Pooled Analysis of 2 Randomized Clinical Trials to Evaluate the Efficacy and Safety of Clotrimazole 1% Otic Solution for the Treatment of Otomycosis in Adults.

Abstract

ImportanceThere is no antifungal otic drug for the treatment of otomycosis approved in the United States. Some current clotrimazole formulations in the market are used off-label.ObjectiveTo evaluate the efficacy and safety of clotrimazole 1% otic solution compared to placebo in treating otomycosis in adults.DesignTwo independent twin multicenter, randomized (2:1), double-blind, controlled clinical trials with identical designs were conducted from February 2020 to October 2021.SettingFifty-three sites located in the United States, Mexico, and Europe.ParticipantsAdults with uncomplicated otomycosis presented with symptoms, debris, and drainage clinically consistent with fungal infection.InterventionPatients received clotrimazole or placebo twice daily for 14 days and were evaluated on visit 1 (day 1), visit 2 (day 8-10), visit 3 (day 15), and follow-up visit 4 (day 24-26).Main Outcome MeasuresAt each visit, pruritus, otalgia, otorrhea, and ear fullness were assessed. Ear exudate was taken for a mycological and microbiological evaluation at baseline and, if present, at subsequent visits. The primary endpoint was a therapeutic cure (mycological and clinical) at visit 4 in the randomized population with positive fungal culture at baseline [mycological intent-to-treat (MITT)].ResultsThree hundred ninety-three patients received study medication (261 clotrimazole and 132 placebo). Efficacy data from the 228 patients (157 clotrimazole and 71 placebo) included in the MITT were analyzed. The clotrimazole group achieved a higher proportion for the primary endpoint than those with the placebo group (68.2% vs 25.4%; P < .0001), with a 42.8 difference in response rate (95% confidence interval: 30.3, 55.3). The treatment was safe and well tolerated, with 2.7% of related adverse events in the clotrimazole versus 1.5% in the placebo group.ConclusionsClotrimazole 1% otic solution has demonstrated its superiority over the placebo in each study and the pooled analysis. These are the results of the first international, multicenter clinical trials in which clotrimazole 1% otic solution demonstrates efficacy for the treatment of otomycosis.