Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

BackgroundWHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.
MethodologyThis multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2–59 months of age, who received either oral amoxycillin (31–54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.
Principal FindingsWe randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).
ConclusionsTreating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.
Trial RegistrationClinicalTrials.gov NCT00407394

背景 世界卫生组织（World Health Organization）定义的需抗生素治疗的肺炎，在发展中国家是导致儿童发病与死亡的重要病因。由于相当比例的肺炎由病毒感染引发，此类患儿更易出现喘息症状，目前抗生素在此类病例中的过度处方问题已引发学界关注。为此本试验旨在验证两种治疗方案——安慰剂与阿莫西林——对于伴喘息的非重症肺炎患儿的治疗等效性，这些患儿在接受沙丁胺醇雾化吸入后仍存在持续性呼吸增快，且胸部X线片结果正常。
方法 本多中心、随机安慰剂对照双盲临床试验旨在探究安慰剂与阿莫西林的等效疗效，试验在印度8家政府医院的门诊医疗环境中开展。研究对象为年龄2~59个月的儿童，他们分别接受口服阿莫西林（31~54 mg/kg/日，分3次给药，疗程3天）或安慰剂，同时联合标准支气管扩张剂治疗。主要结局指标为第4天及之前发生的临床失败。
主要研究结果 本试验共纳入安慰剂组836例、阿莫西林组835例受试者。安慰剂组201例（24.0%）出现临床失败，阿莫西林组166例（19.9%）出现临床失败，风险差为4.2%（抗生素组更具优势，95%置信区间：0.2~8.1）。两组受试者的治疗依从性均高于96%，98.9%的受试者在第4天完成随访。临床失败与以下因素相关：（i）安慰剂治疗（校正比值比=1.28，95%置信区间：1.01~1.62）；（ii）呼吸频率较基线增加超过10次/分钟（校正比值比=1.51，95%置信区间：1.19~1.92）；（iii）入组时存在呕吐症状（校正比值比=1.49，95%置信区间：1.13~1.96）；（iv）既往使用支气管扩张剂史（校正比值比=1.71，95%置信区间：1.30~2.24）；（v）治疗不依从（校正比值比=8.06，95%置信区间：4.36~14.92）。
结论 对于伴喘息的非重症肺炎患儿，安慰剂治疗与口服阿莫西林治疗并不等效。
试验注册 ClinicalTrials.gov NCT00407394