PMID- 36599786 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20230619 IS - 1879-1476 (Electronic) IS - 0385-8146 (Linking) VI - 50 IP - 4 DP - 2023 Aug TI - Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study. PG - 521-533 LID - S0385-8146(22)00242-5 [pii] LID - 10.1016/j.anl.2022.12.013 [doi] AB - OBJECTIVE: The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. METHODS: This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration. RESULTS: In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups. CONCLUSION: The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Takahashi, Masahiro AU - Takahashi M AD - Department of Otorhinolaryngology, International University of Health and Welfare, Mita hospital 1-4-3 Mita, Minato-ku, Tokyo, 108-8329, Japan. FAU - Iwasaki, Satoshi AU - Iwasaki S AD - Department of Otorhinolaryngology, International University of Health and Welfare, Mita hospital 1-4-3 Mita, Minato-ku, Tokyo, 108-8329, Japan. Electronic address: iwasakis@iuhw.ac.jp. FAU - Kawano, Toshiro AU - Kawano T AD - Department of Otolaryngology, Nishiyokohama International Hospital, 56 Gumizawacho, Yokohama Totsuka-ku, Kanagawa, 245-0062, Japan. FAU - Ikoma, Ryo AU - Ikoma R AD - Department of Otolaryngology, Yokohama Minami Kyosai Hospital, 1-21-1 Mutsuurahigashi, Yokohama Kanazawa-ku, Kanagawa, 236-0037, Japan. FAU - Oka, Shigeru AU - Oka S AD - Oka Otolaryngology Clinic, 21-31, Urayasunishimachi, Okayama Minami-ku, Okayama, 702-8025, Japan. FAU - Terasaki, Masako AU - Terasaki M AD - Department of ENT, Head and Neck Surgery, Odawarashi Hospital, 46 Kuno, Odawara, Kanagawa, 250-8558, Japan. FAU - Sato, Hiroaki AU - Sato H AD - Department of Otolaryngology, Head and Neck Surgery, Iwate Medical University, 2-1-1 Idaidori, Shiwa-gun Yahaba-cho, Iwate, 028-3695, Japan. FAU - Kariya, Shin AU - Kariya S AD - Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan. FAU - Takahashi, Haruo AU - Takahashi H AD - Department of Otolaryngology, Nagasaki Harbor Medical Center, 6-39 Shinchi-machi, Nagasaki, 850-8555, Japan. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20230103 PL - Netherlands TA - Auris Nasus Larynx JT - Auris, nasus, larynx JID - 7708170 RN - 0 (Anti-Bacterial Agents) RN - 6GNT3Y5LMF (Levofloxacin) SB - IM MH - Humans MH - Anti-Bacterial Agents/adverse effects MH - Levofloxacin/adverse effects MH - *Otitis Media/drug therapy MH - *Otitis Media, Suppurative/drug therapy MH - Ear, Middle OTO - NOTNLM OT - Antimicrobials OT - Clinical trial OT - Levofloxacin OT - Otic solution OT - Otitis media OT - Resolution of inflammation COIS- Declaration of Competing Interest All the authors have declared that there are no conflicts of interest in connection with this manuscript. EDAT- 2023/01/05 06:00 MHDA- 2023/06/19 13:08 CRDT- 2023/01/04 21:55 PHST- 2022/10/02 00:00 [received] PHST- 2022/12/02 00:00 [revised] PHST- 2022/12/26 00:00 [accepted] PHST- 2023/06/19 13:08 [medline] PHST- 2023/01/05 06:00 [pubmed] PHST- 2023/01/04 21:55 [entrez] AID - S0385-8146(22)00242-5 [pii] AID - 10.1016/j.anl.2022.12.013 [doi] PST - ppublish SO - Auris Nasus Larynx. 2023 Aug;50(4):521-533. doi: 10.1016/j.anl.2022.12.013. Epub 2023 Jan 3.