Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Lima (Perú)

• N = 50 (23 males, 27 females) participants

• Aged 1‐14

• Inclusion criteria: clinical and mycologic diagnosis of non‐inflammatory tinea capitis; weight > 10 kg; normal baseline laboratory evaluation (complete blood cell count, erythrocyte sedimentation rate, liver function tests and urinalysis)

• Exclusion criteria: antimycotic therapy during the month before consultation; bacterial superinfection, systemic illness or unknown intolerance or allergy to terbinafine or griseofulvin

• Fungi isolated

  • T. tonsurans: 74%

  • M. canis: 26%

• No mention of adherence assessment

Interventions

• Group 1: griseofulvin (microsize) tablet, 10‐20 kg: 125 mg/d; 20‐40 kg: 250 mg/d; > 40 kg: 500 mg/d, for 8 weeks (N = 25)

• Group 2: terbinafine tablet, 10‐20 kg: 62.5 mg/d; 20‐40 kg: 125 mg/d; > 40 kg: 250 mg/d, once a day for 4 weeks plus 4 weeks of placebo (N = 25)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 12 weeks

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: There was only one drop‐out (2%, 1/50). Although which group this drop‐out belonged to was unclear and ITT analysis was not performed, the proportion of missing outcomes compared with the observed event risk seemed to be not enough to have a clinically relevant impact on the intervention effect estimate.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: griseofulvin group: black dot 32% (8/25); white‐greyish hair 68% (17/25); terbinafine group: black dot 8% (2/25); white‐greyish hair 92% (23/25)

  • Age: griseofulvin group: 6.72; terbinafine group: 6.84

  • Sex: griseofulvin group: males: 10; females: 15; terbinafine group: males: 13; females: 12

  • Duration of complaint: from 1 week to 4 years

Methods

Single‐blind, parallel group RCT for 8 weeks

Participants

• Iran

• N = 40

• Aged between from 1 to 16; 80% were boys and 20% girls

• Inclusion criteria: clinical and mycologic diagnosis of non‐inflammatory tinea capitis

• Exclusion criteria: a history of allergy to imidazoles; use of oral antifungals within 8 weeks or use of topical antifungals within 4 weeks before screening; a history of congenital or acquired immunodeficiency or disorders affecting kidney or liver function; concurrent therapy with other drugs; and systemic illness

• Fungi isolated

  • T. verrucosum: fluconazole: 26.3%; griseofulvin: 52.4%; total: 40%

  • T. violaceum: fluconazole: 52.6%; griseofulvin: 28.6%; total: 40%

  • M. canis: fluconazole: 21.1%; griseofulvin: 19%; total: 20%

Interventions

• Group 1: griseofulvin 15 mg/kg/d for 6 weeks (N = 21)

• Group 2: fluconazole 5 mg/kg/d for 4 weeks (N = 19)

Outcomes

• The proportion of participants with complete cure after 8 weeks

• The frequency and type of adverse events

• Mycologic cure at the end of treatment

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: Participants were not blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Investigators were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 5 participants (12.5%, 5/40) were lost to follow‐up. It was unclear which group these drop‐outs belonged to. ITT analysis was not performed. The reason for drop‐outs was not clear.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: not mentioned

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability:

  • Mean age: griseofulvin (8.66); fluconazole (7.71)

  • Sex: griseofulvin (males: 17; females: 4), fluconazole (males: 15; females: 4)

  • Mean weight (kg): griseofulvin (23.61); fluconazole (21.60)

  • Severity of disease: similar in both groups at first examination

Methods

3‐arm, parallel group RCT for 1 year

Participants

• China (Kashgar)

• N = 88

• Aged 2‐14 years old. The mean ages were 8.42, 7.69, and 9.13 in the 3 groups, respectively.

• 78.3% males

• Inclusion criteria: "Children with age older than two years old, weight more than 10 kg, no apparent other diseases, not using any steroids, not taking antifungal drugs for 4 weeks, and renal functions were normal."

• Exlcusion criteria: "Children who did not return for observation on time, those who took other antifungal drugs locally and/or orally during treatment, and those who discontinued treatment due to side effects."

• Fungi isolated

  • T. violaceum: 55.1%

  • A. vanbreuseghemi: 30.6%

  • T. tonsurans: 14.3%

• Adherence assessment: not mentioned

Interventions

• Group 1: griseofulvin, doses of 20mg/kg/d, for 4 consecutive weeks (N = 19)

• Group 2: terbinafine, doses depend on weight:< 20 kg, 62.5 mg/d; 20‐40 kg, 125 mg/d; and > 40 kg, 250 mg/d, for 2 consecutive weeks (N = 27)

• Group 3: terbinafine, doses depend on weight:< 20 kg, 62.5 mg/d; 20‐40 kg, 125 mg/d; and > 40 kg, 250 mg/d, for 4 consecutive weeks (N = 23)

No co‐treatment

Outcomes

• Clinical cure rates at 2, 4, 8 weeks, and 1 year after therapy

• Clinical effectiveness rates at 2, 4, 8 weeks, and 1 year after therapy

• Mycological cure rates at 2, 4, 8 weeks, and 1 year after therapy

• The frequency and type of adverse events

• Percentage of drop‐outs as a surrogate for participant adherence

One of the primary outcomes of interest in this review (complete cure rate) was not reported in this study.

Notes

• The enrolled: 88 participants were randomised, 70 participants were evaluated for adverse events, 69 participants were evaluated for clinical results

• Funding: Novartis Pharmaceutica

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Whether the participants and personnel were blinded was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: Investigators were not blinded.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 12.5% (11/88) participants lost to follow‐up. It was unclear which group these drop‐outs belonged to. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: yes, there were no significant differences regarding to gender, weight, age, and severity of signs and symptoms

Methods

Multicentre, single‐blind, parallel group RCT for 10 weeks

Participants

• USA, Peru, UK, Egypt, Russia, and Sourth Africa

• N = 1549

• The mean age was 6.8 years (ranged from 4‐12 years). 62.2% males.

• Inclusion criteria: "Children were included if they were between 4 and 12 years of age and had a clinical diagnosis of tinea capitis confirmed by positive potassium hydroxide (KOH) microscopy at baseline."

• Exclusion criteria: "Patients with protocol‐defined clinically significant biochemistry and hematologic abnormalities were excluded from the study as were those with kerions requiring immediate treatment or treatment with systemic corticosteroids and/or systemic antibiotics, those with a condition or treatment that could interfere with evaluation of drug effect, or those with current or past liver disease. Other criteria for exclusion from study were presence of serious gastrointestinal disease, hypersensitivity to study agents, and history of systemic lupus erythematosus. Patients with systemic antifungal treatment or history of use of any other investigational agent within 2 months before screening; use of immunosuppressant, cytostatic, or radiation therapy within 1 month before screening; or topical treatment of the scalp within 1 week before baseline visit were also excluded from study participation."

• Fungi isolated

  • T. tonsurans 49.3%

  • T. violaceum 15.6%

  • M. canis 15.1%

  • M. audouini 1.5%

  • M. vanbreuseghemi 0.3%

  • T. mentagrophytes 0.2%

  • T. rubrum 0.2%

  • M. gypseum 0.1%

  • Other 6.5%

  • Negative 17.0%

• Adherence assessment: not mentioned

Interventions

• Group 1: terbinafine, doses of 5‐8 mg/kg for 6 weeks (N = 1040)

• Group 2: griseofulvin, doses of 10‐20 mg/kg for 6 weeks (N = 509)

No co‐treatment

Outcomes

• Complete cure rate at 10 weeks

• Clinical cure rate at 10 weeks

• Mycologic cure rate at 10 weeks

• The frequency and severity of adverse events

Notes

This article included 2 RCTs, but the results of the 2 RCTs were reported together.

Funding: Novartis Pharmaceuticals Corporation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 43): "Eligible patients were randomized in a 2:1 ratio to terbinafine and griseofulvin treatment arms, respectively (Fig 1). Patients were randomized to the lowest available randomization number at each site based on treatment allocation cards received by a pharmacist or designee at the site after they had fulfilled the inclusion/exclusion criteria".

Comment: Standared randomisation method was applied

Allocation concealment (selection bias)

Low risk

Quote (page 43): "Randomization data were accessible only to the dispenser of medication and were kept confidential until database lock."

Comment: The method for allocation concealment seemed to be adequate

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote (page 45): "Investigators and others performing assessments, recording data, or analysing data were blinded to treatment identity from the time of randomisation until database lock."

Comment: The method of blinding was not stated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote (page 45): "Investigators and others performing assessments, recording data, or analysing data were blinded to treatment identity from the time of randomisation until database lock."

Comment: The method of blinding was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 3.6% (56/1549) participants lost to follow‐up. Among them, 40 participants were in the terbinafine group and 16 participants in the griseofulvin group. ITT analyses were performed. The proportion of missing outcomes compared with the observed event risk didn't seem to be enough to have a clinically relevant impact on the intervention effect estimate

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: yes, there were no significant differences with regard to baseline demographic and disease characteristics, including infection severity

Methods

Multicentre, single‐blind, parallel group RCT for 10 weeks

Participants

• USA, Guatemala, Chile, Costa Rica and India

• N = 880

• Most participants (71%, 72%, and 73% in the 3 groups, respectively) were black

• Aged 3‐12 years old.

• Inclusion criteria: "male or female between the ages of 3 and 12 years, a potassium hydroxide preparation positive for fungal elements on direct microscopy, a clinical diagnosis of tinea capitis, a guardian capable of providing informed consent who was able to be actively involved in the care and evaluation of the subject, a negative baseline urine pregnancy test if applicable, and otherwise healthy."

• Exclusion criteria: participants with any of the following conditions were excluded: "a negative baseline potassium hydroxide preparation; a kerion requiring immediate treatment with systemic corticosteroids or antibiotics; previous treatment with topical or systemic antifungal therapy within the past 48 hours or 30 days, respectively; elevations in the blood levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase,g‐glutamyl transferase, or total bilirubin higher than two times the upper limit of normal; history of active liver disease; previous treatment with any other investigational agent within eight weeks before enrolment in this study; a disease or condition that could impair absorption from the gastrointestinal tract; underlying liver, kidney, or other organ disease that could result in abnormalities in the absorption or metabolism of griseofulvin, fluconazole, or their metabolites; allergies to the aforementioned drugs, pregnant females or those at risk of becoming such; those currently taking any substance known to inhibit cytochrome P‐450; those with concurrent skin disease that could obscure the diagnosis and treatment of tinea capitis; an immunocompromised state; or an enrolled family member."

• Fungi isolated

  • T.tonsurans 86%

  • M. canis 11%

• Adherence assessment: not mentioned

Interventions

• Group 1: fluconazole, dose of 6 mg/kg for 3 weeks followed by 3 weeks of placebo (N = 302)

• Group 2: fluconazole, dose of 6 mg/kg for 6 weeks (N = 286)

• Group 3: griseofulvin, dose of 11 mg/kg for 6 weeks (N = 292)

No co‐treatment

Outcomes

• Clinical outcomes

  • Clinical cure rate at 3, 6, and 10 weeks

  • Clincial improvement rate at 3, 6, and 10 weeks

  • Clinical failure rate at 3, 6, and 10 weeks

• Combined outcomes

  • Success rate at 3, 6, and 10 weeks

  • Partial success rate at 3, 6, and 10 weeks

  • Failure rate at 3, 6, and 10 weeks

• Mycological outcome

  • The percentage of participants with negative cultures

• Safety outcomes

  • The incidence of all causality and treatment‐related adverse events

  • The frequency and type of adverse event

One of the primary outcomes of interest in this review (complete cure rate) was not reported in this study.

Notes

Main data of this article were from 2 identical studies. The safety data from this article were from 3 studies. Overall, 90% of participants were from USA.

Funding: Prifzer, Inc.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Low risk

Quote (page 799): "Sealed envelopes containing randomly assigned treatments" were applied.

Comment: A standard method of location concealment was done.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Whether the participants and personnel were blinded was not reported.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Investigators were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 9.3% (82/880) participants lost to follow‐up. Among them, 37 participants were in the fluconazole 3 weeks group; 24 participants were in the fluconazole 6 weeks group; and 21 participants were in the griseofulvin group. ITT analyses were performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: yes. There was no significant difference between groups regarding age, gender, weight or height. However, baseline information about severity of infection was not stated.

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• North America

• N = 177 (78% were black; 57.2% males)

• Age was 4 years or older (98% participants < 18 years old; mean age, 7.4 years old), only 3 adults

• Inclusion criteria: male and female participants aged 4 years or older, with clinically diagnosed tinea capitis caused by Trichophyton spp.

• Exclusion criteria: any systemic treatment for tinea capitis in the month before enrolment. Kerions that required immediate treatment, concurrent seborrhoeic dermatitis, or other scalp conditions such as scabies, head lice, psoriasis, or atopic dermatitis. Immunocompromised participants or a history of malignancy within 5 years. Chronic or active liver disease. Serious gastrointestinal disease. Hypersensibility to terbinafine or placebo. Treatment with any other investigative agent within the previous 8 weeks. Pregnancy or lactation.

• Fungi isolated

  • T. tonsurans: 98.74%

  • T. soudanense: 0.63%

  • T. verrucosum: 0.63%

• Adherence assessed by asking participants to return unused medication at each visit

Interventions

• Group 1: oral terbinafine 3‐6 mg/kg/d for 1 week (N = 56)

• Group 2: oral terbinafine 3‐6 mg/kg/d for 2 weeks (N = 59)

• Group 3: oral terbinafine 3‐6 mg/kg/d for 4 weeks (N = 62)

Followed by placebo to complete 4 weeks when needed

Co‐treatment: non‐medicated shampoo twice weekly

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 12 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

• The time taken to cure

• Mycological cure at 12 weeks

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 23.2% (41/177) participants lost to follow‐up. Among them, 14 patents were in the terbinafine for 1 week group; 15 participants were in the terbinafine for 2 weeks group; 12 participants were in the terbinafine for 4 weeks group. ITT analyses were performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type fungi involved: yes

• Baseline comparability

  • Severity of infection: not stated

  • Age: terbinafine for 1 week: 7.1 years; terbinafine for 2 weeks: 8.5 years; terbinafine for 4 weeks: 6.6 years

  • Sex: terbinafine for 1 week (males 28, females 28); terbinafine for 2 weeks: (males 32, females 27); terbinafine for 4 weeks: (males 31, females 31)

Methods

Open‐label, parallel group RCT for 24 weeks

Participants

• UK

• N = 210

• Aged 2‐16 years

• Inclusion criteria: children aged 2‐16 years old with clinical diagnosis of tinea capitis

• Exclusion criteria: immunocompromised children and those receiving any topical antifungal agents within 7 days or systematic antifungal agents within 6 weeks prior to the start of the treatment

• Fungi isolated

  • Microsporum audouini: 13% (13/103) in the terbinafine group and 11.4% (12/107) in the griseofulvin group

  • M. canis: 1.3% (1/103) in the terbinafine group and 1.4% (2/107) in the griseofulvin group

  • M.rivalieri: 0% in the terbinafine group and 1.4% (2/107) in the griseofulvin group

  • Trichophyton tonsurans: 64.9% (67/103) in the terbinafine group and 72.9% (78/107) in the griseofulvin group

  • T. soudanense: 10.4% (11/103) in the terbinafine group and 4.3% (5/107) in the griseofulvin group

  • T. violaceum: 2.6% (3/103) in the terbinafine group and 0% in the griseofulvin group

  • Trichophyton species unknown: 2.6% (3/103) in the terbinafine group and 0% in the griseofulvin group

• Adherence assessed by direct questioning.

Interventions

• Group 1: griseofulvin suspension, 10 mg/kg/d, for 8 weeks (N = 107)

• Group 2: terbinafine tablet, < 20 kg: 62.5 mg/d; 20‐40 kg: 125 mg/d ; > 40 kg: 250 mg/d, for 4 weeks (N = 103)

Co‐treatment: selenium sulphide shampoo, twice weekly for the first 2 weeks of treatment

Outcomes

• Proportion of participants with complete cure at 24 weeks

• Frequency and type of adverse events

• Percentage of drop‐outs as a surrogate for participant adherence: terbinafine group

• Mycological cure at 24 weeks

Notes

Funding: Novartis Pharmaceuticals UK Ltd (Terbinafine).

The report of the study stated that "T. tonsurans accounted for 77% of the terbinafine group and 88% of the griseofulvin group. Microsporum species accounted for 14% of both groups" (i.e. 88% plus 14% = 102%). We used the data from this paper's tables (which seemed to be reliable).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 323): "Computer generated", "participants randomised in blocks of four"

Comment: standard methods of randomisation performed

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: no blinding

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: no blinding

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 54.8% (115/210) participants lost to follow‐up. Among them, 62 participants were in the terbinafine group; 53 participants were in the griseofulvin group. ITT analyses were performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not reported

  • Age: group terbinafine: 5.6; group griseofulvin: 6

  • Sex: group terbinafine: males:69%, females: 31%; group griseofulvin: males:64%, females: 36%

  • Duration of complaint: unknown

Methods

Open‐label, parallel group RCT for 26 weeks

Participants

• USA (Dallas)

• N = 80

• Age 2.1‐11.0 years (mean age 5.2 years).

• The remaining children after the drop‐outs were 63; 55% were female

• Inclusion criteria: children with tinea capitis were eligible for the study

• Exclusion criteria: presence of kerion; if their parents were unable to make a commitment for follow‐up visits, or if there was a history of hepatocellular dysfunction or finally if they had received a systemic antifungal agent in the preceding 6 weeks

• Fungi isolates (94% of the participants had positive fungal cultures)

• • T. tonsurans: 70%.

  • M. canis: 11.6%.

  • T. mentagrophytes: 1.6%.

  • T. violaceum: 1.6%.

  • Uncertain classification: 15%.

• Adherence assessed by history and by quantifying the amount of residual medication brought in by the parents.

Interventions

• Group 1: griseofulvin tablet or suspension, 15 mg/kg/d, single daily dose; 2 to 12‐26 weeks (depending on the participant's clinical response to therapy) (N = 40)

• Group 2: ketoconazole tablet or crushed tablets suspended in sucrose syrup, 5 mg/kg/d, single daily dose 2‐26 weeks depending on the participant's clinical response to the therapy (N = 40)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 and 26 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

• The time taken to cure (scalp clearing)

One of the primary outcomes of interest in the review (adverse events) was not reported in this study.

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 47): "Table of random numbers" was used.

Comment: A standard method of randomisation was performed.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: no blinding

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: no blinding

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 21.3% (17/80) participants lost to follow‐up. Among them, 11 participants were in the griseofulvin group, whereas 6 were in the ketoconazole group. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: publication reported findings on all outcomes listed in the Methods section

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria : yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not reported

  • Age (in months): griseofulvin group (63); ketoconazole group (62)

  • Sex: griseofulvin group (males: 13, females: 15); ketoconazole group (males: 16, females: 20)

  • Duration of complaint (in weeks): griseofulvin group (5.6); ketoconazole group (5.8)

Methods

Multicentre, double‐blind, parallel group RCT for 12 weeks

Participants

• Canada and South Africa

• N = 200

• Inclusion criteria: children aged 6 months or older, with clinical signs and symptoms of tinea capitis with mycology that was positive for Trichophyton spp.

• Exclusion criteria: those who had been or were on topical or oral antifungal agents for 2 or 4 weeks, respectively, prior to the starting therapy

• Fungi isolated

  • griseofulvin group: T. tonsurans: 39/50 and T. violaceum: 11/50

  • terbinafine group: T. tonsurans: 37/50 and T. violaceum: 13/50

  • itraconazole group: T. tonsurans: 35/50 and T. violaceum: 15/50

  • fluconazole group: T. tonsurans: 44/50 and T. violaceum: 6/50

• No mention of adherence assessment

Interventions

• Group 1: microsize griseofulvin 20 mg/kg/d for 6 weeks (N = 50)

• Group 2: terbinafine < 20 kg: 62.5 mg; 20‐40 kg: 125 mg; > 40 kg: 250 mg for 2‐3 weeks (N = 50)

• Group 3: itraconazole 5 mg/kg/d for 2‐3 weeks (N = 50)

• Group 4: gluconazole 6 mg/kg/d for 2‐3 weeks. (N = 50)

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at the end of treatment

• Percentage of drop‐outs as a surrogate for participant adherence

• Mycologic cure at 12 weeks

• Effective therapy (mycologic cure with clinical cure or few residual symptoms) at 12 weeks

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 7% (14/200) participants lost to follow‐up. Among them, 4 were in the griseofulvin group, 2 were in the terbinafine group, 4 were in the itraconazole group, 4 were in the fluconazole group. ITT analysis was not performed. The proportion of missing outcomes compared with the observed event risk seemed to be not enough to have a clinically relevant impact on the intervention effect estimate

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes (only culture positive)

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection

    • Mild: griseofulvin group: 18; terbinafine group: 20; itraconazole group: 9; fluconazole group: 9

    • Moderate: griseofulvin group: 28; terbinafine group: 27; itraconazole group: 36; fluconazole group: 28

    • Severe: griseofulvin group: 4; terbinafine group: 2; itraconazole group: 4; fluconazole group: 11

    • Kerion: griseofulvin group: 0; terbinafine group: 1: itraconazole group: 1; fluconazole group: 2

  • Age: griseofulvin group: 5.9; terbinafine group: 5.6; itraconazole group: 5.2; fluconazole group: 5.9

  • Sex: griseofulvin group: males: 38, females: 12; terbinafine group: males: 37, females: 13; itraconazole group: males: 27, females: 23; fluconazole group: males: 32, females: 18

  • Duration of complaint: not mentioned

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Germany

• N = 35 (16 males and 19 females)

• The mean age was 9.3 years for males and 7.8 for females

• Inclusion criteria: mycologically proven scalp infection

• Fungi isolated

  • M. canis: terbinafine for 1 week: 43.7%; terbinafine for 2 weeks: 26.3%

  • T. tonsurans: terbinafine for 1 week: 37.5%; terbinafine for 2 weeks: 31.5%

  • T. violaceum: terbinafine for 1 week: 6.25%; terbinafine for 2 weeks: 26.3%

  • T. mentagrophytes: terbinafine for 1 week: 12.5%; terbinafine for 2 weeks: 5.3%

  • T. verrucosum: terbinafine for 2 weeks: 5.3%

• No mention of adherence assessment

Interventions

• Group 1: terbinafine 10‐20 kg: 62.5 mg/d; 20‐40 kg: 125 mg/d; > 40 kg: 250 mg/d once daily for 1 week (N = 16)

• Group 2: terbinafine same dose for 2 weeks (N = 19)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The time taken to cure

Notes

Participants were observed for 12 weeks. After 4 weeks, non‐responders were offered an additional 4 weeks of treatment followed by a second observation period

Funding: Novartis (terbinafine)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs reported

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: no

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not stated

  • Age: we are unaware of the mean age for each group

  • Sex: we are unaware of the number of females and males in each group

  • Duration of complaint: not stated

Methods

Parallel group RCT for 12 weeks

Participants

• Pakistan

• N = 105 (49 males, 56 females)

• Aged 2‐65; 94 were < 12 years

• Inclusion criteria: clinical evidence of dermatophytosis of the scalp; participant of any age that weighed more than 10 kg

• Exclusion criteria: concomitant treatment with systemic or X‐ray therapy; topical antifungal therapy within 2 weeks or oral antifungal within 4 weeks of entering the study

• Fungi isolated included

  • T. violaceum: 87.6% (92/105)

  • T. tonsurans: 38% (4/105)

  • T. rubrum: 0.95% (1/105)

  • T. verrucosum: 6.6% (7/105)

  • M. audouinii: 0.95% (1/105)

• No mention of adherence assessment

Interventions

• Group 1: terbinafine 62.5‐250 mg for 4 weeks, plus 4 weeks of placebo (N = 56)

• Group 2; griseofulvin 125‐500 mg for 8 weeks (N = 49)

Outcomes

• Proportion of participants with complete cure at 12 weeks

• Frequency and type of adverse events

• Mycological cure at 12 weeks

Notes

Funding: Sandoz

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: insufficient information although stated to be a "double‐blind comparative study of terbinafine and griseofulvin in tinea capitis"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: insufficient information although stated to be a "double‐blind comparative study of terbinafine and griseofulvin in tinea capitis"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not known

  • Age: terbinafine: 8.6; griseofulvin: 9.1

  • Sex: terbinafine: male: 24, female: 32; griseofulvin: male: 25, female: 24

  • Duration of complaint: not known

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Pakistan

• N = 161 (90 males, 71 females; 156 were children below 12)

• Aged 3‐13

• Inclusion criteria: clinical and mycological evidence of dermatophytosis of the scalp; participants of any age that weighed more than 10 kg

• Exclusion criteria: concomitant treatment with systemic or X‐ray therapy; topical antifungal therapy within 2 weeks or oral antifungal within 4 weeks of entering the study

• Fungi isolated

  • T. violaceum: 71.5%

  • T. tonsurans: 14.9%

  • T. verrucosum: 4.3%

  • M. audouinii: 4.3%

  • M. canis: 2.5%

  • T. schoenleinii: 1.9%

  • T. mentagrophytes: 0.6%

• No mention of adherence assessment

Interventions

• Group 1: terbinafine, 10‐20 kg: 62.5 mg/d; 20‐40 kg: 125 mg/d ; > 40 kg: 250 mg/d, once daily for 1 week plus 3 weeks of placebo (N = 53)

• Group 2: terbinafine same dose for 2 weeks plus 2 weeks of placebo (N = 51)

• Group 3: terbinafine same dose for 4 weeks (N = 57)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 12 weeks

Notes

Funding: Sandoz (terbinafine)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs reported

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not mentioned

  • Age: we are unaware of the mean age in each group

  • Sex: we are unaware of the number of females and males in each group, only the total stated

  • Duration of complaint: not stated

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Pakistan

• N = 55

• Inclusion criteria: subjects of either sex or any age, weighing 10 kg or more and suffering from mycologically confirmed tinea capitis

• Exclusion criteria: history of allergy to imidazoles or allylamines, use of oral antifungals within 8 weeks or topical antifungals within 4 weeks before screening, concurrent therapy with rifampicin, phenytoin, digoxin, oral anticoagulants, cyclosporin, astemizole and terfenadine, psoriasis of the scalp, history of any systemic illness or abnormal liver and renal function tests

• Fungi isolated

  • T. violaceum: itraconazole group: 82.1%; terbinafine group: 88.9%

  • T. tonsurans: itraconazole group: 7.1%; terbinafine group: 3.7%

  • T. mentagrophytes: itraconazole group: 7.1%; terbinafine group:3.7%

  • T. verrucosum: itraconazole group: 3.7%; terbinafine group: 3.7%

• No mention of adherence assessment

Interventions

• Group 1: itraconazole: < 20 kg: 50 mg; 20‐40 kg: 100 mg; > 40 kg: 200 mg ‐ supposed daily ‐ for 2 weeks (N = 28)

• Group 2: terbinafine: < 20 kg: 62.5 mg; 20‐40 kg: 125 mg; > 40 kg: 200‐250 mg ‐ supposed daily ‐ for 2 weeks (N = 27)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• Mycological cure at 12 weeks

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not declared

  • Age: itraconazole group: 7.9 ± 4.58; terbinafine group: 7.8 ± 4.58.

  • Sex: male to female ratio itraconazole group: 1:1; terbinafine group: 1:1.3

  • Duration of complaint: not stated

Methods

Triple‐blind, parallel group RCT for 6 weeks (although the author stated this was a "third party blind" study in the abstract, it was unclear whether they applied blinding method or not).

Participants

• Peshawar (Pakistan)

• N = 120

• Aged 3‐12 years

• 75% participants were males

• Inclusion criteria: "Males and females between the ages of 3 and 12 years with potassium hydroxide preparation positive for fungal elements on direct microscopy were included in the study."

• Exclusion criteria: "Patients with negative baseline KOH preparation, patients having kerion and those having treatment with topical antifungal agents within past 2 weeks or systemic antifungal agents within past 30 days"; "patients with elevated liver enzymes and history of active liver disease"

• Fungi isolated

  • T. tonsurans 75%

  • M. canis 22%

Interventions

• Group 1: terbinafine, <20 kg 62.5 mg; 20‐40 kg 125 mg, for 4 weeks (N = 60)

• Group 2: griseofulvin, 15 mg/kg, for 4 weeks (N = 60)

Co‐treatment: not mentioned

Outcomes

• Clinical cure rate at 2, 4, and 6 weeks

• Mycological cure rate at 2, 4, and 6 weeks

• The type of adverse events

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: unclear, although the author stated this was a "third party blind" study in the abstract

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: unclear, although the author stated this was a "third party blind" study in the abstract

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: not mentioned

Methods

Single‐blind, parallel group RCT for 20 weeks

Participants

• Bangkok (Thailand)

• N = 82

• All participants were children 7 years or older, except for 3 adults, all living in an orphanage

• Fungi isolated: T. tonsurans and M. ferrugineum; proportions not stated

• No mention of adherence assessment

Interventions

• Group 1: terbinafine 62.5‐250 mg according to body weight ‐ supposed once daily ‐ for 1 week. N = 27 completed the study

• Group 2: terbinafine same dose for 2 weeks. N = 28 completed the study

• Group 3: terbinafine same dose for 4 weeks. N = 27 completed the study

Outcomes

• The proportion of participants with complete cure at 12 weeks

One of the primary outcomes of interest in this review (adverse events) was not reported in this study.

Notes

The proportions and percentages were done including the adults, because we are unaware which group they belonged to.

Funding: Sandoz (terbinafine)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: study was described as "single blind and open trial study" but no mention of which one (participant or observers), and the method of blinding was not stated

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: study was described as "single blind and open trial study" but no mention of which one (participant or observers), and the method of blinding was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 8.5% (7/82) participants lost to follow‐up. It was unclear which group these lost participants belonged to. ITT analysis was not performed. The proportion of missing outcomes compared with the observed event risk seemed insufficient to have a clinically relevant impact on the intervention effect estimate.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: very poor

• Exclusion criteria: not mentioned

• Reporting of type of fungi involved: yes

• Baseline comparability: yes, though no statistical differences were noted either reported, among the 3 groups with regard to age, weight and sex ratio

Methods

Multicentre, triple‐blind, parallel group RCT for 16 weeks

Participants

• Europe and South America (22 centres)

• N = 165

• The majority of participants were white (77%); 63% were males and the mean age was 7.7 years, only 3 adults were enrolled in the study; 67% weighed between 20 and 40 kg.

• Inclusion criteria: male or female aged ≥ 4, with tinea capitis confirmed by positive culture of Microsporum spp., who were otherwise healthy outpatients and able to swallow the study drug tablets

• Exclusion criteria: participants with conditions that could interfere with gastrointestinal absorption of terbinafine, with confirmed liver or renal impairment, with kerion or any severe concurrent disease of the scalp. Those using any antifungal therapy, radiotherapy, systemic therapy with cytostatic or immunosuppressive drugs within 1 month prior to the start of the study, and known intolerance or allergy to drugs used in the study

• In addition, participants receiving griseofulvin treatment in this study were subject to exclusion according to the label instruction of that drug

• Fungi isolated

  • M. canis: 98.5%

  • Only 2 participants were infected with M. audouinii

• No mention of adherence assessment

Interventions

• Group 1: terbinafine tablets < 20 kg: 62.5 mg/d; 20‐40 kg: 125 mg/d; > 40 kg: 250 mg/d for 6 weeks, followed by placebo to complete the 12 week double‐blind treatment phase (N = 36)

• Group 2: terbinafine same dose for 8 weeks, followed by placebo to complete the 12 week double‐blind treatment phase (N = 34)

• Group 3: terbinafine same dose for 10 weeks, followed by placebo to complete the 12 week double‐blind treatment phase (N = 33)

• Group 4: terbinafine same dose for 12 weeks, followed by placebo to complete the 12 week double‐blind treatment phase (N = 32)

• Group 5: griseofulvin oral suspension 20 mg/kg/d for 12 weeks (open label) (N = 30)

Participants were provided with baby‐shampoo to clean the scalp.

Outcomes

• The proportion of participants with complete cure at 16 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 16 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

• The time taken to cure

• Mycological cure at 16 weeks

Notes

Funding: Novartis Pharma AG

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "Participants, clinicians and outcome assessors blinded, except for the arm taking griseofulvin, where both participants and investigators were informed from day 1"

Comment: The method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "Participants, clinicians and outcome assessors blinded, except for the arm taking griseofulvin, where both participants and investigators were informed from day 1"

Comment: The method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 21.8% (36/165) participants lost to follow‐up. Among them, 7 were in the terbinafine for 6 weeks group, 4 were in the terbinafine for 8 weeks group, 6 were in the terbinafine for 10 weeks group, 12 were in the terbinafine for 12 weeks group, 7 were in the griseofulvin group. ITT analyses were performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not reported

  • Age: terbinafine for 6 weeks: 9.5; terbinafine for 8 weeks: 7; terbinafine for 10 weeks: 6.8; terbinafine for 12 weeks: 8.8; griseofulvin group: 6.3

  • Sex: % of males: terbinafine for 6 weeks: 66%; terbinafine for 8 weeks: 73%; terbinafine for 10 weeks: 70%; terbinafine for 12 weeks: 53%; griseofulvin group: 50%

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Madrid (Spain)

• N = 35 (23 males and 12 females)

• All participants were children younger than 12 years old, except for 1 adult who was 60 years old

• Inclusion criteria: the presence of dermatophytes

• Fungi isolated

  • T. tonsurans: itraconazole group: 5.5%

  • M. canis: itraconazole group: 88.8%; griseofulvin group: 94.1%

  • T. mentagrophytes: itraconazole group: 5.5%

  • T. violaceum: griseofulvin group: 5.9%

• No mention of adherence assessment

Interventions

• Group 1: itraconazole 100 mg/d for 6 weeks (N = 18, including 1 adult)

• Group 2: griseofulvin (ultra microsize) 500 mg/d for 6 weeks (N = 17)

• No co‐treatment

Outcomes

• The proportion of participants with complete cure at 14 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 14 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

Notes

Funding: Janssen (itraconazole)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 8.6% (3/35) participants lost to follow‐up. Among them, 1 was in the itraconazole group, 2 were in the griseofulvin group. ITT analysis was not performed. The proportion of missing outcomes compared with the observed event risk seemed to be not enough to have a clinically relevant impact on the intervention effect estimate

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: not mentioned

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not reported

  • Age: itraconazole group: 2 to 11; griseofulvin group: 2 to 10

  • Sex: itraconazole group: males: 12, females: 6; griseofulvin group: males: 11, females: 6

  • Duration of complaint: not reported

Methods

Triple‐blind, parallel group RCT for 6 weeks

Participants

• Barcelona (Spain)

• N = 13

• Children aged 2‐16

• Sex distribution not reported

• Inclusion criteria: children suffering from dermatophytic lesions

• Exclusion criteria: not to have received previous antifungal therapy

• Fungi isolated: T. mentagrophytes, M. canis and Epidermophyton floccosum

• Adherence assessed

Interventions

• Group 1: ketoconazole tablet, 100 mg/d at 12‐hourly intervals for 6 weeks (N = 8)

• Group 2: griseofulvin tablet, 350 mg/d, at 12‐hourly intervals for 6 weeks (N = 5)

Co‐treatment: manual depilation in cases of inflammatory tinea capitis.

Outcomes

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at the end of treatment

• Measurement of recurrence of the condition after the end of the intervention period

• The time taken to cure

One of the primary outcomes of interest in this review (complete cure rate) was not reported in this study.

Notes

Tinea corporis and tinea capitis study, information poorly stated
It needs to be taken into account that the study talks about 47 participants, which is the total, tinea capitis and tinea corporis participants, but for the purpose of our review we have only used the results of the 13 tinea capitis participants.

Funding: Laboratories Dr Esteve (ketoconazole)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote (page 38): "Computer generated random number table"

Comment: A standard method of randomisation was done.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: not reported

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Turkey

• N = 78

• Children aged 2‐13 years

• Inclusion criteria: participants with clinically suspected tinea capitis, provisionally confirmed by detection of fungal hyphae in KOH.

• Exclusion criteria: evidence of concomitant candida or bacterial infection

• Fungi isolated

  • T. violaceum: griseofulvin group: 11.4% (4/35); terbinafine group: 15.6% (5/32)

  • T. rubrum: griseofulvin group: 22.8% (8/35); terbinafine group: 15.6%(5/32)

  • M. canis: griseofulvin group: 48.5% (17/35); terbinafine group: 46.8%(15/32)

  • T. tonsurans: griseofulvin group: 5.7% (2/35); terbinafine group: 6.25% (2/32)

  • T. mentagrophytes: griseofulvin group: 5.7% (2/35); terbinafine group: 3.1% (1/32)

  • T. verrucosum: griseofulvin group: 5.7% (2/35); terbinafine group: 3.1% (1/32)

  • M. audouinii: terbinafine group: 3.1% (1/32)

  • Unidentified: terbinafine group: 6.25% (2/32)

• No mention of adherence assessment

Interventions

• Group 1: microsize griseofulvin 20 mg/kg/d for 6 weeks (N = 50)

• Group 2: terbinafine < 20 kg: 62.5 mg; 20 to 40 kg: 125 mg; > 40 kg: 250 mg for 2‐3 weeks (N = 50)

• Group 3: itraconazole 5 mg/kg/d for 2‐3 weeks (N = 50)

• Group 4: gluconazole 6 mg/kg/d for 2‐3 weeks (N = 50)

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only was scored at 12 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

• Mycological cure at 12 weeks

Notes

At the beginning there were 39 participants in each group, after the drop‐outs there were 32 and 35 left, and so the percentages do not match:

• T. violaceum: 13.4%

• T. rubrum: 19.4%

• M. canis: 47.7%

• T. tonsurans: 5.9%

• T. mentagrophytes:4.5%

• T. verrucosum: 4.5%

• M. audouinii : 1.5%

• Unidentified: 3%

These fungi percentages are the total over 67, not over 78 participants.

Funding: not mentioned.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 14.1% (11/78) participants lost to follow‐up. Among them, 7 were in the griseofulvin group, whereas 4 were in the terbinafine group. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not stated

  • Age: griseofulvin group: 6.6; terbinafine group: 7

  • Sex: griseofulvin group: males 26, females 9 ; terbinafine group: males 21, females 11

  • Duration of complaint: not stated

Methods

Open‐label, parallel group RCT for 12 weeks

Participants

• New Zealand

• N = 24

• 16 male and 8 female

• Age ranged between 2 and 15 years old

• Inclusion criteria: paediatric participants under 16 years old with culture positive tinea capitis

• Fungi isolated

  • M. canis 71%

  • T. verrucosum 29%

• No mention of adherence assessment

Interventions

• Group 1: griseofulvin 10 mg/kg/d for 8 weeks (N = 14)

• Group 2: terbinafine < 20 kg: 62.5 mg/d; 20 to 40 kg: 125 mg/d; > 40 kg: 250 mg/d for 4 weeks (N = 10)

Co‐treatment: ketoconazole shampoo twice a week and econazole cream nightly was recommended

Outcomes

• The frequency and type of adverse events

• The proportion of participants with clinical cure only

• Measurement of recurrence of the condition after the end of the intervention period

One of the primary outcomes of interest in this review (complete cure rate) was not reported in this study.

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: no blinding

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: no blinding

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Comment: not mentioned

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: no

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: only total stated

  • Age: only total stated

  • Sex: only total stated

  • Duration of complaint: not stated

Methods

Double‐blind, parallel group RCT for 16 weeks

Participants

• New York (USA)

• N = 27

• 15 females and 13 males aged 2‐15 years

• Inclusion criteria: mycologic confirmation of infection before initiation of therapy; children from 2 to 15 years of age; normal complete blood cell count with differential, liver function test, and SMA‐7; and parental consent

• Exclusion criteria: participants who had received antimycotic therapy within 2 weeks of initial visit; a history of kidney or liver disease; participants with history of hypersensitivity reaction to any of the ingredients of fluconazole; participants receiving interactive medications within preceding 30 days; participants with coexisting immunosuppressive disease; and participants with inflammatory tinea capitis

• Fungi isolated: T. tonsurans 100%

• No mention of adherence assessment

Interventions

• Group 1: fluconazole tablets or suspension 1.5 mg/kg/d for 20 days, N = 8 completed the study

• Group 2: fluconazole tablets or suspension 3 mg/kg/d for 20 days, N = 10 completed the study

• Group 3: fluconazole tablets or suspension 6 mg/kg/d for 20 days, N = 9 completed the study

No co‐treatment

Outcomes

• Proportion of participants with complete cure at 6 to 16 weeks

• Proportion of participants with clinical cure only

• Measurement of recurrence of the condition after the end of the intervention period

One of the primary outcomes of interest in this review (adverse events) was not reported in this study

Notes

Funding: not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants were not blinded, but the outcomes were unlikely to be influenced; clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 51.8% (14/27) participants lost to follow‐up. It was unclear which group these lost participants belonged to. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: not reported

  • Age: not reported

  • Sex: not reported

  • Duration of complaint: not reported

Methods

Single‐blind, parallel group RCT for 12 weeks

Participants

• Brazil

• N = 132 (63 females and 69 males)

• Aged 1‐14 years

• Inclusion criteria: children of both sexes with tinea capitis, aged 1‐14 years, weighing ≥ 20 kg

• Exclusion criteria: use of any systemic antifungal therapy within 1 month or topical antifungal therapy within 2 weeks prior to the start of the study or both; conditions that could interfere with gastrointestinal absorption of terbinafine; confirmed liver/renal impairment, haematological disorders; radiotherapy, systemic therapy with cytostatic or immunosuppressive drugs, or therapy with antibacterial, antiviral or antihelmintic drugs, either currently or during the 2 weeks preceding the beginning of the study

• Fungi isolated

  • T. tonsurans: terbinafine for 1 week: 88.6% (3/35); terbinafine for 2 weeks: 18.5% (7/38); terbinafine for 4 weeks: 26.5% (9/34)

  • T. mentagrophytes: terbinafine for 1 week: 2.8% (1/35); terbinafine for 4 weeks: 5.9% (2/34)

  • M. canis: terbinafine for 1 week: 77.1% (27/35); terbinafine for 2 weeks: 73.3% (28/38); terbinafine for 4 weeks: 55.9% (19/34)

  • T. rubrum: terbinafine for 1 week: 8.6% (3/35); terbinafine for 2 weeks: 7.9% (3/38); terbinafine for 4 weeks: 5.9% (2/34)

  • T. schoenleini: terbinafine for 1 week: 2.8% (1/35); terbinafine for 4 weeks: 2.9% (1/34)

  • M. gypseum: terbinafine for 4 weeks: 2.9% (1/34)

• No mention of adherence assessment

Interventions

• Group 1: terbinafine 10 to 20 kg: 62.5 mg/d; 20 to 40 kg: 125 mg/d; > 40 kg: 250 mg/d once daily for 1 week plus 3 weeks of placebo (N = 42)

• Group 2: terbinafine same dose for 2 weeks plus 2 weeks of placebo (N = 44)

• Group 3: terbinafine same dose for 4 weeks same dose (N = 46)

No co‐treatment

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure only at 12 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

Notes

Funding: Sandoz (terbinafine)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comment: Only participants blinded, but the method of blinding was not stated. The outcomes were likely to be influenced if the clinicians were not blinded.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Comment: Outcome assessors were not blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: 18.2% (24/132) participants lost to follow‐up. Among them, 6 were in the terbinafine for 1 week group, 6 were in the terbinafine for 2 weeks group, and 12 were in the terbinafine for 4 weeks group. ITT analyses were performed. The reasons for drop‐outs were not clear.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: studied but not shown

  • Age: terbinafine for 1 week: 6.5 years; terbinafine for 2 weeks: 6.5 years; terbinafine for 4 weeks: 6.1 years

  • Sex: terbinafine for 1 week: males 26, females 16; terbinafine for 2 weeks: males 17, females 27; terbinafine for 4 weeks: males 26, females 20

  • Duration of complaint: studied but not shown

Methods

Triple‐blind, parallel group RCT for 6 weeks

Participants

• Chicago (USA)

• N = 22

• Inclusion criteria: children 2‐16 years old were eligible if they had clinically diagnosed or mycologically proven tinea capitis

• Exclusion criteria: those that had received systemic antimycotic therapy within 1 month of enrolment, if griseofulvin therapy was contraindicated; if they had a serious concurrent disease or a history of hepatitis; if they were taking warfarin‐like anticoagulants or barbiturates, or if they were pregnant

• Fungi isolated

  • T. tonsurans: 50% (11/22)

  • Scopulariopsis spp. : 4.5% (1/22)

  • Penicillium spp. :4.5% (1/22)

  • Unidentified fungus: 4.5% (1/22)

• Adherence assessed

Interventions

• Group 1: griseofulvin tablet, 500 mg/d, plus 'ketoconazole' placebo tablet (participants < 40 kg: half tablet) for 6 weeks (N = 12)

• Group 2: ketoconazole tablet, 200 mg/d, plus 'griseofulvin' placebo tablet (participants weighing < 40 kg: half tablet) for 6 weeks (N = 10)

Co‐treatment: antiseborrhoeic shampoo

Outcomes

• The frequency and type of adverse events

• Percentage of drop‐outs as a surrogate for participant adherence

• Mycological cure at 12 weeks

One of the primary outcomes of interest in this review (complete cure rate) was not reported in this study

Notes

Funding: Janssen (ketoconazole)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 36.4% (8/22) participants lost to follow‐up. Among them, 3 were in the griseofulvin group, whereas 5 were in the ketoconazole group. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability

  • Severity of infection: (minimum score = 0, maximum score = 21): griseofulvin group: 9.3; ketoconazole group: 8.3

  • Age: griseofulvin group: 6.4; ketoconazole group: 5.7

  • Sex: (male: female): griseofulvin group: 0:7; ketoconazole group: 2:5

  • Duration of complaint: (weeks): griseofulvin group: 16.5; ketoconazole group: 24

Methods

Triple‐blind, parallel group RCT for 12 weeks

Participants

• Chicago (USA)

• N = 79 (65% female)

• 92% black

• Inclusion criteria: children aged 2‐16 years old, with tinea capitis or mycologic evidence of dermatophyte infection of the scalp

• Exclusion criteria: participants receiving systemic antimycotic therapy within 30 days of the initial visit; if they had a history of porphyria, liver disease, or immunodeficiency; if they were pregnant or if they were receiving warfarin‐like anticoagulants or barbiturates

• Fungi isolated

  • T. tonsurans: 64% of the enrolled participants and 74% of the evaluable participants

  • M. canis: 12% of the enrolled participants and 13% of evaluable participants

• Adherence not assessed

Interventions

• Group 1: griseofulvin (microsize) 250 mg tablet ( 10 to 20 mg/kg/d) plus 'ketoconazole' placebo tablet, single daily dose, for 12 weeks (N = 46)

• Group 2: ketoconazole 200 mg tablet (3.3 to 6.6 mg/kg/d) plus 'griseofulvin' placebo tablet in a single daily dose for 12 weeks (N = 33)

Co‐treatment: antiseborrhoeic shampoos

Outcomes

• The proportion of participants with complete cure at 12 weeks

• The frequency and type of adverse events

• The proportion of participants with clinical cure at 12 weeks

• Percentage of drop‐outs as a surrogate for participant adherence

• Mycological cure at 12 weeks

Notes

Not much information given apart from the total cured results
The enrolled : 79 were randomised, 46 were evaluable

Funding: Janssen (ketoconazole)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Comment: 39.2% (31/79) participants lost to follow‐up. Among them, 20 were in the griseofulvin group, whereas 11 were in the ketoconazole group. ITT analysis was not performed.

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: no

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: taken into account but not reported

There were no statistically significant differences between the groups in terms of age, sex, weight or duration of infection

Methods

Triple‐blind, parallel group RCT for 20 weeks

Participants

• Thailand

• N = 42

• Inclusion criteria: not to have received any topical or systemic antifungal therapy in the preceding 2 or 4 weeks, respectively

• Fungi isolated: Microsporum spp.:

  • M. ferrugineum 50% (21/42)

  • M. canis 47.6% (20/42)

  • M. gypseum 2.3% (81/42)

Interventions

• Group 1: oral terbinafine 10 to 20 kg: 62.5 mg/d; 20 to 40 kg: 125 mg/d; over 40 kg: 250 mg/d, in a pulsed regimen (N = 23)

• Group 2: oral terbinafine at double dose, in a similar pulsed regimen (N = 19)

Outcomes

• Proportion of participants with complete cure at 20 weeks

• Mycological cure at 20 weeks.

One of the primary outcomes of interest in this review (adverse events) was not reported in this study

Notes

Funding: Institute of Dermatology Research Funds and Novartis (Thailand)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Comment: There was no information on the method of randomisation.

Allocation concealment (selection bias)

Unclear risk

Comment: There was no information on the method of allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: Participants and clinicians were blinded, but the method of blinding was not stated.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Comment: Outcome assessors were blinded, but the method of blinding was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Comment: no drop‐outs

Selective reporting (reporting bias)

Low risk

Comment: The publication reported findings on all outcomes listed in the Methods section.

Other bias

Unclear risk

• Sample size calculation declared: yes

• Inclusion criteria: yes

• Exclusion criteria: yes

• Reporting of type of fungi involved: yes

• Baseline comparability: not mentioned