羟氯喹治疗轻至中度 2019 冠状病毒病：一项安慰剂对照双盲试验。
Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial.
机构信息
Service des Maladies Infectieuses et Tropicales, CHU d'Angers, Angers, France; CRCINA, Inserm, Université de Nantes, Université d'Angers, Angers, France.
Emergency Department, CHU d'Angers, Angers, France; Institut MitoVasc, UMR CNRS 6215 INSERM 1083, Université d'Angers, Angers, France.
出版信息
Clin Microbiol Infect. 2021 Aug;27(8):1124-1130. doi: 10.1016/j.cmi.2021.03.005. Epub 2021 Apr 1.
OBJECTIVES
To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening.
METHODS
We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10.
RESULTS
The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45-2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points.
CONCLUSION
In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04325893 (https://clinicaltrials.gov/ct2/show/NCT04325893).
目的
确定羟氯喹是否能降低有恶化风险的轻至中度 2019 冠状病毒病（COVID-19）患者的不良结局风险。
方法
我们进行了一项多中心、随机、双盲、安慰剂对照试验，评估羟氯喹在至少有以下一种恶化风险因素的 COVID-19 患者中的作用：需要补充氧气、年龄≥75 岁、年龄在 60 至 74 岁之间、至少有一种合并症。严重需要氧疗>3 L/min 或需要 ICU 治疗的患者被排除在外。符合条件的患者以 1:1 的比例随机分为两组，分别接受羟氯喹 800 mg 治疗，第 0 天 1 次，随后 8 天每天 400 mg，或安慰剂。主要终点为随机分组后 14 天内死亡或开始接受有创性机械通气的复合终点。次要终点包括第 14 天和第 28 天的死亡率和临床转归，以及第 5 天和第 10 天的病毒脱落情况。
结果
由于法国大流行速度放缓，该试验在纳入 250 例患者后停止。意向治疗人群包括安慰剂组和羟氯喹组各 123 例和 124 例患者。中位年龄为 77 岁（58-86 岁），250 例患者中有 151 例（60.4%）需要氧疗。羟氯喹组有 9/124（7.3%）例患者发生主要终点事件，安慰剂组有 8/123（6.5%）例患者发生主要终点事件（相对风险 1.12；95%CI 0.45-2.80）。羟氯喹组第 5 天和第 10 天 SARS-CoV-2 RT-PCR 检测阳性率分别为 72.8%（75/103）和 57.1%（52/91），安慰剂组分别为 73.0%（73/100）和 56.6%（47/83）。两组在其他次要终点均无差异。
结论
在这项纳入主要为年龄较大的轻至中度 COVID-19 患者的小型试验中，接受羟氯喹治疗的患者在临床或病毒学结局方面并未优于接受安慰剂的患者。
试验注册
ClinicalTrials.gov 标识符：NCT04325893（https://clinicaltrials.gov/ct2/show/NCT04325893）。
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