Kennedy 2005.

Methods	2‐arm, double‐blinded, multicentre, parallel‐group RCT, with 6‐week duration of treatment and 9‐week duration of follow‐up
Participants	Location: United States; unclear number of sites Setting of recruitment and treatment: not reported Sample size: 53 Number randomised: 25 in intervention, 28 in comparison Number completed: 21 in intervention, 23 in comparison Participant (baseline) characteristics: Age mean (SD): terbinafine 49 (10); placebo 52 (13) Gender M(%)/F(%): 27(50.9%)/26 (49.1) Main diagnosis: CRS Presence of allergic fungal rhinosinusitis: not reported Positive fungal culture: terbinafine 17/25; placebo 24/28 Presence of eosinophilic CRS: not reported Polyps status: not reported Previous sinus surgery status: not reported Other important effect modifiers, if applicable (e.g. aspirin sensitivity, comorbidities of asthma): none reported Inclusion criteria: all patients were required to have signs and symptoms of CRS for a period of greater than 3 months before screening and to have failed previous medical therapy. Diagnosis of CRS was based on AAO‐HNS definitions. Patients were required to have CT scan evidence of sinusitis (more than 25% opacification/mucoperiosteal thickening in at least 2 of the major paranasal sinuses). Exclusion criteria: sinus surgery within the 3 months before screening
Interventions	Intervention (n = 25): terbinafine, tablets, 625 mg/day, 6 weeks Comparator group (n = 28): identical looking placebo tablets, 6 weeks Use of additional interventions (common to both treatment arms): Use of systemic antibiotics, oral and nasal steroids, anti‐leukotriene inhibitors or antihistamines was allowed during the trial, but the regimen was kept consistent from 6 weeks before randomisation through to the end of the study
Outcomes	Outcomes of interest in the review: Primary outcomes: Health‐related quality of life, using disease‐specific health‐related quality of life scores: Rhino‐sinusitis Disability Index (RSDI): measured at 9 weeks Disease severity symptom score: patient's overall evaluation of sinusitis (4‐point scale), measured at 9 weeks, unclear if higher or lower indicates worse symptoms Significant adverse effect (systemic antifungals): hepatic toxicity (as measured by number of patients with increased AST, ALT or GGT – no definition of "increased" given) Secondary outcomes: CT scan: (1) percentage change from baseline in CT opacification score. CT scans were graded for extent of opacification at baseline and end of week 6 using a modification (total opacification= 50) of the Lund‐Mackay scoring system. (2) Total right and left obstruction score of the frontal recess, middle meatus infundibulum and sphenoethmoid recess Adverse effects (topical antifungals): epistaxis, headache, local discomfort Adverse effects (systemic antifungals): gastrointestinal disturbances, allergic reactions Other outcomes reported by the study: Patient's and physician's overall evaluation of sinusitis (4‐point scale) Patient's and physician's evaluation of therapeutic response Percentage change from baseline in volume of inflammatory sinus mucosal disease Histologic examination
Funding sources	Novartis pharmaceutical corporation
Declarations of interest	No information provided. Authors acknowledge Novartis employee for preparation of the manuscript. Three authors have Novartis as their affiliation.
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed using a validated system that automated the random assignment of treatment codes." Comment: automatic randomisation
Allocation concealment (selection bias)	Low risk	Comment: as randomisation was automated it is assumed that the allocation to treatment group was adequately concealed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Both the patient and investigator were blinded to the treatment assignment."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Both the patient and investigator were blinded to the treatment assignment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "All randomized patients who took at least one dose of study medication and had at least one post baseline assessment were used in the efficacy analysis (intention to treat [ITT] population)." Comment: although withdrawals from the trial overall were 9/53 (17.0%), of which 4/25 (16%) were from the terbinafine and 5/28 (18%) were from the placebo group, the reasons are provided and are equal between the groups
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol mentioned within the paper and no protocol found on clinicaltrials.gov Some outcomes mentioned in methods section are just reported as "not statistically different" in the paper but results are not reported
Other bias (non‐validated instrument)	Unclear risk	Quote:"CT scans were graded for extent of opacification at baseline and end of week 6 using a modification (total opacification=50) of the Lund‐Mackay scoring system." Comment: unclear whether the modified version of the Lund‐Mackay scoring system had been validated
Other bias	Low risk	Comment: no other sources of bias were identified