Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. The LION Study Group

Abstract

Objective: To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis.

Design: Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks.

Setting: 35 centres in six European countries.

Subjects: 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail.

Interventions: Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4).

Main outcome measures: Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail.

Results: At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80. 8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups.

Conclusion: Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis.

Figure 1

Distribution of participants in study, showing randomisation of intention to treat population between four treatment groups and number of patients remaining in each group at weeks 48 and 72. T₁₂ and T₁₆ indicate allocation to terbinafine for 12 or 16 weeks. I₃ and I₄ indicate allocation to itraconazole for 1 week a month for 3 or 4 months. Patients not randomised (n=336) because of negative results on microscopy or fungal culture, or both, at baseline (n=263); protocol violation (n=19); withdrawal of consent (n=18); or other (n=36). Reasons for the 87 withdrawals (for T₁₂, T₁₆, I₃, and I₄, respectively) were adverse events (8, 13, 5, 8); withdrawal of consent (2, 1, 3, 2); protocol violation (0, 2, 2, 5); treatment failure (0, 0, 8, 6); failure to return (4, 4, 4, 4); and other (0, 3, 3, 0)

Figure 2

Rates (%) of mycological cure, clinical cure, and complete cure. All comparisons P<0.0001 except for clinical cure T₁₂ v I₃ P<0.0015, T₁₂ v I₄ P=0.0022; and for complete cure T₁₂ v I₃ P=0.0007, and T₁₂ v I₄ P=0.0044