Zhaori Getu, Lu Lu, Liu Chunyan, Guo Yongli
Medical Journal Center Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
Beijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery MOE Key Laboratory of Major Diseases in Children Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
Pediatr Investig. 2020 Dec 28;4(4):263-274. doi: 10.1002/ped4.12227. eCollection 2020 Dec.
Antiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease. We need to answer the following questions: do we still need to use rigorously designed randomized controlled clinical trials (RCTs)? Or, will it be enough if we use loosened criteria, observational studies or even retrospective case series and case reports? The answer is "No, we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents." In this article, we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19, and found that among the reports on monotherapies, only remdesivir, and among combined antiviral agents, only the combined regimen with interferon-β1b, lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs. The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19, especially at larger doses. Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed, discussed and emphasized from the specific requirements and considerations of antiviral therapies. We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.
使用抗病毒药物进行抗病毒治疗是针对由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019新型冠状病毒病（COVID-19）治疗的一个非常重要的组成部分。在该疾病大流行期间，明确如何评估抗病毒药物治疗COVID-19的疗效和安全性很重要。我们需要回答以下问题：我们是否仍然需要使用设计严谨的随机对照临床试验（RCT）？或者，如果我们使用宽松的标准、观察性研究甚至回顾性病例系列和病例报告是否就足够了？答案是“不，我们仍然需要使用设计严格的、最好是盲法的多中心RCT来评估抗病毒药物”。在本文中，我们回顾了几乎所有关于COVID-19抗病毒药物单药治疗和联合治疗的RCT报告，发现基于RCT证据，在单药治疗报告中，只有瑞德西韦有效且安全，在联合抗病毒药物中，只有β-1b干扰素、洛匹那韦-利托那韦和利巴韦林的联合方案有效且安全。五项关于氯喹或羟氯喹的RCT结果一致表明，它们在治疗COVID-19时无效且不安全，尤其是在大剂量使用时。临床试验设计中的许多方面可能与试验的成败相关，需要从抗病毒治疗的具体要求和考虑因素出发，对相关因素进行分析、讨论和强调。我们希望这样的讨论对设计儿科抗病毒治疗的临床试验有一定帮助。
