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)：对于患有急性中耳炎(AOM)的儿童，10年来一直是几个欧洲国家对年仅6个月大的儿童的标准护理方法。然而，大多数支持警惕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开发的AOM管理指南支持了这种“观察等待”的方法，适用于6-24个月患有非严重疾病和不确定诊断的儿童，以及适用于患有非严重疾病的24个月儿童，无论诊断是否确定。目前尚不清楚抗菌素治疗对患有AOM的幼儿有多大程度的益处，无论他们的病情有多严重。情况可能是这样的：要么可以安全地扩大到患有严重疾病和/或确诊的6-23个月大的儿童，或者从另一方面说，即使是患有非严重疾病的儿童也可以从抗菌治疗中获得足够的好处，从而证明使用抗菌药物是合理的。拟议的研究旨在克服早期研究的方法问题，并解决这一常见疾病影响最大的儿童群体(6-23个月大)的这一重要公共卫生问题。264名儿童将参加一项随机、安慰剂对照的双盲临床试验，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生进行。主要结果将在治疗早期(第4-5天)进行评估，并将比较阿莫西林-克拉维酸组与安慰剂的临床疗效。要在两个治疗组之间进行比较的次要结果包括：(1)治疗结束时(第10-12天)的临床疗效，(2)治疗前7天和研究访问期间的症状负担(使用3个全球评分标准)，(3)在服药72小时前症状恶化的儿童比例，(4)儿童父母服用止痛药的数量，(5)不良事件，(6)对鼻咽细菌定植的影响，(7)鼓室测压结果，(8)直接和间接医疗费用，以及(9)父母对治疗的满意度。我们假设使用阿莫西林-克拉维酸治疗的儿童的最低临床治愈率为85%。因此，每个治疗组总共120名可评估的儿童将允许检测到与安慰剂(85%对70%)15%的差异，80%的力量在0.05的显著水平(双尾)。这项精心设计的针对6-23个月儿童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的解决的特别令人关注的问题，即抗菌治疗和止痛治疗是否能使患有AOM的幼儿比单独使用止痛治疗更早和更全面地改善临床状况(包括缓解不适)。这种更早、更彻底的改善可能构成了抗菌治疗最重要的好处。