Department of Emergency Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
School of Public Health, University of Alberta, Edmonton, AB, Canada.
Br J Clin Pharmacol. 2021 Apr;87(4):1758-1767. doi: 10.1111/bcp.14598. Epub 2020 Nov 24.
To assess whether randomized clinical trials (RCTs) proposed to evaluate the treatment of patients with COVID-19 with hydroxychloroquine (HQ) or chloroquine early in the pandemic included plans to measure outcomes that would translate into meaningful efficacy/effectiveness and safety outcomes.
The World Health Organization International Clinical Trials Registry Platform database was searched for registers of RCTs evaluating HQ or chloroquine, alone or in combination, compared with other treatments for patients diagnosed with COVID-19. The final search was performed on 8 April 2020.
Among 51 registered RCTs (median sample size 262; interquartile range: 100, 520), 34 (67%) reported a clinical outcome, 12 (24%) a surrogate outcome, and 5 (10%) a combination of clinical and surrogate outcomes as primary endpoints. Six (15%) trials included the World Health Organization scale for clinical improvement as a primary clinical outcome. Clinical improvement and mortality accounted for 45% of the unique domains among 18 clinical outcome domains of efficacy. Twenty-four (47%) RCTs did not describe plans to assess safety outcomes; when assessed, safety outcomes were determined in generic terms of total, severe or serious adverse events.
The RCTs investigating HQ or chloroquine during the early stages of the COVID-19 pandemic included heterogeneous and insufficient approaches to measure efficacy/effectiveness and safety relevant to patients and clinical practice. These findings provide insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19. Trialists need to adapt quickly to the research progress on COVID-19, ensuring that core outcome measures are assessed in ongoing RCTs.
评估在 COVID-19 大流行早期提出的评估羟氯喹（HQ）或氯喹治疗 COVID-19 患者的随机临床试验（RCT）是否包含计划测量可转化为有意义的疗效/有效性和安全性结果的结局。
在世界卫生组织国际临床试验注册平台数据库中搜索评估 HQ 或氯喹单独或联合与其他 COVID-19 患者治疗方法比较的 RCT 登记册。最后一次搜索于 2020 年 4 月 8 日进行。
在 51 项已注册 RCT 中（中位数样本量为 262；四分位距：100，520），34 项（67%）报告了临床结局，12 项（24%）报告了替代结局，5 项（10%）报告了临床和替代结局的组合作为主要终点。6 项（15%）试验将世界卫生组织临床改善量表作为主要临床结局。在疗效的 18 个临床结局领域中，临床改善和死亡率占 45%的独特领域。24 项（47%）RCT 未描述评估安全性结局的计划；当评估安全性结局时，以总不良事件、严重不良事件或严重不良事件的一般术语来确定。
在 COVID-19 大流行早期调查 HQ 或氯喹的 RCT 采用了衡量与患者和临床实践相关的疗效/有效性和安全性的异质和不足的方法。这些发现为制定 COVID-19 患者使用这些药物的疗效/有效性和安全性的临床和监管决策提供了参考。试验人员需要迅速适应 COVID-19 研究进展，确保正在进行的 RCT 中评估核心结局测量。
