Treatment of chronic rhinosinusitis with high-dose oral terbinafine: A double blind, placebo-controlled study

Objectives: To evaluate antifungal terbinafine in patients with chronic rhinosinusitis. Study Design: Randomized, double-blind, placebo-controlled multicenter pilot study. Methods: Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/ day (n = 25) or placebo (n = 28) once daily for 6 weeks. Sinus secretions were collected at screening for mycology. Computed tomography was graded for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system. Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index. Results: Positive fungal cultures were found in 41 of 53 patients (17 terbinafine, 24 placebo). (Two subjects from the Terbinafine group and one subject from the control group had no week 6 data). The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo (n = 26) and from 26.3 to 24.2 in terbinafine group (n = 23). The least squares means for percent change from baseline (SE) were -6.0 (8.7) for placebo compared with -7.2 (8.1) for terbinafine; 95% confidence interval for treatment difference (-18.9, 21.1); P = .91. Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis. Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion. Conclusion: Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation samples were positive for fungus on culture. One consideration is that the fungi isolated were not a major pathologic factor in this cohort. It is also possible that, even at high dose, terbinafine may not have maintained therapeutic levels in the nasal secretions.