Efficacy and Safety of Oral Terbinafine in Combination With Other Oral Anti-Fungal Agents for Treatment of Refractory Dermatophytosis

This open-label, comparative randomized clinical trial was conducted over a six-month period from March to August 2021, at the Department of Dermatology and Venereology of Chittagong Medical College Hospital. The study population comprised patients with refractory dermatophytosis attending the department during this period. Participants were conveniently screened against inclusion and exclusion criteria to identify eligible subjects, who were then randomly allocated into three treatment arms. Inclusion criteria encompassed individuals aged 18 years and above, diagnosed with refractory dermatophytosis, characterized by a lack of response to routine treatment, relapse post-treatment, or persistent infection. Exclusion criteria included unwillingness to participate, pregnancy or lactation, history of allergic reactions to the study drugs, significant abnormalities in complete blood counts (CBC), liver function tests (LFT), renal function tests (RFT), and electrocardiogram (ECG), as well as patients with comorbidities like cardiac, liver, or renal disorders, or those with bacterial co-infections. The initial sample size aimed for 50 patients per group, but due to dropouts, the final tally included 138 participants. The treatment groups were: Group A (TF group) receiving Oral Terbinafine (250 mg once daily) and Fluconazole (100 mg twice daily); Group B (TI group) receiving Oral Terbinafine (250 mg once daily) and Itraconazole (100 mg twice daily); and Group C (TV group) receiving Oral Terbinafine (250 mg once daily) combined with Voriconazole, dosed according to body weight at or over 40 kg body weight: 200 mg twice daily and below 40 Kg body weight: 100 mg twice daily. All patients were also administered antihistamines (levocetirizine and hydroxyzine) and were advised against using any other medicines, including topical agents. Patients were followed up at four and six weeks post-treatment initiation to evaluate efficacy and safety. Investigations conducted at baseline and subsequently at every second visit included CBC, LFT, RFT, and ECG. Compliance was monitored through the collection of used medicine strips and reminder communications at each visit. Patients showing less than 25% improvement at the end of four weeks were labeled as 'complete failures', excluded from the study, and provided alternative treatment. Participants with a partial response continued the same treatment for an additional two weeks. Those achieving complete cure at four weeks were monitored for recurrence at the six-week mark, and side effects experienced during the treatment were recorded. Data analysis involved inputting collected