Oral treatments for fungal infections of the skin of the foot.

 

Characteristics of included studies [ordered by study ID]

DeKeyser 1994

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: NS inc & ex crit: yes interv describe: yes compliance: yes ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: yes drop outs: yes
Participants	original sample: 366 total evaluable sample: 117 a: 51; b: 66 exclusion criteria: no systemic antifungals taken three months before study, no topical antifungals taken two weeks before study
Interventions	a: terbinafine 250 mg one active tablet and one placebo capsule taken orally daily for 2 weeks. b: itraconazole 100 mg one active capsule and one placebo tablet taken orally daily for 2 weeks.
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, erythema, scaling, vesiculation, pustules, crusting, pruritus adverse events: a: 23 b: 10
Notes	tinea pedis only 11 withdrawals accounted for.
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Difonzo 1995

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: yes inc & ex crit: yes interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	treatment setting: multicentre original sample: 37 total evaluable sample: 35 a: 17; b: 18 exclusion criteria: no systemic antifungals taken one month before study
Interventions	a: itraconazole 100mg one capsule taken daily for 30 days b: fluconazole 50 mg one capsule taken orally daily for 30 days.
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, erythema, vesicles, desquamation, maceration, fissuring. adverse events: a: 1, b:5
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Fischbein 1992

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: yes inc & ex crit: yes interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: data combined for multiple sites recurrence status: NS drop outs: no
Participants	treatment setting: multicentre original sample: 189 total evaluable sample: 53 a: 27; b: 26 exclusion criteria: no systemic or topical antifungals taken three days before study
Interventions	a: fluconazole 50 mg once daily for an average period of 4 weeks b: ketoconazole 200mg once daily for an average of 4 weeks
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, erythema, vesicles, desquamation, maceration, fissuring. adverse events: reported for multiple sites on the body
Notes	fungal skin infection across multiple sites - tinea pedis data separated out
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Hay 1995

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes sex: yes duration: yes inc & ex crit: yes interv describ: yes compliance: no ITT: yes sample calc: yes: fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	original sample: 190 total evaluable sample: 129 a: 65; b: 64 exclusion criteria:no systemic antifungals taken six weeks before study, no topical antifungals taken seven days before study, no terbinafine or itraconazole taken for three months before study.
Interventions	a: terbinafine 250 mg one active tablet and one placebo capsule taken orally for 14 days, then one placebo tablet and one placebo capsule taken orally daily for 14 days. b: itraconazole 100 mg one active capsule and one placebo tablet taken orally daily for 28 days.
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome:(i) clinical signs and symptoms: erythema, scaling, vesiculation, pruritus. (ii) tolerability adverse events: a: 52, b: 46
Notes	plantar type tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Kim 1993

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Methods	RCT Aim clear: NS blinding: NS double blind study: yes comparability, age: yes, sex: yes duration: NS inc & ex crit: NS interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: no adv events: yes recurrence status: no drop outs: yes
Participants	original sample: 66 total evaluable sample: 44; a 22; b 22 exclusion criteria: concomitant antifungal therapy not allowed
Interventions	a: terbinafine 250 mg taken orally once daily for 2 weeks followed by placebo taken orally once daily for 2 weeks. b: itraconazole 100 mg tablet taken orally once daily for 4 weeks.
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, erythema, scaling, vesiculation, pustules, crusting, pruritus. adverse events: a: 2, b: 3
Notes	moccasin type tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Nozickova 1998

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: NS inc & ex crit: NS interv describ: yes compliance: NS ITT: yes sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: stated as undertaken but not reported drop outs: no
Participants	treatment setting: hospital initial sample: 114 total evaluable sample:63; a: 34; b: 29 exclusion criteria: not stated
Interventions	a: fluconazole 150mg once weekly for a max. of 6 weeks b: fluconazole 50mg once daily for a max. of 6 weeks The intervention ceased when a cured condition was achieved
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical efficiency based on a cured condition and an assessment of clinical signs and symptoms. adverse events: (no of events) a: 2; b: 3 across all intervention groups
Notes	tinea pedis, tinea cruris, tinea corporis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Roberts 1987

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Methods	RCT Aim clear: NS blinding: NS double blind study: yes comparability, age: NS sex: NS, duration: yes inc & ex crit: NS interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: no recurrence status: no drop outs: no
Participants	treatment setting: hospital initial sample 29 total evaluable sample: 29; a:15; b: 14. exclusion criteria: not stated
Interventions	a: ketoconazole 200 mg once daily for 4 weeks b: griseofulvin 1000mg once daily for 4 weeks In both groups participants were offered further treatment of up to four weeks in duration if primary outcome of cure had not been achieved
Outcomes	Primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: peeling, maceration, fissuring, weeping, bleeding, itching, burning. adverse events - not reported
Notes	tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Savin 1990a

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Methods	RCT Aim clear: yes blinding:NS double blind study: yes comparability, age: yes, sex: yes, duration: yes inc & ex crit: yes interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	treatment setting: two treatment centres Initial sample: 50 total evaluable sample: 41; a: 23; b: 18. exclusion criteria: any radiotherapy, treatment with cytostatic or immunosuppressant drugs, antibiotics, antifungals, antivirals or antiparasitics within two weeks prior to study
Interventions	a. terbinafine 125mg taken twice daily for 6 weeks b. placebo taken twice daily for 6 weeks
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: erythema, scaling, vesiculation, pustules, pruritus. adverse events: number of patients (no. of events) a: 3(3) ; b: 3(3).
Notes	moccasin type tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Savin 1990b

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Methods	RCT Aim clear: yes blinding:NS double blind study: yes comparability, age: yes, sex: yes, duration: yes inc & ex crit: yes interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	Initial sample: 36 total evaluable sample: 28; a: 16; b: 12. exclusion criteria: no topical agents taken two weeks , and no systemic agents four weeks before the study starts
Interventions	a. terbinafine 125mg taken twice daily for 6 weeks b. griseofulvin 250mg (microsize) taken twice daily for 6 weeks
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: erythema, pustules, pruritus, desquamation, hyperkeratosis adverse events: number of patients (no. of events) a:(2); b: (4)
Notes	moccasin type tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Svejgaard 1998

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: NS inc & ex crit: yes interv describ: yes compliance: NS ITT: yes sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: stated on entry to trial drop outs: yes
Participants	treatment setting: multicentre initial sample: 72 total evaluable sample: 69; a: 34; b: 35. exclusion criteria: no systemic agent six months before study starts
Interventions	a. itraconazole 200mg taken twice daily for 1 week b. placebo taken twice daily for one week
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, eythema, scaling, vesicular, pustules, crusting, pruritus, itching, burning. Clinical global evaluation was reported adverse events (no of events) a: (7) b: (5)
Notes	moccasin type tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Voravutinon 1993

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: yes inc & ex crit: NS interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	treatment setting: hospital dermatology outpatients Initial sample:50 total evaluable sample: 49; a: 23; b; 26. exclusion criteria: not stated
Interventions	a. terbinafine 250mg taken once daily for 2 weeks b. itraconazole 100mg taken once daily for 4 weeks
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: exudation, erythema, scaling, vesiculation, crusting, pruritus. adverse events: number of patients (no. of events) a: (2); b: (3)
Notes	tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Widyanto 1993

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Methods	RCT Aim clear: yes blinding: NS double blind study: yes comparability, age: yes, sex: yes, duration: NS inc & ex crit: yes interv describ: yes compliance: NS ITT: NS sample calc: NS fungi identified: yes species btwn gps: yes adv events: yes recurrence status: NS drop outs: yes
Participants	Initial sample: 55 total evaluable sample: 43; a:21; b: 22. exclusion criteria: no antifungals taken two weeks prior to start of study
Interventions	a. griseofulvin 500mg per day for 4 weeks b. terbinafine 250mg per day for 4 weeks
Outcomes	primary outcome: cure, demonstrated by negative results on microscopy and no growth of dermatophyte in culture secondary outcome: clinical signs and symptoms: erythema, vesiculation, pustules, crusting, pruritus, maceration, squama. adverse events: none
Notes	tinea pedis
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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 aim clear - study aim clearly described
blinding = blinded assessor of primary outcome
comparability - participants comparable at baseline for age, sex and duration of complaint
inc & ex crit - inclusion and exclusion criteria specified
interv describ - interventions well described
compliance - assessment of compliance
ITT - intention to treat analysis
sample calc - a priori sample size calculation undertaken
species btwn gps - distribution of species between groups
adv events - adverse events reported
drop outs -- number of drop outs stated

 

Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Barnetson 1998	combined data for topical and oral treatments
Degreef 1987	combined data for foot and hand infections
Del Palacio 1993	combined data for foot and hand infections
Hay 1991	combined data for foot and hand infections
Jolly 1983	combined data
Legendre 1980	not enough data reported, unclear length of treatment time
Lynfield 1974	combined data for topical and oral treatments
Russell 1960	no microscopy and culture as an outcome
Savin 1989	duplicate reporting of trial
Savin/b 1990	duplicate reporting of trial
Schuller 1998	combined data for foot and hand infections
Tausch 1998	combined data for foot and hand infections
Van Hecke 1988	combined data for foot and hand infections
Wishart 1994	combined data for foot and hand infections
Won 1993	no microscopy and culture as an outcome

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Comparison 1. ANTIFUNGAL vs PLACEBO

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Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

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 1 Cured (itraconazole, 400 mg/day vs placebo)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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1.1 week 4

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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1.2 week 8

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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1.3 week 9

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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 2 Cured (terbinafine, 250 mg/day vs placebo)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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2.1 week 6

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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2.2 week 8

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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Comparison 2. DIFFERENT TYPES OF ANTIFUNGALS

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Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

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 1 Cured (terbinafine, 250 mg/day vs itraconazole, 100 mg/day)

4

Risk Difference (M-H, Random, 95% CI)

Subtotals only

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1.1 week 2

4

339

Risk Difference (M-H, Random, 95% CI)

0.01 [-0.05, 0.07]

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1.2 week 4

3

222

Risk Difference (M-H, Random, 95% CI)

0.08 [-0.05, 0.20]

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1.3 week 8

3

295

Risk Difference (M-H, Random, 95% CI)

0.12 [-0.08, 0.33]

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1.4 week 12 plus

1

129

Risk Difference (M-H, Random, 95% CI)

0.10 [-0.05, 0.25]

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1.5 common treatment length (4 weeks)

3

222

Risk Difference (M-H, Random, 95% CI)

0.05 [-0.06, 0.17]

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 2 Cured (itraconazole, 100 mg/day vs fluconazole, 50 mg/day)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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2.1 week 4

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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2.2 week 10

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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 3 Cured (fluconazole, 50 mg/day vs ketoconazole, 200 mg/day)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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3.1 week 4

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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3.2 week 7

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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 4 Cured (ketaconazole, 200 mg/day vs griseofulvin, 1000 mg/day)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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4.1 week 2

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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4.2 week 4

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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4.3 week 8

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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 5 Cured ( terbinafine, 250 mg vs griseofulvin, 500 mg)

2

Risk Difference (M-H, Fixed, 95% CI)

Subtotals only

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5.1 week 4

1

43

Risk Difference (M-H, Fixed, 95% CI)

0.53 [0.28, 0.78]

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5.2 week 6

1

28

Risk Difference (M-H, Fixed, 95% CI)

0.69 [0.42, 0.96]

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5.3 week 8

1

28

Risk Difference (M-H, Fixed, 95% CI)

0.5 [0.22, 0.78]

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5.4 last outcome point

2

71

Risk Difference (M-H, Fixed, 95% CI)

0.52 [0.33, 0.71]

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 6 Cured (fluconazole, 150 mg/wk vs fluconazole, 50 mg/day)

1

Risk Difference (M-H, Fixed, 95% CI)

Totals not selected

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6.1 week 6

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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6.2 week 10

1

Risk Difference (M-H, Fixed, 95% CI)

Not estimable

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Comparison 3. PRESENTATION OF TINEA PEDIS

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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Plantar tinea pedis	2	173	Risk Difference (M-H, Random, 95% CI)	0.06 [-0.07, 0.20]
2 Mixed distribution of tinea pedis	2	166	Risk Difference (M-H, Random, 95% CI)	0.18 [-0.11, 0.47]

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Comparison 4. ADVERSE EVENTS AND LOSS TO FOLLOW-UP

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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Summary of adverse events reported for trials of tinea pedis			Other data	No numeric data

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Analysis 4.1 Comparison 4 ADVERSE EVENTS AND LOSS TO FOLLOW-UP, Outcome 1 Summary of adverse events reported for trials of tinea pedis.
Summary of adverse events reported for trials of tinea pedis

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Study	total no of ad event	n (eval / enrolled)
DeKeyser 1994	terbinafine 23 itraconazole 10	117 / 366
Difonzo 1995	itraconazole 1 fluconazole 5	35 / 37
Fischbein 1992	reported for multiple sites	53 / 189
Hay 1995	terbinafine 52 itraconazole 46	129 / 190
Kim 1993	terbinafine 2 itraconazole 3	44 / 66
Nozickova 1998	150 mg fluconazole 2 50 mg fluconazole 3	63 / 114
Roberts 1987	not reported	29 / 29
Savin 1990a	terbinafine 3 placebo 3	41 / 50
Savin 1990b	terbinafin 2 griseofulvin 4	28 / 36
Svejgaard 1998	itraconazole 7 placebo 5	69 / 72
Voravutinon 1993	terbinafine 2 itraconazole 3	49 / 50
Widyanto 1993	none reported	43 / 55

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