Efficacy of Antimicrobials in Young Children with AOM

抗菌药物对患有 AOM 的幼儿的疗效

• 批准号: 7102128
• 负责人: ALEJANDRO HOBERMAN
• 金额: $ 92万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102128
• 关键词: aging; children; clinical research

DESCRIPTION (provided by applicant): A "watchful waiting" approach for children with acute otitis media (AOM) has been the standard of care for 10 years in several European countries for children as young as 6 months of age. However, most reports endorsing watchful waiting are based on meta-analyses which include trials characterized by numerous and serious methodological limitations. AOM management guidelines jointly developed by the American Academy of Pediatrics and the American Academy of Family Physicians endorsed this "watchful waiting" approach in children 6-24 months with non-severe disease and uncertain diagnosis and in children >24 months with non-severe disease regardless of certainty of diagnosis. It remains unclear to what extent antimicrobial treatment is of benefit in young children with AOM, irrespective of the severity of their illness. It may be the case either that the "watchful waiting" approach might safely be extended to include children aged 6-23 months with severe illness and/or certain diagnosis, or on the other hand, that even children with nonsevere illness would benefit sufficiently from antimicrobial treatment to justify its use. The proposed study is designed to overcome the methodological problems of earlier studies and to address this important public health issue in the group of children (6-23 months of age) who experience the greatest impact of this common condition. 264 children will be enrolled in a randomized, placebo-controlled, double-blind clinical trial to be conducted by validated otoscopists at Children's Hospital of Pittsburgh and at an affiliated pediatric practice. Primary outcome will be assessed at the early on-therapy visit (Day 4-5) and will compare the clinical efficacy of amoxicillin-clavulanate vs. placebo. Secondary outcomes to be compared between treatment groups include: (1) clinical efficacy at the end-of-therapy visit (Day 10-12), (2) symptom burden (using 3 global scales) during each of the first 7 days of therapy and at study visits, (3) proportion of children who develop worsening symptoms before 72 hours of medication, (4) quantity of analgesic medication administered by children's parents, (5) adverse events, (6) effects on nasopharyngeal bacterial colonization, (7) tympanometric outcomes, (8) direct and indirect medical costs, and (9) parental satisfaction with therapy. We assume a minimum overall clinical cure rate of 85% for children treated with amoxicillin-clavulanate. Accordingly, a total of 120 evaluable children per treatment group will allow detection of a 15% difference from placebo (85% vs. 70%), with 80% power at a significance level of 0.05 (two-tailed). This carefully designed clinical trial in children 6-23 months will address an issue of particular concern that has not been satisfactorily addressed in previous studies, whether antimicrobial treatment along with analgesic treatment offers young children with AOM an earlier and more complete overall clinical improvement (including relief of discomfort) than analgesic treatment alone. This earlier and more complete improvement may constitute the most important benefit of antimicrobial treatment.

描述（由申请人提供）：10年来，在几个欧洲国家，急性中耳炎（AOM）儿童的“观察等待”方法一直是6个月大儿童的护理标准。然而，大多数支持观察等待的报告都是基于荟萃分析，其中包括具有大量严重方法学局限性的试验。由美国儿科学会和美国家庭医生学会联合制定的AOM管理指南支持这种“观察等待”方法，适用于6-24个月患有非严重疾病和诊断不确定的儿童，以及24个月以上患有非严重疾病的儿童，无论诊断是否确定。目前尚不清楚抗生素治疗在多大程度上对患有AOM的幼儿有益，无论其疾病的严重程度如何。可能的情况是，“观察等待”方法可以安全地扩展到包括6-23个月的患有严重疾病和/或某些诊断的儿童，或者另一方面，即使是患有非严重疾病的儿童也可以从抗菌治疗中充分受益，证明其使用是合理的。这项拟议的研究旨在克服早期研究的方法问题，并解决这一重要的公共卫生问题，在儿童组（6-23个月）谁经历了最大的影响，这种常见的条件。264名儿童将参加一项随机、安慰剂对照、双盲临床试验，该试验将由匹兹堡儿童医院和附属儿科诊所的经验证的耳镜医师进行。将在早期治疗访视（第4-5天）时评估主要结局，并将比较阿莫西林-克拉维汀与安慰剂的临床疗效。治疗组间比较的次要结局包括：（1）治疗结束访视时的临床疗效（第10-12天），（2）症状负荷（使用3个总体量表）在治疗的前7天和研究访视期间，（3）在用药72小时前出现症状恶化的儿童比例，（4）患儿父母给予的镇痛药物的量，（5）不良事件，（6）对鼻咽细菌定植的影响，（7）鼓室测量结果，（8）直接和间接医疗费用，以及（9）父母对治疗的满意度。我们假设阿莫西林-克拉维汀治疗儿童的最低总体临床治愈率为85%。因此，每个治疗组共有120名可评价儿童，可检测到与安慰剂的15%差异（85% vs. 70%），显著性水平为0.05（双尾）时把握度为80%。这项在6-23个月儿童中精心设计的临床试验将解决一个在以前的研究中没有得到令人满意解决的特别关注的问题，即抗菌药物治疗沿着镇痛治疗是否比单独镇痛治疗能使患有AOM的幼儿获得更早和更完全的整体临床改善（包括缓解不适）。这种更早和更完全的改善可能是抗菌治疗最重要的益处。