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: 7243411
• 负责人: ALEJANDRO HOBERMAN
• 金额: $ 89.08万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7243411
• 关键词: Abate; Academy; Acute; Address; Adverse event; Age; Age-Months; Age-Years; Algorithms; American; Amoxicillin; Analgesics; Blur; Caring; Child; Childhood; Clavulanate; Clinical; Clinical Trials; Clinical Trials Design; Communities; Condition; Country; Detection; Diagnosis; Diagnostic; Disease; Dose; Double-Blind Method; Ear; Earache; Earwax; Enrollment; European; Evaluable Disease; Exclusion; Family Physicians; Fever; Goals; Guidelines; Hand; Hour; Incidence; Infant; Infection; Institutes; Investigation; Medical; Membrane; Meta-Analysis; Minor; Otitis Media; Otitis Media with Effusion; Outcome; Parents; Patient observation; Pediatric Hospitals; Pediatrics; Personal Satisfaction; Pharmaceutical Preparations; Placebo Control; Placebos; Probability; Public Health; Publishing; Randomized; Rate; Reporting; Research; Sample Size; Severities; Significance Level; Standards of Weights and Measures; Symptoms; Tail; Time; Treatment Protocols; Tympanic membrane; Tympanostomy; Visit; Visual Analogue Pain Scale; aged; antimicrobial; antimicrobial drug; base; clinical efficacy; comparative; cost; day; design; dosage; experience; follow-up; improved; member; middle ear; pathogen; response; satisfaction

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，针对急性中耳炎 (AOM) 儿童的“观察等待”方法一直是几个欧洲国家对 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，其中包括具有大量且严重的方法学局限性的试验。美国儿科学会和美国家庭医师学会联合制定的 AOM 管理指南认可了这种“观察等待”方法，适用于 6-24 个月的非严重疾病且诊断不确定的儿童以及>24 个月的非严重疾病儿童无论诊断的确定性如何。目前尚不清楚抗菌治疗对患有 AOM 的幼儿有多大益处，无论其病情严重程度如何。可能的情况是，“观察等待”方法可以安全地扩展到包括 6-23 个月大的患有严重疾病和/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能从治疗中充分受益。抗菌治疗以证明其使用的合理性。拟议的研究旨在克服早期研究的方法学问题，并解决受这种常见病症影响最大的儿童（6-23 个月大）群体中的这一重要公共卫生问题。 264 名儿童将参加一项随机、安慰剂对照、双盲临床试验，该试验由匹兹堡儿童医院及其附属儿科诊所经过验证的耳镜医师进行。主要结局将在治疗早期（第 4-5 天）进行评估，并将比较阿莫西林克拉维酸与安慰剂的临床疗效。治疗组之间要比较的次要结果包括：(1) 治疗结束访视时的临床疗效（第 10-12 天），(2) 治疗前 7 天期间每一天的症状负担（使用 3 个全局量表）在研究访问中，(3) 用药 72 小时前出现症状恶化的儿童比例，(4) 儿童父母服用的镇痛药物数量，(5) 不良事件，(6) 对鼻咽细菌的影响定植，(7) 鼓室导抗测试结果，(8) 直接和间接医疗费用，以及 (9) 家长对治疗的满意度。我们假设接受阿莫西林克拉维酸治疗的儿童的最低总体临床治愈率为 85%。因此，每个治疗组总共 120 名可评估儿童将能够检测到与安慰剂相比 15% 的差异（85% 与 70%），80% 的功效在显着性水平 0.05（双尾）下。这项针对 6-23 个月儿童精心设计的临床试验将解决以前的研究中尚未令人满意地解决的一个特别令人关注的问题，抗菌治疗与镇痛治疗是否可以为患有 AOM 的幼儿提供更早、更全面的整体临床改善（包括缓解不适）优于单独镇痛治疗。这种更早、更彻底的改善可能构成抗菌治疗最重要的益处。