Degreef 1999.

Methods	Design: randomised double‐blind controlled trial
Participants	Number of participants randomised: 297 Sex: not stated (both sexes included) Mean age: not stated, range 18‐65 years Number included in analysis: ITT population of 292 (146 in each group); 289 were available for efficacy (145 in itraconazole group and 144 in terbinafine group) Number completed treatment: 258 started the follow‐up period Inclusion criteria: age 18‐65 years, microscopically and culturally proven onychomycosis of the toenail Type/location/characteristics of infection: onychomycosis of toenail caused by dermatophyte with no evidence of a superimposed Candida infection, more than 50% of surface of at least 1 nail affected (or if lunula involved, at least 25% of surface of 1 nail affected) Duration of infection: not stated Exclusion criteria: abnormal LFTs, pregnancy/lactation, psoriasis, concurrent use of rifampicin, phenytoin, digoxin, oral anticoagulants or H2‐receptor antagonists, serious disease, previous hypersensitivity to azoles or terbinafine Washout period: 3 months for systemic antifungals, 1 month for topical antifungals Setting: Europe multicentre Comorbidities: not stated
Interventions	Itraconazole 200 mg daily for 12 weeks Terbinafine 250 mg daily for 12 weeks
Outcomes	Duration of follow‐up: 48 weeks Outcomes measured: mycological cure, clinical evaluation, clinical response Safety and tolerability assessed by: adverse events, blood samples for haematology and biochemistry, LFTs
Source of funding	No information available
Conflict of interest	No conflict of interest identified
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "[p]atients, who gave written informed consent to participate, were randomised to 12 weeks' treatment with itraconazole 200 mg daily or terbinafine 250 mg daily." Comment: method of sequence generation not stated. Demographics ‐ no significant differences between groups
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "[r]andomized double‐blind comparison" Comment: study states that it is blinded, but no method stated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "[r]andomized double‐blind comparison", "secondary efficacy variables were investigator's global clinical evaluation of response to treatment, performed at the end of treatment and at each visit during follow‐up" Comment: study states it is blinded, but no method of assessor blinding stated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "[a] total of 299 patients were recruited into the trial, of whom 297 were randomised to treatment. The intention‐to‐treat population comprised 292 patients, 146 in each group; 289 patients were considered evaluable for efficacy." "The intention‐to‐treat worse‐case analysis was the primary analysis for safety." Comment: dropouts accounted for (except for the 5 participants in the original 297 randomised who were not included in the 292 ITT population). Low dropout rate between ITT group and "those considered evaluable for efficacy". ITT analysis carried out for some outcomes
Selective reporting (reporting bias)	Low risk	All results presented as set out in the Methods. All prespecified outcomes appear to be reported.
Other bias	Low risk	No clear other bias seen