not stated
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: no
Adverse events reported: yes
Number of drop outs stated: yes


ParticipantsTotal evaluable sample size: 43
Exclusion criteria: Extensive chronic tinea pedis of more than six months, antifungal therapy used within one week prior to study


Interventionsa. Sulconazole nitrate 1% cream
Duration: three weeks
Frequency: applied twice daily
b. Miconazole nitrate 2% cream
Duration: three weeks
Frequency: applied twice daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
- itching, erythema, scaling, maceration
Adverse events: b: severe fissuring ansd desquamation, severe burning, erythema and pruritus


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Zaug 1992

MethodsRCT
Study aim clearly defined: yes
Blinded assessor of primary outcome: not stated
Double blind study: yes
Participants comparable at baseline for age: yes Sex: yes Duration of complaint: not stated
Inclusion and exclusion criteria specified: yes
Interventions well described: yes
Assessment of compliance: not stated
Intention to treat analysis: yes
A Priori sample size calculation: not stated
Fungi identified: yes
Distribution of species between groups: yes
Adverse events reported: yes
Number of drop outs stated: no


ParticipantsTotal evaluable sample size: 337
Exclusion criteria: onychomycosis, trichomycosis. Use of antifungal within two weeks prior to study
Treatment setting: 24 centers in Europe and Latin America


Interventionsa. Amorolfine 0.125% cream
Duration: two - six weeks
Frequency: applied once daily
b. Amorolfine 0.25% cream
Duration: two - six weeks
Frequency: applied once daily
c. Amorolfine 0.5% cream
Duration: two - six weeks
Frequency: applied once daily


OutcomesPrimary outcome: cure
Secondary Outcomes: Signs and symptoms
Adverse events: a. 5 b. 4 c. 0


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Albanese 1992Looks at preventative effects rather than curative

Alexander 1972Combined data

Aly 1994Nine patients with yeast only at baseline

Arenas 1991Oral versus topical

Athow Frost 1986Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Avlia 1985Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Baran 2000Compares oral versus topical treatments

Barnetson 1998Oral versus topical treatments

Bjornberg 1986Cannot separate mycological results for tinea pedis from tinea cruris

Clayton 1982Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Cuce 1980Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Cuce 1989No results for culture are given, only microscopy

Daily 1985Positive culture and or KOH at baseline

Del Palacio 1989Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Del Palacio 1991Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Del Palacio 1992Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Del Palacio 1999Combined for candida and dermatophyte infections and sites.

Del Palacio 2000Combined data for candida and dermatophyte infections

Del Palacio A 1992Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Duncan 1975Only half participants had positive culture at entry

Effendy 1987Cannot separate mycological results for dermatophytes from those related to yeasts and moulds

Evans E 1994Duplicate study

Fredriksson 1972Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Fredriksson 1974Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body and those infected with candida infection

Fredriksson 1977Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Fredriksson 1982Microscopy was not performed at baseline

Friedman 1997Oral versus topical treatments. Combined data for finger and toe nails

Fulton 1975Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Galimberti 1984Looks at preventative effects rather than curative

Gip 1983Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Greer 1986Duplicate study

Greer 1987+ve KOH and or culture

Grigoriu 1983Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Grooten 1992Combined data

Kashin 1985There is no definate end of treatment time from which data can be extracted

Katayama 1987No culture assessment is made

Kates 1990Looks at the effects on bacterial infection, not fungal infection

Katz 1972Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Koca 2001Experimental agent is an antiperspirant (aluminium hyroxychloride).

Lassus 1983Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Lassus 1988Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Lauharanta 1992Results not clear

Lebwohl 2001Definitions of population unclear

Lestienne 1982The written report of the study is too confusing to be able to extract the appropriate data

Li 2001Combined data for hands and feet infections

Lison 1985No mycological assessment was carried out

Lynfield 1974Compares systemic treatment with topical treatment

Maibach 1978Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

McVie 1986Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Meinicke 1985Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Mertens 1976Study looks at bacterial infection as well as fungal infection and does not separate the results

Nolting 1992Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Nolting 1993No clear treatment time given
Mycology results are not clear
Only treatment groups one and two are double blind, not group three

Ortiz 1978Incomplete data for diagnosis at entry

Oyeka 1991Cannot separate mycological results for tinea pedis of the skin from infection of the nail

Pariser 1994Detailed numerical reults are not given

Patel 1999One hundred and four (104/217) only had culture confirmed at baseline. No microscopy for any participant

Privat 1982No microscopy

Qadripur 1984Cannot separate mycological results for tinea pedis from those related to fungal infection elsewhere on the body

Reinel 1992Combined finger and toenail data

Reinel 1992aDuplicate report of Reinel 1992

Ruping 1993Combined finger and toenail data

Saple 2001Data combined for three sites; tinea pedis, tinea cruris, tinea corporis

Shellow 1982Culture is used to identify pathogens at baseline but not to assess outcome

Smith 1974Results for mycological cure do not separate out those for tinea pedis from tinea cruris

Smith 1977bData extracted for negative culture only

Stettendorf 1983Cannot separate tinea pedis results from those of tinea corporis and inguilalis

Suschka 2001Only 56% in Clotrimazole group and 60% in ketoconazole group had + ve test results for dermatophytes.

Tanenbaum 1982Combined data for dermatophytes and candida

Tanenbaum 1983Studies effect of treatment on candidiasis, not dermatophytes

Tanuma 2001Fungi demnstrated by direct microscopic exam OR culture

Terragni 1993Combined finger and toenail data

Thomas 1976Unit of analysis sites not patients unclear as to the numbers of units in study

Thomas 1986Unit of analysis site not patient

Tschen 1979Only 63/90 had + culture at baseline

Tsuboi 1996Diagnosis only established by KOH

Weil 1996Study only looks at culture results and not mycology. The data combines that of dermatophytes and yeasts.

Zaug 1995Oral versus topical

 
Comparison 1. Allylamines vs Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure9928Risk Ratio (M-H, Random, 95% CI)0.69 [0.56, 0.87]

    1.1 Naftifine vs Placebo
5612Risk Ratio (M-H, Random, 95% CI)0.75 [0.61, 0.93]

    1.2 Terbinafine vs Placebo
4316Risk Ratio (M-H, Random, 95% CI)0.58 [0.31, 1.08]

 2 Medium term (6 weeks) treatment failure111116Risk Ratio (M-H, Random, 95% CI)0.33 [0.24, 0.44]

    2.1 Naftifine (tx 4 weeks) vs Placebo
5607Risk Ratio (M-H, Random, 95% CI)0.42 [0.30, 0.59]

    2.2 Terbinafine (tx 1 week) vs Placebo
2229Risk Ratio (M-H, Random, 95% CI)0.16 [0.09, 0.26]

    2.3 Terbinafine (tx 2 weeks) vs Placebo
2240Risk Ratio (M-H, Random, 95% CI)0.36 [0.27, 0.48]

    2.4 Terbinafine (tx 4 weeks) vs Placebo
240Risk Ratio (M-H, Random, 95% CI)0.18 [0.04, 0.82]

 3 Medium term (6 weeks) treatment failure. Only >80% follow-up included9876Risk Ratio (M-H, Random, 95% CI)0.31 [0.21, 0.45]

    3.1 Naftifine (tx 4 weeks) vs Placebo
5607Risk Ratio (M-H, Random, 95% CI)0.42 [0.30, 0.59]

    3.2 Terbinafine (tx 1 week) vs Placebo
2229Risk Ratio (M-H, Random, 95% CI)0.16 [0.09, 0.26]

    3.3 Terbinafine (tx 4 weeks) vs Placebo
240Risk Ratio (M-H, Random, 95% CI)0.18 [0.04, 0.82]

 
Comparison 2. Azoles (tx 4-6 weeks) vs Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure5329Risk Ratio (M-H, Random, 95% CI)0.59 [0.43, 0.82]

    1.1 Bifonazole vs Placebo
4176Risk Ratio (M-H, Random, 95% CI)0.52 [0.37, 0.73]

    1.2 Oxiconazole vs Placebo
1153Risk Ratio (M-H, Random, 95% CI)0.79 [0.61, 1.02]

 2 Medium term (6 weeks) treatment failure131235Risk Ratio (M-H, Random, 95% CI)0.40 [0.35, 0.46]

    2.1 Bifonazole (tx 4 weeks) vs Placebo
4182Risk Ratio (M-H, Random, 95% CI)0.36 [0.20, 0.67]

    2.2 Clotrimazole (tx 4-6 weeks) vs Placebo
3371Risk Ratio (M-H, Random, 95% CI)0.42 [0.27, 0.64]

    2.3 Miconazole nitrate (tx 4 weeks) vs Placebo
254Risk Ratio (M-H, Random, 95% CI)0.41 [0.14, 1.14]

    2.4 Oxiconazole (tx 4 weeks) vs Placebo
2451Risk Ratio (M-H, Random, 95% CI)0.37 [0.30, 0.46]

    2.5 Sulconazole nitrate (tx 4-6 weeks) vs Placebo
1117Risk Ratio (M-H, Random, 95% CI)0.48 [0.31, 0.75]

    2.6 Ticonazole (tx 4-6 weeks) vs Placebo
160Risk Ratio (M-H, Random, 95% CI)0.37 [0.22, 0.62]

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included6448Risk Ratio (M-H, Random, 95% CI)0.43 [0.34, 0.53]

    3.1 Clotrimazole (tx 6 weeks) vs Placebo
163Risk Ratio (M-H, Random, 95% CI)0.56 [0.32, 0.98]

    3.2 Miconazole nitrate (tx 4 weeks) vs Placebo
254Risk Ratio (M-H, Random, 95% CI)0.41 [0.14, 1.14]

    3.3 Oxiconazole (tx 4 weeks) vs Placebo
1154Risk Ratio (M-H, Random, 95% CI)0.34 [0.23, 0.52]

    3.4 Sulconazole nitrate (tx 4-6 weeks) vs Placebo
1117Risk Ratio (M-H, Random, 95% CI)0.48 [0.31, 0.75]

    3.5 Ticonazole (tx 4-6 weeks) vs Placebo
160Risk Ratio (M-H, Random, 95% CI)0.37 [0.22, 0.62]

 
Comparison 3. Other topical antifungal treatments vs Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Butenafine vs Placebo
3391Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.78]

    1.2 Ciclopiroxolamine vs Placebo
1168Risk Ratio (M-H, Random, 95% CI)0.43 [0.27, 0.68]

    1.3 Undecanoates vs Placebo
185Risk Ratio (M-H, Random, 95% CI)0.14 [0.06, 0.31]

 2 Medium term (6 weeks) treatment failure9Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Butenafine (tx 1 week) vs Placebo
1271Risk Ratio (M-H, Random, 95% CI)0.33 [0.24, 0.45]

    2.2 Butenafine (tx 4 weeks) vs Placebo
180Risk Ratio (M-H, Random, 95% CI)0.19 [0.08, 0.43]

    2.3 Ciclopiroxolamine (tx 4 weeks) vs Placebo
2461Risk Ratio (M-H, Random, 95% CI)0.27 [0.11, 0.66]

    2.4 Tea tree oil (tx 4 weeks) vs Placebo
2185Risk Ratio (M-H, Random, 95% CI)0.73 [0.48, 1.11]

    2.5 Tolciclate (tx 6 weeks) vs Placebo
140Risk Ratio (M-H, Random, 95% CI)0.04 [0.00, 0.63]

    2.6 Tolnaftate (tx 4 weeks) vs Placebo
2115Risk Ratio (M-H, Random, 95% CI)0.30 [0.13, 0.72]

    2.7 Undecanoates (tx 4-6 weeks) vs Placebo / no treatment
285Risk Ratio (M-H, Random, 95% CI)0.29 [0.12, 0.70]

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Ciclopiroxolamine (tx 4 weeks) vs Placebo
1144Risk Ratio (M-H, Random, 95% CI)0.39 [0.23, 0.66]

    3.2 Tea tree oil (tx 4 weeks) vs Placebo
171Risk Ratio (M-H, Random, 95% CI)0.88 [0.68, 1.16]

    3.3 Tolciclate (tx 6 weeks) vs Placebo
140Risk Ratio (M-H, Random, 95% CI)0.04 [0.00, 0.63]

    3.4 Tolnaftate (tx 4 weeks) vs Placebo
2115Risk Ratio (M-H, Random, 95% CI)0.30 [0.13, 0.72]

    3.5 Undecanoates (tx 4-6 weeks) vs Placebo / no treatment
2125Risk Ratio (M-H, Random, 95% CI)0.24 [0.08, 0.74]

 
Comparison 4. Comparisons between different allylamines or allylamine regimes

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure2Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Naftifine once daily vs Naftifine twice daily
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.2 Naftifine vs Terbinafine
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Medium term (6 weeks) treatment failure4Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Naftifine once daily (tx 4 weeks) vs Naftifine twice daily (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Naftifine (tx 2 weeks) vs Terbinafine (tx 2 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Terbinafine (tx 5-7 days) vs Terbinafine (tx 1 -3 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.4 Terbinafine (tx 4 weeks) vs Terbinafine (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.3Risk Ratio (M-H, Random, 95% CI)Totals not selected

    3.1 Naftifine once daily (tx 4 weeks) vs Naftifine twice daily (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.2 Naftifine (tx 2 weeks) vs Terbinafine (tx 2 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.3 Terbinafine (tx 5-7 days) vs Terbinafine (tx 1-3 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 4 Long term (12 weeks onwards) treatment failure2Risk Ratio (M-H, Random, 95% CI)Totals not selected

    4.1 Terbinafine (tx 5-7 days) vs Terbinafine (tx 1 -3 days)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.2 Terbinafine (tx 4 weeks) vs Terbinafine (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 5. Comparisons between different azoles or azole regimes

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Clotrimazole vs Econazole
2497Risk Ratio (M-H, Random, 95% CI)1.13 [0.92, 1.39]

    1.2 Econazole gel vs Econazole cream
1329Risk Ratio (M-H, Random, 95% CI)0.86 [0.60, 1.23]

    1.3 Miconazole nitrate vs Sulconazole nitrate
141Risk Ratio (M-H, Random, 95% CI)6.30 [0.83, 47.80]

    1.4 Oxiconazole twice daily vs Oxiconazole once daily
1105Risk Ratio (M-H, Random, 95% CI)1.05 [0.74, 1.49]

 2 Medium term (6 weeks) treatment failure12Risk Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Bifonazole (tx 3 weeks) vs Bifonazole removed after 1 hr (tx 3 weeks)
173Risk Ratio (M-H, Random, 95% CI)4.34 [0.51, 37.01]

    2.2 Bifonazole (tx 3 weeks) vs Croconazole (tx 3 weeks)
136Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Bifonazole (tx 3 weeks) vs Miconazole (tx 3 weeks)
128Risk Ratio (M-H, Random, 95% CI)0.8 [0.27, 2.37]

    2.4 Clotrimazole (tx 4 weeks) vs Clotrimazole (tx 1 week)
189Risk Ratio (M-H, Random, 95% CI)0.36 [0.18, 0.72]

    2.5 Clotrimazole (tx 2-4 weeks) vs Econazole (tx 2-4 weeks)
2497Risk Ratio (M-H, Random, 95% CI)0.95 [0.31, 2.88]

    2.6 Econazole gel (tx 2 weeks) vs Econazole cream (tx 2 weeks)
1313Risk Ratio (M-H, Random, 95% CI)0.78 [0.53, 1.16]

    2.7 Clotrimazole (tx 4 weeks) vs Ketoconazole (tx 4 weeks)
1100Risk Ratio (M-H, Random, 95% CI)1.06 [0.63, 1.76]

    2.8 Miconazole (tx 6 weeks) vs Ticonazole (tx 6 weeks)
2120Risk Ratio (M-H, Random, 95% CI)1.29 [0.77, 2.16]

    2.9 Oxiconazole+fluctic (tx 4 weeks) vs Oxiconazole (tx 4 weeks)
1201Risk Ratio (M-H, Random, 95% CI)0.53 [0.33, 0.87]

    2.10 Oxiconazole twice daily (tx 4 weeks) vs Oxiconazole once daily (tx 4 weeks)
1110Risk Ratio (M-H, Random, 95% CI)1.23 [0.61, 2.46]

    2.11 Bifonazole (tx 4 weeks) vs flutrimazole (tx 4 weeks)
1264Risk Ratio (M-H, Random, 95% CI)0.21 [0.14, 0.31]

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.9Risk Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Bifonazole (tx 3 weeks) vs Bifonazole removed after 1 hr (tx 3 weeks)
173Risk Ratio (M-H, Random, 95% CI)4.34 [0.51, 37.01]

    3.2 Bifonazole (tx 3 weeks) vs Croconazole (tx 3 weeks)
136Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.3 Bifonazole (tx 3 weeks) vs Miconazole (tx 3 weeks)
128Risk Ratio (M-H, Random, 95% CI)0.8 [0.27, 2.37]

    3.4 Clotrimazole (tx 2-4 weeks) vs Econazole (tx 2-4 weeks)
2497Risk Ratio (M-H, Random, 95% CI)0.95 [0.31, 2.88]

    3.5 Econazole gel (tx 2 weeks) vs Econazole cream (tx 2 weeks)
1313Risk Ratio (M-H, Random, 95% CI)0.78 [0.53, 1.16]

    3.6 Miconazole (tx 6 weeks) vs Ticonazole (tx 6 weeks)
2120Risk Ratio (M-H, Random, 95% CI)1.29 [0.77, 2.16]

    3.7 Oxiconazole+fluctic (tx 4 weeks) vs Oxiconazole (tx 4 weeks)
1201Risk Ratio (M-H, Random, 95% CI)0.53 [0.33, 0.87]

    3.8 Oxiconazole twice daily (tx 4 weeks) vs Oxiconazole once daily (tx 4 weeks)
1110Risk Ratio (M-H, Random, 95% CI)1.23 [0.61, 2.46]

 4 Long term (12 weeks onwards) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    4.1 Clotrimazole (tx 4 weeks) vs Clotrimazole (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 6. Allylamines 1-2 weeks vs Azoles 1-2 weeks

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure101519Risk Ratio (M-H, Random, 95% CI)0.86 [0.70, 1.06]

    1.1 Naftifine vs Bifonazole
198Risk Ratio (M-H, Random, 95% CI)1.07 [0.78, 1.47]

    1.2 Naftifine vs Clotrimazole
4617Risk Ratio (M-H, Random, 95% CI)0.78 [0.53, 1.14]

    1.3 Naftinfine/Terbinane vs Oxiconazole
190Risk Ratio (M-H, Random, 95% CI)0.84 [0.65, 1.09]

    1.4 Terbinafine vs Bifonazole
142Risk Ratio (M-H, Random, 95% CI)0.31 [0.14, 0.66]

    1.5 Terbinafine vs Clotrimazole
3672Risk Ratio (M-H, Random, 95% CI)1.16 [0.86, 1.55]

 2 Medium term (6 weeks) treatment failure2173Risk Ratio (M-H, Random, 95% CI)0.34 [0.22, 0.52]

    2.1 Naftinfine/Terbinane vs Oxiconazole
190Risk Ratio (M-H, Random, 95% CI)0.33 [0.20, 0.56]

    2.2 Terbinafine vs Clotrimazole
183Risk Ratio (M-H, Random, 95% CI)0.36 [0.17, 0.75]

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.190Risk Ratio (M-H, Random, 95% CI)0.33 [0.20, 0.56]

    3.1 Naftinfine/Terbinane 2 weeks vs Oxiconazole 2 weeks
190Risk Ratio (M-H, Random, 95% CI)0.33 [0.20, 0.56]

 4 Long term (12 weeks onwards) treatment failure175Risk Ratio (M-H, Random, 95% CI)0.28 [0.14, 0.58]

    4.1 Terbinafine vs Clotrimazole
175Risk Ratio (M-H, Random, 95% CI)0.28 [0.14, 0.58]

 
Comparison 7. Allylamines 1 week vs Azoles 4 weeks

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Medium term (6 weeks) treatment failure5962Risk Ratio (M-H, Random, 95% CI)0.75 [0.33, 1.72]

    1.1 Terbinafine vs Clotrimazole
4771Risk Ratio (M-H, Random, 95% CI)0.64 [0.24, 1.75]

    1.2 Terbinafine vs Miconazole
1191Risk Ratio (M-H, Random, 95% CI)1.45 [0.36, 5.91]

 2 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.3685Risk Ratio (M-H, Random, 95% CI)0.50 [0.10, 2.54]

    2.1 Terbinafine vs Clotrimazole
3685Risk Ratio (M-H, Random, 95% CI)0.50 [0.10, 2.54]

 
Comparison 8. Allylamines 4-6 weeks vs Azoles 4-6 weeks

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Medium term (6 weeks) treatment failure91003Risk Ratio (M-H, Random, 95% CI)0.63 [0.42, 0.94]

    1.1 Naftifine vs Bifonazole
197Risk Ratio (M-H, Random, 95% CI)1.96 [0.63, 6.08]

    1.2 Naftifine vs Clotrimazole
6775Risk Ratio (M-H, Random, 95% CI)0.53 [0.34, 0.81]

    1.3 Terbinafine vs Bifonazole
142Risk Ratio (M-H, Random, 95% CI)Not estimable

    1.4 Terbinafine vs Clotrimazole
189Risk Ratio (M-H, Random, 95% CI)1.07 [0.44, 2.60]

 2 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.6854Risk Ratio (M-H, Random, 95% CI)0.55 [0.34, 0.89]

    2.1 Naftifine vs Bifonazole
197Risk Ratio (M-H, Random, 95% CI)1.96 [0.63, 6.08]

    2.2 Naftifine vs Clotrimazole
5757Risk Ratio (M-H, Random, 95% CI)0.48 [0.30, 0.76]

 3 Long term (12 weeks onwards) treatment failure2141Risk Ratio (M-H, Random, 95% CI)0.47 [0.22, 1.02]

    3.1 Naftifine vs Clotrimazole
156Risk Ratio (M-H, Random, 95% CI)0.46 [0.08, 2.56]

    3.2 Terbinafine vs Clotrimazole
185Risk Ratio (M-H, Random, 95% CI)0.47 [0.20, 1.13]

 
Comparison 9. Allylamines vs Other antifungal topical skin treatments

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Terbinafine vs Butenafine
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Medium term (6 weeks) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Terbinafine 1% (tx 1 week) vs Ajoene 0.6% (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Terbinafine 1% (tx 1 week) vs Ajoene 1% (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 10. Azoles vs Other antifungal topical skin treatments

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Clotrimazole vs Ciclopiroxolamine
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Medium term (6 weeks) treatment failure2Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Bifonazole (tx 6 weeks) vs Amorolfine (tx 6 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Clotrimazole (tx 4 weeks) vs Ciclopirox olamine (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 3 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.2Risk Ratio (M-H, Random, 95% CI)Totals not selected

    3.1 Bifonazole (tx 6 weeks) vs Amorolfine (tx 6 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    3.2 Clotrimazole (tx 4 weeks) vs Ciclopirox olamine (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 11. Comparisons between other topical antifungal treatments

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short term (2 weeks) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Salicylic acid + nitrite vs Salicylic acid
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 2 Medium term (6 weeks) treatment failure7Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Ajoene 1.0% (tx 1 week) vs Ajoene 0.6% (tx 1 week)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.2 Amorolfine 0.25 (tx 4 weeks) vs Amorolfine 0.125 (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.3 Amorolfine 0.5 (tx 4 weeks) vs Amorolfine 0.125 (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.4 Amorolfine 0.5 (tx 4 weeks) vs Amorolfine 0.25 (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.5 Haloprogen (tx 4 weeks) vs Tolnaftate (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.6 Salicylic acid + nitrite (tx 4 weeks) vs Salicylic acid (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.7 Tea tree oil 50% (tx 4 weeks) vs Tea tree oil 25% (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.8 Tea tree oil (tx 4 weeks) vs Tolnaftate (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    2.9 Tolnaftate (tx 4 weeks) vs Undecylenate acid (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 3 Long term (12 weeks onwards) treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    3.1 Whitfields (tx 8 weeks) vs Varotin(tx 8 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 4 Medium term (6 weeks) treatment failure. Only >=80% follow-up included.5Risk Ratio (M-H, Random, 95% CI)Totals not selected

    4.1 Amorolfine 0.25 (tx 4 weeks) vs Amorolfine 0.125 (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.2 Amorolfine 0.5 (tx 4 weeks) vs Amorolfine 0.125 (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.3 Amorolfine 0.5 (tx 4 weeks) vs Amorolfine (tx 0.25 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.4 Haloprogen (tx 4 weeks) vs Tolnaftate (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.5 Salicylic acid + nitrite (tx 4 weeks) vs Salicylic acid (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.6 Tea tree oil (tx 4 weeks) vs Tolnaftate (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

    4.7 Tolnaftate (tx 4 weeks) vs Undecylenate acid (tx 4 weeks)
1Risk Ratio (M-H, Random, 95% CI)Not estimable

 
Comparison 12. Treatments for onychomycosis (nail infections)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Treatments versus placebo, treatment failure4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Ciclopiroxolamine versus placebo. Outcomes at 48 weeks
2460Risk Ratio (M-H, Random, 95% CI)0.32 [0.20, 0.52]

    1.2 Fungoid Tincture versus Placebo. Outcomes at 12 months
120Risk Ratio (M-H, Random, 95% CI)0.17 [0.02, 1.14]

    1.3 Butenafine 2% & tea tree oil vs placebo. Outcomes at 36 weeks
160Risk Ratio (M-H, Random, 95% CI)0.03 [0.00, 0.47]

 2 Comparisons between active treatments, treatment failure1Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Amorolfine 5% + methylene versus Amorolfine 5% + ethanol outcomes at 3 days
1Risk Ratio (M-H, Random, 95% CI)Not estimable