Background Around 15%–20% of children with acute otitis media present with ear discharge due to a spontaneous tear or perforation of the eardrum (AOMd). Current guidance recommends clinicians to consider oral antibiotics as first-line treatment in this condition. The opening in the eardrum however should allow topical antibiotics to enter the middle ear directly. Local administration of antibiotics does not expose children to systemic side effects and may put less selective resistance pressure on bacteria. Evidence on the effectiveness of this approach in children with AOMd is lacking. Methods and analysis A primary care-based, open, individually randomised, controlled, non-inferiority trial. The trial aims to recruit 350 children aged 6 months to 12 years with AOMd and ear pain and/or fever. Participants will be randomised to 7 days of hydrocortisone-bacitracin-colistin eardrops five drops three times daily or amoxicillin oral suspension 50 mg/kg body weight per day, divided over three doses. Parents will keep a daily diary of AOM symptoms, adverse events and complications for 2 weeks. In addition, they will record AOM recurrences, healthcare utilisation and societal costs for 3 months. The primary outcome is the proportion of children without ear pain and fever at day 3. Secondary outcomes include ear pain and fever intensity/severity; days with ear discharge; eardrum perforation at 2 weeks; adverse events during first 2 weeks; costs; and cost effectiveness at 2 weeks and 3 months. The primary analyses will be intention-to-treat and per-protocol analyses will be conducted as well. Ethics and dissemination The medical research ethics committee Utrecht, The Netherlands has given ethical approval (17-400/G-M). Parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. Trial registration number The Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017.

中文翻译：

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耳部分泌物急性中耳炎患儿的局部或口服抗生素：随机对照非劣效性试验的研究方案

背景 大约 15%–20% 的急性中耳炎儿童由于耳膜自发性撕裂或穿孔 (AOMd) 而出现耳分泌物。目前的指南建议临床医生考虑将口服抗生素作为这种情况下的一线治疗。然而，鼓膜中的开口应允许局部抗生素直接进入中耳。抗生素的局部给药不会使儿童暴露于全身性副作用，并且可能对细菌施加较小的选择性抗药性压力。缺乏证据表明这种方法对 AOMd 儿童的有效性。方法和分析 一项基于初级保健、开放、个体随机、对照、非劣效性试验。该试验旨在招募 350 名 6 个月至 12 岁患有 AOMd 和耳痛和/或发烧的儿童。参与者将被随机分配到为期 7 天的氢化可的松-杆菌肽-粘菌素滴耳剂，每天 3 次，每次 5 滴，或每天 50 mg/kg 体重的阿莫西林口服混悬液，分三剂服用。父母将在 2 周内每天记录 AOM 症状、不良事件和并发症。此外，他们将记录 3 个月的 AOM 复发、医疗保健利用率和社会成本。主要结果是第 3 天没有耳痛和发烧的儿童比例。次要结果包括耳痛和发烧强度/严重程度；耳朵有分泌物的天数；耳膜穿孔 2 周; 前 2 周的不良事件；费用；以及 2 周和 3 个月的成本效益。主要分析将是意向治疗，也将进行符合方案分析。伦理和传播 荷兰乌得勒支医学研究伦理委员会已给予伦理批准 (17-400/GM)。参与者的父母/监护人将提供书面知情同意书。研究结果将提交在同行评审的医学期刊上发表，并在相关（国际）国家科学会议上发表。试验登记号荷兰国家试验登记处；NTR6723。注册日期：2017 年 11 月 27 日。