From Aga Khan University, Karachi, Pakistan (F.J., I.N., S.K., B.B., N.B., N.R., A.R., Y.S., A.K.M.Z.); Uppsala University, Uppsala, Sweden (N.B.); and the Bill and Melinda Gates Foundation, Seattle (A.K.M.Z.).
N Engl J Med. 2020 Jul 2;383(1):24-34. doi: 10.1056/NEJMoa1911998.
The World Health Organization (WHO) recommends oral amoxicillin for patients who have pneumonia with tachypnea, yet trial data indicate that not using amoxicillin to treat this condition may be noninferior to using amoxicillin.
We conducted a double-blind, randomized, placebo-controlled noninferiority trial involving children at primary health care centers in low-income communities in Karachi, Pakistan. Children who were 2 to 59 months of age and who met WHO criteria for nonsevere pneumonia with tachypnea were randomly assigned to a 3-day course of a suspension of amoxicillin (the active control) of 50 mg per milliliter or matched volume of placebo (the test regimen), according to WHO weight bands (500 mg every 12 hours for a weight of 4 to <10 kg, 1000 mg every 12 hours for a weight of 10 to <14 kg, or 1500 mg every 12 hours for a weight of 14 to <20 kg). The primary outcome was treatment failure during the 3-day course of amoxicillin or placebo. The prespecified noninferiority margin was 1.75 percentage points.
From November 9, 2014, through November 30, 2017, a total of 4002 children underwent randomization (1999 in the placebo group and 2003 in the amoxicillin group). In the per-protocol analysis, the incidence of treatment failure was 4.9% among placebo recipients (95 of 1927 children) and 2.6% among amoxicillin recipients (51 of 1929 children) (between-group difference, 2.3 percentage points; 95% confidence interval [CI], 0.9 to 3.7). Results were similar in the intention-to-treat analysis. The presence of fever and wheeze predicted treatment failure. The number needed to treat to prevent one treatment failure was 44 (95% CI, 31 to 80). One patient (<0.1%) in each group died. Relapse occurred in 40 children (2.2%) in the placebo group and in 58 children (3.1%) in the amoxicillin group.
Among children younger than 5 years of age with nonsevere pneumonia, the frequency of treatment failure was higher in the placebo group than in the amoxicillin group, a difference that did not meet the noninferiority margin for placebo. (Funded by the Joint Global Health Trials Scheme [of the Department for International Development, Medical Research Council, and Wellcome] and others; RETAPP ClinicalTrials.gov number, NCT02372461.).
世界卫生组织（WHO）建议对呼吸急促的肺炎患者使用口服阿莫西林，但试验数据表明，不使用阿莫西林治疗这种情况可能与使用阿莫西林治疗效果相当。
我们在巴基斯坦卡拉奇的低收入社区的基层医疗中心进行了一项双盲、随机、安慰剂对照的非劣效性试验。年龄在 2 至 59 个月、符合 WHO 呼吸急促非严重肺炎标准的儿童，按照 WHO 体重分组（体重 4 至<10kg 者，每 12 小时给予 50mg/ml 的阿莫西林混悬液；体重 10 至<14kg 者，每 12 小时给予 1000mg；体重 14 至<20kg 者，每 12 小时给予 1500mg），随机分为 3 天疗程的阿莫西林（活性对照）组或匹配容量的安慰剂（试验方案）组。主要结局为阿莫西林或安慰剂治疗 3 天内的治疗失败。预设的非劣效性边界为 1.75 个百分点。
2014 年 11 月 9 日至 2017 年 11 月 30 日，共有 4002 名儿童接受了随机分组（安慰剂组 1999 名，阿莫西林组 2003 名）。在符合方案分析中，安慰剂组治疗失败的发生率为 4.9%（1927 名儿童中的 95 名），阿莫西林组为 2.6%（1929 名儿童中的 51 名）（组间差异，2.3 个百分点；95%置信区间 [CI]，0.9 至 3.7）。意向治疗分析结果相似。发热和喘鸣提示治疗失败。预防 1 例治疗失败所需的治疗人数为 44 人（95%CI，31 至 80）。每组各有 1 名（<0.1%）儿童死亡。安慰剂组 40 名（2.2%）儿童和阿莫西林组 58 名（3.1%）儿童出现复发。
在 5 岁以下患有非严重肺炎的儿童中，安慰剂组的治疗失败频率高于阿莫西林组，但差异未达到安慰剂的非劣效性边界。（由国际发展部、医学研究委员会和惠康共同资助的联合全球健康试验计划[以及其他机构]；RETAPP ClinicalTrials.gov 编号，NCT02372461。）
