Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study.

OBJECTIVE: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91. SETTING: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices). PATIENTS: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies. INTERVENTIONS: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7. MAIN OUTCOME MEASURES: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. RESULTS: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated. CONCLUSIONS: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.

Current trends of balloon laryngoplasty in Thailand.

OBJECTIVE: To describe the current trend in balloon laryngoplasty usage and experience by practicing otolaryngologists in Thailand. STUDY DESIGN: Anonymous 11 question online and paper survey of otolaryngologists on their current balloon laryngoplasty practices. SUBJECTS AND METHODS: Current practices and experience in balloon laryngoplasty were queried with multiple choice and open-ended questions. RESULTS: Laser use is the most commonly utilized instrument to treat airway stenosis in Thailand. 86% of respondents do not have experience with balloon dilatation; yet, almost half (47.6%) report they perform a minimum of five airway surgeries per year. Most respondents had been in practice for less than 6 years (41%) and reported that they did not have exposure to balloon use during residency training. The largest barrier reported for the use of balloon instrumentation in the airway is inexperience (44.4%) followed by cost (38.3%), yet most feel that treatment in airway stenosis could benefit by usage of balloons (95.5%). CONCLUSIONS: Most otolaryngologists in Thailand do not have experience with the use of balloon dilatation and lack of exposure remains the largest barrier to its use. Otolaryngologists in Thailand feel that increased usage of balloons in the airway could improve airway stenosis treatment in the country.