Determining the impact of Benzathine penicillin G prophylaxis in children with latent rheumatic heart disease (GOAL trial): Study protocol for a randomized controlled trial
Determining the impact of Benzathine penicillin G prophylaxis in children with latent rheumatic heart disease (GOAL trial): Study protocol for a randomized controlled trial
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DOI：
10.1016/j.ahj.2019.06.001
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发表时间：
2019-09-01
影响因子：
4.8
通讯作者：
Steer, Andrew
中科院分区：
文献类型：
--
作者：
Beaton, Andrea;Okello, Emmy;Steer, Andrew
背景 风湿性心脏病（RHD）在低收入和中等收入国家仍然是一种高患病率。大多数 RHD 患者就诊较晚，错过了从二级抗生素预防中受益的机会。超声心动图筛查可以检测潜伏性 RHD，但二级预防对筛查检测到的个体的影响尚不清楚。 方法/设计 本试验旨在确定每 4 周注射一次苯甲乙胺青霉素 G (BPG) 进行二级预防是否可以改善诊断为潜伏性 RHD 的儿童的预后。这是一项随机对照试验，对象是乌干达北部 5 至 17 岁的自愿儿童，根据 2012 年世界心脏联合会标准，经超声心动图证实患有边缘性 RHD 或轻度明确 RHD。符合条件的儿童将被随机分配接受每 4 周肌内注射 BPG 或不接受医疗干预，并进行为期 2 年的随访。将通过为干预组和对照组的参与者建立同伴支持小组来支持试验中持续干预的坚持和保留。由四名独立专家组成的盲法超声心动图评审小组将通过共识审查确定入组时的超声心动图分类和轨迹。主要结果是与对照组相比，BPG 组中表现出潜在 RHD 超声心动图进展的儿童比例。次要结果是与对照组相比，BPG 组中超声心动图显示潜在 RHD 消退的儿童比例。假设对照组进展 15%，916 名参与者的样本量将提供 90% 的功效来检测 50% 的相对风险降低。计划研究持续时间为 2018 年至 2021 年。 讨论 由于缺乏二级预防益处的证据，有关超声心动图筛查 RHD 作用的政策决策已陷入停滞。我们的研究结果将立即为被诊断患有潜在 RHD 的儿童提供护理标准，并将在 2-3 年内制定实用且可扩展的计划，从而大大减轻我们一生中 RHD 的负担。
Background Rheumatic heart disease (RHD) remains a high prevalence condition in low- and middle-income countries. Most individuals with RHD present late, missing the opportunity to benefit from secondary antibiotic prophylaxis. Echocardiographic screening can detect latent RHD, but the impact of secondary prophylaxis in screen-detected individuals is not known.Methods/Design This trial aims to determine if secondary prophylaxis with every-4-week injectable Benzathine penicillin G (BPG) improves outcomes for children diagnosed with latent RHD. This is a randomized controlled trial in consenting children, aged 5 to 17 years in Northern Uganda, confirmed to have borderline RHD or mild definite RHD on echocardiography, according to the 2012 World Heart Federation criteria. Qualifying children will be randomized to every-4-week injectable intramuscular BPG or no medical intervention and followed for a period of 2 years. Ongoing intervention adherence and retention in the trial will be supported through the establishment of peer support groups for participants in the intervention and control arms. A blinded echocardiography adjudication panel consisting of four independent experts will determine the echocardiographic classification at enrollment and trajectory through consensus review.The primary outcome is the proportion of children in the BPG-arm who demonstrate echocardiographic progression of latent RHD compared to those in the control arm. The secondary outcome is the proportion of children in the BPG-arm who demonstrate echocardiographic regression of latent RHD compared to those in the control arm. A sample size of 916 participants will provide 90% power to detect a 50% relative risk reduction assuming a 15% progression in the control group. The planned study duration is from 2018-2021.Discussion Policy decisions on the role of echocardiographic screening for RHD have stalled because of the lack of evidence of the benefit of secondary prophylaxis. The results of our study will immediately inform the standard of care for children diagnosed with latent RHD and will shape, over 2-3 years, practical and scalable programs that could substantially decrease the burden of RHD in our lifetime.