Gupta 2001c.

Methods	Design: single‐blind, randomised, prospective study
Participants	Number of participants randomised: 190 (IIT: 93, TTT: 97). 14 participants who did not meet inclusion/exclusion criteria did not commence the study ‐ 176 started treatment (IIT: 81, TTT: 95) Number included in analysis: 165 (IIT: 75, TTT: 90) Number completing treatment: 165 (IIT: 75, TTT: 90) Sex (M/F): IIT 33/42, TTT 60/30 Mean age: 35.6 years (range 25‐53) Inclusion criteria: at least 18 years old, clinical diagnosis of distal and lateral onychomycosis of the toes. Dermatophyte had to be aetiologic organism Type/location/characteristics of infection: distal and lateral onychomycosis of the toes Duration of infection: not stated Exclusion criteria: those who had received oral antifungal therapy within the previous 3 months or applied topical antifungal to the feet during the previous 1 month, proximal subungual or white superficial onychomycosis, onychomycosis caused by Candida or nondermatophyte moulds, participants taking medications known to interact with itraconazole or terbinafine, individuals with concomitant nail disease such as psoriasis or lichen planus. Prengnancy, lactation, inadequate contraception, history of renal disease, participants with baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) elevated to more than twice the upper limit of normal Washout period: not stated Setting: 3 outpatient dermatology offices in North America Comorbidities: not stated
Interventions	2 pulses of itraconazole (200 mg twice daily for a week constitutes 1 pulse) followed by 1 pulse of terbinafine (250 mg twice daily for a week), each successive pulse of active therapy separated by a period of 3 weeks 3 pulses of terbinafine with 3 weeks off between successive pulses
Outcomes	Duration of follow‐up: 72 weeks Outcomes measured: mycological cure rate (negative light microscopy and culture), clinical cure (nail plate appeared completely normal), effective therapy (mycological cure and outgrowth of at least 5mm new clinically unaffected nail plate) and complete cure (mycological and clinical cure simultaneously), recurrence rate Safety and tolerability assessed by: adverse effect reporting; liver enzymes changes are stated but whether they were tested for routinely is unclear
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: "[r]andomised", "Patients were assigned to one arm of the study or the other in balanced blocks of 6 at each centre". "The baseline characteristics of age, race, duration of onychomycosis, causative organism, and percentage of toenail involved were similar, with no statistically significant difference between the 2 treatment groups". Comment: method of random sequence generation not stated. Baseline characteristics similar between treatment groups
Allocation concealment (selection bias)	Unclear risk	Quote: "[t]he nature of the treatment was discussed with each patients, and informed consent was obtained". Comment: method of allocation concealment not stated
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "[t]he study was single‐blinded with the evaluator of the primary and secondary outcome measures not being aware of the randomization order or the treatment being administered to the patient". Comment: high risk of performance bias as participants and personnel likely not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "[t]he study was single‐blinded with the evaluator of the primary and secondary outcome measures not being aware of the randomization order or the treatment being administered to the patient". Comment: likely adequate blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "[a] total of 190 patients were found to have dermatophyte toe onychomycosis after initial screening for the study and were randomised (IIT: 93, TTT: 97). Fourteen patients were found to violate inclusion/exclusion criteria or decided not to start therapy after randomization but before start of treatment. The number of patients who received intervention therapy were IIT 81 and TTT 95. At the end of week 72, there were 75 patients in the IIT group who were regarded as having completed the study with 6 withdrawals. In the TTT group, the corresponding numbers were 90 and 5 patients, respectively." Comment: low number of exclusions with reasons for exclusion stated in the text. Enough data provided to perform an ITT analysis
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