Ranakusuma Respati W, McCullough Amanda R, Safitri Eka D, Pitoyo Yupitri, Widyaningsih Widyaningsih, Del Mar Christopher B, Beller Elaine M
Institute for Evidence-Based Healthcare, Bond University, 14 University Drive, Robina, QLD 4226 Australia.
Clinical Epidemiology and Evidence-Based Medicine Unit, Dr. Cipto Mangunkusumo General Hospital - Faculty of Medicine Universitas Indonesia, Diponegoro 71, Jakarta, 10430 Indonesia.
Pilot Feasibility Stud. 2020 Aug 29;6:121. doi: 10.1186/s40814-020-00671-5. eCollection 2020.
Acute otitis media (AOM) is associated with high antibiotic prescribing rates. Antibiotics are somewhat effective in improving pain and middle ear effusion (MEE); however, they have unfavourable effects. Alternative treatments, such as corticosteroids as anti-inflammatory agents, are needed. Evidence for the efficacy of these remains inconclusive. We conducted a pilot study to test feasibility of a proposed large-scale randomised controlled trial (RCT) to assess the efficacy of corticosteroids for AOM.
We conducted a pilot, pragmatic, parallel, open-label RCT of oral corticosteroids for paediatric AOM in primary and secondary/tertiary care centres in Indonesia. Children aged 6 months-12 years with AOM were randomised to either prednisolone or control (1:1). Physicians were blinded to allocation. Our objectives were to test the feasibility of our full RCT procedures and design, and assess the mechanistic effect of corticosteroids, using tympanometry, in suppressing middle ear inflammation by reducing MEE.
We screened 512 children; 62 (38%) of 161 eligible children were randomised and 60 were analysed for the primary clinical outcome. All study procedures were completed successfully by healthcare personnel and parents/caregivers, despite time constraints and high workload. All eligible, consenting children were appropriately randomised. One child did not take the medication and four received additional oral corticosteroids. Our revised sample size calculation verified 444 children are needed for the full RCT. Oral corticosteroids did not have any discernible effects on MEE resolution and duration. There was no correlation between pain or other symptoms and MEE change. However, prednisolone may reduce pain intensity at day 3 (Visual Analogue Scale mean difference - 7.4 mm, 95% confidence interval (CI) - 13.4 to - 1.3, = 0.018), but cause drowsiness (relative risk (RR) 1.8, 95% CI 1.1 to 2.8, = 0.016). Tympanometry curves at day 7 may be improved (RR 1.8, 95% CI 1.0 to 2.9). We cannot yet confirm these as effects of corticosteroids due to insufficient sample size in this pilot study.
It is feasible to conduct a large, pragmatic RCT of corticosteroids for paediatric AOM in Indonesia. Although oral corticosteroids may reduce pain and improve tympanometry curves, it requires an adequately powered clinical trial to confirm this.
Study registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018.
急性中耳炎（AOM）与高抗生素处方率相关。抗生素在改善疼痛和中耳积液（MEE）方面有一定效果；然而，它们也有不良影响。需要替代治疗方法，如使用皮质类固醇作为抗炎剂。这些治疗方法的疗效证据尚无定论。我们进行了一项试点研究，以测试拟议的大规模随机对照试验（RCT）评估皮质类固醇治疗AOM疗效的可行性。
我们在印度尼西亚的初级和二级/三级护理中心进行了一项针对小儿AOM的口服皮质类固醇的试点、实用、平行、开放标签的RCT。6个月至12岁患有AOM的儿童被随机分为泼尼松龙组或对照组（1:1）。医生对分组情况不知情。我们的目标是测试完整RCT程序和设计的可行性，并使用鼓室图评估皮质类固醇通过减少MEE来抑制中耳炎症的机制性效果。
我们筛查了512名儿童；161名符合条件的儿童中有62名（38%）被随机分组，60名儿童被分析了主要临床结局。尽管存在时间限制和高工作量，但医护人员以及家长/照顾者都成功完成了所有研究程序。所有符合条件且同意参与的儿童都被适当地随机分组。一名儿童未服药，四名儿童额外接受了口服皮质类固醇。我们修订后的样本量计算证实完整的RCT需要444名儿童。口服皮质类固醇对MEE的消退和持续时间没有任何明显影响。疼痛或其他症状与MEE变化之间没有相关性。然而，泼尼松龙可能在第3天减轻疼痛强度（视觉模拟量表平均差异 -7.4 mm，95%置信区间（CI）-13.4至-1.3，P = 0.018），但会导致嗜睡（相对风险（RR）1.8，95%CI 1.1至2.8，P = 0.016）。第7天的鼓室图曲线可能有所改善（RR 1.8，95%CI 1.0至2.9）。由于本试点研究样本量不足，我们尚不能确认这些是皮质类固醇的作用。
在印度尼西亚对小儿AOM进行皮质类固醇的大规模实用RCT是可行的。尽管口服皮质类固醇可能减轻疼痛并改善鼓室图曲线，但需要有足够效力的临床试验来证实这一点。
研究注册号：ACTRN12618000049279。注册机构名称：澳大利亚新西兰临床试验注册中心（ANZCTR）。注册日期：2018年1月16日。
