Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy

Abstract

To study the safety and efficacy of continuous intratympanic dexamethasone-phosphate (Dex-P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of systemic therapy. Randomized, double-blind, placebo controlled multicenter trial. Patients with ISSHL and insufficient recovery (mean 4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either Dex-P (4 mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the round window niche via a temporarily implanted catheter. For ethical reasons, intratympanic treatment was continued with Dex-P in all patients for another 14 days after the placebo-controlled study period. According to a two-step adaptive study design an interim analysis was performed after inclusion of 23 patients. Intention-to-treat analysis for the primary outcome criterion (4PTA: 0.5-3 kHz) during the placebo controlled study period (14 days) showed an average hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: -7.1-24.1) was statistically not significant (p = .26). Of the secondary outcome parameters, the largest benefit of local salvage therapy was found for maximum speech discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5% (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow-up period (i.e. after all patients received intratympanic Dex-P) hearing improvement in the two groups was very similar. No serious adverse events were observed. Sample size calculation after the interim analysis resulted in stopping of the trial. The tendency toward better hearing improvement in the treatment group, the rather conservative inclusion criteria, the limited placebo-controlled observation period and the absence of serious adverse events supports further investigation local inner ear drug delivery as a first or second line treatment option for ISSHL.